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Background and Aims Over 80 monogenic causes of very early onset inflammatory bowel disease [VEOIBD] have been identified. Prior reports of the natural history of VEOIBD have not considered monogenic disease status. The objective of this study is to describe clinical phenotypes and outcomes in a large single-centre cohort of patients with VEOIBD and universal access to whole exome sequencing [WES]. Methods Patients receiving IBD care at a single centre were prospectively enrolled in a longitudinal data repository starting in 2012. WES was offered with enrollment. Enrolled patients were filtered by age of diagnosis <6 years to comprise a VEOIBD cohort. Monogenic disease was identified by filtering proband variants for rare, loss-of-function, or missense variants in known VEOIBD genes inherited according to standard Mendelian inheritance patterns. Results This analysis included 216 VEOIBD patients, followed for a median of 5.8 years. Seventeen patients [7.9%] had monogenic disease. Patients with monogenic IBD were younger at diagnosis and were more likely to have Crohn's disease phenotype with higher rates of stricturing and penetrating disease and extraintestinal manifestations. Patients with monogenic disease were also more likely to experience outcomes of intensive care unit [ICU] hospitalisation, gastrostomy tube, total parenteral nutrition use, stunting at 3-year follow-up, haematopoietic stem cell transplant, and death. A total of 41 patients [19.0%] had infantile-onset disease. After controlling for monogenic disease, patients with infantile-onset IBD did not have increased risk for most severity outcomes. Conclusions Monogenic disease is an important driver of disease severity in VEOIBD. WES is a valuable tool in prognostication and management of VEOIBD. [ABSTRACT FROM AUTHOR]

Background: Sex plays an important role in the incidence, prognosis, and mortality of cancers, but often is not considered in disease treatment. Methods: We quantified sex differences in cancer incidence using the United States Cancer Statistics (USCS) public use database and sex differences in cancer survival using Surveillance, Epidemiology, and End Results (SEER) public use data from 2001 to 2016. Age-adjusted male-to-female incidence rate ratios (IRR) with 95% confidence intervals (CI) were generated by primary cancer site, race, and age groups. In addition, age-adjusted hazard ratios with 95% CI by sex within site were generated. Results: In general, cancer incidence and overall survival were lower in males than females, with Kaposi sarcoma (IRR: 9.751; 95% CI, 9.287-10.242; P < 0.001) having highest male-to-female incidence, and thyroid cancers (HR, 1.774; 95% CI, 1.707-1.845) having largest male-to-female survival difference. Asian or Pacific Islanders had particularly high male-to-female incidence in larynx cancers (IRR: 8.199; 95% CI, 7.203-9.363; P < 0.001), relative to other races. Among primary brain tumors, germ cell tumors had the largest male-to-female incidence (IRR: 3.03; 95% CI, 2.798-3.284, P < 0.001). Conclusions: Overall, incidence and survival of cancer vary significantly by sex, with males generally having lower incidence and survival compared with females. Male-to-female incidence differences were also noted across race and age groups. These results provide strong evidence that the fundamental biology of sex differences affects cancers of all types. Impact: This study represents the most recent and comprehensive reporting of sex differences in cancer incidence and survival in the United States. Identifying disadvantaged groups is critical as it can provide useful information to improve cancer survival, as well as to better understand the etiology and pathogenesis of specific cancers. [ABSTRACT FROM AUTHOR]

Objectives: Air pollutants are known neurotoxicants. In this updated systematic review, we evaluate new evidence since our 2019 systematic review on the effect of outdoor air pollution exposure on childhood and adolescent brain structure and function as measured by magnetic resonance imaging (MRI)., Methods: Using PubMed and Web of Science, we conducted an updated literature search and systematic review of articles published through March 2024, using key terms for air pollution and functional and/or structural MRI. Two raters independently screened all articles using Covidence and implemented the risk of bias instrument for systematic reviews informing the World Health Organization Global Air Quality Guidelines., Results: We identified 222 relevant papers, and 14 new studies met our inclusion criteria. Including six studies from our 2019 review, the 20 publications to date include study populations from the United States, Netherlands, Spain, and United Kingdom. Studies investigated exposure periods spanning pregnancy through early adolescence, and estimated air pollutant exposure levels via personal monitoring, geospatial residential estimates, or school courtyard monitors. Brain MRI occurred when children were on average 6-14.7 years old; however, one study assessed newborns. Several MRI modalities were leveraged, including structural morphology, diffusion tensor imaging, restriction spectrum imaging, arterial spin labeling, magnetic resonance spectroscopy, as well as resting-state and task-based functional MRI. Air pollutants were associated with widespread brain differences, although the magnitude and direction of findings are largely inconsistent, making it difficult to draw strong conclusions., Conclusion: Prenatal and childhood exposure to outdoor air pollution is associated with structural and functional brain variations. Compared to our initial 2019 review, publications doubled-an increase that testifies to the importance of this public health issue. Further research is needed to clarify the effects of developmental timing, along with the downstream implications of outdoor air pollution exposure on children's cognitive and mental health., Competing Interests: Competing Interests The authors declare no competing interests.