Latest Research 2016
"Research is expensive, but no-one knows a cheaper way to make progress"
"Never, never, never give up"
The Need for Critical Research
Every research study conducted at Schneider Children’s Medical Center of Israel begins with the desire to help children suffering from diseases that rob them of their innocence and quash their dreams. By conquering the mysteries of the unknown, medical researchers promise a better future for sick kids everywhere. Their discoveries increase survival, recovery and rehabilitation, giving youngsters renewed hope and an improved quality of life.
Research at Schneider Children’s isn't about laboratories. It is about the child, about vision, creative thought and unwavering dedication. It is about bold ideas that are nurtured and developed into life-saving procedures or therapies. And it is about challenge, instinct, and not a little daring, all of which come together in the quest for better healing of sick kids.
Research at Schneider – Our Calling Card for Excellence
The unprecedented advances in biomedical, technological and medical research have brought about major changes in health care in the past two decades, underscoring the fact that ongoing research saves more lives and consequent survival rates, extends life expectancy and enhances quality of life.
Schneider Children's takes great pride in the multiple research areas, novel technologies and medical breakthroughs that have been made at the institution since the hospital’s inception in 1992. The ability to bring the fruits of basic research “from bench to bedside” is one of the most significant and unique aspects of Schneider Children’s, and accentuates the wisdom of incorporating high quality research activity into a tertiary pediatric medical facility not only for the immediate benefit of its young patients but to the world of medicine as a whole.
Affiliated with the Sackler School of Medicine at Tel Aviv University, over half of Schneider Children’s physicians serve as faculty, while some 15% hold the title of professor. Two of the hospital’s leading physicians, the late Prof. Rina Zaizov, and Prof. Zvi Laron, are recipients of the State of Israel’s highest honor, The Israel Prize for Medical Research.
Unique Patient Pool
As the only tertiary care hospital providing multidisciplinary, comprehensive care to children in Israel and the Middle East, Schneider Children’s patient body is comprised of children and adolescents from diverse backgrounds. The medical center therefore is in the unique position to carry out wide-ranging research studies to respond to the very different medical, emotional, psychological and social needs of children from varying ethnic origins. In addition, the State of Israel has absorbed millions of immigrants from all corners of the globe, contributing towards rich population sectors in the country representing a microcosm of peoples almost unrivalled in the world.
Schneider Children’s is actively involved in many areas of research. Many are published in leading medical journals around the world. Among them:
Victimization Among European Adolescents: A Ten-Country Study, November 2016
The study examined the association between victimization by bullying and direct-self-injurious behavior (D-SIB) among a large representative sample of male and female adolescents in Europe. Students were administered a self-report survey within the classroom, in which they were asked about three types of victimization by bullying (physical, verbal and relational) as well as direct self-injurious behavior (D-SIB). The results clearly demonstrated the cross-sectional association between specific types of victimization with self-injurious behavior among adolescents and what may be part of the risk and protective factors in this complex association.
Food Allergies, September 2016
Diagnosis relies on the recognition of symptom patterns. Further studies are needed for a better understanding of the pathomechanism, which will lead eventually to the development of diagnostic tests and treatments. Empiric prolonged avoidance of food allergens should be limited to minimize nutrient deficiency and feeding disorders/food aversions in infants.
Artificial Pancreas Clinical Trials, July 2016
Research on and commercial development of the artificial pancreas (AP) continue to progress rapidly, and the AP promises to become a part of clinical care. In this report, members of the JDRF Artificial Pancreas Project Consortium in collaboration with the wider AP community 1) advocate for the use of continuous glucose monitoring glucose metrics as outcome measures in AP trials, in addition to HbA1c, and 2) identify a short set of basic, easily interpreted outcome measures.
Cystic Fibrosis, A Retrospective Review, July 2016
Population carrier screening (PCS) has been available in Israel since 1999. CF rate per 100,000 live births decreased from 14.5 in 1990 to 6 in 2011. From 2004-2011 there were 95 CF births. At diagnosis, age was 6 (0-98) months; 53/95 had respiratory symptoms, 41/95 failure to thrive and 19/95 pseudomonas. As children regularly have significant disease at diagnosis, a balanced approach is suggested utilizing both PCS and newborn screening.
