Akhil Maheshwari

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—Jhuma1971 (talk) 13:05, 20 January 2021 (UTC)

Akhil Maheshwari is a neonatologist. In addition to seminal work in neonatology, he has developed the Global Newborn Society, a worldwide organization that aims to promote international scientific and social efforts focused on newborn health.

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Akhil Maheshwari

Education

Maheshwari received early education in Meerut, Uttar Pradesh, India. Per the education norms in India, he was able to compete in medical school entrance examinations immediately after high school, and was selected to the Institute of Medical Sciences at Banaras Hindu University, which is one of the leading medical institutions in India. He completed his Bachelor of Medicine, Bachelor of Surgery (MBBS). Subsequently, he relocated to a program for MD training in Pediatrics at the Postgraduate Institute of Medical Education and Research, Chandigarh, India. After 5 years, he moved to the University of Florida College of Medicine, Gainesville, Florida for further education. Here, he received a shortened clinical residency training in pediatrics. He then relocated with the research team to the University of South Florida Morsani College of Medicine, Tampa, Florida, where he continued his medical research and received fellowship training in neonatology.

Faculty positions

In 2004, after completing his fellowship training, Maheshwari was recruited as a physician-scientist and Assistant Professor at the University of Alabama at Birmingham, Alabama. He studied innate immunity and the pathogenesis of acute 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 or critically ill newborn infant become inflamed and lose viability. His research was supported first by the American Heart Association and the American Gastroenterological Association, and then as an independent scientist, by the National Institutes of Health.

In 2010, he was appointed as the Head of the Division of Neonatology at the University of Illinois College of Medicine at Chicago, Illinois. He developed new clinical, teaching and research programs in the Department of Pediatrics, and continued his own research focused on the mechanisms of inflammation in NEC.

In 2014, he was recruited back to the University of South Florida Morsani College of Medicine as a Full Professor on an endowed chair, as the Head of Neonatology and Assistant Dean for Medical Education. He grew the academic program in neonatology and the neonatal intensive care unit at the Tampa General Hospital, Tampa, Florida, and developed a scientific collaboration network. In his own laboratory, he developed important scientific programs focused on the role of intestinal macrophages and platelets in the development of NEC.

In 2018, he moved to the Johns Hopkins University School of Medicine, Baltimore, Maryland on another endowed professorship, as the Head of Neonatology, and Vice-Chairman of the Department of Pediatrics. After having led neonatology programs at several institutions over a decade, he relinquished these administrative positions to pursue his academic goals and to develop the Global Neonatology Society.

Academic work

In his scientific work, Maheshwari is an expert in understanding of necrotizing enterocolitis. In addition to more than 120 peer-reviewed publications, he has authored three medical textbooks, and is currently developing three more. He has also contributed 25 chapters in various leading textbooks of neonatology. His research work has covered the following topics:

Ingested inflammatory proteins and intestinal development

Maheshwari noted that several proteins such as interleukin-8 and related CXC chemokines, which recruit white blood cells and are therefore, perceived in adults as potentially harmful inflammatory mediators, are expressed in high concentrations in the amniotic fluid and in human milk. Therefore, the developing fetus and the newborn infant ingests these cytokines in large amounts. Interestingly, all these proteins play important maturational roles in the developing intestine. Interleukin-8 can be detected in multiple potentially-beneficial isoforms. These proteins are also secreted by epithelial cells in the neonatal intestine and play a protective role for the mucous membrane.

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

Inflammatory changes in necrotizing enterocolitis

Maheshwari elucidated the mechanisms by which white blood cells get recruited into the intestinal loops affected by NEC. He has also evaluated the hematological changes in NEC, particularly blood monocyte and platelet counts. In collaboration with other leading scientists, he has identified some of the genetic risk factors associated with NEC. He has also contributed to our understanding of how a newborn infant develops immune tolerance to the millions of bacteria that begin to live in our intestines after birth.

The three broad themes of his research on NEC have been (a) hematological changes that can be useful in clinical evaluation of infants with Feeding difficulties, for early diagnosis of NEC; (b) investigation of inflammatory intracellular signaling, to identify novel treatment measures; and (c) genetic and epigenetic markers associated with intestinal injury, for risk assessment and timely diagnosis of NEC in infants with epidemiological risk factors known to be associated with this disease.

Maturation of intestinal macrophages and the risk of developing necrotizing enterocolitis

Maheshwari has shown that macrophages, which are an important subpopulation of resident white blood cells in a newborn infant’s intestinal wall, are immunologically immature and are readily activated by inflammatory stimuli because of the developmental deficiency of a cytokine called transforming growth factor-beta (TGF-β), particularly its isoform TGF-β2. Similar to blood monocytes, these immature intestinal macrophages are readily stimulated by bacteria and their components, and this leukocyte hyper-reactivity can explain the intense, dysregulated intestinal and systemic inflammation in NEC. Interestingly, many infants who develop this disease have low plasma levels of TGF-β since birth. His team has identified some ways to increase TGFβ2 expression in the intestinal epithelium.

The protective effects of mother’s milk against feeding intolerance and NEC in babies could be related to its TGF-β content. Mother's milk contains large amounts of TGFβ2, but most of it normally remains in inactive forms that are bound to matrix carbohydrates such as chondroitin sulfate. Maheshwari has identified ways to activate some of these latent forms of TGFβ2 for therapeutic purposes.

