Aug 05 2014

Climate Change Could Mean More Kidney Stones

kidney stones

The delay between high daily temperatures and kidney stone presentation was short, peaking within three days of exposure to hot days.

As daily temperatures increase, so does the number of patients seeking treatment for kidney stones. In a study that may both reflect and foretell climate change’s impact on human health, a research team found a link between hot days and kidney stones in 60,000 patients in several U.S. cities with varying climates.

“We found that as daily temperatures rise, there is a rapid increase in the probability of patients presenting over the next 20 days with kidney stones,” said Gregory E. Tasian, MD, MSc, MSCE, a pediatric urologist and epidemiologist at The Children’s Hospital of Philadelphia. Along with CHOP’S Ron Keren, MD, MPH, Dr. Tasian published the study team’s findings recently in Environmental Health Perspectives, the journal of the National Institute of Environmental Health Sciences.

Kidney stones are a painful condition that brings half a million patients a year to emergency rooms. While stones remain more common in adults, the numbers of children developing kidney stones have climbed at a dramatically high rate over the last 25 years. When patients cannot pass stones on their own, surgery may be necessary.

The investigators analyzed the records of more than 60,000 adults and children with kidney stones between 2005 and 2011 in Atlanta, Chicago, Dallas, Los Angeles and Philadelphia, in connection with weather data. Dr. Tasian and colleagues described the risk of stone presentation for the full range of temperatures in each city. The delay between high daily temperatures and kidney stone presentation was short, peaking within three days of exposure to hot days.

The study’s broader context is in patterns of global warming. The authors note that other scientists have reported that overall global temperatures between 2000 and 2009 were higher than 82 percent of temperatures over the past 11,300 years. Furthermore, increases in greenhouse gas emissions are projected to raise earth’s average temperatures by 2 to 8 ͦF (1 to 4.5 ͦC) by 2100.

“These findings point to potential public health effects associated with global climate change,” said Dr. Tasian. “However,” he cautioned, “although 11 percent of the U.S. population has had kidney stones, most people have not. It is likely that higher temperatures increase the risk of kidney stones in those people predisposed to stone formation.” Higher temperatures contribute to dehydration, which leads to a higher concentration of calcium and other minerals in the urine that promote the growth of kidney stones.

The researchers also found that very low outdoor temperatures increased the risk of kidney stones in three cities: Atlanta, Chicago and Philadelphia. The authors suggest that as frigid weather keeps people indoors more, higher indoor temperatures, changes in diet, and decreased physical activity may increase their risk of kidney stones. Moreover, the researchers argue that the number of hot days in a given year may better predict kidney stone risk than the mean annual temperature.

“Kidney stone prevalence has already been on the rise over the last 30 years, and we can expect this trend to continue, both in greater numbers and over a broader geographic area, as daily temperatures increase,” concluded Dr. Tasian. “With some experts predicting that extreme temperatures will become the norm in 30 years, children will bear the brunt of climate change.”

To read more about kidney stones and urology research, see the Hospital’s website.

Permanent link to this article:

Jul 31 2014

CKiD Study Spurs New Insights Into Chronic Kidney Disease

chronic kidney diseaseIdentifying the best strategies to slow the progression to kidney failure for children with chronic kidney disease (CKD) is a constant challenge for clinicians. They must finely tune their treatment plans and judiciously anticipate when to begin dialysis or place patients on a kidney transplant waiting list.

The Chronic Kidney Disease in Children Study (CKiD) is a prospective cohort study that was initiated in 2003 to provide evidence to help inform these disease management decisions. A decade later, almost 900 children between the ages of 1 and 16 with decreased kidney function have entered the study. As a one of two clinical coordinating centers for CKiD, The Children’s Hospital of Philadelphia has contributed many research projects under the leadership of principal investigator Susan L. Furth, MD, chief of the division of nephrology.

The data collected from the CKiD has prompted new insights and approaches to improve care for children with CKD. These include a new gold standard in the measurement of kidney function, identification of acidosis and low birth rate as risk factors for poor growth, models to predict overall rates of decline of kidney function over time, and awareness that children with chronic kidney disease have a remarkable constellation of risk factors for heart disease.

