Jun 11 2014

Autism Gene Networks Could Offer Treatment Targets


Many of these genes with very rare defects belong to gene families that may offer druggable targets.

After analyzing the DNA from thousands of patients, investigators from Children’s Hospital have uncovered several gene networks that may play important roles in autism. These networks may offer attractive targets for developing new autism drugs or repurposing existing drugs that act on components of the networks.

Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics, and his team also found that one of the autism-related gene pathways also affects some patients with attention deficit hyperactivity disorder (ADHD) and schizophrenia, which raises the possibility that a class of drugs may treat particular subsets of all three neurological disorders.

Autism spectrum disorders (ASDs), of which autism is the best known, are a large group of heritable childhood neuropsychiatric conditions characterized by impaired social interaction and communication, as well as by restricted behaviors. Dr. Hakonarson and his team note that recent investigations suggest that up to 400 distinct ASDs exist.

The investigators conducted a genome-wide association study that drew data from CHOP’s genome center as well as from the Autism Genome Project and the AGRE Consortium, both part of the organization Autism Speaks. The study compared more than 6,700 patients with ASDs to over 12,500 control subjects and represents one of the largest-ever studies of copy number variations (CNVs) in autism. CNVs are deletions or duplications of DNA sequences, as distinct from single-base changes in DNA.

The study focused on CNVs within defective gene family interaction networks (GFINs) — groups of disrupted genes acting on biological pathways. In patients with autism, the team found three GFINs in which gene variants perturb how genes interact with proteins. Of special interest to the study group was the metabotropic glutamate receptor (mGluR) signaling pathway, defined by the glutamate receptor metabotropic (GRM) family of genes that affects the neurotransmitter glutamate, a major chemical messenger in the brain regulating functions such as memory, learning, cognition, attention, and behavior.

In ASDs and other complex neurodevelopmental disorders, common gene variants often have very small individual effects, while very rare gene variants exert stronger effects. Many of these genes with very rare defects belong to gene families that may offer druggable targets.

Dr. Hakonarson’s team and other investigators previously reported that 10 percent or more of ADHD patients have CNVs in genes along the GRM pathway, while other teams have implicated GRM gene defects in schizophrenia.

“Even though our own study was large, it captures only about 20 percent of genes causing ASDs,” said Dr. Hakonarson, who added that still larger studies are needed to further unravel the genetic landscape of autism. “However, strong animal data support an important role for the glutamate receptor pathway in socially impaired behaviors modeling ASDs. Because the GRM pathway seems to be a major driver in three diseases — autism, ADHD and schizophrenia — there is a compelling rationale for investigating treatment strategies focused on this pathway.”

Based on the results of the study, Dr. Hakonarson is planning a clinical trial in selected ADHD patients of a drug that activates the GRM pathway. “If drugs affecting this pathway prove successful in this subset of patients with ADHD, we may then test these drugs in autism patients with similar gene variants,” he said.

The study appeared in the journal Nature Communications. Additional details are available here.

Permanent link to this article: http://www.research.chop.edu/blog/autism-gene-networks-offer-treatment-targets/

Jun 09 2014

Research Terminology Must Harmonize to Advance Science

research terminologyWhat one researcher describes as asthma, another might call reactive airway disease. Unfortunately, such examples demonstrate the lack of a common pediatric research terminology, which presents a barrier to data reuse, sharing, and integration.

Thought leaders at The Children’s Hospital of Philadelphia published a state-of-the-art review article in the March issue of Pediatrics that encourages the research community to start talking the same language. They described a project under way, called the Pediatric Terminology Harmonization Initiative, that aims to provide uniform definitions and descriptions of clinical observations and data in pediatric research.

The National Institute of Child Health and Human Development is coordinating the effort in collaboration with the Enterprise Vocabulary Services of the National Cancer Institute, in order to fill a gap in the pediatric research infrastructure in the U.S.

