Tag Archive for: Koutroulis

illustration of bacterial outbreak

$2.2m grant to support AI-driven sepsis program for pediatric care

illustration of bacterial outbreak

Sepsis is a rapidly progressing, life-threatening condition characterized by organ dysfunction (OD) resulting from an immune response to infection.

Researchers at Children’s National Hospital are investigating pediatric sepsis, a leading cause of in-hospital death, particularly in underserved and minoritized populations.

A new Maximizing Investigators’ Research Award (MIRA) (R35) is granting over $2.2 million to Children’s National to establish a comprehensive sepsis program that will include a diagnostic artificial intelligence (AI) based, biomarker-enhanced platform for early recognition of pediatric sepsis and cutting-edge, extracellular vesicle-based therapeutics that can significantly decrease mortality and long-term disease sequelae.

MIRA provides support for research in an investigator’s laboratory that falls within the mission of The National Institute of General Medical Sciences.

Why it matters

Sepsis, defined as a rapidly progressive, is a life-threatening organ dysfunction (OD) due to an immune dysregulation as a response to infection. In the U.S., it results in over 75,000 pediatric admissions on an annual basis with an associated mortality rate of 5 to 20%.

“Sepsis has been linked to 20% of deaths worldwide and despite some recent advances in diagnostic tools, the lack of accurate definitions and heterogeneity of this clinical syndrome have led to delays in recognition and treatment with deleterious effects on the health of millions of children, especially those from minority groups,” says Ioannis Koutroulis, M.D., Ph.D., M.B.A., research director of Emergency Medicine at Children’s National. “Additionally, current sepsis therapeutic regimens are mostly supportive, lack the necessary personalization and fail to address the underlying physiological processes leading to sepsis-induced life threating organ failure.”

How does it move the field forward

High mortality rates and no significant new treatments in recent years due to sepsis presents a critical opportunity to make a global impact. Advancements in early recognition and intervention could save millions of lives. By utilizing AI and biomarkers for the early detection of sepsis in children, medical professionals could have the potential to greatly improve outcomes by enabling timely treatment.

“There is an urgent need to focus more attention on this condition and develop effective solutions to combat its devastating effects,” Dr. Koutroulis adds.

How we’re leading the way

The high-volume pediatric emergency room will serve as a crucial site for recruiting patients. With access to state-of-the-art laboratories, the research will be conducted in facilities equipped with cutting-edge technology, ensuring accurate and efficient analysis. This combination of a high patient volume and advanced research infrastructure will enable the program to deliver reliable results and make significant strides in the fight against pediatric sepsis.

“This grant will allow for early recognition of pediatric sepsis and treatment with an innovative approach using extracellular vesicle-based therapies that can directly affect immune and metabolic processes,” Dr. Koutroulis said.

American Pediatric Society logo

Children’s National expands 2025 American Pediatric Society class with new inductees

American Pediatric Society logoChildren’s National Hospital has expanded its class of American Pediatric Society (APS) members with three new inductees for 2025. The newest APS members include Ioannis Koutroulis, MD, PhD, MBA, research director and emergency medicine physician, Beth Tarini, MD, MPH, MBA, co-director of the Center for Translational Research, and Pavan Zaveri, MD, MEd, emergency medicine physician.

Dr. Tarini will also receive the 2025 Norman J. Siegel New Member Outstanding Science Award for her considerable contributions to pediatric science during the APS Presidential Plenary at the Pediatric Academic Societies 2025 Meeting in Honolulu, Hawaii, April 24 – April 28.

“I am deeply honored to receive the Norman J. Siegel New Member Outstanding Science Award from the American Pediatric Society,” said Dr. Tarini. “This recognition is a testament to the steadfast encouragement and support I have received from my mentors, colleagues, and family throughout my journey. I consider the opportunity to conduct research that optimizes health services for children and their families a privilege and a joy.”

APS members are recognized child health leaders of extraordinary achievement who work together to shape the future of academic pediatrics. Current members nominate new members by recognizing individuals who have distinguished themselves as child health leaders, teachers, scholars, policymakers and clinicians.