“The rationale for CKiD was that chronic kidney disease and end stage renal disease in this country in adults really are a substantial burden,” Dr. Furth said. “The latest estimate is 10 million Americans have chronic kidney disease. It’s very likely that many of the origins of chronic kidney disease in adults start in children. We’ve found ways that we can intervene to extend life and promote the health of these kids.”

The primary goals of CKiD are to determine participants’ risk factors for decline in renal function, track their behavior and abilities to learn and think, monitor their growth, and evaluate possible connections to future cardiovascular disease. Several CHOP investigators recently have published studies related to CKiD and also presented their findings at the Pediatric Academic Societies Annual Meeting (PAS) held in May.

chronic kidney diseaseIn a study presented at PAS by Michelle Denburg, MD, MSCE, an attending nephrology physician at CHOP, researchers used CKiD data to show for the first time that children with CKD have increased risk of fracture, especially among teenage boys. Children with CKD have problems with absorbing calcium from the foods that they eat, and often as their kidney function worsens, their calcium gets low. In order to compensate, their bodies secrete a hormone that takes calcium out of their bones, which weakens them.

The study results showed that the incidence of fracture in a CKiD cohort of 556 children was two-fold higher than general population rates. Fractures of the arm and elbow were most common. These findings support the need for future CKiD research that will focus on bone frailty as an important therapeutic target in the pediatric CKD population.

Erum A. Hartung, MD, also an attending nephrology physician at CHOP, and colleagues published a study in the May issue of Pediatric Nephrology that concentrated on the neurocognition of a particular group of children with autosomal recessive polycystic kidney disease (ARPKD) who are born with abnormal kidneys. A previous CKiD study demonstrated that children with CKD have normal IQs, but they have challenges in the areas of attention and their ability to make and carry out plans. Parents of children with ARPKD had expressed concerns that their children could face increased risks for behavior and learning difficulties because they have early onset CKD and more severe high blood pressure — both of which are known risk factors for neurocognitive deficits.

The study’s results were reassuring to parents because they showed that the cognitive function of children with ARPKD was comparable to children in the CKiD cohort with mild-to-moderate kidney disease from other causes. The investigators concluded that, “Further studies are needed to determine if these findings are applicable to children with more severe manifestations of ARPKD.” Dr. Hartung also shared this study’s results at the PAS.

Dr. Furth encourages other investigators and collaborators to access the “wealth of data” in the CKiD’s national database to conduct research projects that potentially could lead to better outcomes for children with CKD. In the meantime, the CKiD’s second wave has begun, which involves a cohort of about 280 children.

“We’re looking more at vascular health and added tests of vascular stiffness to this study as we move forward,” Dr. Furth said. “Increased stiffness of the blood vessels, as measured by pulse wave velocity, has been associated with increased risk of adverse cardiovascular events in adults. We’re trying to see if this happens even earlier in children.”

Dr. Furth also is excited about a new partnership called the 4C Study with investigators in Europe. The aim is to gather a total sample size of about 1,500 children, including CKiD study participants and another cohort from a recently concluded interventional study in children with CKD called the ESCAPE trial, in order to conduct a genome-wide search for genetic risk markers of CKD progression.

“We’re finding out if there are new genetic associations with structural abnormalities of the kidney and also if there’s genetic variability that contributes to things like accelerated kidney function decline or anemia,” Dr. Furth said.

The National Institute of Diabetes and Digestive and Kidney Diseases, in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute, recently renewed funding for the CKiD. It is a cooperative agreement between the two clinical coordinating centers — CHOP and Children’s Mercy Hospital in Kansas City — a central biochemistry laboratory at the University of Rochester in New York, and a data coordinating center at Johns Hopkins School of Public Health in Baltimore.

Permanent link to this article:

Jul 30 2014

Unique Collaboration Leads to “Dream Teams” to Advance Pediatric Research

dream teamTwo dedicated “dream teams” of investigators will shape innovative solutions to address unmet pediatric medical needs, as part of a research partnership with The Children’s Hospital of Philadelphia, Drexel University, and The Hebrew University of Jerusalem.

The joint projects each will receive $250,000 over two years in institutional funding, as administrators seek external investors interested in advancing exciting pediatric translational research with commercial viability. The dream teams rose to the top of 20 proposals submitted as a result of a research symposium in January that gave researchers from all three institutions the opportunity to connect and share ideas.

