Research and Activities

Research and Activities

If you have any questions about the Pediatric Sepsis Program, please contact us by phone at 215-590-5505 or via our online contact form.

Clinical pathways

These pathways are used for the evaluation and treatment of infants and children with severe sepsis/septic shock.

Active quality improvement projects, research, and activities

Title: Organ Dysfunction Based Outcomes in a Hospital-wide Sepsis Quality Improvement Program
Project lead: Julie Fitzgerald, MD, PhD; Fran Balamuth, MD, PhD, MSCE; Christian Minnich and others

Title: Sepsis Alert Performance in Children with High-risk Conditions
Project lead: Sarah Fesnak, Fran Balamuth, MD, PhD, MSCE

Title: Improving ED Sepsis Alert/Huddle Process
Project lead: Ellie Souganidis, Fran Balamuth, MD, PhD, MSCE

Title: Sepsis Screening in Hospitalized Pediatric Patients
Project lead: Ms. Sharon Kaminski
Funding: CHOP OCQI
Objective: To develop and implement a highly sensitive and reasonably specific electronic health record based alert to guide clinicians in the early recognition of sepsis for hospitalized patients

Title: Sepsis Registry and Adjudication
Project lead: Julie Fitzgerald, MD, PhD 
Funding: CHOP Department of Pediatrics Chair’s Initiative
Objective: To review and confirm the diagnosis of sepsis in cases identified by sepsis screening to ensure appropriate cases are identified and quality metrics are tracking in patients with true sepsis.

Title: Long-term Follow-up of Pediatric Sepsis Survivors
Project lead: Scott Weiss, MD, MSCE 
Funding: CHOP Department of Pediatrics Chair’s Initiative
Objective: To develop a process or clinic dedicated to assess long-term morbidity in pediatric sepsis survivors

Title: Sepsis Screening in a Community Pediatric Emergency Department
Project lead: Ronald Marchese, MD; Fran Balamuth, MD, PhD, MSCE 
Funding: CHOP Department of Pediatrics Chair’s Initiative
Objective: To translate the CHOP ED sepsis screen to a community site

Title: Sepsis Screening in the Pediatric Emergency Department
Principal investigator: Fran Balamuth, MD, PhD, MSCE
Co-investigator: Ellie Souganidis, MD
Funding: CHOP Division of Emergency Medicine
Objective: Developed and implemented a vital sign based screen for sepsis in the Emergency Department which decreased missed sepsis cases by 76 percent. We are currently working to further refine the alert by evaluating cases missed under the screening system.

Title: Racial Disparities in Sepsis Screening and Treatment in the Emergency Department
Principal investigator: Ms. Jenny Raman, Tiffani Johnson MD, MS; Lena Winestone, MD; Fran Balamuth MD, PhD, MSCE 
Funding: CHOP
Objective: To evaluate racial disparities in sepsis alert performance as well as sepsis care in the Emergency Department

Title: Mitochondrial Dysfunction in Pediatric Sepsis
Project Lead: Scott Weiss, MD, MSCE
Funding: NIH
Objective: The objective of this study is to determine if mitochondrial dysfunction contributes to the severity and duration of organ dysfunction and immune dysregulation in pediatric sepsis.

Title: A Data Driven Analysis of Pediatric Organ Dysfunction Patterns to Discover Sepsis Phenotypes
Project Lead: (CHOP) Scott Weiss, MD, MSCE (PI: Sanchez-Pinto)
Funding: NICHD (Prime: Lurie Children’s Hospital)
Objective: The objectives of this study are to: (1) Calibrate and validate the subscores of a pediatric version of the Sequential Organ Failure Assessment sore, and (2) use the subscore to discover relevant phenotypes of sepsis by analyzing the early patterns of organ dysfunction in critically ill children with sepsis. This will be accomplished through secondary analysis of electronic health records from 8 pediatric intensive care units.

Title: Emergency Medical Services for Children: Pediatric Emergency Care Applied Research Network
Project Lead: (CHOP) Fran Balamuth (PI: Kupperman, Nodal)
Funding: NIH
Objective: The purpose of this network is to conduct high priority multi-institutional research on the prevention and management of acute illness and injuries in youth and children of all ages.

Title: PED Screen: Pediatric Sepsis EHR Registry, Clinical Outcomes, and Prediction Model
Project Lead: (CHOP) Fran Balamuth (PI: Alpern)
Funding: NICHD
Objective: The project proposes to build a multicenter pediatric sepsis registry, use the multicenter dataset to derive and validate a prediction model of organ dysfunction in pediatric sepsis, and develop and HER clinical decision support prototype for early diagnosis of severe sepsis.