“I am deeply honored to be selected as a member of the American Pediatric Society,” said Dr. Zaveri. “I look forward to the opportunity to engage with esteemed leaders in pediatrics across various disciplines as we work together to advance the society’s mission and contribute to the growth of pediatrics through research and mentorship.”

Benefits of APS membership include:

  • Recognition and acknowledgment as a leader in pediatrics: APS members include individuals who have distinguished themselves as academic leaders, teachers and researchers whose contributions to academic pediatrics have garnered national and international recognition.
  • A network of child health professionals: Membership in APS is dedicated to the advancement of child health through the promotion of pediatric research, recognition of achievement and cultivation of excellence through advocacy, scholarship, education and leadership development.
  • Advocacy for child health: In order to speak with one voice on behalf of child health, APS provides representation in Washington, D.C., through the Pediatric Policy Council which combines the advocacy efforts of the APS, the Society for Pediatric Research, the Association of Medical School Pediatric Department Chairs and the Academic Pediatric Association.

“I am grateful to accept this honor from the APS,” said Dr. Koutroulis. “As both a physician and a researcher, I look forward to collaborating with distinguished experts within this network to help advance the development of pediatric care.”

newborn in incubator

Neuroprotective effect of Src kinase in neonates affected by HIE

newborn in incubator

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality worldwide.

In a systematic review published by Frontiers in Neuroscience, and co-authored by Panagiotis Kratimenos, M.D., neonatologist at Children’s National Hospital, Ioannis Koutroulis, M.D., pediatric emergency medicine physician at Children’s National and Javid Ghaemmaghami, M.S., researcher with the Center for Neuroscience Research at Children’s National, it was concluded that Src kinase is an effective neuroprotective target in the setting of acute hypoxic injury.

The paper reviews hypoxic-ischemic encephalopathy (HIE), a major cause of neonatal morbidity and mortality worldwide (one in four perinatal deaths is attributed to hypoxic-ischemic). While therapeutic hypothermia has improved neurodevelopmental outcomes for some survivors of HIE, this treatment is only available to a subset of affected neonates. Src kinase, an enzyme central to the apoptotic cascade, is a potential pharmacologic target to preserve typical brain development after HIE. This paper, a product of collaboration for a Master’s Thesis with the Aristotle University School of Medicine, Thessaloniki, Greece, where Dr. Kratimenos holds the appointment of Visiting  Professor,  presents evidence of the neuroprotective effects of targeting Src kinase in preclinical models of HIE.

The systematic review shows that while heterogeneity and risk for bias were limiting factors, the overall results indicate that Src-i neuroprotective properties could be a promising therapeutic strategy for neonates after hypoxic events.

Read more about the full review.

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Children’s National Hospital at the 2022 Pediatric Academic Societies Meeting

Are you attending the 2022 Pediatric Academic Societies meeting this week? There will be over 20 Children’s National Hospital-affiliated participants at this year’s meeting. We have compiled their sessions into a mini schedule below.