“We are thrilled by the potential for discovery that this portfolio of projects holds, and much of this important work should appeal to future donors,” said The Children’s Hospital of Philadelphia CEO Steven M. Altschuler, MD.

Funding these initial grants internally demonstrates the institutions’ commitment to be a hub of collaboration and exemplifies the inventive, diverse, and entrepreneurial spirit that formed their research consortium initiative. Dr. Altschuler, Drexel President John A. Fry, and The Hebrew University of Jerusalem President Menahem Ben-Sasson signed the research agreement in November as part of a trade mission that Philadelphia Mayor Michael A. Nutter took to Israel.

“These inaugural awards are just the beginning of what the ongoing collaboration between The Children’s Hospital of Philadelphia, Hebrew University and Drexel can accomplish,” said Drexel President John A. Fry. “Together we can create new and unique opportunities that will address unmet needs in pediatrics through innovative commercial pediatric therapeutics and diagnostics.”

One dream team will be based at Drexel with Amy Throckmorton, PhD, as the principal investigator of the “Giving Kids a Chance” project that will investigate a new intravascular blood pump for pediatric patients with congenital heart disease (CHD).

The treatment of single ventricle (SV) anomalies is a formidable and costly challenge for clinical teams caring for patients with CHD, which is the most common major birth defect affecting nearly 1 percent of all newborns. Palliative repair of a SV is generally performed in a series of open-heart procedures over several years. The end result is a man-made physiology in which a SV drives blood flow through the entire circulatory system without the presence of a “right-sided” pulmonary ventricle to pump blood to the lungs. A heart transplant is a treatment option in difficult cases, if the child can survive the waiting period.

As interest is growing about the use of mechanical assistance as a bridge-to-transplant or treatment strategy, the dream team aims to develop a uniquely designed, new therapeutic device for patients with dysfunctional SV physiology. Their goal is to advance the state-of-the-art in blood pump technology, reversing the deleterious characteristics of current approaches and helping to prevent premature congestive heart failure.

dream team

“These inaugural awards are just the beginning of an ongoing collaboration between The Children’s Hospital of Philadelphia, Hebrew University and Drexel can accomplish,” said Drexel President John A. Fry.

The interdisciplinary team will combine its broad expertise in engineering, pediatric cardiology, congenital heart and cardiothoracic surgery, medical device development, and manufacturing for artificial organs. Members from Drexel will include Dr. Throckmorton, J. Yasha Kresh, PhD, and Randy Stevens, MD. They will be joined by four investigators from CHOP: David J. Goldberg, MD; Matthew Gillespie, MD; Kevin K. Whitehead, MD, PhD; and Joseph Rossano, MD. Amnon Hoffman of The Hebrew University of Jerusalem and Amiram Nir of Hadassah Medical Center will round out the team.

They will work with four industry partners: Rotor Bearing Solutions International of Charlottesville, Va.; Cardiac Assist Inc. of Pittsburgh, Pa.; Applied Rapid Technologies of Fredericksburg, Va.; and Laserage Technology Corp. of Waukegan, Ill.

A second dream team will be based at CHOP with Robert J. Levy, MD, as the principal investigator of a research project “Pediatric Transcatheter Valve Replacements: Preventing Device Failure due to Structural Degeneration.”

These investigations also will focus on CHD with a concentration on Tetralogy of Fallot (TOF). These “blue babies” have insufficient oxygen and need cardiac surgery early in life. Postoperatively patients with TOF are left with chronic malfunction of their pulmonary valve.

Ongoing research at CHOP has demonstrated that transcatheter pulmonary valve (TPV) therapy — the current best option — is susceptible to oxidative damage and structural failure. This interdisciplinary team seeks to gain a better understanding of the inflammatory and oxidative events responsible and to inhibit the early inflammatory response to TPV. They will attempt to modify the TPV material with an antioxidant as a way to prevent oxidative damage to the TPV leaflets.

Dr. Levy will collaborate with Matthew Gillespie, MD from CHOP and Joseph H. Gorman, MD and Robert C. Gorman, MD, from Penn, along with Kenneth Barbee, PhD, and Kara Spiller, PhD, from Drexel, and Gershon Golomb from The Hebrew University of Jerusalem.

