Medicine and Health Sciences Commons^™

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 …

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 …

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 …

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 …

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 …