Name Department Role Topic Date Time
Kristen Sgambat, Ph.D., R.D. Center for Translational Research Speaker Fueling our patients for success: Optimizing nutritional support for kids with kidney disease 4/22/2022 2:30 PM
Priti Bhansali, M.D., M.Ed. Child Health Advocacy Institute Co-speaker APA Division Directors/Faculty Development Combined SIG 4/23/2022 8:00 AM
Karen Smith, M.D., M.Ed.
Neha Shah, M.D., M.P.H.		 Workshop co-leaders Don’t Struggle In Solitude: Recovery and Peer Support after Unanticipated Outcomes, Errors, and Difficult Conversations 4/23/2022 8:00 AM
Ian Chua, M.D., M.H.P.E.
Gabrina Dixon, M.D., M.Ed.
Margarita Ramos, M.D., M.S.		 Workshop co-leaders Finding the DEI in LGBTQIA: Incorporating LGBTQIA diversity in your environment 4/23/2022 8:00 AM
Kevin M. Cook, Ph.D. Co-presenter Early exposure to the extra-uterine environment in premature infants is associated with altered functional brain connectivity compared to in-utero age-matched fetuses 4/23/2022 8:15 AM
Gabrina Dixon, M.D., M.Ed.
Terry Kind, M.D., M.P.H.		 Workshop co-leaders Changing the system: Best practices in supporting and advancing underrepresented in medicine (UIM) medical students 4/23/2022 10:00 AM
Yao Wu, Ph.D. Oral abstract presenter Impaired prenatal brain growth predicts adverse neurodevelopmental outcomes in infants with congenital heart disease 4/23/2022 10:00 AM
Lee S. Beers, M.D. General and Community Pediatrics Moderator Scholarship in the Domain of Child Health Advocacy: Making It Work in the Academic Medical Center 4/23/2022 10:00 AM
Chaya Merrill, Dr.P.H. Center for Translational Research Speaker Using data to advance advocacy in the academic medical center 4/23/2022 10:00 AM
Yuan-Chiao Lu, Ph.D. Oral abstract presenter Delayed Fetal Cortical Maturation Predicts 18-Month Neurodevelopment in Infants with Congenital Heart Disease 4/23/2022 10:15 AM
Olanrewaju O. Falusi, M.D., M.Ed. Child Health Advocacy Institute Speaker Generating currency for advancement and professional development in the domain of advocacy 4/23/2022 10:15 AM
Subechhya Pradhan, Ph.D. Oral abstract presenter Abnormal in-vivo brain biochemistry in fetuses with complex congenital heart disease 4/23/2022 10:30 AM
Lenore R. Jarvis, M.D., M.Ed. Emergency Medicine and Trauma Services Speaker Academic advocacy for the subspecialist 4/23/2022 10:30 AM
Jillian E. Nickerson, M.D., M.S. Emergency Medicine and Trauma Services Presenter Utilizing an Online Module Platform to Teach Newborn Delivery and Resuscitation Skills to Pediatric Emergency Medicine Providers 4/23/2022 10:30 AM
Lee S. Beers, M.D. General and Community Pediatrics Presenting Author Leadership in legislative advocacy at the national level 4/23/2022 11:00 AM
Kevin M. Cook, Ph.D. Oral abstract presenter Relative neighborhood disadvantage is associated with increased functional network segregation in fetal brains 4/23/2022 11:15 AM
Jung-Hoon Kim, Ph.D. Presenting Author Gestational age-related changes in the fetal functional connectome: in utero evidence for the global signal 4/23/2022 1:00 PM
Ioannis Koutroulis, M.D., Ph.D., M.B.A. Emergency Medicine and Trauma Services Oral abstract presenter Immunometabolism in septic encephalopathy: a novel therapeutic target 4/23/2022 1:00 PM
Terry Kind, M.D., M.P.H. General and Community Pediatrics Workshop co-leaders Making Meaning from the Data: Exploring Coding in Qualitative Research 4/23/2022 1:00 PM
Josepheen D. Cruz, M.D., Ph.D. Oral abstract presenter Cortical thickness changes in fetuses exposed to heightened maternal psychological distress 4/23/2022 1:30 PM
Monika Goyal, M.D., M.S.C.E. Emergency Medicine and Trauma Services Moderator Adolescent Medicine II 4/24/2022 8:00 AM
Binny Chokshi, M.D., M.Ed.
Yael Smiley, M.D.		 Workshop co-leaders Applying The Collective Impact Model to Pediatric Health Interventions 4/24/2022 8:00 AM
Aisha Barber, M.D. M.Ed. Hospital Medicine Workshop co-leaders Demystifying DEI in Recruitment: Strategies for Creating a Diverse and Inclusive Residency and Fellow Training Environment 4/24/2022 8:00 AM
Panagiotis Kratimenos, M.D., Ph.D. Neonatology Oral abstract presenter Maternal Immune Activation and Hypoxia Induces Cerebellar Injury 4/24/2022 8:45 AM
Monika Goyal, M.D., M.S.C.E. Emergency Medicine and Trauma Services Co-moderator Emergency Medicine I 4/24/2022 10:00 AM
Priti Bhansali, M.D., M.Ed. Hospital Medicine Workshop co-leaders Making the Most of Peer Mentors within a Diverse Developmental Network: Supporting Scholarship and Academic Advancement 4/24/2022 10:00 AM
Ian Chua, M.D., M.H.P.E.
Gabrina Dixon, M.D., M.Ed.
Karen Smith, M.D., M.Ed.		 Hospital Medicine