Permanent link to this article:

Jul 28 2014

CIRP Engineering Expert Accepts New Leadership Role


Most recently, Dr. Arbogast has extended her work to include the study of concussions, not only from motor vehicle crashes, but also from sports

The Center for Injury Research and Prevention (CIRP) proudly announced the promotion of Kristy Arbogast, PhD, to co-scientific director. She was previously and continues to serve as the Center’s director of engineering.

Dr. Arbogast has been with CIRP since its establishment in 1996 to advance the safety and health of children, adolescents, and young adults through comprehensive research that encompasses before-the-injury prevention to after-the-injury healing. She joined Flaura K. Winston, MD, PhD, and Dennis R. Durbin, MD, MSCE, as a co-investigator on the seminal Partners for Child Passenger Safety (PCPS) project, a 10-year-long national study that led to significant policy and safety design advances for child motor vehicle occupants.

“This is a natural transition for CIRP,” said Dr. Winston, scientific director and founder of CIRP. “As Kristy’s career has matured and flourished, so has CIRP. She has helped to grow our Center’s international reputation as a thought leader in child injury prevention and pediatric biomechanics.”

Dr. Arbogast has dedicated her career to safety research, focusing on the development of new auto and restraint safety designs and biofidelic child anthropomorphic dummies. Her work was recently recognized by the receipt of an honorary doctorate from Chalmers University, Sweden.

As CIRP’s co-scientific director, Dr. Arbogast will join Dr. Winston and Ayana Bradshaw, MPH, CIRP’s administrative director, in leading a group of behavioral scientists, clinicians, epidemiologists, biostatisticians, engineers, public health practitioners, and communications professionals that focus on injury prevention, violence prevention, physical and emotional recovery following injury, digital health, and pediatric biomechanics.

“I have benefitted from the interdisciplinary structure of CIRP,” Dr. Arbogast said. “Working with colleagues from diverse academic backgrounds and research interests has expanded my own understanding of child injury prevention. We are all dedicated to translating our research into action to reduce preventable child injuries and deaths.”

Most recently, Dr. Arbogast has extended her work to include the study of concussions, not only from motor vehicle crashes, but also from sports. She served on the Institute of Medicine Committee on Sports Concussions in Youth and is also a member of the National Council on Youth Sports Safety. Since 2011, Dr. Arbogast has co-led a multi-disciplinary project at CHOP called Minds Matter: Improving Pediatric Concussion Management that streamlined and standardized concussion diagnosis, treatment, and follow-up care across the CHOP network.

Dr. Arbogast continues to serve as the co-director of the National Science Foundation-sponsored Center for Child Injury Prevention Studies (CChIPS) at CHOP, University of Pennsylvania and The Ohio State University. She is also research associate professor of pediatrics at the University of Pennsylvania.

Permanent link to this article:

Jul 23 2014

Platelet Granule Formation Gives Insight Into Rare Disease

plateletIf you take a normal platelet and examine it under an electron microscope, you will see a bunch of black dots. The specks may not seem like much at first, but cell biologists at The Children’s Hospital of Philadelphia Research Institute speculate that these dense granules hold the key to unlocking the mechanisms behind a rare disease called Hermansky-Pudlak syndrome (HPS) and other forms of bleeding disease.

HPS is estimated to affect one in 500,000 to one in 1,000,000 individuals worldwide. In certain places, like Puerto Rico, it is much more prevalent — about one in 1,800 individuals. People with the disease have a tendency to bruise and difficulties with blood clotting, which can be deadly under certain circumstances such a pregnancy, major surgery, or dental surgery.

“Those dense granules don’t get made in a set of patients, and the consequence of that is the patients bleed too much, and they’re not able to make blood clots efficiently,” said Michael S. Marks, PhD, who received a grant in May from the National Heart, Lung, and Blood Institute to better understand how platelet dense granules form and why their creation is disrupted in HPS.

Dense granules are lysosome-related organelles (LROs) within platelets that act as a storage compartment for small molecules such as calcium, adenosine diphosphate, and serotonin. These molecules are released when platelets begin to accumulate at sites of blood vessel damage.

“We know that there are important things stored in those granules, but we have no idea how they get there,” Dr. Marks said. “This is the first time anybody’s taken an approach to try and understand how dense granules are put together and how those molecules get stored in them.”

