Association between preoperative respiratory symptoms and perioperative respiratory adverse events in pediatric patients with positive viral testing.

STUDY OBJECTIVE: To determine the association between the presence of upper respiratory tract viral infection symptoms and occurrence of perioperative respiratory adverse events (PRAE) in children with positive viral screening, and to analyze the risk of PRAE in children with SARS-CoV-2 compared to non-SARS-CoV-2 infection. DESIGN: A prospective cohort study. SETTING: A tertiary, freestanding pediatric hospital in Dallas, Texas. PATIENTS: Children <18 years of age with positive respiratory viral testing who underwent general anesthesia. INTERVENTION: Measurement of incidence of PRAE and severe adverse events during the first 7 postoperative days. MEASUREMENTS: The primary outcome was a composite of PRAE: oxygen saturation < 90% for >5 min, supplemental oxygen for >2 h after anesthesia, laryngospasm, and bronchospasm. The secondary outcome was severe adverse events: high flow nasal cannula >6 l of oxygen per minute, admission to the ICU for escalation of respiratory support post-anesthetic, acute respiratory distress syndrome, postoperative pneumonia, cardiovascular arrest, extracorporeal life support, and death. MAIN RESULTS: In this convenience sample of 196 children, 83 were symptomatic and 113 were asymptomatic. The risk of PRAE was similar in children with active viral symptoms and asymptomatic children (risk difference: -1.9%; 95% CI: -10.9, 7.9%), but higher among children with documented fever within 48 h of the anesthetic (risk difference: 20.8%; 95% CI: 5.3, 39.7%). The multivariable adjusted odds ratio of PRAE was 0.68 (95% CI: 0.25, 1.85) for symptomatic compared to asymptomatic patients, and 0.46 (95% CI: 0.14, 1.44) for patients with SARS-CoV-2 compared to non-SARS-CoV-2 infection. CONCLUSIONS: There was no significant difference in the incidence of PRAE between symptomatic and asymptomatic children with laboratory confirmed viral respiratory infection, and between children with the Omicron variant of SARS-CoV-2 compared to non-SARS-CoV-2 respiratory viruses. However, the risk was increased in children with recent fever.

DNMT1-associated long non-coding RNAs regulate global gene expression and DNA methylation in colon cancer.

The cancer epigenome exhibits global loss of DNA methylation, which contributes to genomic instability and aberrant gene expression by mechanisms that are yet to be fully elucidated. We previously discovered over 3300 long non-coding (lnc)RNAs in human cells and demonstrated that specific lncRNAs regulate gene expression via interactions with chromatin-modifying complexes. Here, we tested whether lncRNAs could also associate with DNA methyltransferases to regulate DNA methylation and gene expression. Using RIP-seq, we identified a subset of lncRNAs that interact with the DNA methyltransferase DNMT1 in a colon cancer cell line, HCT116. One lncRNA, TCONS_00023265, which we named DACOR1 (DNMT1-associated Colon Cancer Repressed lncRNA 1), shows high, tissue-specific expression in the normal colon (including colon crypts) but was repressed in a panel of colon tumors and patient-derived colon cancer cell lines. We identified the genomic occupancy sites of DACOR1, which we found to significantly overlap with known differentially methylated regions (DMRs) in colon tumors. Induction of DACOR1 in colon cancer cell lines significantly reduced their ability to form colonies in vitro, suggesting a growth suppressor function. Consistent with the observed phenotype, induction of DACOR1 led to the activation of tumor-suppressor pathways and attenuation of cancer-associated metabolic pathways. Notably, DACOR1 induction resulted in down-regulation of Cystathionine ß-synthase, which is known to lead to increased levels of S-adenosyl methionine-the key methyl donor for DNA methylation. Collectively, our results demonstrate that deregulation of DNMT1-associated lncRNAs contributes to aberrant DNA methylation and gene expression during colon tumorigenesis.