Hypokalaemia in Children, July 2016
The aim of the study was to review the aetiology of hypokalaemia, suggest a diagnostic algorithm, and discuss the management of patients with various aetiologies of hypokalaemia. Understanding the pathophysiology of hypokalaemic states, along with a detailed medical history, physical examination and specific laboratory tests are required for proper diagnosis and appropriate treatment.
Post Liver Transplantation Risk of Bacterial Infections, June 2016
Although infections post-liver transplantation are a main cause of morbidity and mortality, data are limited on transplanted children. Clinical and laboratory data were retrospectively collected for all febrile pediatric LTR hospitalized from 2004 to 2012.
Acute Diarrhoea, April 2016
The Working Group on Acute Diarrhoea previously developed a core outcome set for clinical trials on acute diarrhoea. The study aimed to create a core outcome measurement set to complement it.The outcome measurement set can be used to evaluate therapeutic or preventive strategies and can be recommended for use in future acute diarrhoea trials.
Spinal Muscular Atrophy, March 2016
The results of this preliminary human study are encouraging, as no serious or notable AEs were reported after a single injection. Intrathecal treatment was associated with prolonged drug CSF half-life, and some clinical motor improvement was detected.
Central Precocious Puberty, a case control study, October 2015
Extracted from the database were demographic data, medical history, medications dispensed, recorded anthropometric measurements, vital signs, and laboratory data. CPP (treated or untreated) is not associated with increased risk of obesity, metabolic derangements, or cancer morbidities in young adulthood. The finding that the health status of former CPP women is similar to that of the general population is reassuring.
Dexamethasone Therapy for Septic Arthritis in Children, October 2015
This study sought to evaluate the effect of this regimen outside of a randomized controlled trial. Children with septic arthritis treated early with a short course of adjuvant dexamethasone show earlier improvement in clinical and laboratory parameters than children treated with antibiotics alone.
Acute Gastroenteritis (AGE), October 2015
We aimed to evaluate the efficacy of yogurt consumption for the management of AGE in children. In this systematic review, a number of databases, including MEDLINE, EMBASE, and the Cochrane Library, with no language restrictions, were searched. The consumption of yogurt had a positive effect on weight gain, but no consistent effect on AGE outcomes in hospitalized children. The effect of yogurt consumption in the ambulatory setting is unknown.
Engraftment of Mouse and Human Embryonic Lung Cells, August 2015
Repair of injured lungs represents a longstanding therapeutic challenge. Recipients of the single cell suspension transplant exhibited marked improvement in lung compliance and tissue damping reflecting the energy dissipation in the lung tissues. Our study provides proof of concept for lung reconstitution by canalicular-stage human lung cells after preconditioning of the pulmonary niche.
Atypical Teratoid Rhabdoid Tumors in Children, May 2015
Lack of biological understanding of the substantial clinical heterogeneity of these tumors restricts therapeutic advances. An integration of clinical risk factors and tumor molecular groups can be used to identify patients who are likely to have improved long-term radiation-free survival and might help therapeutic stratification of patients with atypical teratoid rhabdoid tumors.
Suicide Prevention: the SEYLE cluster-randomised, controlled trial, April 2015
The Saving and Empowering Young Lives in Europe (SEYLE) study is a multicenter trial. The primary outcome measure was the number of suicide attempt(s) made. Youth Aware of Mental Health Program (YAM) was effective in reducing the number of suicide attempts and severe suicidal ideation in school-based adolescents. These findings underline the benefit of universal suicide preventive intervention in schools.
Type 1 Diabetes, April 2015
To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip, was developed, from which four new T1D-associated regions (P < 5 × 10(-8)) were identified. The associated SNPs localized to enhance sequences active in thymus, T and B cells, and CD34(+) stem cells. Enhancer-promoter interactions can now be analyzed in these cell types to identify which particular genes and regulatory sequences are causal.
