Disparities in detection of suspected child abuse.

BACKGROUND: Child abuse is a significant cause of injury and death among children, but accurate identification is often challenging. This study aims to assess whether racial disparities exist in the identification of child abuse. METHODS: The 2010-2014 and 2016-2017 National Trauma Data Bank was queried for trauma patients ages 1-17. Using ICD-9CM and ICD-10CM codes, children with injuries consistent with child abuse were identified and analyzed by race. RESULTS: Between 2010-2014 and 2016-2017, 798,353 patients were included in NTDB. Suspected child abuse victims (SCA) accounted for 7903 (1%) patients. Of these, 51% were White, 33% Black, 1% Asian, 0.3% Native Hawaiian/Other Pacific Islander, 2% American Indian, and 12% other race. Black patients were disproportionately overrepresented, composing 12% of the US population, but 33% of SCA patients (p < 0.001). Although White SCA patients were more severely injured (ISS 16-24: 20% vs 16%, p < 0.01) and had higher in-hospital mortality (9% vs. 6%, p = 0.01), Black SCA patients were hospitalized longer (7.2 ± 31.4 vs. 6.2 ± 9.9 days, p < 0.01) despite controlling for ISS (1-15: 4. 5.7 ± 35.7 vs. 4.2 ± 6.2 days, p < 0.01). In multivariate regression, Black children continued to have longer lengths of stay despite controlling for ISS and insurance type. CONCLUSIONS: Utilizing a nationally representative dataset, Black children were disproportionately identified as potential victims of abuse. They were also subjected to longer hospitalizations, despite milder injuries. Further studies are needed to better understand the etiology of the observed trends and whether they reflect potential underlying unconscious or conscious biases of mandated reporters. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: III.

Does shock index, pediatric age-adjusted predict mortality by trauma center type?

BACKGROUND: Pediatric trauma patients are treated at adult trauma centers (ATCs), mixed pediatric and ATCs (MTC), or pediatric trauma centers (PTCs). Shock index, pediatric age-adjusted (SIPA) can prospectively identify severely injured children. This study characterized the differences in mortality and hospital length of stay (LOS) among pediatric trauma patients with elevated SIPA (eSIPA) at different trauma centers types. METHODS: Pediatric patients (1-14 years) were queried from the 2013 to 2016 National Trauma Data Bank. Patients with eSIPA were included for analysis. The primary outcome was mortality. Secondary outcomes included rates of splenectomy, computed tomography chest scans, laparotomy, and hospital LOS. Unadjusted frequencies and multivariable regression analyses were performed. An alpha level of 0.01 was used to determine significance. RESULTS: Out of 189,003 pediatric trauma patients, 15,832 were included for analysis. After controlling for age, race, sex, payment method, Injury Severity Score, Glasgow Coma Scale score, hospital teaching status, and number of hospital beds, there was no significant difference in mortality among eSIPA patients at ATCs (odds ratio [OR], 0.753; p = 0.078) and MTCs (OR, 1.051; p = 0.776) when compared with PTCs. This remained true even among the most severely injured eSIPA patients (Injury Severity Score > 25). Splenectomy rates were higher at ATCs (OR, 3.234; p = 0.005), as were computed tomography chest scan rates (ATC OR, 4.423; p < 0.001; MTC OR, 6.070; p < 0.001) than at PTCs. There was a trend toward higher splenectomy rates at MTCs (OR, 2.910; p = 0.030) compared with PTCs, but this did not reach statistical significance. Laparotomy rates and hospital LOS were not significantly different. CONCLUSION: Among eSIPA pediatric trauma patients, there was no difference in mortality between trauma center types. However, other secondary findings indicate that specialty care at PTCs may help optimize the care of pediatric trauma patients. LEVEL OF EVIDENCE: Retrospective cohort study, level IV.

Epigenetic Mechanisms Underlying Organic Solute Transporter ß Repression in Colorectal Cancer.

Colorectal cancer (CRC) is known to be the third most common cancer disease and the fourth-leading cause of cancer-related deaths worldwide. Bile acid, especially deoxycholic acid and lithocholic acid, were revealed to play an important role during carcinogenesis of CRC. In this study, we found organic solute transporter ß (OSTß), an important subunit of a bile acid export transporter OSTα-OSTß, was noticeably downregulated in CRC. The decline of OSTß expression in CRC was determined by Western blot and real-time polymerase chain reaction (RT-PCR), whereas chromatin immunoprecipitation (ChIP) was used to evaluate the histone acetylation state at the OSTß promoter region in vivo and in vitro. CRC cell lines HT29 and HCT15 were treated with trichostation A (TSA) for the subsequent determination, including RT-PCR, small interfering RNA (siRNA) knockdown, ChIP, and dual-luciferase reporter gene assay, to find out which histone acetyltransferases and deacetylases exactly participated in regulation. We demonstrated that after TSA treatment, OSTß expression increased noticeably because of upregulated H3K27Ac state at OSTß promoter region. We found that stimulating the expression of p300 with CTB (Cholera Toxin B subunit, an activator of p300) and inhibiting p300 expression with C646 (an inhibitor of p300) or siRNA designed for p300 could control OSTß expression through modulating H3K27Ac state at OSTß promoter region. Therefore, downregulated expression of p300 in CRC may cause low expression of OSTß in CRC via epigenetic regulation. Generally, we revealed a novel epigenetic mechanism underlying OSTß repression in CRC, hoping this mechanism would help us to understand and inhibit carcinogenesis of CRC. SIGNIFICANCE STATEMENT: Organic solute transporter ß (OSTß) expression is lower in colon cancer tissues compared with adjacent normal tissues. We revealed the epigenetic mechanisms of it and proved that p300 controls OSTß expression through modulating H3K27Ac state at OSTß promoter region and hence causes low expression of OSTß in colorectal cancer.

Inhibition of histone deacetylase 7 reverses concentrative nucleoside transporter 2 repression in colorectal cancer by up-regulating histone acetylation state.

BACKGROUND AND PURPOSE: The concentrative nucleoside transporter 2 (CNT2) mediates the uptake of both natural nucleosides and nucleoside-derived drugs. Therefore, it is important both physiologically and pharmacologically. However, CNT2 expression is significantly repressed in colorectal cancer (CRC). Here, we have elucidated the mechanism(s) underlying CNT2 repression in CRC. EXPERIMENTAL APPROACH: Repression of CNT2 in tumour samples from patients with CRC was identified using Western blot and RT-qPCR. The histone acetylation state at the CNT2 promoter region was then evaluated with chromatin immunoprecipitation and trichostatin A (TSA) treatment. To find the key enzyme responsible for hypoacetylation at the CNT2 promoter region, siRNA knockdown and RT-qPCR were used. Effects of combining HDAC inhibitors and cladribine were studied in HCT15 and HT29 cells. KEY RESULTS: Histone deacetylase 7 was significantly up-regulated in CRC, leading to histone hypoacetylation at the CNT2 promoter region, especially at sites H3K9Ac, H3K18Ac and H4Ac. This hypoacetylation condensed the chromatin structure and reduced CNT2 expression. All these effects were reversed by treatment with TSA, a histone deacetylase inhibitor. In HCT15 and HT29 cells, inhibition of histone deacetylase increased cell uptake and decreased IC50 for cladribine. CONCLUSIONS AND IMPLICATIONS: Histone hypoacetylation due to increased levels of histone deacetylase 7 results in CNT2 repression in CRC tumour tissue and could lead to decreased uptake of and consequent resistance to nucleoside anti-cancer agents. Such resistance could be overcome by combining inhibitors of histone deacetylase with the nucleoside anti-cancer agent.