“It is of critical importance to address this gap if we’re going to advance our scientific understanding of the causes of childhood disease,” said Christopher B. Forrest, MD, PhD, professor of pediatrics at CHOP. “Science advances through reproducibility. And when we all use different terms, we’re not able to reproduce research.”

Dr. Forrest compared the initiative to the Rosetta Stone, an ancient tablet with passages of identical meaning written in three languages that helped to decode the riddle of hieroglyphics.

“The Rosetta Stone was a big advance that allowed us to translate different languages,” Dr. Forrest said. “That’s what the terminology project does. It’s a common language that eventually will act as a Rosetta Stone for different research projects. It will allow communication across research studies.”

Traditionally, when a research team sets up a study, they have many questions in mind to tackle. But perhaps another study team across the country with the same study concept phrases their questions in an entirely different way. This could convolute attempts to pool the results.

Michael A. Padula, MD, MBI, medical director of informatics for the Division of Neonatology at CHOP, gave an example from three studies that the National Institutes of Health had funded about the off-label use of nitric oxide in premature infants. The New England Journal of Medicine published the three studies’ results: Two found it not to be beneficial, but the other found it was beneficial. The NIH convened a panel to interpret the results, but they were unable to make any conclusions because each study used slightly different definitions of bronchopulmonary dysplasia, which was the main outcome that the studies measured.

“They spent a great deal of money to fund these studies, but in the end they weren’t much farther along,” Dr. Padula said. “It was a missed opportunity. Had they been able to retrieve a granular level of data to allow them to harmonize the different definitions, then they would have been able to make a more definitive conclusion about the therapy.”

It can be a challenge for the research community to reach consensus on an accurate definition of a complex disease such as bronchopulmonary dysplasia or even on a common condition such as asthma. Some researchers may be reluctant to embrace a set vocabulary because they prefer certain customized terms. L. Charles Bailey, MD, PhD, an assistant professor in CHOP’s divisions of oncology and hematology, used the analogy of how people describe different shades of colors — red vs. rose, for instance.

“The research community must make a conceptual leap to say that we’re all going to agree to call this red in certain contexts, even though we can tell the shades apart, because it is more important for us to collaborate than it is for me to say exactly that my color is rose,” Dr. Bailey said.

That is where subject matter experts assembled through the Pediatric Terminology Harmonization Initiative jump in to develop semantic interoperability. They systematically go piece by piece through each field of medical specialization to align like concepts, define them appropriately so that they relate to both research and clinical care, and then tether them to reference terminology sets that researchers can access easily.

Although the scope of the terminology project is substantial and time-consuming, CHOP’s experts explained why it is important to pursue it now. First, it is increasingly becoming important to perform collaborative pediatric research to answer questions from broader perspectives.

For example, PEDSnet is a national initiative of children’s hospitals and disease specific networks that are working together to reduce the barriers to rapid and better clinical research. PEDSnet will tap into the pediatric research terminology effort as it begins to create a common data model, said Dr. Forrest, who is principal investigator of PEDSnet.

A common pediatric research terminology also will be an essential part of the National Children’s Health Study, led by Steven Hirschfeld, MD, PhD, who co-authored the Pediatrics article. The National Children’s Health study will be collecting huge amounts of data that must be aligned to allow translation of the evidence into clinical practice.

Second, the era of health care information exchange is creating a sea change because the care that clinicians provide is now linked to electronic health records (EHRs) that operate using specific languages and terminologies. However, most EHR systems currently do not describe pediatric conditions thoroughly or support pediatric research. Organizers of the pediatric terminology project want to get their foot into the door as EHRs are constructed so that they all map to the same standardized concepts when referring to pediatric patients.

“From the research side, this is a fabulous opportunity because all kinds of information are being collected,” Dr. Bailey said.

Yet, one of the biggest barriers to widespread adoption of a common pediatric research terminology is raising awareness, Dr. Bailey said. The NICHD website already has harmonized several terminology reference subsets for pediatric specialties that researchers can consult and begin to deliberately design studies to be consistent and interoperable.