HPS can be difficult to diagnose because it affects multiple organs, and the symptoms can be variable and nonspecific. Mutations in the genes associated with HPS prevent the formation of LROs or impair their performance in platelets, pigment cells, and lung cells. Subsequently, in addition to excessive bleeding, a main feature of the disease is oculocutaneous albinism, which causes abnormally light coloring of the skin, hair, and eyes. By the time people with HPS reach their 30s, a lung defect called pulmonary fibrosis appears that rapidly worsens, and the lung scarring often is fatal.

“Getting a good diagnosis early would be really important,” Dr. Marks said. “That would be the most immediate impact of this grant.”

The study aims to achieve a better understanding of two dense granule integral platelet membrane proteins that Dr. Marks’ team at CHOP and a collaborating group in Colorado recently identified — SLC35D3 and VMAT2 — which may act as vehicles to import dense granule contents. The investigators suspect that this delivery is impaired in HPS, and the dense granules do not form completely. Necessary machinery could be missing at a crucial time when a dense granule’s membrane coalesces from other membranes in megakaryocytes, which are platelets’ precursor cells that reside in bone marrow. It appears that this occurs during a late stage of differentiation of platelets from megakaryocytes.

In order to test this hypothesis, scientists in Dr. Marks’ lab will collaborate with another group of experts in megakaryocyte and platelet formation from the lab of Mortimer Poncz, MD, division chief of hematology at CHOP. They will take megakaryocytes from mice and then modify them by adding fluorescent proteins that hopefully will allow the investigators to visualize dense granule formation using live cell imaging. The next step will be to put the megakaryocytes back into the mice where they will produce platelets, and then take the platelets out to analyze them.

Dr. Marks also will compare the same mutations in human cells by using megakaryocytes created from stem cells of patients with HPS. Deborah L. French, PhD, a specialist in making induced pluripotent stem cells, will assist with this part of the project. Dr. French is director of the Human Stem-Cell Vector Core within the Center for Cellular and Molecular Therapeutics at CHOP.

The investigators will determine if SLC35D3 and VMAT2 live on dense granule membranes and whether or not they are expressed on platelet membranes in both the human and mouse HPS models. What they discover could guide new diagnostic approaches.

“If we’re right, then we could make antibodies to those proteins,” Dr. Marks said. “Then it should be a very simple test to look for exposure of that protein when you activate platelets.”

Such a diagnostic test would be helpful for identifying HPS as well as other forms of bleeding disease due to mutations in genes that encode proteins on these dense granules. As researchers learn more about the proteins’ structure and the jobs that they perform, this knowledge could be applied to designing drug therapies that either enhance the proteins’ activity, as would be the case in HPS, or decrease the proteins’ activity, which could potentially modulate diseases that cause too much blood clotting.

“Ultimately, maybe, we’ll be able to come up with some kind of treatment,” Dr. Marks said. “That will depend on whether we’re right with some of our guesses about the proteins that are on dense granules and whether we can characterize them further and identify steps that would be downstream from them.”

Dr. Marks also is looking forward to working on a future study with Susan Guttentag, MD, that recently received grant funding. That investigation will focus on the formation of another LRO, the lamellar body, in lung epithelial cells. Dr. Guttentag and colleagues have shown that HPS models interfere with this process which underlies the lung fibrosis in HPS.

Permanent link to this article:

Jul 21 2014

Putting a Dollar Amount to Autism Pays Off

autismAutism spectrum disorders (ASDs) have an enormous price tag, and experts at The Children’s Hospital of Philadelphia are hoping that all those dollar signs add up to increased attention on new research and more coordinated ways to support patients with autism throughout adulthood.

One in 68 children in the United States has ASD, making it the fastest-growing disability. It is a complex neurological and developmental condition characterized by marked deficiencies in social interaction and communication and various behavioral issues. While individual presentations may vary, the signs of ASD usually appear during the first three years of life.

David S. Mandell, ScD, associate director of the Center for Autism Research at CHOP, and co-investigators in London updated estimates of the economic effects of ASDs on individuals and their families in the U.S. and U.K. They published their results online recently in JAMA Pediatrics. The lifetime cost of supporting a patient with an ASD and intellectual disability was $2.2 million in the U.S., and the lifetime cost for a patient with an ASD without an intellectual disability was $1.4 million in the U.S.

