June 5, 2020
In This Issue

Research Spotlight:
Dr. Alix Seif Advances Treatment of Childhood Leukemia

CPCE In the News:
AAP updates guidance on newborns whose mothers have suspected or confirmed COVID-19

CPCE In the News:
Leading Philly's coronavirus response: Meet 15 key people in the city health department

CPCE In the News:
COVID-19 Reflections from Greece

CPCE In the News:
Should schools reopen? Kids' role in pandemic still a mystery

Upcoming Events

Recent Publications
Dr. Alix Seif Advances Treatment of Childhood Leukemia
On May 15, CPCE welcomed Alix E. Seif, MD, MPH for a faculty webinar titled “A Delicate Balance: Immune-Mediated Anti-Tumor Responses and Toxicities in Childhood Leukemia.” Dr. Seif is an Attending Physician specializing in blood and marrow transplant and hematologic malignancies. She held the Richard and Sheila Sanford Endowed Chair in Pediatric Oncology, and she joined CPCE in late 2019.

Dr. Seif began her presentation with an anecdote. Her first patient as a first year oncology fellow was a baby with leukemia who relapsed and developed a severe infection. After surviving the infection, the child’s leukemia was no longer detectable; the infection had stimulated an immune response which caused the leukemia to go into remission. As a result, Dr. Seif’s research to date has focused primarily on manipulating the immune system of children with leukemia to improve treatment.

Prognosis for children with leukemia has improved over the past 50-60 years. Overall survival for acute lymphoblastic leukemia (ALL) is now 80% or better, and for acute myeloid leukemia (AML) is around 50-60%. These improvements are due in part to the development of various immunotherapies, such as Chimeric Antigen Receptor (CAR) T cell therapy. However, these therapies are not perfect, and so Dr. Seif and others continue to investigate other forms of immunotherapy.

Along the way, Dr. Seif was invited to the cancer and infectious diseases epidemiology research group led by Richard Aplenc, MD, PhD and Brian Fisher, DO, MSCE. This group used the Pediatric Health Information System (PHIS) database to create a cohort of over 8,000 kids newly diagnosed with ALL. Using this cohort, they found significant hospital-level variability in induction mortality, with those hospitals with a higher proportion of publicly-insured patients reporting a higher rate of induction mortality.

They then developed a method to identify relapse and hematopoietic stem cell transplantation (HSCT) within the PHIS ALL cohort. Their method identified five-year relapse incidence of about 10% of patients, which is consistent with national patterns. They also found higher rates of relapse in higher-risk demographic groups: infants, patients over 10 years of age, and those with high-risk ALL at presentation. They also identified higher relapse rates in Black/African American and Hispanic patients and in patients with public insurance. HSCT is the standard treatment for many children with relapsed ALL, and HSCT rates were higher in high-risk subgroups. However, Black/African American and publicly insured children did not show expected increases in HSCT rates despite higher relapse rates, raising concern for health disparities in these children. This work established that administrative data can be used to identify relapse and HSCT in ALL patients whether they occur on- or off-therapy, whereas previously published studies were based on post-therapy data only.

Dr. Seif’s earlier laboratory research has shown that innate immune stimulation can lead to memory immune responses and multi-antigen recognition. She wondered if this translated to the clinical setting, i.e., would innate immune stimulation protect children from leukemia? Using the PHIS ALL cohort, as well as a PHIS cohort of AML patients merged with Children’s Oncology Group (COG) data, Dr. Seif and colleagues are currently studying this question using septic shock as a proxy for immune stimulation.

Other ongoing work includes optimizing stem cell transplant, and Prevention of Relapse by Employing Early MRD-directed therapy in Post-Transplant Acute Lymphoblastic Leukemia (the PREEMPT ALL Study).
AAP updates guidance on newborns whose mothers have suspected or confirmed COVID-19

Karen Puopolo, MD, PhD is a lead author on the American Academy of Pediatrics (AAP) report " FAQs: Management of Infants Born to Mothers with Suspected or Confirmed COVID-19," which was updated May 21, 2020. The report updates earlier guidance in order “to address some common clinical issues that were being brought to the AAP by clinicians caring for babies,” Dr. Puopolo said.

Leading Philly's coronavirus response: Meet 15 key people in the city health department

Kristen Feemster, MD, MPH, MSHP is among a group of Philadelphia Department of Public Heath (PDPH) professionals featured by Billy Penn for their roles in managing the city's COVID-19 response. Normally, Dr. Feemster runs Philadelphia's immunization program, in addition to maintaining her affiliation with CHOP and Penn. The pivot to COVID-19 took many by surprise. “Even being in public health, it was a surprise, even for me. It was quick,” Dr. Feemster said. A companion article described how PDPH rapidly reorganized in response to the pandemic.

