Akhil Maheshwari

Akhil Maheshwari is a neonatologist. He has developed the Global Newborn Society, a worldwide organization that aims to promote international scientific and social efforts focused on newborn health.

Akhil Maheshwari
Akhil Maheshwari001.jpg
Born
India
EducationInstitute of Medical Sciences, Banaras Hindu University, India

Postgraduate Institute of Medical Education and Research, India

University of Florida at Gainesville, Florida

University of South Florida, Tampa and St. Petersburg, Florida
OccupationChair, Global Newborn Society Editor-in-Chief, Newborn, Official Journal of The Global Newborn Society
Years active2004–present
HonorsPamela and Leslie Endowed Chair of Pediatrics at University of South Florida in 2014 Josephine S. Sutland Professorship of Newborn Medicine at Johns Hopkins University in 2018

EducationEdit

Akhil Maheshwari received medical education at Banaras Hindu University, Varanasi and the Postgraduate Institute of Medical Education and Research, Chandigarh in India, and then relocated to the University of Florida at Gainesville, Florida for further training in clinical pediatrics and laboratory research. Two years later, he relocated with the same team to the University of South Florida Morsani College of Medicine, Tampa, Florida, to receive fellowship training in neonatology and to continue his medical research.

Faculty positionsEdit

In 2004, Maheshwari was recruited as an Assistant Professor at the University of Alabama at Birmingham, Alabama. He studied innate immunity and the pathogenesis of gut mucosal and systemic inflammation in newborn infants, with a particular focus on a disease called necrotizing enterocolitis (NEC). In NEC, the intestines of a premature newborn infant become inflamed and lose viability. His research was supported by the American Gastroenterological Association and the National Institutes of Health.[1]

In 2010, he joined the University of Illinois College of Medicine at Chicago, Illinois as the Head of Neonatology.[2]

In 2014, he moved back to the University of South Florida as the Pamela and Leslie Muma Professor, Head of Neonatology, and Assistant Dean for Medical Education.[3] He administered the academic and the clinical programs at the neonatal intensive care unit at Tampa General Hospital, Tampa, Florida. In his laboratory, he investigated the role of intestinal macrophages and platelets in NEC.[4]

In 2018, he moved to the Johns Hopkins University School of Medicine, Baltimore, Maryland as the Josephine S. Sutland Professor of Newborn Medicine, Head of Neonatology, and Vice-Chairman of the Department of Pediatrics.[5] After having led neonatology programs at several institutions over a decade, he has relinquished these administrative positions to pursue his academic goals and to develop the Global Neonatology Society.

Academic workEdit

In his scientific work, Maheshwari is an expert in understanding of NEC.[6] In addition to more than 200 invited lectures, he has over 100 peer-reviewed articles[7] with 5 more in press, authored five medical textbooks with two more in press, and has contributed 50 chapters in various leading textbooks of neonatology. His research work has covered the following topics:

Effects of inflammatory proteins on intestinal development in the fetus/newborn infantEdit

Maheshwari noted that proteins such as interleukin-8,[8] which are perceived in adults as harmful inflammatory mediators, are expressed in high concentrations in the amniotic fluid and in human milk, and are, therefore, ingested in large amounts by the developing fetus and the newborn infants.[9] These proteins are expressed in multiple isoforms, and actually promote maturation of the developing intestine.[10][11]

 
Microscopic image of intestine that had to be surgically removed because of necrotizing enterocolitis

Inflammatory changes in NECEdit

Maheshwari has investigated the mechanisms involved in the recruitment of white blood cells into the inflamed intestine during NEC. He has also evaluated the importance of decreased blood monocyte and platelet counts for early diagnosis of NEC in these patients.[12] Some of his studies have focused on intracellular molecular mechanisms of NEC, and helped identify some genetic markers or changes in gene expression as risk/diagnostic markers of NEC.[13] His work has helped in our understanding of how a newborn infant develops tolerance to the millions of bacteria that populate our intestines after birth.[14]

Maturation of intestinal macrophages and the risk of developing NECEdit

Maheshwari has shown that immature macrophages[15] in a newborn infant’s intestinal wall get overly activated upon exposure to bacteria because the intestines of newborn infants are deficient in a suppressant protein called transforming growth factor-beta (TGF-β), especially the isoform, TGF-β2. This hyper-reactivity of the white blood cells can explain the intense inflammation seen in NEC.[16][17] His team has identified some ways to increase TGF-β expression in the newborn intestine.[18]

His laboratory has shown that some of the protective effects of mother’s milk against NEC in babies could be related to its high TGF-β content.[19] Maheshwari has identified some molecular tools to enhance these protective effects by further activating milk-borne TGF-β, a strategy which could be clinically important.[20][21]

Increased risk of NEC in severely anemic infants after RBC transfusionsEdit

Premature and critically ill babies often develop severe anemia.[22] In anemic infants, insufficient tissue oxygenation can disrupt the intestinal barrier against bacteria present in the gut lumen.[23][24] To defend against these bacteria, the intestine of a newborn infant does contain macrophages, but these cells are still immature.[25] However, if blood transfusions are given to correct this anemia, intestinal macrophages get activated, and can trigger NEC. So, the most appropriate medical approach is still unclear.