Etiological importance of severe anemia and subsequent red blood cell transfusions in the development of necrotizing enterocolitis

Premature and critically ill babies often develop severe anemia due to a multitude of reasons. In these severely anemic infants, the low levels of tissue oxygenation can damage the intestinal barrier against bacteria normally present in the intestinal lumen. In infants who have bacterial overgrowth in the intestine, the risk of these bacteria invading into the bowel wall and causing intestinal and systemic inflammation is even higher. To defend against these bacteria, the intestine of a newborn infant does contain appropriate white blood cells such as macrophages, but as noted above, these cells are still immature and produce dysregulated, overly severe inflammatory responses. At this high level of severity, anemia may also affect other organs, including the brain. If blood transfusions are given to correct the underlying anemia, these macrophages in the intestinal wall get further activated, and can trigger NEC.

As described above, Maheshwari and his research team have developed a murine model to investigate the observed association between severe anemia, red blood cell transfusions, and NEC. Mouse pups were rendered anemic by timed, repeated phlebotomies performed between postnatal days 2-10, and then given red blood cell transfusions on day 11. These pups developed NEC-like intestinal injury within 18-48 hours, with prominent necrosis, inflammation, and submucosal edema in the ileocecal region and large intestine. The anemic intestine was infiltrated by monocyte-derived immature, hyper-inflammatory macrophages. Studies showed that these macrophages were activated by degradation products of the transfused red blood cells. These hyperactive macrophages produced secondary mediators such as reactive oxygen species and inflammatory cytokines, and caused tissue damage. Intestinal injury worsened with increasing severity and the duration of anemia prior to transfusion.

Pathophysiological importance of platelets in severity of necrotizing enterocolitis

NEC is typically associated with a drop in blood platelet counts and thrombocytopenia. These infants may be at risk of bleeding in vital organs such as the brain. Maheshwari has described the frequency, temporal evolution, and the mechanisms of thrombocytopenia both in infants with NEC and in murine models of this disease. This thrombocytopenia is potentially dangerous, but if platelet transfusions are given to correct the blood platelet counts, these transfused platelets can augment the inflammatory response and increase tissue damage both in the NEC-affected bowel and in various other organ systems.

Scientific research organizations

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 several committees set up to review scientific grant applications at the National Institutes of Health and the American Heart Association in the USA, the College of Reviewers at the the Canadian Institutes for Health Research, and other such committees in the United Kingdom, Belgium, The Netherlands, and Hong Kong, China. He serves on the editorial board of 13 peer-reviewed medical scientific journals and as a reviewer on another 75.

Pediatric Health Care Organizations

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

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Global Newborn Society

Maheshwari and Professor Dr. Minesh Khashu from the United Kingdom have together established a worldwide organization, the Global Newborn Society (GNS) (here is a website that may be easier to access on mobile phones), with guidance from clinical, research, and social experts and with important participation of opinion leaders from all over the world. The Society has started with four main objectives: (a) education and development of clinical protocols/guidelines, seeking to develop a panoramic view of clinical needs in this process; (b) collection of accurate epidemiological information, to create awareness about the high rates of morbidity and mortality in newborn infants; (c) find new medical solutions by energizing basic, translational, and clinical research, aiming for innovation and good clinical practice; and (d) altruistic (even at some personal cost) philanthropy, seeking social engagement to reduce disease and deaths in newborn infants.

The GNS seeks to remind everyone that Every Baby Counts; even today, millions of infants are lost due to reasons that could be minimized by appropriately-directed medical and logistical measures. We need to remember that Each Time We Lose an Infant, We Lose an Entire Life and its Potential. The aim is to bring together health care professionals, parents & families, citizens who had to endure critical illness during infancy, charitable organizations, government agencies, policy makers, and everyone 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 "big data" with multi-modality longitudinal follow-up, to generate insights beyond those possible from conventional paradigms. Some biomedical scientists aim to develop scoring systems to accurately predict clinical outcomes, which can help in better allocation of resources. Finally, consolidation of data from screening programs for inborn errors of metabolism across the world may generate novel insights.

NEC Society

Maheshwari is a committed member of the NEC Society and serves as a Senior Scientific Mentor to its Scientific Advisory Council. The NEC Society is a charitable organization dedicated to building a world without NEC through research, advocacy, and education; by bringing together patient-families, clinicians, and other diverse stakeholders. The Scientific Advisory Council of the NEC Society is comprised of leading clinicians and scientists who provide critical feedback and share insights, strategies, and expertise.

American Pediatric Society and Society for Pediatric Research

Maheshwari is an active member of the American Pediatric Society (APS), which seeks to promote child adolescent health by promoting pediatric research, recognition of achievement, and cultivation of excellence in pediatric advocacy, scholarship, education, and leadership development of a diverse, inclusive, and engaged group of pediatricians. The APS is engaged in implementing policies, programs, and practices to eliminate structural inequities such as racism and sexism, and to promote inclusiveness and equity both within the organization and in the greater academic community and the nation. The Society also seeks to promote an intentional strategy to advance the causes of pediatric medicine and the health and well-being of all infants, children, and adolescents. The APS partners with the Society for Pediatric Research (SPR), which is a voluntary association of multidisciplinary scientists seeking to promote pediatric research endeavors. 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 and other pediatric associations every year. In this session, a leading expert in this disease reviews the latest advances in our understanding of this disease and current barriers to progress.

Nationwide Quality of Care Network

Maheshwari is serving as an advisor to the Nationwide Quality of Care Network (NQCN), a network of volunteer teams working to improve perinatal care in 15 states of India and 10 other countries in Asia: Bangladesh, Myanmar, Sri Lanka, Nepal, Bhutan, Indonesia, Thailand, Democratic People’s Republic of Korea, Maldives, and Timor-Leste (East Timor). In these efforts, the NQCN collaborates with the the Government of India (GOI) Ministry of Health and Family Welfare and its Labour room & Quality Improvement Initiative (LaQshya), the United Nations Children's Emergency Fund (UNICEF), and the World Health Organization (WHO) South-East Asia Regional Organization (SEARO). This initiative tracks nearly 550 thousand deliveries every year at 131 health care facilities.

References

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