“Start thinking about how the research you’re doing connects to the questions that your colleagues are trying to answer and how everyone could benefit from shared terminology,” Dr. Bailey said.

Permanent link to this article: http://www.research.chop.edu/blog/researchers-must-talk-talk-advance-science/

Jun 06 2014

Capturing a Snapshot: the CHOP Scientific Symposium

Scientific SymposiumWith more than 500 investigators (plus fellows, assistants, and a staff in the thousands) spread across a campus comprising more than 1.5 million square feet of space, The Children’s Hospital of Philadelphia Research Institute is a big place. Research Institute investigations run the gamut of scientific inquiry, from those focused on injury research to genomic studies to clinical and surgical projects.

Now in its 11th year, the Research Institute Scientific Symposium aims to capture a snapshot of some of the groundbreaking work going on at the Institute every day. This year’s Symposium, featured presentations on the role of the circadian rhythm in lung function, the effects of brain tumors on survivors and their families, and genetic investigation of rare pediatric diseases.

In his opening remarks — which focused on genomics and politics — Philip R. Johnson, MD, Chief Scientific Officer and director of the Research Institute, noted that when it comes to detailed biological and genetic information, “the more we know the less we know.” For example, a person’s genome can now be sequenced in just a few days for several thousand dollars. But deciphering and managing the abundance of information generated by next-generation sequencing methods remains a challenge, Dr. Johnson said.

Touching on politics, Dr. Johnson noted unpredictable levels of federal support have led to uncertainty throughout the field. We need Congress to ensure a stable level of funding, Dr. Johnson said, because “basic science is where the real discoveries come from.”

“Fundamental, basic biological research is a very important part of what we do here at CHOP,” said one of the day’s presenters, Janis Burkhardt, PhD.

Sleep, Sheep, and Green

The day began with a series of mentored presentations, with senior and junior researchers presenting jointly. Phyllis Dennery, MD, and Shaon Sengupta, MDDS, MPH, led off with a talk on the role of the circadian rhythm in the neonatal lung. A key question of their research, Dr. Dennery said, was whether clinical care could be optimized to match circadian rhythms. For example, she pointed out, heart attacks are more likely in the morning than at night.

This talk was followed by a presentation led by fetal surgery pioneer Alan Flake, MD. Along with Emily Partridge, MD, Dr. Flake has been working on a groundbreaking project to develop an extrauterine life support system that could help improve outcomes for severely premature babies. A combined engineering and medical challenge, Drs. Flake and Partridge have been working on a tank-based external uterus, going so far as to raise several (now healthy) premature lambs.

In addition to mentored presentations, the 2014 Scientific Symposium also featured a number of collaborative talks, given by investigators who worked together on projects, often across disciplines. But the day’s highlights were its keynote speeches. The internal keynote speaker was Joseph W. St. Geme, III, MD, CHOP’s new Physician-in-Chief and Chair of the Department of Pediatrics at the University of Pennsylvania, who researches bacterial host-pathogen interactions. The Symposium’s external keynote speaker, meanwhile, was Eric Green, MD, PhD, director of the National Human Genome Research Institute. Dr. Green spoke about the history and future of genomic medicine.

Since the end of the Human Genome Project in 2001, “our knowledge of epigenomics has exponentially grown,” Dr. Green said. “We’ve learned a lot in 11 years, but we really have to be realistic and recognize that we’re probably going to study this for decades.”

“It is a remarkable time we’re living in,” Dr. Green opined.

To learn more about 2014 CHOP Research Scientific Symposium, see this month’s issue of Bench to Bedside.

Permanent link to this article: http://www.research.chop.edu/blog/capturing-snapshot-chop-scientific-symposium/

Jun 04 2014

AfterTheInjury.org/es Offers Expert Tips in Spanish

AftertheInjuryA growing number of Spanish-speaking families in the United States look for health and parenting information online. Each year 8 million children – including nearly 1 million Hispanic children –experience an injury that requires emergency room care or a hospital stay. A team of experts at The Children’s Hospital of Philadelphia launched a new Spanish-language website, AfterTheInjury.org/es, to help Spanish-speaking parents help their children recover after an injury.