Title: Taste of Medicines for Children: Genetic Variation and Medical Adherence
Project Lead: (CHOP) Fran Balamuth (PI: Lowenthal, Menella)
Funding: NICHD
Objective: This project proposes to assess genomic differences in children and their correlation with taste perception and adherence to treatment with liquid clindamycin for skin and soft tissue infections.

Title: Pediatric Sepsis Acute Kidney Injury: Personalizing Antibiotic Dosing Through Understanding Acute Kidney Injury Risk Factors and Biomarker Profiles
Project Lead: Julie Fitzgerald
Funding: NIH
Objective: This proposal will evaluate urine biomarkers to improve early detection of those at risk for pediatric sepsis-associated acute kidney injury, determine potentially modifiable risk factors related to medication therapies fo sepsis that are associated with risk of acute kidney injury progression, use these biomarkers and risk factors to improve pharmacologic models predicting antibiotic dosing, and test these new pharmacologic models for antibiotic dose adjustments in a pilot trial, which may lead to more effective antibiotic treatment in sepsis with lower risk of toxicity.

Title: Fungal Biomarkers for Diagnosis and Response to Therapy for Pediatric Candidemia
Project Lead: (CHOP) Julie Fitzgerald (PI: Steinbach, Fisher)
Funding: NIH
Objective: The goal is to establish the utility of biomarkers for diagnosing candidemia in children and monitoring response to therapy.

Title: Sepsis from Bedside to Bench to Bedside (PERSEVERE)
Project Lead: (CHOP) Julie Fitzgerald (PI: Wong)
Funding: NIH
Objective: The deliverable of this program will be a set of novel tools to more effectively stratify patients with septic shock. Child health will be positively impacted by developing the capability to more effectively stratify patients for interventional clinical trials and for the application of high risk therapies in children with septic shock.

Title: Transfusion Associated Pathophysiology of MODS (TRAP-MODS)
Project Lead: (CHOP) Julie Fitzgerald (PI: Sapru)
Funding: NIH
Objective: Ancillary to ABC PICU to Study MOD in Critically Ill Children. The goal is to characterize molecular biomarkers and the microbiome, and to examine these variables’ relationship to MODS and mortality.

Title: Patient Critical Care Trials Group – St. Baldrick’s Foundation
Project Lead: (CHOP) Julie Fitzgerald (PI: Steiner)
Funding: The University of Minnesota – Pediatric HSCT/Oncology
Objective: This retrospective record review and analysis is being undertaken to determine risk factors, treatments, and outcomes of PH patients, define any predominant clinical management strategy, and inform initial prospective intervention design based on results.

Title: Pathogen Identification in Pediatric Hematopoietic Stem Cell Transplant Patients with Suspected Lower Respiratory Tract Infections (PBMTC)
Project Lead: (CHOP) Julie Fitzgerald (PI: Zinter)
Funding: Children’s Hospital of Los Angeles

Title: American Heart Association: Transformational Award for Studies to Prevent Microvascular Thrombosis in Sepsis
Project Lead: (CHOP) Kandace Gollomp
Funding: American Heart Association: Transformational Award
Objective: Study of platelet biology and thrombosis in sepsis and in relationship to HIT.

Title: Implementing Diagnostic Stewardship: An Essential First-step to Antibiotic stewardship and reducing antibiotic resistance in critically ill children
Project Lead: (CHOP) Kathleen Chiotos, Charlotte Woods-Hill (PI: Milstone)
Funding: AHRQ
Objective: The goal of this project is to explore how diagnostic stewardship can be leveraged to reduce unnecessary antibiotic resistance.

Title: Pedsnet Scholars: A Training Program for Pediatric Learning Health System Researchers
Project Lead: (CHOP) Kathleen Chiotos (PI: Forrest)
Funding: NIH
Objective: A training program for Pediatric Learning Health System Researchers Project Summary/Abstract Creating learning health systems (LHSs) that improve child health will require a new generation of researchers embedded in healthcare organizations’ clinical operations and translational research programs.

Title: Serial High-Dimensional Immunophenotyping and Functional Testing in Pediatric MODS (PARADIGM-SHIFT)
Project Lead: Brad Lindell
Funding: Thrasher Research Fund
Objective: Our objectives are (1) to determine the association between patterns of immune dysfunction and clinical outcomes in pediatric MODS, and (2) to identify disease-and-treatment-specific risk factors associated with innate and adaptive immune suppression in pediatric MODS.

Title: Clinical and Proteomic Characterization of Nucleosoms in Pediatric Acute Respiratory Distress Syndrome
Project Lead: Nadir Yehya
Funding: NIH
Objective: The goal of this project is to delineate the histone composition of circulating nucleosomes in pediatric acute respiratory distress syndrome, and correlate with clinical outcomes.

