Digital Commons Network^™

A Phase 1 Study Of Intravenous Busulfan As A Conditioning Regimen For Multiple Myeloma, Sabarinath V. Radhakrishnan, Michael Boyer, Catherine M. Sherwin, Maurizio Zangari, Guido Tricot

Pediatrics Faculty Publications

The efficacy of melphalan (MEL) 140 mg/m 2 pre-transplant conditioning versus MEL 200 mg/m 2 for the elderly is still debated. We hypothesized that single-agent intravenous busulfan (BU) would show significant anti-myeloma efficacy and be better tolerated by elderly patients. A prospective 3+3 dose escalation study enrolled symptomatic multiple myeloma (MM) patients 65 years or older with SWOG performance 0–2 for treatment with intravenous BU pre-transplant at different administration levels. The primary objective was to determine the maximum tolerated dose (MTD) of BU that could be safely given over the least number of days. All patients, except one, received maintenance …

Statistical Multiscale Mapping Of Idh1, Mgmt, And Microvascular Proliferation Inhuman Braintumors From Multiparametric Mr And Spatially-Registered Core Biopsy, Jason G. Parker, Emily E. Diller, Sha Cao, Jeremy T. Nelson, Kristen W. Yeom, Chang Ho, Robert M. Lober

Pediatrics Faculty Publications

We propose a statistical multiscale mapping approach to identify microscopic and molecular heterogeneity across a tumor microenvironment using multiparametric MR (mp-MR). Twenty-nine patients underwent pre-surgical mp-MR followed by MR-guided stereotactic core biopsy. The locations of the biopsy cores were identified in the pre-surgical images using stereotactic bitmaps acquired during surgery. Feature matrices mapped the multiparametric voxel values in the vicinity of the biopsy cores to the pathologic outcome variables for each patient and logistic regression tested the individual and collective predictive power of the MR contrasts. A non-parametric weighted k-nearest neighbor classifier evaluated the feature matrices in a leave-one-out cross …

Optocardiography And Electrophysiology Studies Of Ex Vivo Langendorff-Perfused Hearts., Luther M. Swift, Rafael Jaimes Iii, Damon Mccullough, Morgan Burke, Marissa Reilly, Takuya Maeda, Hanyu Zhang, Nobuyuki Ishibashi, Jack M. Rogers, Nikki Gillum Posnack

Pediatrics Faculty Publications

No abstract provided.

Myeloid-Derived Suppressor Cells And Pancreatic Cancer: Implications In Novel Therapeutic Approaches, Anita Thyagarajan, Mamdouh Salman A. Alshehri, Kelly L.R. Miller, Catherine M. Sherwin, Jeffery B. Travers, Ravi P. Sahu

Pediatrics Faculty Publications

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating human malignancy with poor prognosis and low survival rates. Several cellular mechanisms have been linked with pancreatic carcinogenesis and also implicated in inducing tumor resistance to known therapeutic regimens. Of various factors, immune evasion mechanisms play critical roles in tumor progression and impeding the efficacy of cancer therapies including PDAC. Among immunosuppressive cell types, myeloid-derived suppressor cells (MDSCs) have been extensively studied and demonstrated to not only support PDAC development but also hamper the anti-tumor immune responses elicited by therapeutic agents. Notably, recent efforts have been directed in devising novel approaches to target …

Child And Parent Perceptions Of Participating In Multimethod Research In The Acute Aftermath Of Pediatric Injury, Christine Kindler, Nancy Kassam-Adams, Tia Borger, Meghan L. Marsac

Pediatrics Faculty Publications

Background:

Despite growing evidence that participation in psychological trauma research is well tolerated by children and parents, ethics boards may voice concerns regarding research with families with recent acute trauma exposure. Factors impacting child and parent experiences of research participation are not well documented, particularly for methodologies including observational components.

Objectives:

This study describes child and parent perceptions of research participation involving an observational task following an acute traumatic event and explores potential relationships between research experience and selected demographic factors (race/ethnicity, sex, age, prior trauma exposure), and post-traumatic stress symptoms.