Short and Tall Stature, April 2015
Normal growth in children depends not only on growth hormone (GH)-insulin-like growth factor 1 (IGF-1) but also on multiple hormones, paracrine factors, extracellular matrix molecules and intracellular proteins. Mutations in the genes that encode many of these local proteins cause short stature or tall stature. These findings point to a new conceptual framework for understanding short and tall stature that is centered not on two particular hormones but rather on the growth plate, which is the structure responsible for height gain.
Progressive Myoclonus Epilepsy (PME), January 2015
A recurrent de novo mutation, c.959G>A (p.Arg320His), in KCNC1 was identified as a new major cause for PME. Functional analysis of the Arg320His mutant channel showed a dominant-negative loss-of-function effect. Ten cases had pathogenic mutations in known PME-associated genes. Identification of mutations in PRNP, SACS and TBC1D24 expand their phenotypic spectra to PME. These findings provide insights into the molecular genetic basis of PME and show the role of de novo mutations in this disease entity.
C-Reactive protein levels in children with primary herpetic gingivostomatitis, November 2014
C-reactive protein (CRP) is often used to distinguish bacterial from viral infections. To evaluate the distribution of CRP levels in children with primary herpetic gingivostomatitis, the electronic database was searched for all inpatients with a diagnosis of primary herpetic gingivostomatitis without bacterial coinfection. High values of CRP are prevalent in patients with primary herpetic gingivostomatitis, similar to adenoviral infections and some bacterial infections.
Celiac Disease, October 2014
International research found that neither the age an infant is exposed to gluten, nor nursing them - including those at risk - affects the appearance of celiac disease. The new study questioned current recommendations by the World Health Organization where 4-6-month-old predisposed infants should be exposed to small amounts of gluten. The research paper was published in the October 2, 2014 edition of The New England Journal of Medicine.
Fetal Length, September 2014
Specialists at Schneider Children’s, together with researchers at Tel Aviv University, developed an innovative technique for measuring the length of newborns and premature infants. The new method accorded maximum precision without the need for restraint and discomfort. Research results were published in the March 2014 edition of the international journal, Archives of Disease in Childhood.
New Microcephaly Syndrome Discovered, August 2014
In a multinational study, specialists discovered a new syndrome in Primary Microcephaly (small head circumference) in children, located on chromosone number 12. Over recent years, the team in the Neurogenetic Clinic has discovered 12 new neurologically-based genetic syndromes in collaboration with the team in the Genetics Institute at Schneider.
Artificial Pancreas, June 2014
Another breakthrough was achieved by specialists when the latest trial successfully tested management of children’s glucose levels over three consecutive days via a tablet, thus obviating the need for diabetics to check glucose levels at all times of the day and night. During the trial – a first in the world - the children participated in activities, slept in their beds at home, and went out with their friends while connected to the automated system.
New Gene Discovery: Fatal Epilepsy, February 2014
Specialists at Schneider Children’s discovered a new gene that causes fatal epilepsy in children. As part of a research study headed by Prof. Lina Basel, Director of the Pediatric Medical Genetics Unit, a new and rare disease was also identified. Results of the study were published in the American Journal of Human Genetics.
Fetal Alcohol Syndrome, January 2014
Research conducted in 2010 by experts at Schneider Children’s found that more than 15% of pregnant women in Israel drink alcohol in varying amounts during their pregnancy. This led to the opening of a new clinic for children in January 2014. The clinic works in cooperation with the Israel Anti-Drug and Alcohol Authority.
3-D Hologram, October 2013
A research trial representing the first of its kind in the world to test a 3-D Hologram of the heart during cardiac catheterization, was successfully conducted at Schneider Children’s in cooperation with Phillips (Phillips Healthcare) and RealView Imaging Ltd. Clinical research proved the ability to create a cardiac hologram from the image obtained through ultrasound and fluoroscopy during catheterization.
