An international scientific team has discovered a gene associated with a high risk of severe childhood asthma. The specific gene variant may be an actual cause of this form of asthma, a leading cause of hospitalization in young children.
“Because asthma is a complex disease, with multiple interacting causes, we concentrated on a specific phenotype — severe, recurrent asthma occurring between ages two and six,” said co-lead author of the study, Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics (CAG). “Identifying a risk susceptibility gene linked to this phenotype may lead to more effective, targeted treatments for this type of childhood asthma.”
The study, published in Nature Genetics, includes collaborators from centers in five countries. The study’s corresponding author, Klaus Bonnelykke, MD, PhD, is from the University of Copenhagen in Denmark, while Dr. Hakonarson’s collaborators from CHOP are Patrick Sleiman, PhD, and Michael March, PhD.
The study team performed a genome-wide association study (GWAS) on DNA from Danish national health registries and the Danish National Screening Biobank. In the discovery phase of their study, they compared genomes from 1,173 children aged 2 to 6 years from the Copenhagen Prospective Study on Asthma in Childhood (COSPAC) with genomes from 2,522 adult and pediatric control subjects without asthma.
In addition to finding further evidence for four genes previously implicated as asthma susceptibility genes, the researchers identified a novel gene, CDHR3, which is particularly active in epithelial cells lining the surfaces of airways. The study team then replicated their findings using data from other children of both European and non-European ancestry.
“Asthma researchers have been increasingly interested in the role of the airway epithelium in the development of asthma,” said Dr. Hakonarson. “Abnormalities in the epithelial cells may increase a patient’s risk to environmental triggers by exaggerating immune responses and making the airway overreact. Because the CDHR3 gene is related to a family of proteins involved in cell adhesion and cell-to-cell interaction, it is plausible that variations in this gene may disrupt normal functioning in these airway cells, and make a child vulnerable to asthma.”
Dr. Hakonarson said that the current findings are consistent with previous investigations by CAG, suggesting that other genes linked to childhood asthma play a role in oversensitive immune reactions. Further studies are needed to better understand how the CDHR3 gene may function in asthma, with the eventual goal of using such knowledge to design better treatments for children with severe cases of this disease, Dr. Hakonarson added.
Direct link: http://btob.research.chop.edu/severe-childhood-asthma-gene-variant-discovered/
A trade mission to Israel led by Philadelphia Mayor Michael A. Nutter has led to a new research agreement between The Children’s Hospital of Philadelphia (CHOP), Drexel University, and the Hebrew University of Jerusalem. The partnership will be focused on pediatric translational research and moving investigations from the bench to the bedside. In addition, a January conference will give researchers from all three institutions the chance to connect and share ideas.
“I am proud to see two great Philadelphia institutions, CHOP and Drexel University, expand their research overseas,” said Mayor Nutter. “The partnership with Hebrew University will allow all three parties to share research and ultimately improve children’s healthcare.” The research agreement was signed in a ceremony at Jerusalem’s City Hall on November 11.
And the upcoming conference, to be held January 27 and 28 at the CHOP Research Institute, will bring together investigators from CHOP, Drexel, and Hebrew University for presentations and discussions aimed at fostering cooperation and teamwork.
“The goal of the symposium is to present cutting-edge science that has the potential to benefit from collaboration among investigators at each institution,” said Tom Curran, PhD, FRS, deputy scientific director of CHOP Research.
“The collaboration between The Children’s Hospital of Philadelphia, Drexel University, and Hebrew University will create an excellent environment for translating basic science into practical applications,” said President of the Hebrew University of Jerusalem, Menahem Ben-Sasson, PhD.
Prior to the recent agreement, Drexel University and Hebrew University already had a partnership of their own in place, the Joint Drexel-Hebrew University Institute for Drug Research Hub. The new collaboration with CHOP will “address unmet needs in pediatrics through innovative commercial pediatric therapeutics and diagnostics,” said John A. Fry, president of Drexel University.