 

 Workshop co-leaders The Art of Negotiation: Applying Negotiation Frameworks to Get More of What You Want in Your Academic Career 4/24/2022 10:00 AM
Matthew Magyar, M.D. Hospital Medicine Oral abstract presenter The association between social needs and unscheduled healthcare utilization among a nationally representative sample of children with asthma 4/24/2022 10:00 AM
Lena A. Saleh, M.D., M.P.H. Oral abstract presenter Machine Learning to Predict the Need for Intensive Care for Pediatric Asthma Exacerbation 4/24/2022 10:30 AM
Christina R. Rojas, M.D. Emergency Medicine and Trauma Services Oral abstract presenter Pediatric Emergency Department Undertriage for Patients with Limited English Proficiency 4/24/2022 10:30 AM
Ololade Okito, M.D. Neonatology Workshop co-leaders Best Practices in DEI Recruitment: Holistic Review and Addressing Systemic Bias 4/25/2022 8:00 AM
Jennifer H. Klein, M.D. Presenter Geography of pediatric health: Using geospatial analysis tools in pediatric care 4/25/2022 8:00 AM
Anand Gourishankar, M.B.B.S., M.R.C.P., M.A.S. Hospital Medicine Presenter Geospatial analysis in pediatric health: Principles, pitfalls, and practice 4/25/2022 8:00 AM
Sarah D. Schlatterer, M.D., Ph.D. Neurology Oral abstract presenter Autonomic Dysfunction and Hemodynamic Instability Precedes Cardiac Arrest in Infants with Congenital Heart Disease 4/25/2022 8:15 AM
Chaya Merrill, Dr.P.H. Presenter Mapping neighborhood-level inequities using the Childhood Opportunity Index 4/25/2022 8:20 AM
Jennifer H. Klein, M.D. Speaker Geospatial distribution of congenital heart disease 4/25/2022 8:40 AM
Ioannis Koutroulis, M.D., Ph.D., M.B.A. Emergency Medicine and Trauma Services Panelist APA Urgent Care SIG 4/25/2022 10:00 AM
Priti Bhansali, M.D., M.Ed. Hospital Medicine Workshop co-leaders From Mediocre to Masterly: Using Cognitive Interviewing to Improve the Validity of Your Survey 4/25/2022 10:00 AM
Beth A. Tarini, M.D., M.S. General and Community Pediatrics Speaker SPR Presidential Plenary: “Transforming the Culture of Pediatric Research: We Are the Problem and the Solution 4/25/2022 10:00 AM
Deena Berkowitz, M.D., M.P.H. Emergency Medicine and Trauma Services Speaker 2. UC fellowships and accreditation: the APA pipeline 4/25/2022 10:30 AM
John T. Kulesa, M.D. Hospital Medicine Oral abstract presenter A Descriptive Model for Prioritization and Resource Allocation in Academic Global Health Partnerships 4/25/2022 10:30 AM
Ariella Slovin, M.D. General and Community Pediatrics Speaker APA Well-being and Vitality SIG 4/25/2022 1:00 PM
Melissa Baiyewu, M.H.A., C.H.E.S.
Lin Chun-Seeley, M.A.
Desiree D. de la Torre, M.P.H., M.B.A.
Olanrewaju O. Falusi, M.D., M.Ed.
Chaya Merrill, Dr.P.H.		 General and Community Pediatrics Workshop co-leaders Training Faculty Members to Model and Teach Health Equity: A New Faculty Development Curriculum 4/25/2022 1:00 PM
Ariella Slovin, M.D. General and Community Pediatrics Speaker Wellness and Vitality SIG: Overview of endeavors to date and status report on well-being of APA Members 4/25/2022 1:30 PM
Beth A. Tarini, M.D., M.S. General and Community Pediatrics Speaker Navigating Research Careers Through the Currents of Policy and Politics 4/25/2022 1:36 PM
Rebecca S. Lundberg, M.D. Oral abstract presenter Early parenteral nutrition support and preterm cerebellar metabolic maturation 4/25/2022 2:00 PM
Aisha Barber, M.D., M.Ed. Hospital Medicine Workshop co-leader Moving with the Tide: Taking Steps Toward Anti-Racism and Equity 4/233/22 1:00 PM