The website is a comprehensive free resource for parents, developed by a team of pediatricians, psychologists, trauma surgeons and trauma nurses, based on more than a decade of research on childhood injury and its emotional effect on kids and their parents.

“With all the doctors and nurses who treat a child when he or she is first hurt, it’s still parents who play the most important role in their child’s physical and emotional recovery,” said Flaura Koplin Winston, MD, PhD, a pediatrician, director of the Center for Injury Research and Prevention and co-developer of the English and Spanish websites. “Medical care is often brief, and parents may have questions later and not know where to turn. We created this site, with the guidance of parents, to help them find the information they want, exactly when they need it.”

Researchers at CHOP have developed and tested ways to identify traumatic stress reactions in Spanish- and English-speaking children. Based on the latest research, the team has created a wide range of Spanish and English tip sheets for children and parents about dealing with injury, illness, and being in the hospital.

AfterTheInjury.org/es includes expert advice on everything from how to handle a hospital visit, to cast care and pain management, to what to do if a child is having nightmares after an accident.

For more information about emotional reactions to injury or to download resources and tip sheets, visit AfterTheInjury.org/es or AfterTheInjury.org/.

A full press release also available in Spanish at the following link: http://bit.ly/1ovtOmj

Permanent link to this article: http://www.research.chop.edu/blog/aftertheinjury-orges-offers-expert-tips-spanish/

Jun 02 2014

Children’s Hospital Launches Violence Prevention Initiative

violence_preventionThe Children’s Hospital of Philadelphia recently unveiled its Violence Prevention Initiative (VPI) in a press conference at the Karabots Pediatric Care Center in West Philadelphia. A set of programs designed to reduce the severity and impact of violence and aggression on children and families not only in Philadelphia communities but also across the country, at the VPI’s launch Philadelphia Mayor Michael Nutter, Councilwoman Jannie L. Blackwell, Department of Human Services Commissioner Anne Marie Ambrose, and the School District of Philadelphia’s Chief of Student Services Karyn Lynch delivered remarks in support of the initiative.

“Every day we see the consequences of violence in our Emergency Department, in our operating rooms and on our patient units,” said Steven M. Altschuler, MD, CEO of The Children’s Hospital of Philadelphia. “Just since May 1st, 38 people — including six children — have been injured by gun violence in the City of Philadelphia. This number does not include non-gun-related violence, or the trauma imposed on witnesses, friends, family, and communities in which the threat of violence is a daily reality.”

“As an institution that exists to promote the health and well-being of children and as the nation’s leading pediatric hospital, it is our responsibility to find ways to prevent this epidemic from spreading,” Dr. Altschuler added.

VPI is led by a multidisciplinary team made up of some of the nation’s foremost experts in hospital-based violence intervention, evidence-based anti-bullying methods, and trauma-informed care. Through the strength of its long-time partnerships with community organizations, CHOP’s VPI builds on years of rigorous public health research to address and prevent ongoing concerns such as bullying in schools, intimate partner violence in the home, and assaults in the community.

“More than 40 percent of young people in the U.S. are exposed to some form of violence,” said Stephen Leff, PhD, a CHOP psychologist and co-director of VPI. “Youth can be exposed to violence in their homes, schools and communities with serious, lifelong consequences, including poor emotional and developmental health; long-term changes within the brain and stress reactions; school failure, drug abuse and delinquency; and the likelihood to perpetuate violence.”

The VPI programs concentrate CHOP’s medical training, mental health programs, provider training, research expertise, and knowledge of public health policies to interrupt violence while ensuring that limited resources are spent efficiently with the greatest chance for impact. Interventions occur at locations that are relevant to CHOP patients: within schools, primary care, and hospital sites.