Title: A Phase 2 Study of Inotuzumab Ozogamicin (NSC#772518, IND#133494) in Children and Young Adults with Relapsed or Refractory CD22+ B-Acute Lumphoblatic Leukemia (Aspire)
Project Lead: (CHOP) Nadir Yehya (PI: O’Brien)
Funding: Pfizer
Objective: The specific aim of this sub-award is to quantify candidate biomarkers associated with development of sinusoidal obstruction syndrome, specifically angiopoietin 2 (Ang2) and L-ficolin, in children exposed to study drug.

Title: Linking Endotypes and Outcomes in I Pediatric Acute Respiratory Distress Syndrome (LEOPARDS)
Project Lead: Nadir Yehya
Funding: NIH
Objectives: Our overall goal is to risk stratify pediatric ARDS patients and to identify endotypes with shared biology in order to appropriately target therapies in future trials.

Title: PRone and OScillation Pediatric Clinical Trial (PROSpect)
Project Lead: (CHOP) Nadir Yehya (PI: Curley)
Funding: NIH
Objectives: This study will provide objective measures of PARDS, intermediate outcomes for clinical trials and allow for early intervention and prevention of PARDS.

Basic/translational scientific research

Title: Mitochondrial Dysfunction in Pediatric Sepsis
Principal investigator: Scott L. Weiss, MD, MSCE 
Funding: NIH
Objective: Test noninvasive measures of mitochondrial dysfunction using circulating mononuclear blood cells and plasma to identify subsets of children with sepsis and organ failure who could be targeted for mitochondrial-based therapies

Title: Role of the Intestinal Microbiome in Mitochondrial-induced Immune Dysregulation in Pediatric Sepsis
Principal Investigator: Scott L. Weiss, MD, MSCE 
Funding: Society of Critical Care Medicine
Objective: Test the overall hypothesis that sepsis impacts mitochondrial-induced immune dysregulation via alterations in short-chain fatty acids derived from an abnormal intestinal microbiome

Title: PRoMPT BOLUS
Principal Investigator: Fran Balamuth, MD, PhD, MSCE; Scott L. Weiss, MD, MSCE
Funding: NIH/CHOP
Objective: Pragmatic randomized clinical trial to test the comparative effectiveness of different crystalloid fluids for resuscitation of pediatric septic shock

Title: RNA Expression Profiling and Pediatric Sepsis Recognition
Principal investigator: Fran Balamuth, MD, PhD, MSCE
Funding: NIH
Objective: To determine the association between peripheral blood RNA expression profiles at sepsis diagnosis and both organ dysfunction at hospital day 2 and source pathogen

Title: Mitochondrial Dysfunction in EBV-Transformed Lymphoblasts and Induced Pluripotent-derived human Stem Cells (iPSCs) in Pediatric Sepsis
Principal investigator: Scott L. Weiss, MD, MSCE
Funding: NIH
Objective: To model the mitochondrial-targeted effects of sepsis on immune or organ cells

Title: Biomarkers of Endothelial Dysfunction in Critically Ill Children with Sepsis and Acute Respiratory Distress Syndrome
Principal investigator: TBD
Funding: CHOP
Objective: To determine if biomarkers linked to endothelial dysfunction are associated with development of acute respiratory distress syndrome (ARDS) in children with sepsis

Clinical research

Title: CMV Reactivation in Pediatric Sepsis    
Principal investigator: MoonJoo Han, MD
Funding: CHOP Foerderer Award for Excellence in Research
Objective: To determine the cumulative incidence and clinical significance of CMV viremia and CMV reactivation in pediatric severe sepsis

Title: Urine Biomarkers to Detect and Predict Acute Kidney Injury in Pediatric Septic Shock  
Principal investigator: Julie Fitzgerald, MD, PhD, MSCE  
Funding: CHOP Division of Critical Care Medicine
Objective: To identify urine biomarkers that can be measured noninvasively and are sensitive and specific for predicting acute kidney injury in children with septic shock

Title: Severe Sepsis and Septic Shock in Immunocompromised Children: Risk Factors for PICU Mortality   
Principal Investigator: Julie Fitzgerald, MD, PhD, MSCE; Robert B. Lindell, MD  
Funding: CHOP Division of Critical Care Medicine
Objective: To identify risk factors for PICU mortality in immunocompromised children with severe sepsis or septic shock using a nation multicenter PICU database

Title: Clinical prediction modeling for organ dysfunction in suspected pediatric sepsis
Principal investigator: Fran Balamuth MD, PhD, MSCE; Hanna Gu, MD
Funding: CHOP
Objective: To use machine learning methods to identify clinical and laboratory predictors of organ dysfunction in the first three hospital days for children presenting to the ED with suspected sepsis

Research publications and Scientific presentations

Physicians and researchers from the Pediatric Sepsis Program at Children's Hospital of Philadelphia are regular contributors to clinical publications and frequent speakers at national conferences. Find some of their publications and presentations.