Methods:

As part of a larger study on the …

Antibiotic Treatment Of Suspected And Confirmed Neonatal Sepsis Within 28 Days Of Birth: A Retrospective Analysis, Jadon S. Wagstaff, Robert J. Durrant, Michael G. Newman, Rachael Eason, Robert M. Ward, Catherine M.T. Sherwin, Elena Y. Enioutina

Pediatrics Faculty Publications

Neonatal sepsis causes significant mortality and morbidity worldwide. Diagnosis is usually confirmed via blood culture results. Blood culture sepsis confirmation can take days and suffer from contamination and false negatives. Empiric therapy with antibiotics is common. This study aims to retrospectively describe and compare treatments of blood culture-confirmed and unconfirmed, but suspected, sepsis within the University of Utah Hospital system. Electronic health records were obtained from 1,248 neonates from January 1, 2006, to December 31, 2017. Sepsis was categorized into early-onset (≤3 days of birth, EOS) and late-onset (>3 and ≤28 days of birth, LOS) and categorized as culture-confirmed …

Implementing A Novel Quality Improvement-Based Approach To Data Quality Monitoring And Enhancement In A Multipurpose Clinical Registry, Jesse Pratt, Daniel Jeffers, Eileen C. King, Michael D. Kappelman, Jennifer Collins, Peter Margolis, Howard Baron, Julie A. Bass, Mikelle D. Bassett, Genie L. Beasley, Keith J. Benkov, Jeffrey A. Bornstein, Jose M. Cabrera, Wallace Crandall, Liz D. Dancel, Monica P. Garin-Laflam, John E. Grunow, Barry Z. Hirssch, Edward Hoffenberg, Esther Israel, Traci W. Jester, Fevronia Kiparissi, Arathi Lakhole, Sameer P. Lapsia, Phillip Minar, Fernando A. Navarro, Haley Neef, Kt Park, Dinesh S. Pashankar, Ashish S. Patel, Victor M. Pineiro, Chrles M. Samson, Kelly C. Sandberg, Steven J. Steiner, Jennifer A. Strople, Boris Sudel, Jillian S. Sullivan, David L. Suskind, Vikas Uppal, Prateek D. Wali

Pediatrics Faculty Publications

Objective: To implement a quality improvement based system to measure and improve data quality in an observational clinical registry to support a Learning Healthcare System.

Data Source: ImproveCareNow Network registry, which as of September 2019 contained data from 314,250 visits of 43,305 pediatric Inflammatory Bowel Disease (IBD) patients at 109 participating care centers.

Study Design: The impact of data quality improvement support to care centers was evaluated using statistical process control methodology. Data quality measures were defined, performance feedback of those measures using statistical process control charts was implemented, and reports that identified data items not following data quality checks …

Learning From Experience: Avoiding Common Pitfalls In Multicenter Quality Improvement Collaboratives, Jonathan D. Thackeray, Carrie A. Baker, Rachel P. Berger

Pediatrics Faculty Publications

Clinicians and researchers often tout the newest breakthrough or latest successful intervention. Sharing wins, however, is often done at the expense of sharing obstacles, failures, and subsequent adjustments, which are the cornerstone of quality improvement (QI).^1–3 Here, we share 3 key lessons from 2 hospital-based QI initiatives—the Ohio Timely Recognition of Abuse Injuries (TRAIN) Collaborative and the University of Pittsburgh Medical Center (UPMC) Child Abuse Initiative (UPMC-CAI). Both focus on early identification, proper evaluation, and accurate reporting of child maltreatment. These are important clinical issues because many children who die or nearly die from maltreatment had been …

Predicted Disease Compositions Of Human Gliomas Estimated From Multiparametric Mri Can Predict Endothelial Proliferation, Tumor Grade, And Overall Survival, Emily E. Diller, Sha Cao, Beth Ey, Robert M. Lober, Jason G. Parker

Pediatrics Faculty Publications

Background and Purpose: Biopsy is the main determinants of glioma clinical management, but require invasive sampling that fail to detect relevant features because of tumor heterogeneity. The purpose of this study was to evaluate the accuracy of a voxel-wise, multiparametric MRI radiomic method to predict features and develop a minimally invasive method to objectively assess neoplasms. Methods: Multiparametric MRI were registered to T1-weighted gadolinium contrast-enhanced data using a 12 degree-of-freedom affine model. The retrospectively collected MRI data included T1-weighted, T1-weighted gadolinium contrast-enhanced, T2-weighted, fluid attenuated inversion recovery, and multi-b-value diffusion-weighted acquired at 1.5T or 3.0T. Clinical experts provided voxel-wise annotations …

Plasticizer Interaction With The Heart: Chemicals Used In Plastic Medical Devices Can Interfere With Cardiac Electrophysiology., Rafael Jaimes, Damon Mccullough, Bryan Siegel, Luther Swift, Daniel Mcinerney, James Hiebert, Erick A Perez-Alday, Beatriz Trenor, Jiansong Sheng, Javier Saiz, Larisa G Tereshchenko, Nikki Gillum Posnack

Pediatrics Faculty Publications

BACKGROUND: Phthalates are used as plasticizers in the manufacturing of flexible, plastic medical products. Patients can be subjected to high phthalate exposure through contact with plastic medical devices. We aimed to investigate the cardiac safety and biocompatibility of mono-2-ethylhexyl phthalate (MEHP), a phthalate with documented exposure in intensive care patients.