The majority of children reached by VPI may never be CHOP patients, but witness violence in their schools or communities. VPI works within schools to provide evidence-based, whole-school approaches to bullying prevention for children in third through eighth grade. These programs address the multiple forms that aggression and bullying can take, including physical, social (such as gossiping and threatening to withdraw friendships), and cyber-bullying. This training gives them tools to handle and avoid more dire forms of violence as they grow older.

In addition, intimate partner violence (IPV) counselors support clinical staff in screening for and addressing IPV and teen dating violence in our patient population. This is a partnership with Lutheran Settlement House, with the goal of minimizing the adverse effects of childhood IPV exposure. Healthcare provider training and parenting education is also provided.

And children ages 8 through 18 who arrive in CHOP’s Emergency Department with injuries from an assault receive long-term intensive support from a violence prevention counselor in the hospital and after discharge to reduce re-injury or retaliation and to promote physical and emotional healing.

“VPI programs reach beyond the hospital and doctors office into schools, homes, neighborhoods, and recreation centers by empowering and training kids and adults to interrupt the cycle of violence,” said Joel Fein, MD, MPH, a CHOP Emergency Physician and co-director of VPI, adding that the initiative “aims to become a national model for hospital-led youth violence prevention.”

Further information about the Violence Prevention Initiative and its specific programs can be found at chop.edu/violence.

Permanent link to this article: http://www.research.chop.edu/blog/childrens-hospital-launches-violence-prevention-initiative/

May 29 2014

Severe Retinopathy of Prematurity Associated With Functional Disability

retinopathy of prematurity

ROP is a disorder of the blood vessels of the retina, which are not completely developed until a baby reaches full term.

A study led by a CHOP neonatology expert showed that infants with severe retinopathy of prematurity (ROP) diagnosed and treated under modern protocols remain at risk of nonvisual disabilities, even if blindness can be averted in most children.

ROP is a disorder of the blood vessels of the retina, which are not completely developed until a baby reaches full term. A baby born prematurely may have growth of abnormal blood vessels, or damage and scarring of existing blood vessels in the retina. This can lead to retinal scarring or detachment from the back of the eye, resulting in vision loss.

Severe ROP is not a rare condition, and its incidence has been rising. It occurs in at least 10 percent of unselected and extremely preterm infants — those born at less than 29 out of 40 weeks of gestation. Moreover, it is a serious problem in middle-income countries where even moderately preterm babies are affected.

“It is therefore important to research the association between this neonatal complication and adverse long-term child development,” said Barbara Schmidt, MD, MSc, an attending neonatologist at Children’s Hospital of Philadelphia and also a professor of pediatrics and Kristine Sandberg Knisely Chair in Neonatology, Perelman School of Medicine at the University of Pennsylvania.

This exploratory analysis reported in the Journal of the American Medical Association used data from a cohort of very low-birth-weight infants involved in the Caffeine for Apnea of Prematurity trial. Study participants included 1,582 children born at 31 centers between 1999 and 2004 and followed up at age 5. Of the 95 children who had severe ROP, 12 were bilaterally blind at 5 years. The study found that motor impairment, cognitive impairment, and severe hearing loss were three to four times more common in children with severe ROP than those without severe ROP.

These findings remind clinicians and parents that while blindness often can be prevented by timely retinal therapy in the neonatal intensive care unit, severe ROP remains a predictor of functional disability. It reinforces the need for long-term visual and developmental follow-up for infants who are diagnosed with severe ROP.

Yet, it remains unclear why there is an association between the development of severe ROP and the presence of nonvisual disabilities.

“We can only speculate,” Dr. Schmidt said. “The retina has been called a ‘window to the brain;’ hence, severe damage to the developing retina in a very immature baby may also indicate damage to the developing brain.”

Future studies could examine whether the association that investigators observed between severe ROP and nonvisual disability represents a “cause and effect” relationship. Dr. Schmidt also suggested that more research on effective strategies in the neonatal intensive care unit to prevent severe ROP is needed.