“We are thrilled to collaborate with two exceptional institutions — Drexel University and Hebrew University’s School of Pharmacy — whose expertise in technology and drug delivery respectively will create a unique partnership that enables high-quality, rapid advancement of new treatments in pediatric medicine for children around the world,” said CHOP CEO Steven M. Altschuler, MD.
For more information, see the press release about the announcement.
Direct link: http://btob.research.chop.edu/trade-mission-to-israel-leads-to-pediatric-research-agreement/
In late October, the Institute of Medicine (IOM) and the National Research Council released an extensive report on sports-related concussions in children and teens that found helmets do not prevent concussions in youth athletes. And according to the IOM report, “Sports-Related Concussion in Youth: Improving the Science, Changing the Culture,” despite an increased awareness of concussions, there remains a culture “that resists both the self-reporting of concussions and compliance with appropriate concussion management plans.”
The report was authored by a committee of experts, including the Center for Injury Research and Prevention’s (CIRP) Kristy Arbogast, PhD, and the University of Pennsylvania’s Susan S. Margulies, PhD. CIRP’s Engineering Core Director and an Associate Professor of Pediatrics at the University of Pennsylvania, Dr. Arbogast studies the biomechanics of pediatric injury, child safety seats, and concussion care. Other members of the committee include George Washington University’s Robert Graham, MD, the Sackler Institute for Developmental Psychobiology’s B.J. Casey, PhD, and Kasisomayajula Viswanath, PhD, of Harvard University and the Dana-Farber Cancer Institute.
In a post on the CIRP blog, Dr. Arbogast writes that the answer to whether helmets prevent concussions is “no.” While helmets “have been proven effective at preventing skull fractures and more serious traumatic brain injuries and should continue to be used in competitive and recreational sports … the Committee found that research was needed to better understand the biomechanics of how pediatric concussions occur before any protective device can be scientifically proven to prevent them,” Dr. Arbogast notes.
Because of this, there must be a sea change in the way athletes and coaches approach concussions, she says. “There must be a shift in the culture of athletics — among parents, coaches, school personnel, and the youth athletes themselves — to treat concussion as an injury that requires serious attention, even if it means missing “the big game” or an entire season of play.”
Direct link: http://btob.research.chop.edu/institute-of-medicine-report-examines-sports-related-concussion-in-youths/
Children’s Hospital recently lent its support to a major violence prevention conference that brought together violence prevention researchers, government officials, and community advocates. Along with Drexel University and the Oakland, Calif.-based urban youth advocacy organization Youth Alive!, the Hospital sponsored the fourth annual National Network of Hospital-based Violence Intervention Programs (NNHVIP) conference.
Conceived during a 2009 violence intervention conference held by Youth Alive!, the mission of the NNHVIP is to “strengthen existing hospital-based violence intervention programs and help develop similar programs in communities across the country,” according to the NNHVIP site. Since its inception, the NNVIP has grown to comprise 22 programs in 14 states and the District of Columbia, and NNHVIP members provide technical assistance to a number of “emerging” programs around the country and in Canada. These include the Minneapolis Youth Violence Intervention Program, the Manitoba Institute of Child Health, and Brooklyn, N.Y.-based Kings Against Violence Initiative.
The NNHVIP conference, which was held at the National Museum of American Jewish History in Philadelphia, brought together experts from around the country for two days of presentations on youth violence prevention, collaboration with law enforcement, and methods of working with mental health professionals to provide care.
Along with his fellow co-director of the NNHVIP headquarters Ted Corbin, MD, MPP, Children’s Hospital’s Joel Fein, MD, MPH, delivered the conference’s welcoming remarks. The director of outreach for CHOP’s Center for Pediatric Trauma Stress, Dr. Fein is also the co-director of CHOP’s Violence Prevention Initiative, a member of the boards of directors of both The Institute for Safe Families and the Society for the Advancement of Violence and Injury Research, and an attending physician in CHOP’s Emergency Department.
