Virtual Mini-Hack to address problems amplified by COVID-19

Pediatric nurses, caregivers, data scientists and more are invited to join an upcoming virtual “Mini Hack” to solve problems magnified by the COVID-19 crisis.

Co-hosted by CHOC Children’s and UC Irvine, the Aug. 3 CHOC-ZOT!-ZOOM COVID-19 Mini-Hack Virtual Event gathers these groups, along with business leaders, computer science and nursing students, entrepreneurs and industry leaders to solve real-world conundrums.

The day of collaboration is designed to help solve problems falling into many categories including school reintegration; work reintegration/remote work; pediatric mental health; telenursing/telemedicine/remote care; ensuring families feel safe to seek care; and ensuring healthcare workers feel safe to provide care.

Participants will work in teams to devise answers, develop prototypes and pitch solutions to their problem. In doing so, they will learn how to solve real-life problems through design-thinking concepts, while interacting with innovation leaders and mentors to get hands-on experience with pitching ideas.

Further, the event provides potential opportunities for commercialization, including the potential sharing of net profits.

Register here.

Rapid genome testing for infants saves lives, costs

Its name conjures up images of a familiar fairy tale, but Project Baby Bear has produced some very impressive real-world results that could save the lives of thousands of seriously ill infants.

The recently completed two-year pilot program at five clinical sites in California – including CHOC Children’s – helped doctors target a baby’s specific genetic disease in a matter of days, instead of the four to six weeks required for standard genetic tests.

That means quicker diagnoses leading to quicker treatments, less time in the hospital and more answers for anxious parents.

“It can be a real game changer,” said Dr. Jason Knight, a pediatric critical care physician and medical director of CHOC’s pediatric intensive care unit and one of the physician leads on the project. “It’s a tool we didn’t have a few years ago.”

Changing the game

By employing rapid whole genome sequencing (rWGS), doctors could gather vital information that changed the decisions families and clinicians made, and ultimately saved lives and resources. The procedure has historically been used only as a last resort.

By pinpointing the cause of rare disease with rWGS, physicians can customize treatment. And having a genetic diagnosis can eliminate the need for further tests, improve outcomes, reduce hospital stay length and improve the experience of care for families – all while also reducing costs.

In addition, substantial reductions in healthcare spending — $2.5 million — accrued largely because rWGS permitted doctors to discharge babies sooner and reduce the number of procedures that may have been performed in the absence of a precise diagnosis.

Avoided procedures included 11 major surgeries and 16 fewer diagnostic tests such as  open muscle, liver and other biopsies that are performed under general anesthesia.

Success story

In one case, a newborn baby girl with a life-threatening irregular heartbeat was admitted to CHOC Children’s Hospital. Instead of undergoing an arduous battery of tests, the child was diagnosed within two days with Timothy Syndrome, an extremely rare cardiac condition that put her at risk for sudden death.

With the genetic diagnosis in hand, CHOC physicians were able to treat the infant with the appropriate medication  for her condition. Her heartbeat was restored to normal, significantly reducing the risk of sudden cardiac death. Her physicians, secure in her diagnosis, implanted a pacemaker, dramatically improving her chances for a happy and healthy childhood.

She recently celebrated her first birthday.

“Without the results of her rapid whole genome sequence, she would have gone home on a different medication and been at a much higher risk for sudden death,” Dr. Knight said. “She got the right diagnosis and we gave her a pacemaker so her risk of sudden death went to zero.”

In all, Project Baby Bear provided diagnoses for 76 of the 178 babies who completed rWGS. This led to a change in the care of 66 babies. It diagnosed 35 rare conditions that occur in less than one in 1 million births. About 150,000 children could benefit from rWGS.

Turning every stone

Even if the test doesn’t diagnose a problem, it can help comfort families, Dr. Knight said.

“Even a negative test can be helpful for some families to know we’re not missing something,” he said. “It gives them assurance that we’ve turned over every stone.”