Contributing authors to the JAMA study are from the University of Melbourne, Australia; University of Toronto, Canada; the University of British Columbia, Canada; and McMaster University, Canada.

Permanent link to this article: http://www.research.chop.edu/blog/severe-retinopathy-prematurity-associated-functional-disability/

May 28 2014

CHOP, Drexel Consortium to Boost Pediatric Medical Device Pipeline

mecial deviceFor medical devices, as with many medicines, the market for children is a small fraction of the adult market, and there are far fewer child-sized devices. But the need for pediatric medical devices exists, even if proper devices may not.

“It’s not simply a matter of scaling down adult equipment for pediatric use,” said Children’s Hospital bioengineer Matthew Maltese, PhD. “Pediatricians have long known that children are not just small adults, and adults are not just big children.”

Dr. Maltese is the principal investigator of the Philadelphia Regional Pediatric Medical Device Consortium (PPDC), which brings engineers and biomedical researchers from CHOP, Drexel University, and the University of Pennsylvania to address the shortage of medical devices designed for children. The PPDC recently received a $1.5 million, five-year grant from the U.S. Food and Drug Administration (FDA). One of only seven pediatric device consortia nationwide recently funded by the FDA, the consortium will provide clinical, business, and regulatory expertise, as well as seed funding, to help translate innovative ideas into commercial devices for use in young patients.

“For a variety of reasons, it is difficult to advance pediatric medical devices beyond the idea stage,” said Dr. Maltese. “We provide innovators with the support they need to transform concepts into practical and available medical devices that benefit children.”

Robert Levy, MD, who holds William J. Rashkind Endowed Chair in Pediatric Cardiology at CHOP and is a co-principal investigator of the PPDC, also sees opportunities to help children, saying that the consortium “will help to address unmet needs for pediatric medical devices.” Dr. Levy’s medical device experience is reflected in his 35 issued U.S. patents that have led to extensive licensing activities, both to established medical device companies and to start-ups. One such example is the CHOP spinout firm, Vascular Magnetics, which is developing magnetically guided devices to precisely deliver drugs to injured arteries in children and adults.

As the center of the nation’s largest pediatric care network, CHOP offers a large, diverse pool of pediatric patients, allowing for carefully regulated clinical trials to test potential medical devices.

In addition, the PPDC will benefit from Dr. Maltese’s own experience adapting medical devices for children in his position in Critical Care Medicine at CHOP. The Hospital is currently collaborating with industry partners to develop pediatric versions of existing FDA-approved cardiopulmonary resuscitation (CPR) quality feedback tools developed for adults. These smartphone-sized devices measure motion and force on a patient’s chest during CPR to rapidly produce sound and visual prompts that improve the quality of CPR and save lives.

To read more about the PPDC, see the full press release.

Permanent link to this article: http://www.research.chop.edu/blog/chop-drexel-consortium-boost-pediatric-medical-device-pipeline/

May 27 2014

Hat Trick! Cell Therapy Expert Scores Trio of Honors

cell therapy expertIt has been a busy few weeks for The Children’s Hospital of Philadelphia’s Stephan Grupp, MD, PhD. Dr. Grupp, the director of Translational Research at the Center for Childhood Cancer Research, recently received three awards for his groundbreaking immune therapy work using genetically engineered, cancer-fighting T cells. Dr. Grupp received awards from the Clinical Research Forum, the European Society for Blood and Marrow Transplantation, and was honored alongside the University of Pennsylvania by the bioscience organization Pennsylvania Bio.

Dr. Grupp has received a great deal of attention for his investigation of using cell therapy to treat an aggressive form of childhood leukemia, acute lymphoblastic leukemia (ALL). Last year his work — conducted in partnership with the University of Pennsylvania’s Carl June, MD — led to dramatic, extraordinary results published in The New England Journal of Medicine: two children with untreatable ALL achieved a complete response after being treated with immune therapy. Since receiving the treatment one of those patients remains healthy and cancer-free two years later.