“They are staggering numbers in many ways,” said Dr. Mandell, who is also an associate professor of psychiatry and pediatrics at the University of Pennsylvania’s Perelman School of Medicine, where he directs the Center for Mental Health Policy and Services Research. “What is most intriguing about the study is what is driving those costs.”

For families, when their child with autism is young, special education costs were the largest cost component. Lost parental wages — especially for mothers who often must leave the workplace in order to care for their children — was another hefty economic hit. Productivity loss was estimated to be $18,720 annually for U.S. caregivers of children with ASD.

A key finding, Dr. Mandell pointed out, is that most of the expenses associated with autism accrue in adulthood. Society tends to think of autism as a pediatric concern, but it is a lifelong disorder. Residential care represents a substantial portion of those annual costs in the U.S.: $36,000 for adults with an ASD who have an intellectual disability, and about half that amount for adults with an ASD without an intellectual disability.

While some adults with autism have significant impairments and require expensive 24-hour residential care in a stable, supervised environment, many others who have participated in early interventions continue to develop their skills when given social coaching and job training so that they can work and live in less restrictive housing arrangements.

“I hope that advocates will use this information to support the importance of paying for intensive, evidence-based care for children with autism that has the goal of increasing their potential for full participation in their communities, which also may come with cost-savings,” Dr. Mandell said.

Part of the challenge to conducting this study, Dr. Mandell said, is that no gigantic spreadsheet listing all of these costs in one place exists. In addition to performing an extensive literature review conducted in 2013 concentrating on U.S. and U.K studies, Dr. Mandell and his co-authors relied on a number of sources to estimate cost-related data. For future studies, he encourages multiple systems to collaborate and perform longitudinal, population-based data collection so that researchers have easier access to metrics that can be used to assess the efficiency and effectiveness of autism care on a more regular basis.

Autism Speaks, the world’s leading autism science and advocacy organization, supported this study.

Permanent link to this article:

Jul 17 2014

Study Shows Evaluators Can Screen for Eye Disease Remotely

retinopathy of prematurityA study recently published in JAMA Ophthalmology shows trained evaluators who studied retinal images transmitted to computer screens successfully identified newborn infants likely to require a specialized evaluation for retinopathy of prematurity (ROP), a leading cause of treatable blindness. Findings from a new study strengthen the case for using telemedicine to address unmet medical needs of preterm babies worldwide who cannot be initially evaluated by ophthalmologists.

“This study provides validation for a telemedicine approach to ROP screening and could help prevent thousands of kids from going blind,” said lead investigator Graham E. Quinn, MD, MSCE, a pediatric ophthalmologist at The Children’s Hospital of Philadelphia. Dr. Quinn is the corresponding author and principal investigator of the study of remote evaluation of ROP conducted by the e-ROP Cooperative Group, a collaboration among neonatal intensive care units in 13 North American centers.

ROP involves an abnormal growth of blood vessels in the retina that may lead to scarring, retinal detachment and, in severe cases, blindness. Some degree of retinopathy of prematurity occurs in more than half of all infants born at 30 weeks gestation or earlier, but only five to eight percent of cases become severe enough to warrant treatment. Because early detection and prompt treatment are essential to identifying high-risk eyes, the American Academy of Ophthalmology recommends routine screening for all infants born at or before 30 weeks gestation or weighing less than 3.3 pounds.

In recent years, the U.S. has seen a decline in the number of ophthalmologists who conduct ROP screening examinations. To address the public health issue of detecting potentially serious ROP, the e-ROP Cooperative Group tested the validity of a telemedicine approach by comparing evaluations by ophthalmologists with those done independently by trained non-physician image readers.

Study Examined Patients Across the U.S. and Canada

The study team analyzed results in 1,257 premature infants in neonatal intensive care units (NICUs) at centers in the U.S. and Canada from 2011 to 2013. On average, the babies were 13 weeks premature and all weighed less than 1251 grams (about 2.75 pounds) at birth.

The infants all received regularly scheduled diagnostic examinations by an ophthalmologist who determined whether their ROP had a severity that warranted referral for further evaluation (designated RW-ROP). In addition, NICU staff members, called certified retinal imagers, took retinal photographs of all the infants, and those images were transmitted to trained image readers at the University of Pennsylvania. The image readers, all of them non-physicians, followed a standard protocol to assess whether features of RW-ROP were present in retinal images.