COVID-19 Reflections from Greece

CPCE Core Faculty member Theoklis Zaoutis, MD, MSCE has spent the past year on sabbatical in Athens, Greece, working with the Greek government to control hospital-acquired infections and antimicrobial resistance. When the COVID-19 pandemic emerged, his work pivoted, as many healthcare professionals' did. He provided his reflections on this experience for the CHOP Global Health Center in the May 5, 2020 edition of the center's newsletter. Dr. Zaoutis was invited to serve on the Ministry of Health COVID-19 Task Force, served as a media spokesperson, helped establish and train healthcare workers at COVID-19 care centers, and was involved in developing the country's plans for reopening. "It has been an amazing experience to be part of the Greek COVID-19 response team," he wrote. "Since Greece is a relatively small country, I have been able to observe the inner workings and processes that are involved in mounting such a large-scale public health response." Read the full article here.
Should schools reopen? Kids' role in pandemic still a mystery

While there are some indications that children may be less likely to catch COVID-19, experience milder symptoms compared to adults, and less likely to transmit it to others, questions remain about the safety of reopening schools. Susan Coffin, MD, MPH commented on the necessity of continued research to assess risk. “Doing studies as schools reopen will be really important,” she said. Dr. Coffin joined PolicyLab Director David Rubin, MD, MSCE, School District of Philadelphia Superintendent Dr. William Hite and others for a related conversation titled “Health & Safety Considerations for Reopening K-12 Schools,” on June 2, 2020. View the recording via YouTube.

Upcoming Events

COVID-19 in Context: Racism, Segregation, and Racial Inequities in Philadelphia
Date: TODAY, Friday, June 5, 2020
Time: 11:00 AM-12:00 PM
The department of Epidemiology and Biostatistics at the Drexel University Dornsife School of Public Health presents Sharrelle Barber ScD, MPH, assistant research professor in the department of Epidemiology and Biostatistics and the Urban Health Collaborative at Dornsife. Learn more here .

Black Death to Yellow Fever: Disease, Death, & Distancing in World History
Date: Tuesday, June 9, 2020
Time: 12:00 - 1:00 pm
What can history teach us about the current pandemic? Perry World House presents Professor Alex Chase-Levenson and Professor Ada Kuskowski of the University of Pennsylvania Department of History. Learn more and register here .
 
The Role of Science Communication in Addressing the Disproportionate Effects of COVID-19 on Vulnerable Populations
Date: Friday, June 12, 2020
Time: 10:00 am - 12:30 pm
The National Academies’ Standing Committee on Advancing Science Communication invites you to join a webinar focusing on the role of science communication and engagement to meet the needs of communities disproportionately affected by COVID-19, including low-income African-American, Native American, and diverse, multi-lingual communities. Learn more and register here .
 
CPCE/PolicyLab Virtual Seminar Series*
Date: Friday, June 12, 2020
Time: 12:00 noon - 1:00 pm
Fran Balamuth, MD, PhD - TBD
 
CPCE/PolicyLab Virtual Seminar Series*
Date: June 19, 2020
Time: 12:00 noon - 1:00 pm
Meredith Matone, DrPH, MHS - "Incidence of high-risk postpartum opioid use among young mothers" 

CPCE/PolicyLab Virtual Seminar Series*
Date: Friday, July 31, 2020
Time: 12:00 noon - 1:00 pm
Molly Candon, PhD - "Trends in Antipsychotic Prescribing to Youth Enrolled in Philadelphia Medicaid" 

*For CPCE/PolicyLab Virtual Seminar Series: If you would like to participate in any of the virtual events and did not receive a BlueJeans link, please contact crosss2@email.chop.edu
Recent Publications

An interdisciplinary CHOP team including Kathleen Chiotos, MD, MSCE and Joyce Chang, MD, MSCE present a series of six critically ill children with Multisystem Inflammatory Syndrome in Children (MIS-C). Key findings of this syndrome include fever, diarrhea, shock, and variable presence of rash, conjunctivitis, extremity edema, and mucous membrane changes.

Patients with single ventricle (SV) heart defects have two primary surgical options for superior cavopulmonary connection (SCPC): bidirectional Glenn (BDG) and hemi-Fontan (HF). Outcomes based on type of SCPC have not been assessed in a multi-center cohort. A team including Andrew Glatz, MD, MSCE conducted a retrospective cohort study using the Single Ventricle Reconstruction (SVR) Trial public use dataset. Infants who survived to SCPC were evaluated through 1 year of age, based on type of SCPC. They found that mortality after SCPC overall is low and there is no difference in mortality at 1 year of age based on type of SCPC. Differences in support time and post-operative complications support the preferential use of the BDG, but additional longitudinal follow-up is necessary to understand whether these differences have implications for long-term outcomes.