The Clinical Research Forum (CRF) award, the 2014 Herbert Pardes Clinical Research Excellence Award, is one of ten recent awards handed out by the CRF to projects “that benefit the health and wellbeing of the general public.” The 2 Herbert Pardes Award is the CRF’s top prize, and was awarded at an April 10 reception in Washington, DC.

The European Society for Blood and Marrow Transplantation (EBMT), meanwhile, handed a team of researchers led by Dr. Grupp the 2014 van Bekkum Award. The EBMT’s van Bekkum award is given to the best abstract presented at the Society’s annual meeting, held March 30 to April 2 in Milan, Italy.

The data presented at the Clinical Research Forum and EBMT update the data published in the New England Journal of Medicine. “Our group has now treated 25 kids and 5 adults with relapsed/refractory ALL,” said Dr. Grupp. “We have seen unexpectedly high rates of complete remission: 90 percent in this group of patients, many of who had no other treatment options. These results are leading to a phase 2 trial at six pediatric hospitals, with CHOP as the lead site.”

Rounding out the list of plaudits, at the recent 2014 Pennsylvania Bio Annual Dinner & Awards Celebration, CHOP and Penn were jointly honored for their cell therapy work with PA Bio’s Patient Impact Award.

“It’s an honor to have our cell therapy research recognized by such prestigious organizations,” said Dr. Grupp. “This is potentially revolutionary work, but its success to date — and going forward — would not have been possible without multidisciplinary, truly collaborative input from investigators across CHOP and Penn. I cannot thank my colleagues enough.”

To learn more about cancer research at The Children’s Hospital of Philadelphia, see the Center for Childhood Cancer Research website or the Hospital’s Cancer Center.

Permanent link to this article: http://www.research.chop.edu/blog/hat-trick-cell-therapy-expert-scores-trio-honors/

May 22 2014

Distinguished Career Award Goes to CHOP Oncologist

BLBeverly J. Lange, MD, an exemplary physician and researcher at The Children’s Hospital of Philadelphia (CHOP) for over 40 years, received the 2014 Distinguished Career Award from the American Society of Pediatric Hematology/Oncology (ASPHO). Given during ASPHO’s 27th Annual Meeting in Chicago, the award recognizes Dr. Lange’s outstanding lifetime contributions to the care of children with cancer.

The ASPHO Distinguished Career Award honors a professional whose career “has had a major impact on the subspecialty through some combination of research, education, patient care, and advocacy.”

Dr. Lange served as a senior physician and director of clinical affairs in the Division of Oncology at CHOP, where she worked from 1976 until her retirement in 2013. She also held the Yetta Deitch Novotny Chair in Pediatric Oncology at the Hospital, and was a professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania. She continues to volunteer with CHOP’s Division of Oncology.

Although Dr. Lange’s clinical work has explored many types of childhood cancer, she is most associated with groundbreaking investigations of pediatric leukemia. There is no question that Dr. Lange “is synonymous with evidence-based improvements in the treatment of pediatric acute myeloid leukemia (AML),” ASPHO said. Much of her work has focused on conducting landmark clinical trials to discover optimum combination treatments for AML, including reducing and even preventing side effects of cancer treatments.

Since Dr. Lange began working on AML, survival rates have improved to their current level of over 55 percent. Her expertise has also produced advancements in treating high-risk forms of another childhood cancer, pediatric acute lymphoblastic leukemia. In addition, Dr. Lange has published extensively in top-tier scientific journals, has contributed her expertise to professional organizations such as ASPHO and the multicenter Children’s Oncology Group, and has mentored countless young investigators.

With the ASPHO award, Dr. Lange joins the ranks of other CHOP oncologists who have previously received the ASPHO Distinguished Career Award, including Giulio D’Angio, MD, in 1990, Audrey E. Evans, MD, in 1995, and Anna Meadows, MD, in 2004.