With the success of the study, Dr. Knight hopes to see the service expand to reach more patients.

“Should we be doing this with all newborns?” he asked. “Based on our experience with Project Baby Bear, it would seem feasible that for newborns and children in intensive care units without clear diagnoses, this should be part of our diagnostic process and the earlier the better.”

Multidisciplinary, multi-site effort

CHOC’s role in Project Baby Bear is a collaborative, multi-disciplinary effort involving many clinicians and staff, including research coordinators Cathy Flores, Erum Naeem and Ofelia Vargas-Shiraishi, and physician leads Drs. John Cleary, Juliette Hunt, Adam Schwarz and Neda Zadeh, in addition to Dr. Knight.

Led by Rady Children’s Hospital-San Diego, Project Baby Bear helps infants who are undergoing intensive care and covered by Medi-Cal. The other participating hospitals include UCSF Benioff Children’s Hospital Oakland, UC Davis Children’s Hospital in Sacramento, and Valley Children’s Healthcare in Madera.

The $2 million Project Baby Bear was funded by the State of California. In-kind contributions of $400,000 from Rady Children’s Hospital ensured more than 90 percent of the state funds were used to support the care and management of critically ill babies.

Learn more about the CHOC Children’s Research Institute.

Multisystem Inflammatory Syndrome in children (MIS-C) and COVID-19: What providers should know

Multisystem inflammatory syndrome in children, or MIS-C, is a new syndrome that has been reported worldwide in an increasing number of children who had or were exposed to COVID-19. MIS-C shares many characteristics with Kawasaki disease, an inflammatory disease of childhood that can affect blood vessels.

This Q & A with Dr. Negar Ashouri, a pediatric infectious disease specialist at CHOC Children’s, explores what providers should know about MIS-C, including recently released guidance from the American Academy of Pediatrics.

What is MIS-C?

MIS-C is a rare complication temporally associated with COVID-19. Here is the case definition, per a U.S. Centers for Disease Control Health Advisory:

  • An individual aged <21 years presenting with fever (>38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours); laboratory evidence of inflammation (Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, D-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin.); and evidence of clinically severe illness requiring hospitalization, with multisystem (≥2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurological); AND
  • No alternative plausible diagnoses; AND
  • Positive for current or recent SARS-CoV-2 (COVID-19) infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the four weeks prior to the onset of symptoms.

Is MIS-C dangerous?

MIS-C can be serious, but most children have recovered. MIS-C, like Kawasaki disease, can be a very uncomfortable illness because it causes prolonged fever, irritation and inflammation in many tissues of the body. The main concern with MIS-C and Kawasaki disease is heart and blood vessel involvement.

Conditions that involve inflammation in the heart, such as MIS-C or Kawasaki disease, can affect the heart in different ways. They may cause the heart muscle to be irritated and inflamed, affecting the overall function of the heart.

They may also weaken the wall of one or more of the coronary arteries causing them to bulge or balloon out. Blood clots can form in the ballooned area and possibly block the blood flow through the coronary artery. When this happens, the heart muscle will no longer receive an adequate supply of oxygen-rich blood, and the heart muscle can be damaged.

Dr. Negar Ashouri, pediatric infectious disease specialist, CHOC Children’s

What are the symptoms of MIS-C?

Though clinicians have described differing presentations, sign and symptoms can include an ongoing fever, inflammation detected by blood test, and evidence of organ dysfunction or shock. Here are additional common symptoms:

  • Kawasaki disease-like features including conjunctivitis; red eyes; red or swollen hands and feet; rash; red cracked lips; and swollen glands. Some children have presented with coronary artery enlargement or aneurysms. Some children may present with  more gastrointestinal (abdominal pain or diarrhea) or neurologic (headaches/meningitis) manifestations.
  • Toxic shock syndrome-like features with hemodynamic instability.
  • Cytokine storm/macrophage activation or hyperinflammatory features.
  • Shortness of breath suggestive of congestive heart failure.
  • Respiratory symptoms typically reported in adults with COVID-19 may not be present in pediatric patients with MIS-C.