The image readers were unaware of which infants had been designated by the ophthalmologists as needing referral. The two groups had broadly similar results: the image readers identified 90 percent of the infants that ophthalmologists rated as having RW-ROP. When the readers did not find RW-ROP on grading, 87 percent of the time the ophthalmologist had not noted RW-ROP on the examination either.

Among the 244 babies that the ophthalmologists identified as having findings consistent with RW-ROP, 162 subsequently received treatment. Of these 162 infants, the non-physician image readers identified RW-ROP in 159 of them, meaning that 98 times out of a hundred, the eye was identified as a high-risk eye.

The investigators pointed out several potential advantages of telemedicine screening for ROP. Non-physician imagers could perform retinal imaging more frequently than ophthalmologists, and NICU staff can implement an imaging schedule individualized to specific babies. Grading of retinal photographs could allow a more standardized approach to ROP screening, while reducing the numbers of babies needing to be examined by ophthalmologists could thus lower the costs of routine retinopathy of prematurity screening. Finally, remote screening could decrease the number of unnecessary patient transfers to larger nurseries with more on-site ophthalmologists.

To see a video about e-ROP, visit the National Eye Institute YouTube channel at

Permanent link to this article:

Jul 15 2014

CHOP Researchers Discover Postsurgical Pain Gene Variants

painIn the first genome-wide analysis of postsurgical pain in children, pediatric researchers identified variations in genes that affect a child’s need for pain-control drugs. The findings suggest that at some point physicians may calibrate pain-medication dosages according to a child’s individual genetic makeup.

“Although this research is only a first step for our team, it provides tremendous new insight into the biological mechanisms and brings us a little closer to personalizing medicine for pain control,” said Scott D. Cook-Sather, MD, a pediatric anesthesiologist at The Children’s Hospital of Philadelphia. Dr. Cook-Sather and colleagues — including Hakon Hakonarson, MD, PhD, the director of the Center for Applied Genomics — published the study recently in the journal Pain.

The study team performed a genome-wide association study (GWAS) of more than 600 children between ages 4 and 18 who had tonsils and adenoids removed in day long surgery procedures. The retrospective study analyzed whether gene variants were associated with the need for higher or lower than average dosages of morphine for pain control. The researchers also analyzed genetic links to postoperative pain scores. The GWAS identified one gene location linked to increased morphine requirement.

“While scientists already know that morphine works by binding to specific opioid receptors in the nervous system,” added Dr. Cook-Sather, “we don’t know exactly why there is, in this setting, a tenfold variation in how much morphine patients require for pain relief.” The study team found that two single-base gene variants at the TAOK3 locus were associated with approximately 8 percent of that tenfold variance in morphine requirement, comparable to that portion of the variance associated with age, body mass and overall health status combined.

Dr. Cook-Sather explained that multiple genes are assumed to contribute to these analgesic effects, and that further investigations, with larger numbers of patients, are needed to understand and prioritize the full array of genes that modify morphine response.

Within their initial sample of 617 children, the researchers found that the association between the variants in TAOK3 and the morphine dose needed for pain relief held up for children of European ancestry but not for African-American children. In both groups, however, the gene variants correlated with increased postoperative pain. “Future investigations,” said Dr. Cook-Sather, “may help us predict which patients will need more pain medicine than the standard dose. We could customize an appropriate dose while the child is still under anesthesia in order to minimize the pain when the child regains consciousness.”

“We have identified a novel biological pain target, and even though the variants we identified in this study explain only about 8 percent of the difference in pain sensation between individuals, they give us a strong lead in developing new therapies,” said Hakonarson. “This proof-of-concept study may advance the process of individualizing pain therapy in children.”

Permanent link to this article:

Jul 10 2014

Electrocardiogram Use Varies for Infants With ALTEs

ElectrocardiogramWhen frantic parents arrive at the emergency room and report that their infant experienced a frightening combination of symptoms including a prolonged lapse in breathing, change in color or muscle tone, or coughing or gagging, clinicians likely will describe the episode as an apparent life-threatening event (ALTE). Yet, it can be a frustrating conclusion because often these symptoms have resolved by the time the patient arrives at the ER, and the clinician is left to discern the exact cause.