In addition to Drs. Corbin and Fein, speakers at the NNHVIP conference included Acting Assistant Attorney General of the U.S. Department of Justice Tony West, and Anne Marie Ambrose, commissioner of Philadelphia’s Department of Human Services. Associate Attorney General West spoke about trauma-informed care and youth violence prevention, while Commissioner Ambrose discussed youth violence prevention collaborations.
Toni Rivera-Joachin, the project manager of the Children’s Hospital of Wisconsin in Milwaukee’s Project Ujima, also gave a talk at the NNHVIP conference. According to the project’s website, Project Ujima is a “multidisciplinary collaboration addressing youth and adult violence through individual, family and community intervention and prevention strategies,” helping youth and adult victims of violence and violent crime recover.
The Project’s mission is to “stop the cycle of violent crimes by reducing the number of repeat victims of violence through individual, family and community interventions and prevention strategies.” In her talk, Rivera-Joachin discussed the importance of community partnerships to Project Ujima’s work.
Indeed, a recent speech by Mayors Mitch Landrieu of New Orleans and Michael Nutter of Philadelphia at the National Press Club highlighted the growing problem of violence and violent crime in America, particularly among and by young African American men. Calling violence and murder an “urgent, national issue,” New Orleans Mayor Landrieu said “the challenge of murder is both wide and deep, and must be addressed broadly as an issue of public health, with close connection to economics, education, poverty, law enforcement, race, and yes, American culture.” The mayors called for increased collaborations between government agencies and advocacy organizations to work to prevent violence.
“From 1980 to 2012, 626,000 people, American citizens, a disproportionate number young African American men, were murdered on the streets of America. That’s more Americans that were lost during World War I, World War II, Korea, Vietnam, the Persian Gulf War, the war in Iraq, and the war in Afghanistan combined,” Mayor Landrieu said.
For his part, Mayor Nutter noted that “we must change…this is a national problem with national implications that deserves a national response and action, everyone doing their part.” According to the Philadelphia Police Department, in 2012, there were 331 homicides in Philadelphia, and as of October 1, 2013, there were 187 homicides. Of the 2012 victims, 67.8 percent were black.
“If we do not have the urgency to stand up now and say enough, then when?” Mayor Nutter asked.
To learn more about ways the NNHVIP works to prevent violence, see the organization’s website.
Direct link: http://btob.research.chop.edu/multidisciplinary-collaborations-highlighted-at-violence-intervention-conference/
Physician-scientist Vinay M. Nadkarni, MD, recently received a Distinguished Career Award from the American Association of Pediatrics (AAP). The medical director of the Center for Simulation, Advanced Education, and Innovation, Dr. Nakarni is a leading critical care and resuscitation science researcher.
Dr. Nadkarni received his award at the recent AAP National Conference and Exhibition. Held October 26-30 in Orlando, Fla., the AAP conference was attended by more than 10,000 pediatricians and providers for discussions, poster presentations, and networking events. Dr. Nadkarni received his award from the AAP’s Section on Critical Care, which has the mission of optimizing “optimize the care of critically ill and injured children of all ages through the educational and professional support of its members.”
“Dr. Nadkarni is an internationally recognized physician-scientist with a longstanding commitment to the discovery, translation, and implementation of shock, trauma, and resuscitation science,” said chief of Critical Care Medicine at Children’s Hospital Robert Berg, MD.
After receiving his MD from the University of Maryland School of Medicine in 1984, Dr. Nadkarni continued his training at the Children’s National Medical Center in Washington, DC, joining Children’s Hospital in 2001. In addition to his roles at CHOP, Dr. Nadkarni is also associate director of the University of Pennsylvania’s Center for Resuscitation Science, and has contributed his time to serving on the boards and committees of a number of professional and charitable organizations, including Operation Smile.