In order to develop a clinical practice guideline for systemic antifungal prophylaxis in pediatric patients with cancer and hematopoietic stem-cell transplantation (HSCT) recipients, a team including Brian Fisher, DO, MSCE conducted a systematic review of 68 randomized trials, including six which were conducted in a solely pediatric population. A strong recommendation was made to administer a mold-active agent with an echinocandin or a mold-active azole when systemic antifungal prophylaxis is warranted. Implementation and assessment of guideline-concordant rates and impacts are important future steps.

Childhood cancer care is delivered by interprofessional healthcare teams; however little is known about how parents perceive overall team-delivered care (TDC). A team including Chris Feudtner, MD, PhD, MPH sought to describe parent perceptions of TDC and associated factors, including care rendered by individual clinicians, teamwork, information consistency, and patient and parent characteristics. Eighty-six parents of children with recurrent/refractory cancer responded to cross sectional surveys. Among respondents, more than one-third report less-than-excellent TDC. Additionally, less than half report excellent teamwork, and ratings of care rendered by individual clinicians are highly variable. Findings suggest interventions are needed to enhance interprofessional teamwork in the care of children with advanced cancer.

High-quality clinical research of resuscitations in a pediatric emergency department is challenging because of the limitations of traditional methods of data collection (chart review, self-report) and the low frequency of cases in a single center. To facilitate valid and reliable research for resuscitations in the pediatric emergency department, investigators from 3 pediatric centers, each with experience completing successful single-center, video-based studies, formed the Videography In Pediatric Emergency Research (VIPER) collaborative. The investigative team includes Sage Myers, MD, MSCE. Initial simulation-based testing suggests video-based data collection using the VIPER registry is feasible and reliable. Next steps are to assess feasibility and reliability for actual pediatric resuscitations and to complete several prospective, hypothesis-based studies of specific aspects of resuscitative care, including of cardiopulmonary resuscitation, tracheal intubation, and teamwork and communication.

Michelle Denburg, MD, MSCE and Gregory Tasian, MD, MSc, MSCE and colleagues investigated the relationship between the composition and function of gut microbial communities and early-onset calcium oxalate kidney stone disease, via a case-control study of 88 total patients aged 4-18 years. Participants who were kidney stone formers had a significantly less diverse gut microbiome compared with controls.

A team including Alexandra Psihogios, PhD and Lisa Schwartz, PhD led this mixed methods study to assess adolescent and young adult (AYA) adherence to three cancer treatment recommendations (medications, diet, physical activity), and determine the individual, family, and health system factors associated with suboptimal adherence. Adherence challenges were identified across medications, diet, and physical activity. Multilevel contextual factors were associated with suboptimal adherence, including poorer HRQOL and family functioning. Findings support the need to improve clinical adherence assessment and develop contextually tailored interventions.

In newborns at risk for early-onset sepsis, empiric antibiotics are often initiated while awaiting the results of blood cultures. The duration of empiric therapy can be guided by the time to positivity (TTP) of blood cultures. The objective of this study conducted by Sagori Mukhopadhyay, MD, MMSc, Karen Puopolo, MD, PhD and their colleagues was to determine the TTP of neonatal blood cultures for early-onset sepsis and the factors which may impact TTP. They found that pathogens are isolated by 36 hours after blood culture collection in 94% of neonatal early blood cultures, regardless of maternal antibiotic administration.

While gender-affirming hormones (GAH) may impact the fertility of transgender and gender diverse (TGGD) youth, few pursue fertility preservation (FP). Nadia Dowshen, MD, MSHP and colleagues conducted a study to understand youth and parent attitudes toward FP decision-making. The majority of TGGD youth and parents did not find having biological offspring important and were not willing to delay GAH for FP. Discomfort with reproductive anatomy was a major influencing factor for youth FP decision-making and their child's wishes was a major factor for parents. Future qualitative research is needed to understand TGGD youth and parent attitudes toward FP and to develop shared decision-making tools.

The increased relative risk of heart failure (HF) from systemic lupus erythematosus (SLE) is greatest at younger ages, but the etiology remains unclear. A team including Joyce Chang, MD, MSCE, Andrea Knight, MD, MSCE, and Pamela Weiss, MD, MSCE sought to identify risk factors for HF in children and adults with SLE and evaluate associations between SLE manifestations and HF. Hypertension remains an important traditional CV risk factor across all ages and should be managed aggressively even in younger patients with SLE. Cardiac dysfunction due to acute cardiac manifestations of SLE may contribute to the very high relative incidence of early HF diagnoses among younger SLE patients. Therefore, future prospective studies will need to address heterogeneity in the types and severity of heart failure in order to determine etiology and which patients should be monitored.

About CPCE

We are a pediatric research center dedicated to discovering and sharing knowledge about best practices in pediatric care by facilitating, organizing and centralizing the performance of clinical effectiveness research -- research aimed at understanding the best ways to prevent, diagnose and treat diseases in children. CPCE’s multidisciplinary team conducts research on a diverse range of clinical effectiveness topics.

CPCE E-News is edited by Holly Burnside. Please feel free to contact us with questions or feedback.