Congratulations to Dr. Steve McElroy (neonatology) for his recent article accepted for publication/published online in the Journal of Pediatrics on Necrotizing Enterocolitis (NEC).

Necrotizing Enterocolitis: Using Regulatory Science and Drug Development to Improve Outcomes.

Abstract portion:

In this review, the International Neonatal Consortium NEC working group addresses key issues that relate to the diagnosis, prevention, and treatment of NEC while suggesting a path forward to evaluate the safety and efficacy of each product. Despite years of clinical investigation, additional key data elements are needed to meet the requirements of regulatory agencies and evidence-based medicine.4 These include reliable diagnostic criteria, biomarkers predictive of risk and prognosis, and criteria for the design and conduct of clinical trials with consistent and clinically meaningful outcome measures for therapeutic trials.

Congratulations to Dr. Uc on her recent publication in the Journal of Pediatric Gastroenterology and Nutrition on Pancreatitis in children.

• Liu QY, Abu-El-Haija M, Husain SZ, Barth B, Bellin M, Fishman DS, Freedman SD, Gariepy CE, Giefer MJ, Gonska T, Heyman MB, Himes R, Lin TK, Maqbool A, Mascarenhas M, McFerron BA, Morinville VD, Nathan JD, Ooi CY, Perito ER, Pohl JF, Rhee S, Schwarzenberg SJ, Shah U, Troendle D, Werlin SL, Wilschanski M, Zimmerman MB, Lowe ME, Uc A. Risk Factors for Rapid Progression From Acute Recurrent to Chronic Pancreatitis in Children: Report From INSPPIRE. J Pediatr Gastroenterol Nutr. 2019 May 23. doi: 10.1097/MPG.0000000000002405. [Epub ahead of print]

OBJECTIVE: The aim of the study was to determine the rate of progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children and assess risk factors.

CONCLUSIONS: Children with ARP rapidly progress to CP, exocrine pancreatic insufficiency, and diabetes. The progression to CP is faster in children who were 6 years or older at the first episode of AP or with pathogenic PRSS1 variants. The factors that affect the aggressive disease course in childhood warrant further investigation.

Congratulations for Drs. Bassuk (Neurology) and Feguson (Rheumatology) on their recent publication in the Proceedings of the National Academy of Sciences.

• Abe K, Cox A, Takamatsu N, Velez G, Laxer RM, Tse SML, Mahajan VB, Bassuk AG, Fuchs H, Ferguson PJ, de Angelis MH. Gain-of-function mutations in a member of the Src family kinases cause autoinflammatory bone disease in mice and humans. PNAS 2019.

Abstract: Autoinflammatory syndromes are characterized by dysregulation of the innate immune response with subsequent episodes of acute spontaneous inflammation. Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder that presents with bone pain and localized swelling. Ali18 mice, isolated from a mutagenesis screen, exhibit a spontaneous inflammatory paw phenotype that includes sterile osteomyelitis and systemic reduced bone mineral density. To elucidate the molecular basis of the disease, positional cloning of the causative gene for Ali18 was attempted. Using a candidate gene approach, a missense mutation in the C-terminal region of Fgr, a member of Src family tyrosine kinases (SFKs), was identified. For functional confirmation, additional mutations at the N terminus of Fgr were introduced in Ali18 mice by CRISPR/Cas9-mediated genome editing. N-terminal deleterious mutations of Fgr abolished the inflammatory phenotype in Ali18 mice, but in-frame and missense mutations in the same region continue to exhibit the phenotype. The fact that Fgr null mutant mice are morphologically normal suggests that the inflammation in this model depends on Fgr products. Furthermore, the levels of C-terminal negative regulatory phosphorylation of FgrAli18 are distinctly reduced compared with that of wild-type Fgr. In addition, whole-exome sequencing of 99 CRMO patients including 88 trios (proband and parents) identified 13 patients with heterozygous coding sequence variants in FGR, including two missense mutant proteins that affect kinase activity. Our results strongly indicate that gain-of-function mutations in Fgr are involved in sterile osteomyelitis, and thus targeting SFKs using specific inhibitors may allow for efficient treatment of the disease.

Congratulations to Matt O’Brien, PhD in the Division of Developmental and Behavioral Pediatrics on his recent article published in Behavior Analysis in Practice.

The Promise of Accountable Care Organizations: “The Code,” Reimbursement, and an Ethical No-Win Situation for Behavior Analysts. March 2019,12(1),247-254.

Abstract: Clinical ethics, with its emphasis on the actions of clinicians, risks overlooking the ways in which broader health-care structures influence the behavior of health-care providers. Analysis of a factual case study demonstrates that status quo reimbursement practices may place behavior analysts in a position where, no matter how they act, they risk acting unethically. By contrast, the reimbursement model set by accountable care organizations (ACOs), part of the Patient Protection and Affordable Care Act (also known as Obamacare), may offer a solution. However, making good on the promise of ACOs will require more resources than any individual behavior analyst possesses. In order to encourage institutional structures that facilitate ethical practice, behavior analysts’ professional organizations should engage in contemporary political discussions about the state of American health care.

Congratulations to Dr. Matt Rysavy (current fellow in neonatology) for his recent editorial in JAMA!

Rysavy MA, Ehret DEY. Extremely Preterm Birth Outcomes in Sweden JAMA. 2019;321(12):1163-1164. doi:10.1001/jama.2019.2020.

Congratulations to Dr. Bell, Dr. Colaizy, and Dr. Rysavy for their most recent article in JAMA Pediatrics!

Brumbaugh JE, Hansen NI, Bell EF, Sridhar A, Carlo WA, Hintz SR, Vohr BR, Colaizy TT, Duncan AF, Wyckoff MH, Baack ML, Rysavy MA, DeMauro SB, Stoll BJ, Das A, Higgins RD, for the National Institute of Child Health and Human Development Neonatal Research Network. Outcomes of Extremely Preterm Infants With Birth Weight Less Than 400 g. JAMA Pediatr. Published online March 25, 2019. doi:10.1001/jamapediatrics.2019.0180.

Conclusions and Relevance Infants born with a birth weight less than 400 g are at high risk of mortality and significant morbidity. Although 21% of infants survived to 18 to 26 months’ corrected age with active treatment, neurodevelopment impairment was common among survivors

Congratulations to Dr. Uc on another publication in the Journal of Pediatric Gastroenterology and Nutrition!

Schwarzenberg SJ, Uc A, Zimmerman B, Wilschanski M, Wilcox CM, Whitcomb DC, Werlin SL, Troendle D, et al. Chronic Pancreatitis: Pediatric and Adult Cohorts Show Similarities in Disease Progress Despite Different Risk Factors. J Pediatr Gastroenterol Nutr. 2019 Apr;68(4):566-573. doi: 10.1097/MPG.0000000000002279.

“Despite disparity in age of onset, children and adults with chonic pancreatitis (CP) exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.”