Maheshwari and coworkers developed a mouse model to investigate the association between severe anemia, red blood cell transfusions, and NEC.[26] Mouse pups were first rendered anemic by timed, repeated blood draws performed between days 2-10 after birth, and were then given transfusions on day 11. These pups developed NEC-like intestinal injury within 18-48 hours. The macrophages that were expected to protect against invading bacteria, became hyperactivated by degradation products of hemoglobin released from the transfused red blood cells, and paradoxically, damaged the intestine.

Role of platelets in severity of NECEdit

Most premature infants with NEC have decreased blood platelet counts,[27] which increases the risk of bleeding both locally and in vital organs such as the brain. Maheshwari has described the frequency and the mechanisms of platelet consumption in NEC.[28] Decreased platelet counts are dangerous, but platelet transfusions are also not safe. Transfused platelets can augment inflammation both in the NEC-affected bowel and in other organ systems.[29] His team has investigated the involved mechanisms and identified some potential treatment approaches to these difficulties.

Scientific research organizationsEdit

Maheshwari has led several committees to review scientific proposals at the National Institutes of Health and at the American Heart Association. He also serves on the College of Reviewers at the Canadian Institutes for Health Research,[30] and other such committees in the United Kingdom, Belgium, The Netherlands, and Hong Kong, China. He serves on the editorial board of multiple medical journals.

Pediatric health care organizationsEdit

Maheshwari has been closely associated with several major pediatric health care organizations.

Global Newborn SocietyEdit

Maheshwari is the Chair of a worldwide organization, the Global Newborn Society (GNS).[31] He established this organization with help from Professor Dr. Minesh Khashu from the United Kingdom and with clinical, research, and social experts from all over the world. The GNS has four main objectives: (a) education and development of clinical protocols/guidelines; (b) collection of accurate epidemiological information, to help prioritize the organization's efforts; (c) find new medical solutions by energizing basic, translational, and clinical research, aiming for innovation in clinical practice; and (d) philanthropy, seeking social engagement to reduce neonatal disease and deaths.

The GNS works to raise awareness that even today, millions of infants are lost due to reasons that could be minimized by appropriately-directed medical and logistical measures. The aim is to bring together health care professionals, families, citizens who had to endure critical illness during infancy, charitable organizations, government agencies, policy-makers, and everyone else who wishes to support these changes. Many experts are working to standardize quality-improvement measures in all aspects of neonatal care. Others seek to establish large data sets with multi-modality longitudinal follow-up, to generate insights beyond those possible from conventional paradigms.

The GNS has recently started a new peer-reviewed scientific journal, the Newborn, with an editorial board composed of experts from all over the world. Maheshwari is serving as the Editor-in-Chief. The first issue is anticipated in February 2022. He is working on various endeavors to lower the cost of this journal, books, and scientific instruments relevant for newborn care.

NEC SocietyEdit

Maheshwari is a committed member of the NEC Society, a charitable organization dedicated to building a world without NEC through research, advocacy, and education. He served as a Senior Scientific Mentor to its Scientific Advisory Council until September 2021.

American Pediatric Society and Society for Pediatric ResearchEdit

Maheshwari is an active member of the American Pediatric Society (APS), which seeks to promote child and adolescent health by promoting pediatric advocacy, scholarship, education, and leadership development. The APS partners with the Society for Pediatric Research, a voluntary association of multidisciplinary scientists. Since 2017, Maheshwari has been organizing a 'NEC Focus Group' plenary event at the Pediatric Academic Societies (PAS) Meetings that are conducted jointly by these two associations, to review the latest advances in our understanding of this disease.