 

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Children’s National Hospital at the 2021 Pediatric Academic Societies Meeting

Attending the 2021 Pediatric Academic Societies meeting this week? There will be over 20 Children’s National Hospital-affiliated participants at this year’s meeting. We have compiled their sessions into a mini schedule:

Name Program/Department Session and role Date Time
Taeun Chang, M.D.  Neonatal Neurology and Neurocritical Care Program PAS Postgraduate Course: Neonatal Neurology: HIE-focused Project-Based (Chair) Friday, 30 April

 

 9:00 AM –
4:00 PM
CT
Taeun Chang, M.D. Neonatal Neurology and Neurocritical Care Program PAS Postgraduate Course: Neonatal Neurology: HIE-focused Project-Based (Presenter) Friday, 30 April 9:30 AM – 10:00 AM
CT
Yuan-Chiao Lu, Ph.D. Developing Brain Research Laboratory Cardiology Poster: Care of the Fetus and Newborn with CHD (Presenter) Saturday, May 1 4:30 PM – 4:45 PM
CT
Chidiogo Anyigbo, M.D., M.P.H. General and Community Pediatrics Poster: Health Services Research I (Presenter)

 

 Saturday, May 1 5:15 PM – 5:30 PM
CT
Panagiotis Kratimenos, M.D. Neonatology Platform (moderator) Saturday, May 1 4:30 PM – 6:00 PM
CT
Sudeepta Basu, MBBS, MS Neonatology Hot Topic Symposia: The Neurological Implications of Abnormal Glycemia in Neonatal Encephalopathy and Prematurity (Chair) Sunday, May 2 9:00 AM – 12:00 PM
CT
Sudeepta Basu, MBBS, MS Neonatology Hot Topic Symposia: The Neurological Implications of Abnormal Glycemia in Neonatal Encephalopathy and Prematurity (Presenter) Sunday, May 2 9:55 AM – 10:15 AM
CT
Ashraf Harahsheh, M.D., F.A.C.C., F.A.A.P.

 

 Cardiology Cardiology: Heart Disease in the Older Child Sunday, May 2 10:00 AM – 12:00 PM
CT
Rana F. Hamdy, M.D., MPH, MSCE Infectious Diseases

 

 Expanding Outpatient Antibiotic Stewardship: Practical Strategies, Novel Settings, and Sociobehavioral Influences (Presenter) Sunday, May 2 10:15 AM – 10:30 AM
CT
Rana F. Hamdy, M.D., MPH, MSCE Infectious Diseases

 

 Hot Topic Debates: Antibiotic Use in Hospitalized Children (Chair) Sunday, May 2 1:00 PM – 3:00 PM
CT
John Idso, M.D. Critical Care Poster: Resuscitation and Potpourri (presenter) Sunday, May 2 2:20 PM – 2:30 PM
CT
Michael Shoykhet, M.D., Ph.D. Critical Care Medicine

 

 Critical Care Poster: Resuscitation and Potpourri (presenter) Sunday, May 2 2:20 PM – 2:30 PM
CT
Panagiotis Kratimenos, M.D. Neonatology Neonatal Neurology: Basic & Translational I (moderator) Sunday, May 2