Patients with the following symptoms ought to seek emergency care:

  • Persistent fevers
  • Trouble breathing
  • Pain or pressure in the chest that does not go away
  • New confusion
  • Inability to wake or stay awake
  • Bluish lips or face
  • Severe abdominal pain

How is MIS-C diagnosed?

Children who present with symptoms may undergo expanded laboratory testing and a cardiac workup that may include:

  • Routine screening labs including CBC with diff, CRP, CMP, and appropriate cultures;
  • If expanded work-up is warranted for hospitalized patients, it may include  troponin, pro-B-type natriuretic peptide, triglycerides, creatine kinase, ,  D-dimer, prothrombin time/partial thromboplastin time, international normalized ratio,  ferritin, lactic acid dehydrogenase,  and fibrinogen, if not already conducted;
  • COVID-19 testing performed with RT-PCR assay and serologic testing in every case;
  • echocardiogram;
  • electrocardiogram;
  • chest X-ray; and
  • abdominal ultrasound.

When should a provider suspect MIS-C?

Per the AAP, any child with suspected MIS-C should also be evaluated for infectious and noninfectious etiologies.

An initial sign may be a persistent fever without a clear clinical source. Providers should be suspicious of any fever accompanied by symptoms concerning in their severity or coincident with recent exposure to COVID-19.

Some children clinically progress rapidly and may develop hemodynamic compromise. These children should be followed and cared for in a hospital with tertiary pediatric/cardiac intensive care units.


How is MIS-C treated?

Kawasaki and MIS-C are best treated in the hospital by a qualified multidisciplinary group of pediatric specialists who will work to reduce inflammation and minimize long-term heart damage.

Here is the APP guidance for treatment:

  • Some patients with MIS-C have been treated with IVIG, Occasionally,  Patients have also been treated with steroid therapy  and or biologics that may require taper of the medications overtime.
  • Given the need for early intervention and the need to initiate treatment for multiple possible etiologies, many patients have received concurrent antibiotic therapy.
  • A multidisciplinary group is generally involved which may include Infectious disease specialists, cardiologists, intensivists, hospitalists and rheumatologists.

What is the follow-up for patients with MIS-C?

Children who have had serious cases of MIS-C should have close outpatient follow-up care by a group of specialists which may include cardiology, hematology and infectious diseases.

Refer a patient to the infectious disease team at CHOC Children’s.

CHOC hematologist appointed to national COVID-19 therapy evaluation oversight committee

Dr. Diane Nugent has been named co-chair of the Steering Committee for the National Heart, Lung, and Blood Institute (NHLBI) Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies, or CONNECTS, which will coalesce projects into a national, coordinated effort. She will also serve on the Executive committee for CONNECTS to facilitate the rapid turnaround and implementation of these grants throughout the country.

In addition to her work at CHOC, Dr. Nugent, in this new role, will help fulfill the objectives and ensure compliance for CONNECTS, which will be will be responsible for selection, implementation and analysis of all COVID clinical trials; data streams; biorepository/cohorts; and molecular and phenotypic correlations with the overarching mission to fast track therapies and vaccines that are validated through the hypothesis driven process and proven truly effective.  

“I am honored to help advance the body of knowledge around COVID-19 treatments and contribute meaningfully to work that is so critically needed as we confront this global crisis,” says Dr. Nugent, medical director of hematology at CHOC. “I also wish to stress the importance of research specifically in children and patients with chronic disease to help us understand why certain individuals are at high risk and how this infection impacts health at various ages, and over time. We are beginning to see the late and long-term effects in patients now and need to be prepared for future evolution of disorders in the heart, lung, blood vessels and brain over the next years and decades.”