ReferencesEdit

  1. ^ https://grantome.com/grant/NIH/R01-HD059142-01.
  2. ^ https://www.researchgate.net/profile/Akhil-Maheshwari
  3. ^ https://hscweb3.hsc.usf.edu/blog/2016/03/29/usf-neonatologist-studies-inflammatory-pathways-that-may-lead-to-new-treatments-for-sickest-newborns/.
  4. ^ https://grantome.com/grant/NIH/R01-HL124078-03
  5. ^ https://clinicalconnection.hopkinsmedicine.org/participant/akhil-maheshwari-mbbs-md.
  6. ^ Akhil Maheshwari's bibliography as seen on the Google Scholar web search engine.
  7. ^ "AKHIL MAHESHWARI's Bibliography". National Library of Medicine.
  8. ^ Maheshwari et al. "Effects of interleukin-8 on the developing human intestine." Cytokine. 2002;20:256-67.
  9. ^ Maheshwari et al. "ELR+ CXC chemokines in human milk.">> Cytokine. 2003;24:91-102.
  10. ^ Maheshwari et al. "Developmental changes in circulating IL-8/CXCL8 isoforms in neonates." Cytokine. 2009;46:12-6.
  11. ^ Maheshwari et al. "Interleukin-8/CXCL8 forms an autocrine loop in fetal intestinal mucosa." Pediatric Research. 2004;56:240-9.
  12. ^ Maheshwari. "Immunologic and Hematological Abnormalities in Necrotizing Enterocolitis." Clinics in Perinatology. 2015;42:567-85.
  13. ^ Jilling et al. "Surgical necrotizing enterocolitis in extremely premature neonates is associated with genetic variations in an intergenic region of chromosome 8." Pediatric Research. 2018;83:943-53.
  14. ^ Ho et al. "Dichotomous development of the gut microbiome in preterm infants." Microbiome. 2018;6:157.
  15. ^ Mezu-Ndubuisi and Maheshwari. "Role of macrophages in fetal development and perinatal disorders." Pediatric Research. 2020 Oct 18; doi: 10.1038/s41390-020-01209-4. Epub ahead of print.
  16. ^ Remon et al. "Acute drop in blood monocyte count differentiates NEC from other causes of feeding intolerance." Journal of Perinatology. 2014;34:549-54.
  17. ^ Maheshwari et al. "Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight infants." Pediatric Research. 2014;76:100-8.
  18. ^ Namachivayam et al. "All-Trans Retinoic Acid Induces TGF-β2 in Intestinal Epithelial Cells via RhoA- and p38α MAPK-Mediated Activation of the Transcription Factor ATF2." PLOS One. 2015;10:e0134003.
  19. ^ Frost et al. "Maternal breast milk transforming growth factor-beta and feeding intolerance in preterm infants." Pediatric Research. 2014;76:386-93.
  20. ^ Namachivayam et al. "Transforming growth factor-β2 is sequestered in preterm human milk by chondroitin sulfate proteoglycans." American Journal of Physiology. Gastrointestinal and Liver Physiology. 2015;309:G171-80.
  21. ^ Namachivayam et al. "Preterm human milk contains a large pool of latent TGF-β, which can be activated by exogenous neuraminidase." American Journal of Physiology. Gastrointestinal and Liver Physiology. 2013;304:G1055-65.
  22. ^ Aucott and Maheshwari "To transfuse or not transfuse a premature infant: the new complex question." Journal of Perinatology. 2019;39:351-353.
  23. ^ Mohankumar et al. "Severe neonatal anemia increases intestinal permeability by disrupting epithelial adherens junctions.". American Journal of Physiology. Gastrointestinal and Liver Physiology. 2020;318:G705-G716.
  24. ^ Remon et al. "Depth of bacterial invasion in resected intestinal tissue predicts mortality in surgical necrotizing enterocolitis." Journal of Perinatology. 2015;35:755-62.
  25. ^ Whitehead et al. "Progressive anemia of prematurity is associated with a critical increase in cerebral oxygen extraction." Early Human Development. 2019;140:104891.
  26. ^ MohanKumar et al. "A murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions." Nature Communications. 2019;10:3494.
  27. ^ Namachivayam et al. "Neonatal mice with necrotizing enterocolitis-like injury develop thrombocytopenia despite increased megakaryopoiesis." Pediatric Research. 2017;81:817-824.
  28. ^ Maheshwari. "Role of platelets in neonatal necrotizing enterocolitis." Pediatric Research. 2020 Jun 29; doi: 10.1038/s41390-020-1038-8. Online ahead of print.
  29. ^ Patel et al. "Platelet transfusions and mortality in necrotizing enterocolitis." Transfusion. 2019;59:981-988.
  30. ^ https://www.canada.ca/en/institutes-health-research/search.html?cdn=irsccihr&st=s&num=10&langs=eng&st1rt=0&s5bm3ts21rch=x&q=akhil+maheshwari#wb-land
  31. ^ https://www.globalnewbornsociety.org/background