Earlier this year, Drs. Nadkarni and Berg contributed to a study published in Circulation that showed extending cardiopulmonary resuscitation (CPR) longer than previously thought useful can save lives in children and adults. After analyzing the hospital records of 3,419 children in the U.S. and Canada from 2000 through 2009, the investigators found that among children who suffered in-hospital cardiac arrest, more children than expected survived after prolonged CPR. The conventional thinking has been that CPR is futile after 20 minutes, but these results challenge that, said Dr. Berg.
Since the Circulation study’s publication, Dr. Nadkarni has contributed to or led a number of other studies, including investigations of improving chest compression quality and a quantitative analysis of CPR in children during in-hospital cardiac arrests, both published in Resuscitation, as well as leading a study in Critical Care in Medicine of organ transplantation following cardiopulmonary resuscitation.
Dr. Nadkarni’s “efforts and passion for advancing the field of critical care medicine worldwide have facilitated learning, idea generation, and he has championed change which has helped save lives,” Dr. Berg said.
To read more about Dr. Nadkarni’s award, see the full press release. For more information on CPR and resuscitation research being conducted at CHOP, visit the Department of Anesthesiology and Critical Care Medicine.
Direct link: http://btob.research.chop.edu/resuscitation-expert-vinay-nadkarni-md-receives-aap-award/
A new Children’s Hospital study found that while most children improved cognitive function while in inpatient rehabilitation, those with traumatic brain injury (TBI) were discharged with significant cognitive functioning deficits affecting memory, problem solving, and verbal communication that would require continued support. Researchers recommend that parents and their child’s primary care physician coordinate reentry to home and school.
The study, published in the Journal of Pediatrics, analyzed the cognitive deficits of nearly 14,000 children ages 7 to 18 years from 2002-2011, before and after admission to inpatient rehabilitation for trauma-related injuries. Children with TBI had more cognitive disability when entering inpatient rehab than other seriously injured children, including those with spinal cord injury, multiple fractures/amputation, and burns. While all injury groups showed improvements upon discharge, the TBI group had severe cognitive disability upon admission, and improved to only moderate disability upon discharge.
“At discharge, children with moderate cognitive disability can usually communicate and express needs but may need prompting for problem solving and memory,” said the study’s leader, Mark Zonfrillo, MD, MSCE, an investigator at the Center for Injury Research and Prevention (CIRP) and associate director of research in the Division of Emergency Medicine. “These children may continue to improve after discharge, so this transition is a critical point in their care.” In addition to Dr. Zonfrillo, CIRP’s Dennis Durbin, MD, MSCE, and Flaura K. Winston, MD, PhD, also contributed to the investigation.
A previous study led by Dr. Zonfrillo, published last year in Pediatrics, assessed physical disabilities for this same group of children. That study also demonstrated improvements throughout rehabilitation, but children with spinal cord injuries had longer lengths of stays and more physical disability at discharge. Even though many of these children improved functionally, they still required assistance for day-to-day tasks.
According to Dr. Zonfrillo, while primary care providers do not care for these children in the hospital ICU or during inpatient rehabilitation, they are responsible for a patient’s ongoing holistic care. Thus primary care providers, rehabilitation staff, and parents need to communicate with each other during this transition period. Additionally, many states have programs and services that can help these efforts, including brain injury associations and organizations.
“There is a concern that socioeconomically disadvantaged families may have additional challenges with their child reentering society,” said Dr. Zonfrillo. “Some families may not have the social support or economic means to know how to help their child after returning home, and they need to know that their child’s primary care provider can coordinate access to the resources they need.”
The researchers next plan to look at the demographics of serious pediatric injury recovery, including which specific injuries cause the most long-term care needs and which groups have better health outcomes for these specific injuries. Factors to be analyzed include sex, socioeconomic status, insurance, race, access to care, and injury severity.
“The goal of this line of research at CHOP is to maximize access to trauma systems and to optimize acute and rehabilitation care for young patients with serious injuries,” said Dr. Zonfrillo. “If we have a complete picture of the scale of pediatric traumatic injuries and related long-term needs, as well as the differences between injury patterns and various outcomes, we can predict the type and level of support necessary upon discharge from inpatient rehabilitation.”