 

 4:30 PM – 6:00 PM
CT
Monika Goyal, M.D. Emergency Medicine and Trauma Services Injury Prevention (moderator) Sunday, May 2 10:00 AM – 12:00 PM
CT
Ioannis Koutroulis, M.D., Ph.D., M.B.A. Genetic Medicine Research

 

 Emergency Medicine III (moderator) Tuesday, May 4 2:00 PM – 4:00 PM
CT
Sudeepta Basu, MBBS, MS Neonatology Neonatal Neurology: Clinical: HIE and Other Insults (moderator) Tuesday, May 4 4:30 PM – 6:00 PM
CT
Josepheen De Asis-Cruz, M.D., Ph.D. Center for the Developing Brain Neonatal Neurology: Clinical: HIE and Other Insults (presenter) Tuesday, May 4 4:30 PM – 4:45 PM
CT
Asad Bandealy, M.D., MPH
Priti Bhansali, M.D. Monika Goyal, M.D.
Sabah Iqbal, M.D. Kavita Parikh, M.D. Shilpa Patel, M.D.		 Workshop. ThisIsSTILLOurLane: Protect Kids, Not Guns Monday, May 10 9:00 AM – 11:00 AM
CT
Cara Lichtenstein, M.D. General and Community Pediatrics APA Injury Control/Advocacy Training Combined SIG (SIG Chair) Monday, May 10 1:00 PM – 3:00 PM
CT
Terry Kind, M.D., MPH General and Community Pediatrics

 

 APA Women in Medicine / Qualitative Research Combined SIG (SIG Chair) Wednesday, May 12 9:00 AM – 11:00 AM
CT

Phase I: April-30-May 4 and Phase II: May 10-June 4

PAS 2021 Virtual Schedule

structure of EGFR

Study suggests EGFR inhibition reverses alterations induced by hypoxia

structure of EGFR

The study suggests that specific molecular responses modulated by EGFR (seen here) may be targeted as a therapeutic strategy for HX injury in the neonatal brain.

Hypoxic (HX) encephalopathy is a major cause of death and neurodevelopmental disability in newborns. While it is known that decreased oxygen and energy failure in the brain lead to neuronal cell death, the cellular and molecular mechanisms of HX-induced neuronal and glial cell damage are still largely undefined.

Panagiotis Kratimenos, M.D., and colleagues from the Center for Neuroscience Research at the Children’s National Research Institute, discovered increased expression of activated-epidermal growth factor receptor (EGFR) in affected cortical areas of neonates with HX and decided to further investigate the functional role of EGFR-related signaling pathways in the cellular and molecular changes induced by HX in the cerebral cortex.

The researchers found that HX-induced activation of EGFR and Ca2+/calmodulin kinase IV (CaMKIV) caused cell death and pathological alterations in neurons and glia. EGFR blockade inhibited CaMKIV activation, attenuated neuronal loss, increased oligodendrocyte proliferation and reversed HX-induced astrogliosis.

The researchers also performed, for the first time, high-throughput transcriptomic analysis of the cortex to define molecular responses to HX and to uncover genes specifically involved in EGFR signaling in brain injury. Their results indicate that specific molecular responses modulated by EGFR may be targeted as a therapeutic strategy for HX injury in the neonatal brain.

This study defines many new exciting avenues of scientific exploration to further elucidate the beneficial impact of EGFR blockade on perinatal brain injury at the cellular and molecular levels. This analysis could potentially result in the identification of new therapeutic targets associated with EGFR signaling in the developing mammalian brain that are linked with specific long-term abnormalities caused by perinatal brain injury.

Children’s National researchers who contributed to this study include Panagiotis Kratimenos, M.D., Ioannis Koutroulis, M.D., Ph.D., M.B.A., Susan Knoblach, Ph.D., Payal Banerjee, Surajit Bhattacharya, Ph.D., Maria Almira-Suarez, M.D., and Vittorio Gallo, Ph.D.

Read the full article in iScience.