Sowmya Kolluru

Introduction: Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality among infants in the neonatal intensive care unit. With an overall prevalence of 1%, NEC is found in about 11% of infants with very low birthweights (VLBW) and 22% in infants of extremely low birthweights. A disease of prematurity, NEC has a multifactorial pathogenesis involving a combination of feeding regimens, gut microbiome, and birth weight. This study aims to elucidate the demographic factors associated with NEC- mediated infant mortality, with the goal of guiding future research into disease diagnosis and management. Methods: The CDC WONDER database was queried to collect data on mortality from NEC of infants <1 year old between 1999 and 2023. Data was stratified by sex, race/ethnicity, urbanization status, and census region. Crude mortality rate (CMR) was determined, and Joinpoint analysis was conducted to identify significant changes in mortality trends. Results: Overall NEC-related CMR decreased slightly between 1999 and 2023. CMR was higher in males than females throughout the study period, though mortality decreased slightly in the male population. When stratified by race, Non-Hispanic (NH) Black or African American patients had the highest overall CMR, followed by Hispanic or Latino and NH White patients, respectively. Regionally, the South had the highest CMR across the four studied census regions, though Southern mortality decreased over the study period. The West reported the lowest mortality from NEC and was the only census region with reported increase in CMR. In both urban and rural areas, mortality initially increased before a subsequent decrease throughout the study period. Discussion: This study builds on prior research efforts into mortality trends in NEC to highlight the disproportionate mortality burden associated with NEC faced by certain groups, including males, NH Black of African American patients, and patients from the Southern United States. Further research into the implications of different socioeconomic determinants of health and biomarker variability by demographic cohort can guide more effective diagnostic and management strategies.

Desmoplastic small round cell tumor (DSRCT) is a rare but aggressive soft tissue sarcoma of the abdomen. With an asymptomatic course and rapid dissemination, DSRCT’s prognosis is poor at diagnosis. This study characterizes the demographic variation and genomic profile of DSRCT to guide studies into diagnosis and treatment. The AACR GENIE database was utilized to identify genetic alterations in DSRCT. Data was queried to identify disease prevalence by different demographic variables. Information was collected on frequency of somatic mutations and copy number alterations, rates of mutation co-occurrence, and mutations seen in primary and metastatic samples. ARID1A, TP53, ATM, TERT, and FGFR4 were the most frequently identified somatic mutations. Copy number alterations seen in DSRCT were commonly homozygous deletions in tumor suppressor genes. Independent of sex, WT1 mutations were most common. Non-White patients saw single occurrences of many mutations but recurrent ones in ANKRD11 and KMT2C. Co-occurrence was found between FGFR4 and EP300. Moreover, primary tumor samples had exclusive mutations in AKAP9, KDM2B, MAGED1, MKI67, PCLO, and TRAF1. Metastatic samples had exclusive mutations in FIP1L1 and NRIP1. Our data highlights mutational variation across demographic cohorts. These patterns are vital to future studies into identifying diagnostic markers or therapeutic targets.