Tic Disorders, April 2013
Research found that the percentage of teenagers reporting tics to doctors was 3.4 times higher than that reported by their parents: 4.4% of Israeli teenagers reported tics as opposed to 1.3% of their parents. In addition, the percentage of reports in western countries by teenagers with tics is between 0.4%-3.8%, which is lower than the incidence in Israel.
Ritalin Use Doubles, March 2013
A broad-sweeping study by specialists from Schneider Children's and Clalit's Sharon Shomron District, who reviewed over 121,000 children and youth, shows that the number of youngsters between the ages of 6-18 receiving Ritalin has doubled during the past 4 years. In 2007, 3.6% of children received Ritalin, while in 2011, this number rose to 7%.
Artificial Pancreas, March 2013
The results of an automated artificial pancreas clinical study, which was performed for the first time outside a hospital at a diabetes camp, were published in the February 28th issue of the New England Journal of Medicine. The prospective, randomized, multicenter, multinational clinical trial within the DREAM consortium involved 56 children, adolescents and young adults with insulin dependent type 1 diabetes, who were treated overnight either with the existing state-of-the-art insulin pumps and glucose sensors, or with the MD-Logic artificial pancreas system developed by the Diabetes Technology Center at the National Center for Childhood Diabetes at Schneider Children’s.
New Genes Discovery: Mental Retardation Genes, January 2013
Utilizing recently-developed genomic technology, researchers identified genes EIF2S3 and UBE3B as responsible for the development of genetic mental retardation. Research results were publicized in two leading international journals: Molecular Cell and the American Journal of Human Genetics.
Gene Discovery: Liver Dysfunction, September 2012
Specialists discovered and identified a mutated gene that causes increased fats in the blood (triglycerides), impairment in liver function with scarring and cirrhosis of the liver. The research results were published in January 2012 in The American Journal of Human Genetics.
Parental Authority vs Diabetic Adolescents Response, October 2011
The study showed that the treatment of diabetes in the adolescent is more effective when the style of parental authority, particularly in fathers, is more authoritarian although not rigid and aggressive.
Joint Ancestor in Patients with CDA-II, August 2011
Research revealed a mutation in patients with the rare genetic disease Congenital Diserythropoietic Anemia (CDA II) whose origin is a joint ancestral father dating back 2,400 years following the Babylonian exile.
Growth Stimulation Therapy, July 2011
Physicians jointly initiated a research study to test whether a new nutritional supplement developed by a team of specialists at the hospital could stimulate the growth process in low-stature and underweight children and significantly improve their quality of life.
New Gene Discovery: Mental Retardation, December 2010
Scientists identified SOBP, a gene responsible for the development of mental retardation. The results of the research were published in the October 2010 edition of the American Journal of Human Genetics.
Atopic Dermatitis - Prospective Study, January 2008
Children aged 2-10 years with Atopic Dermatitis were invited to participate in a three-month study by the Dermatology Unit at Schneider Children’s. The research aimed to investigate the effectiveness of a new cream for treatment.
Cotton Buds, May 2007
A prospective study was conducted with the aim of investigating the causes of Otitis Externa (OE) and reducing the incidence of infection. It revealed that that more than 70% of the participants presenting OE had their ears cleaned with cotton buds within the preceding 10 days. The results of the research appeared in the International Journal of Pediatric Otorhinolaryngology.
Obese Children and Cardiovascular Disease, May 2007
The study reviewed the medical folders of 262 children and adolescents (all above the 95th percentile of body mass weight according to age and gender) from the ages of 5-18½, and found that about half the children had high blood pressure; about a third showed high cholesterol levels in the blood; while others suffered from fatty livers and resistance to insulin.
New Gene Discovery: Hair Dandruff, March 2007
Researchers announced the discovery of a new gene ST14 that causes skin dandruff and other hair ailments. Their findings were published in the American Journal for Human Genetics. Schneider’s geneticists worked in cooperation with dermatologists and described a new genetic syndrome that causes flaking of the skin and changes in the hair called Autosomal Recessive Ichthyosis and Hypotrichosis (ARIH).