Dr. Diane Nugent, medical director of hematology at CHOC Children’s

CONNECTS is an integration of major NHLBI clinical networks to collaboratively and efficiently conduct clinical trials while ensuring standardization, shared resources and data, and flexibility to nimbly shift studies as needed based on new knowledge and the changing pandemic clinical landscape. Master protocol-driven adaptive platform trials will be aligned with, or formally part of, National Institutes of Health’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Initiative.

CONNECTS is directed by NHLBI in collaboration with the Biomedical Advanced Research and Development Authority (BARDA), U.S. Department of Health & Human Services’ Operation Warp Speed, and NIH initiatives.

The Executive and Steering committees are charged with overseeing the design, implementation, and analysis of CONNECTS study protocols, including:

  • interpretation, presentation and publication of results;
  • use of common data elements and data standards across CONNECTS study protocols; and
  • sharing of data, biospecimens, images, and other research products developed by CONNECTS.

A prolific author on innovative medicine, Dr. Nugent has coauthored more than 100 journal articles and book chapters. She specializes in all aspects of hematology, bone marrow failure, anemias, immune disorders, bleeding and clotting disorders. Her clinical and research interests include blood disorders, bone marrow failure, bleeding and clotting disorders, and white cell and immune deficiencies.

Refer a patient to a CHOC Children’s hematologist.

The forefront of CAR T-Cell immunotherapy research for high-risk pediatric leukemia patients

Innovative research conducted at the Hyundai Cancer Institute at CHOC Children’s includes investigations into immunotherapy, which has emerged as an effective therapeutic modality for patients with hematologic malignancies. Chimeric Antigen Receptor (CAR) T-cell therapy is capturing the attention of the medical community as a prominent example of cellular immunotherapy and is often referred to as a “living drug.”

“CAR T-cell therapy has revolutionized the treatment landscape of relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) — a disease that was historically considered to have a very poor prognosis,” says pediatric oncologist Dr. Van Huynh, who leads the CAR T-cell program at CHOC “With this remarkable approach, we are able to harness the patient’s own immune system to potentially cure their leukemia.”

Dr. Van Huynh, pediatric oncologist at the Hyundai Cancer Institute at CHOC Children’s

CHOC was one of the first pediatric sites for CAR T-cell therapy clinical trials in 2015. Along with providing access to innovative clinical trials for CAR T-cell therapy and other immunotherapy, CHOC is now a certified treatment center for providing the recent U.S. Food and Drug Administration-approved CAR T-cell therapy called KYMRIAH. It is available to pediatric and adolescent/young adult (AYA) patients who are up to 25 years of age with second or later relapse or refractory (R/R) B-cell ALL or patients with R/R large B-cell lymphoma.

CAR T-cell therapy involves the collection of a patient’s own T-cells and genetic modification of these cells to express a CAR that can recognize a tumor antigen such as CD19 on leukemia cells. The CAR T-cells are then expanded in the lab and later re-infused back into the patient, where they continue to expand and seek out the target antigens to eradicate the leukemia.

CAR T-cell therapy has given hope to many patients who otherwise had no other treatment options. Furthermore, dramatic initial clinical responses and high rates of complete remission have been observed. Relapses can occur due to antigen loss (leukemia cells no longer express the target antigen) or CAR T-cell exhaustion (the CAR T-cells no longer provide protection).

“Currently, researchers are looking into ways to overcome these two barriers to make this therapy even more effective,” Dr. Huynh says. “I’m also excited for the potential of CAR-Ts to target other antigens besides CD19 and the possibility that it may be able to treat other types of cancer.”

Our Care and Commitment to Children Has Been Recognized

CHOC Children’s was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-2021 Best Children’s Hospitals rankings and ranked in the cancer specialty.

Learn how CHOC’s pediatric oncology treatments, expertise and support programs preserve childhood for children in Orange County, Calif., and beyond.