Direct link: http://btob.research.chop.edu/injured-children-need-continued-care-following-rehabilitation/
A new book edited by a Children’s Hospital investigator examines the role genetic variants play in causing or raising the risk of obesity. The Genetics of Obesity is a comprehensive “review of efforts aimed at uncovering genetic variants associated with obesity,” and discusses the history of obesity research as well as recent breakthroughs.
In his role as the book’s editor, Struan F.A. Grant, PhD, associate director of the Center for Applied Genomics, brought together contributors from institutions in the United States, U.K., France, and Germany. The authors’ affiliations include the Broad Institute, the Wellcome Trust Centre for Human Genetics, Lille Pasteur Institute, Heinrich Heine University, the University of Michigan, Imperial College London, and the University of Cambridge’s Wellcome Trust-MRC Institute of Metabolic Science.
The Genetics of Obesity features chapters on genetic obesity syndromes, genome-wide association studies (GWAS) of obesity, and the relation of genetic pleiotropies — or when genes cause multiple physical effects — to obesity. The opening chapter, which outlines the lead up to genome-wide genetic approaches, was written by Children’s Hospital’s Shana E. McCormack, MD. And for his part, Dr. Grant contributed a chapter titled “Genetics of Childhood Obesity,” in which he discusses efforts to understand “the genetic architecture of childhood obesity.”
“There is now clear evidence that genetics plays a role in the risk of presenting with obesity, and the areas covered in this book outline the progress that has been made in defining what genomic factors have been characterized to date,” Dr. Grant said.
A significant portion of Dr. Grant’s research has been related to obesity and metabolic diseases. Last year, he led a study published in Nature Genetics that discovered two new gene variants that increase the risk of common childhood obesity, and earlier this year he co-lead a study on the genetics of birth weight and co-authored studies that discovered new loci associated with body mass index and body fat distribution in adults of African ancestry. Recently, he has also been working to better understand the genetic links between type 2 diabetes (which is often associated with obesity) and cancer.
To learn more about The Genetic of Obesity, see the publisher’s website.
Direct link: http://btob.research.chop.edu/genetics-expert-struan-grant-phd-edits-book-examining-genetics-and-obesity/
The Children’s Hospital of Philadelphia’s Stephan A. Grupp, MD, PhD, along with his young patient Emily Whitehead, have been named 2013 WebMD Health Heroes. The Center for Childhood Cancer Research’s Director of Translational Research, Dr. Grupp has been leading a groundbreaking trial of immune therapy to treat childhood leukemia that led to Emily’s dramatic recovery.
Designed to honor “visionary Americans who met a health challenge and gave back to others in an inspiring way,” Dr. Grupp and Emily Whitehead were among a small group of advocates, parents, and activists honored by WebMD. In addition to Dr. Grupp and Emily, other honorees include Lee Morgan, DVM, who works to help care for injured service dogs, and Manny Hernandez, who established social networks for people with diabetes. Dr. Grupp was the only clinician honored in 2013.
Dr. Grupp’s trial is focused on using engineered T cells to treat acute lymphoblastic leukemia (ALL), an aggressive childhood leukemia. The most common form of leukemia found in children, ALL is largely curable, with a roughly 85 percent cure rate. However, the remaining 15 percent of ALL cases resist standard therapy.
When Emily came to Dr. Grupp, her ALL had relapsed for the second time and was resistant to chemotherapy. In April of 2012 she became the first pediatric patient to receive the engineered T cells. And though the treatment led to a life-threatening illness — known as cytokine release syndrome — Emily eventually recovered after Dr. Grupp and his team were able to treat her symptoms. Since receiving the T cells, Emily remains healthy and cancer-free.
“We are so grateful to these doctors who spend their lives curing cancer,” Emily’s father Tom Whitehead said.
Direct link: http://btob.research.chop.edu/chop-cancer-researcher-patient-named-webmd-health-heroes/
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