For more information about cancer research at The Children’s Hospital of Philadelphia, see the Cancer Center.

Permanent link to this article: http://www.research.chop.edu/blog/distinguished-career-award-goes-chop-oncologist/

May 21 2014

Study Reports Outcomes of Tracheostomy in Preterm Infants

preterm infantsNeonatologists at The Children’s Hospital of Philadelphia frequently face the intricate decision of whether to place a tracheostomy in a preterm infant with severe lung disease and when to do it. A lack of relevant literature about this procedure makes it a challenging consideration.

A recent study in the Journal of Pediatrics led by a CHOP neonatologist gives more guidance on this problem by evaluating the developmental outcomes of infants born before 30 weeks’ gestation who underwent tracheostomy. With these data in hand, clinicians contemplating a tracheostomy for a preterm infant can supplement clinical status and medical history to help parents comprehend potential long-term outcomes.

Premature infants’ lungs, especially the air sacs, are not fully developed. While many premature infants must use a mechanical ventilator and extra oxygen for breathing, a minority ultimately undergo tracheostomy placement. A tracheostomy is the insertion of an artificial airway into the windpipe through a surgical incision to provide a safe, long-term way to ventilate a child.

When Sara B. DeMauro, MD, MSCE, an attending neonatologist and medical director of Neonatal Follow-up Programs at CHOP, and co-investigators looked at a dataset collected at 16 sites from 2001 to 2011 by the NICHD Neonatal Research Network, they identified 304 preterm infants with tracheostomies to include in a retrospective cohort study.

“This is the first time anybody has ever performed a comprehensive evaluation of the developmental outcomes of these children at 18-22 months,” Dr. DeMauro said.

The researchers demonstrated that even when they performed adjusted analyses controlling for many of the factors known to be predictive of poor developmental outcomes in preterm infants, those with tracheostomies still had significantly increased odds of adverse outcomes. These outcomes consisted of neurologic impairment, developmental delay, or visual or hearing impairment.

Dr. DeMauro pointed out that while this study suggests that tracheostomy is a marker for a risk of adverse developmental outcomes in this vulnerable population, it does not indicate that tracheostomy causes these problems.

“Based on their entire medical histories, these children are predisposed to having poor developmental outcomes,” Dr. DeMauro said. “This is almost a way to measure that. If they’re so sick that they need a tracheostomy, then they’re so sick that they’re at very high risk for having an adverse outcome.”

This clinical conundrum has another nuance: If a preterm infant needs a tracheostomy, when should the procedure be performed?

Again, Dr. DeMauro and colleagues found a paucity of literature to guide that decision. So they assessed the impact of timing by comparing outcomes of infants who underwent tracheostomy before and after 120 days of life. Their study suggests a possible association between earlier (<120 days) tracheostomy and better neurodevelopmental outcomes.

While more studies must be done to determine if earlier decisions about tracheostomy placement are advantageous, Dr. DeMauro described how it is possible that a “sooner than later” approach could have benefits in the NICU.

“Before their tracheostomy is placed, infants aren’t allowed to move around too much because they could dislodge their tube. Therefore, they can’t engage in developmentally appropriate play and are often heavily sedated,” Dr. DeMauro said. “As soon as they have a tracheostomy that is in place and healed, you get them out of bed, you play with them, and you take them off sedation.”

Further data also is needed on the outcomes of tracheostomy in preterm infants who have lung disease compared to those who also have airway disease. Delving into these complexities will help clinicians have more complete information when they speak with families about pursuing tracheostomy placement, Dr. DeMauro said.

“This study is an important first step in understanding what the range of outcomes for these children tends to be,” she said. “When these data are combined with a child’s individual clinical situation and any additional risk factors for poor outcomes, it allows you to make a much more informed decision about whether a tracheostomy is a good choice.”

Grants from the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development for the Neonatal Research Network supported this study.

Permanent link to this article: http://www.research.chop.edu/blog/study-reports-outcomes-tracheostomy-preterm-infants/

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