Insulin Pump Therapy, January 2007
Research found that the subcutaneous insulin pump, a continuous infusion beneath the skin which hourly discharges pre-determined amounts of insulin, not only eradicated the need for a painful injection thrice daily, but also dramatically improved the control of diabetes.
Nasal Sprays, November 2006
Research found that flu vaccination via nasal spray is 53% more effective than vaccination via injection. The study involved 114 medical centers around the world. The research findings have been published in the Pediatric Infectious Disease Journal.
New Gene Discovery: Infantile Bilateral Striatal Necrosis (IBSN), September 2006
Researchers identified the mutated gene causing the fatal degenerative disease Infantile Bilateral Striatal Necrosis (IBSN). The gene, whose name is NUP62, was found on chromosome 19, and controls the passage of protein from the cell’s cytoplasm to the nucleus.
Obesity Prevention – Prospective Study, August 2006
Children between the ages of 5-8 with a propensity towards obesity were invited to participate in a study which included nutritional counseling, medical checks and psychological support.
Omega 3 for Childhood Depression, June 2006
Research revealed that Omega 3 is an effective agent in treating the problem of depression in children without the need for further psychiatric drugs.
Precocious Puberty is Likely Hereditary, May 2006
Precocious Puberty (early onset of physical signs of sexual maturity), previously thought to occur at random, is likely an inherited condition.
New Gene Discovery: Mental Retardation, December 2005
Schneider researchers were the recipients of two prizes by the Israel Genetics Society and the Israeli Pediatricians Society for their discovery of a new gene causing mental retardation. The results of the research were presented in October at the Conference for the American Society of Human Genetics in Salt Lake City, USA. The researchers initially located the defective gene on chromosome 19, after which they identified the gene itself. The biological function of the new gene called CC2D1A was previously unknown.
Scientific Advisory Committee
Efforts to conduct multicenter research studies of the highest standards prompted Schneider Children's to establish an international Scientific Advisory Committee in mid-2009. Leading scientists from some of the finest institutions in the world have joined this august team:
- Prof. Marc E. Rothenberg, Director of the Division of Allergy and Immunology at Cincinnati Children's Hospital Medical Center
- Prof. Steven Altschuler, President and CEO of The Children’s Hospital of Philadelphia
- Dr. Sheldon L. Kaplan, Head of the Department of Medicine at Texas Children’s Hospital in Houston
- Prof. Wieland Kiess, Dean and Chairman of the Board of the Medical Faculty at the University of Leipzig, Germany, and Director of the Hospital for Children and Adolescents in Leipzig
- Prof. Mark A. Sperling, Professor of Pediatric Endocrinology and Chair Emeritus of the Department of Pediatrics at the University of Pittsburgh School of Medicine, Children’s Hospital of Pittsburgh
Schneider Children's is located alongside the Felsenstein Medical Research Center, which houses 50 laboratories dedicated to applied medical research. They include:
- The Cardiac Research Laboratory, which conducts physiological research
- The Medical Genetics Laboratories - Molecular Genetics and Cytogenetics
- The Pediatric Endocrinology and Diabetes Laboratory
- Diabetes Technology Center
- Six Hematology-Oncology Research Laboratories
- - Hematology
- - Cancer Immunology
- - Cancer Cytogenetics
- - Hematopoiesis Stem Cell, Bone Marrow
- - Molecular Genetics in Hematology
- - Molecular Oncology and Molecular Genetics of Childhood Cancer
- The Child Study Center in the Department of Psychological Medicine
- Immunology and Allergy Laboratories comprise a General Laboratory, HIV Laboratory, and an HTLV-I/HTLV-II Molecular Biology Laboratory
- The Pulmonary Function Laboratory
- The Infectious Diseases Laboratory
Future Research Perspectives
The referral pattern of patients to Schneider Children's results in relatively large numbers of complex and rare disorders gathering under the care of a hospital team. Such experience with rare conditions not only provides the opportunity to optimize care, but also enables pioneering research to be undertaken. Increasingly, research that will lead to patient benefit has been highlighted as a critical focus for the research carried out in the medical center. The future goal of medical research in general and pediatrics in particular, is to enable medicine to become:
Therefore, in the coming years, we will aim our research at two of these important goals:
Research Related to Pediatric Disease Prevention