The most common underlying diagnoses related to ALTEs are gastroesophageal reflux and upper respiratory illness. Clinicians also consider cardiac causes, but no standardized method is used to evaluate patients with ALTEs, especially with regard to electrocardiograms (ECGs) as a diagnostic tool. An ECG measures a heart’s electrical activity and generates a graphic representation, or tracing, that can indicate heart-related conditions.

A study team of physicians from The Children’s Hospital of Philadelphia’s Department of Pediatrics and Cardiac Center wanted to determine the prevalence of cardiac diagnoses in children who present with ALTEs and how often ECGs are used.

“This is the largest study of its kind and the first multicenter study looking into the evaluation of cardiac etiologies of ALTEs,” said Matthew D. Elias, MD, a CHOP pediatric cardiology fellow physician. “Hopefully it will contribute to the knowledge base of those providing for patients with ALTEs of what their institutions are using as a diagnostic workup for these patients and what other institutions are doing.”

Dr. Elias conducted the study with V. Ramesh Iyer, MD, MRCP, an attending electrophysiologist, and Meryl S. Cohen, MD, an attending cardiologist and director of the echocardiography laboratory. They reported their findings in the April issue of Pediatric Emergency Care.

The study team analyzed data from the Pediatric Health Information System database and found that ALTEs are relatively common, accounting for 2,179 hospital encounters at 43 children’s hospitals during a 15-month period from 2009 until 2010. Their analysis showed that 16 percent of these patients (355) had a cardiac diagnosis; however, due to the database’s limitations, the study team could not determine that cardiac pathology was related to the ALTEs.

The study’s main finding was that the hospitals had a wide range in the use of diagnostic ECGs, which highlights the absence of a systematic approach to ALTEs.

“Some hospitals almost never ordered an ECG, and others almost 100 percent of the time ordered an ECG,” Dr. Elias said. “On average, ECGs were ordered 43 percent of the time.”

When the study team looked deeper into the demographic information to determine any reasons why some patients with ALTEs would receive an ECG and some would not, the one statistically significant finding was that those patients who were older at presentation were more likely to have an ECG ordered.

“ALTEs typically present within the first three months of life, and if a patient were to present later on at several months of age, we think that those providing for the patients might expand their differential diagnosis and start suspecting a possibility of a cardiac disease,” Dr. Elias said.

This study raises a larger question for future research of whether or not ECGs could be helpful as a screening tool to detect or rule out particular cardiac diagnoses for patients with ALTEs.

Permanent link to this article:

Jul 08 2014

60 Minutes Revisits Cancer Therapy Pioneered at CHOP

curing cancerAustralia’s 60 Minutes recently revisited its story from last year about the revolutionary immune therapy treatment spearheaded by The Children’s Hospital of Philadelphia’s Stephan A. Grupp, MD, PhD. The therapy, in which modified versions of patients’ own immune cells are used to treat acute lymphoblastic leukemia (ALL) has led to dramatic, inspirational results, with several patients achieving complete responses.

“It could be one of the greatest medical breakthroughs of the 21st century: a cure for childhood cancer,” said host Michael Usher.

The most common form of leukemia found in children, ALL has a roughly 85 percent cure rate. However, the remaining 15 percent of ALL cases resist standard therapy. The 60 Minutes piece focused on the researchers’ use of HIV, which the program called “one of the most notorious killers of our time,” to treat ALL. Dr. Grupp and his team have used HIV to deliver engineered T cells — the workhorses of the immune system — to selectively kill another type of immune cell called B cells, which had become cancerous.

HIV “is a terrible virus,” Dr. Grupp said, “but there’s a good property, and the good property of the virus is its ability to put a gene into cells. We isolate just that property and we get rid of all of the bad stuff, so yes, HIV’s been retasked to do good in this kind of treatment.”

The piece is also focused on one of Dr. Grupp’s patients, 5-year-old Austin, whom 60 Minutes profiled in its original piece. Diagnosed with ALL when he was 2, Austin is now in complete remission for the first time. “To see him doing normal things is a relief, and a dream come true, because those were things that were put on hold for awhile,” said Austin’s mother Kim, who called the treatment “a miracle.”

“I think we do have a potential new treatment that didn’t exist before that we hope will be available to other patients and other hospitals soon, and across the world, in the next year or two,” Dr. Grupp said.

To watch the 60 Minutes report, see below!

Permanent link to this article:

Older posts «

» Newer posts