METHODS: Optical mapping of transmembrane voltage and pacing studies were performed on isolated, Langendorff-perfused rat hearts to assess cardiac electrophysiology after MEHP exposure compared with controls. MEHP dose was chosen based on reported blood concentrations after an exchange transfusion procedure.

RESULTS: Thirty-minute exposure to MEHP increased the atrioventricular node (147 …

Evaluation Of The Project P.A.T.H.S. In Mainland China: Findings Based On Student Diaries, Daniel T. L. Shek, Xiaoqin Zhu, Janet T. Y. Leung, Tak Yan Lee, Florence K. Y. Wu

Pediatrics Faculty Publications

Objectives: Based on 859 student diaries, the present study evaluated a positive youth development program entitled “Tin Ka Ping (TKP) Positive Adolescent Training through Holistic Social programs (P.A.T.H.S.) ” project implemented in mainland China during the 2015–2016 academic year. Method: To understand the perceived effectiveness of the students, the study analyzed quantitative as well as qualitative data derived from the student diaries. Results: The students held very positive views toward the program and the implementers. The narratives of the students also showed that they perceived improvement in the intrapersonal, interpersonal, familial, and societal domains after joining the program. Conclusion: In …

Venoarterial Extracorporeal Membrane Oxygenation And Implantable Cardioverter-Defibrillator Implantation In A Hemodynamically Unstable Infant With Ventricular Tachycardia From Multiple Cardiac Rhabdomyomas, Victor Kieu, Richard J. Czosek, Timothy K. Knilans, James A. Quintessenza, Roosevelt Bryant Iii, Shaun Mohan

Pediatrics Faculty Publications

Tuberous sclerosis complex (TSC) is a neurocutaneous disorder characterized by benign tissue hamartomas in multiple organ systems, including cardiac rhabdomyomas. Though prevalent in TSC, cardiac tumors are rare in children, occurring in about 0.03%–0.17%. Rhabdomyomas are the most common, accounting for 45%. When present, they are multiple and in the ventricular myocardium. Frequently, they regress and surveillance is all that is required until spontaneous regression. Intervention is necessary when life-threatening obstruction or hemodynamically significant refractory arrhythmias occur. This case highlights the course of a 6-month-old infant with TSC and cardiac rhabdomyomas who presented in refractory ventricular tachycardia (VT) with decompensation …

Eeg Findings In Infants With Neonatal Abstinence Syndrome Presenting With Clinical Seizures, Murali Reddy Palla, Gulam Q. Khan, Zahra M. Haghighat, Henrietta S. Bada

Pediatrics Faculty Publications

Neonatal abstinence syndrome (NAS) refers to a constellation of signs occurring in newborn infants who were exposed to opioids or opiates in utero. These manifestations include poor feeding, gastrointestinal disorders, abnormal sleep patterns, and neurological signs such as jitteriness, tremors, and seizures (1, 2). Myoclonus, jitteriness, and tremors often may be interpreted as seizures and therefore treated as epileptic seizures.

Objective: To determine whether seizure like activity observed in infants with NAS correlate with electroencephalogram (EEG) findings.

Design/ Method: We reviewed the standard EEG or video electroencephalogram (VEEG) of infants with NAS who were admitted because of seizure-like clinical …

A Parent-Led Intervention To Promote Recovery Following Pediatric Injury: Study Protocol For A Randomized Controlled Trial, Meghan L. Marsac, Ginny Sprang, Leila Guller, Kristen L. Kohser, John M. Draus Jr., Nancy Kassam-Adams

Pediatrics Faculty Publications

Background: Injury is one of the most prevalent potentially emotionally traumatic events that children experience and can lead to persistent impaired physical and emotional health. There is a need for interventions that promote full physical and emotional recovery and that can be easily accessed by all injured children. Based on research evidence regarding post-injury recovery, we created the Cellie Coping Kit for Children with Injury intervention to target key mechanisms of action and refined the intervention based on feedback from children, families, and experts in the field. The Cellie Coping Kit intervention is parent-guided and includes a toy (for engagement), …

Decreasing Door-To-Door Times For Infliximab Infusions In A Children's Hospital Observation Unit, Kelly C. Sandberg, Janet N. Lucien, Denise Stoll, Erica Yanney, Adam Mezoff

Pediatrics Faculty Publications

Introduction:

Children with inflammatory bowel disease (IBD) often require infliximab infusions to manage their disease. Infusions administered in the hospital setting require the patient and their families to devote many hours away from home. Changing to a rapid infusion protocol has been shown in the literature to be safe and has the potential to decrease time spent in the hospital receiving infusions.