Undoubtedly the greatest advances in translational medicine over the past decade have been in the area of genetics. The advent of next-generation sequencing technologies has made the identification of genetic variants that influence the development of disease possible. Whole-exome or whole-genome sequencing enables us to effectively study genetic determinants of various diseases including mendelian disorders, multifactorial conditions such as allergy or asthma, inflammatory bowel disease, immunodeficiency and other common pediatric conditions. Many chronic severe diseases still cannot be treated effectively. Therefore, we decided to aim our research at identifying genetic factors leading to the development of severe pediatric diseases in order to achieve effective prevention and prophylaxis of such diseases by using modern genomic technologies. For instance, research teams in our hospital recently identified new genes causing cognitive disability and severe neurodegenerative diseases; this discovery enables effective prevention of intellectual disability and lethal neurological diseases in at-risk populations. Next-generation sequencing technologies will facilitate identification of new pathogens causing pediatric infections and development of new vaccines and treatments related to these pathogens. It is now clear that genomic analysis will have a major impact on our ability to diagnose and treat cancer, and our research efforts will be aimed at deciphering molecular changes related to development of various types of cancer in order to improve its diagnosis, classification and, eventually, treatment of pediatric cancer.
Translational Research for the Development of Personalized Medicine
The modern concept of personalized medicine is stimulated by the idea that genomic medicine may help to prevent and treat diseases by the use of the individual genetic information of the host, tumor and biological organisms such as bacteria. Our future goals are to develop a multidisciplinary translation research agenda that will include more clinical and population-based research, and merge this research with basic research using modern genomic technologies. In order for the discipline of genomic medicine to fulfil its maximum utility in the clinic, it is necessary to be able to characterize different forms of genetic variation in an individual patient's genome. During the coming years, we are planning to use an innovative exome sequencing approach to associate specific variation with clinical disease phenotypes. In addition, a very important research area is studying patient's genetic variation and using this information in order to guide the selection of drugs or treatment processes, leading to a more successful outcome from the medical treatment.
Every two years, Schneider Children's holds Research Day for hospital personnel and invited guests from Israel and abroad. Proceedings include the presentation of select studies, publication of Research Abstracts, exhibition of winning posters, and presentation of awards for excellence to young investigators.
The 7th Research Conference took place on Thursday, March 26, 2015. Guest speaker was Dr. Roni Potsman, Senior Deputy Director of Research and Development at Rafael Military Industries, who spoke about “Iron Dome – Research and Development”.
Three prizes were awarded to the winners of the Young Investigators Competition for Original Research:
Zippora Shvalb, RN, MHA, Head Nurse, Day Care Hospitalization
“The Association between Parental Perception and Eating Disorder Severity, and Compliance with Therapy in a Day Care Ward”
Maya Muhlbauer Avni, BMedSc, Institute of Pediatric Neurology
“Assessment of the Association between Pediatric Idiopathic Intracranial Hypertension and the Olfactory Function”
Noa Benaroya-Milshtein, MD, PhD
Platelet Functioning Following Sertraline Treatment for Depression and Anxiety in Children w/wo Hemato-Oncological Disease”\
Schneider Children's management established the Research Authority in August 2010 thus demonstrating the inseparable bond between medical excellence and research. The Authority has been allocated an increased budget that provides a supportive infrastructure to every researcher with accessible services to accompany all stages of research, as well as promote investigative studies alongside clinical practice.
The Authority is headed by Prof. Joseph Press, Director of Schneider Children's. Members of Management comprise Prof. Moshe Phillip, Director of the Institute of Endocrinology and Diabetes, Prof. Raanan Shamir, Director of the Institute of Gastroenterology, Nutrition and Liver Diseases, Prof. Shai Ashkenazi, Director of Pediatrics A, and Dana Reznik. Osnat Hochman serves as the Research Coordinator.