Methods:

We describe stepwise changes made over a 4-month period to improve infliximab infusion efficiency and lessen the time spent in the hospital by IBD patients and their families. These changes included the implementation of a standardized order …

Attending To The Not-So-Little "Little Things": Practicing Trauma-Informed Pediatric Health Care, Aimee K. Hildenbrand, Scottie B. Day, Meghan L. Marsac

Pediatrics Faculty Publications

No abstract provided.

Lights, Camera, Path Splitter: A New Approach For Truly Simultaneous Dual Optical Mapping Of The Heart With A Single Camera., Rafael Jaimes, Damon Mccullough, Bryan Siegel, Luther Swift, James Hiebert, Daniel Mclnerney, Nikki Gillum Posnack

Pediatrics Faculty Publications

Background: Optical mapping of transmembrane voltage and intracellular calcium is a powerful tool for investigating cardiac physiology and pathophysiology. However, simultaneous dual mapping of two fluorescent probes remains technically challenging. We introduce a novel, easy-to-use approach that requires a path splitter, single camera and excitation light to simultaneously acquire voltage and calcium signals from whole heart preparations, which can be applied to other physiological models - including neurons and isolated cardiomyocytes.

Results: Complementary probes were selected that could be excited with a single wavelength light source. Langendorff-perfused hearts (rat, swine) were stained and imaged using a sCMOS camera outfitted with …

Kiaa1549-Braf Expression Establishes A Permissive Tumor Microenvironment Through Nfκb-Mediated Ccl2 Production, Ran Chen, Chanel Keoni, Christopher A. Waker, Robert M. Lober, Robert M. Lober, Yihsien Chen, David H. Gutmann

Pediatrics Faculty Publications

KIAA1549-BRAF is the most frequently identified genetic mutation in sporadic pilocytic astrocytoma (PA), creating a fusion BRAF (f-BRAF) protein with increased BRAF activity. Fusion-BRAF-expressing neural stem cells (NSCs) exhibit increased cell growth and can generate glioma-like lesions following injection into the cerebella of naïve mice. Increased Iba1+ monocyte (microglia) infiltration is associated with murine f-BRAF-expressing NSC-induced glioma-like lesion formation, suggesting that f-BRAF-expressing NSCs attract microglia to establish a microenvironment supportive of tumorigenesis. Herein, we identify Ccl2 as the chemokine produced by f-BRAF-expressing NSCs, which is critical for creating a permissive stroma for gliomagenesis. In addition, f-BRAF regulation of Ccl2 production …

Wire Guided Cannulation Facilitates Endoscopic Management Of Buried Bumper Syndrome: A Novel Technique, Jacquelin Peck, Kaitlin Sapp, Alexander Wilsey, Michael Wilsey

Pediatrics Faculty Publications

Buried bumper syndrome is a rare but potentially severe complication of percutaneous endoscopic gastrostomy tube insertion. Though this complication is uncommon, it may lead to pressure necrosis, bleeding, perforation, peritonitis, sepsis, or death. Each case of buried bumper syndrome is unique in terms of patient comorbidities and anatomic positioning of the buried bumper. For this reason, many approaches have been described in the management of buried bumper syndrome. In this case report, we describe the case of an adolescent Caucasian female who developed buried bumper syndrome three years after undergoing percutaneous endoscopic gastrostomy insertion. We review diagnosis and management of …

Down The Rabbit Hole-Considerations For Ingested Foreign Bodies, Jerry Brown, Molly Kidder, Abigail Fabbrini, Jonathan Devries, Jason Robertson, Nicole Chandler, Michael Wilsey

Pediatrics Faculty Publications

We report the case of a seven-year-old boy with an ingested foreign body, which was retained within the appendix for a known duration of ten months, ultimately requiring appendectomy. The ingested foreign body was incidentally discovered by abdominal x-ray at an emergency room visit for constipation. Despite four bowel cleanouts, subsequent x-rays showed persistence of the foreign body in the right lower quadrant. While the patient did not have signs or symptoms of acute appendicitis, laparoscopic appendectomy was performed due to the risk of this foreign body causing appendicitis in the future. A small metallic object was found within the …

Lamotrigine Odt-Induced Seizure In A 3-Year-Old Child After Accidental Ingestion, Ashley Griswold, Briana Tully, Kenneth Katz, Gillian Beauchamp, Matthew Cook, Robert Cannon

Pediatrics Faculty Publications

Lamotrigine is a new generation antiepileptic which blocks sodium channels and can cause significant toxicity in overdose. A case of a three-year-old child who suffered a seizure and required endotracheal intubation after accidental lamotrigine ingestion is presented. The lamotrigine concentration measured 23.2 mcg/mL which is the highest reported after accidental pediatric exposure. A review of the literature regarding pediatric lamotrigine poisoning is also included.