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Introduction: Hundreds of children suffer burn injuries each day, yet care guidelines regarding the need for acute inpatient treatment vs outpatient follow-up vs no required follow-up remain nebulous. This gap in the literature is particularly salient for the emergency clinician, who must be able to rapidly determine appropriate disposition.Methods: This was a retrospective review of patients presenting to a Level II pediatric trauma center, January 1, 2017–December 31, 2019, and discharged with an International Classification of Diseases, Rev 10, burn diagnosis. We obtained and analyzed demographics, burn characteristics, and follow-up data using univariate and bivariate analysis as well as logistic regression modeling. Patients were stratified into three outcome groups: group 1—patients who underwent emergent evaluation at a burn center or were admitted at their first follow-up appointment; group 2—patients who followed up at a burn center (as an outpatient) or at the emergency department (and were discharged home); and group 3—patients with no known follow-up.Results: A total of 572 patients were included in this study; 58.9% of patients were 1–5 years of age. Sixty-five patients met group 1 criteria, 189 patients met group 2 criteria, and 318 patients met group 3 criteria. Sixty-five percent of patients met at least one American Burn Association criteria, and 79% of all burns were second-degree burns. Flame and scald burns were associated with increased odds (odds ratio [OR] 1.21,O1.12) of group 1 vs group 2 + group 3 (P = 0.02, P < 0.001). Second/third-degree burns and concern for non-accidental trauma were also associated with increased odds of group 1 vs 2 or 3 (OR = 1.11, 1.35, P ≤ 0.001, 0.001, respectively). Scald burns were associated with increased odds of group 2 compared to group 3 (OR 1.11, P = 0.04). Second/third degree burns were also associated with increased odds of group 2 vs 3 (OR 1.19, P ≤ 0.001).Conclusion: There were few statistically significant variables strongly associated with group 1 (emergent treatment/admission) vs group 2 (follow-up/outpatient treatment) vs group 3 (no follow- up). However, one notable finding in this study was the association of scald burns with treatment (admission or follow-up) suggesting that the presence of a scald burn in a child may signify to clinicians that a burn center consult is warranted.

Abstract: The stroma that surrounds the tumor in many solid cancers exhibits potent immunosuppressive activity to promote tumor progression and confer resistance to immune-based therapies. Cancer associated fibroblasts (CAFs) encompassing functionally distinct populations are key components of the stroma that are emerging as a key cell type in regulating an immune response. However, the mechanisms by which CAFs can directly suppress the immune activity to promote tumor growth is not clear. Here, we identify that a subset of CAF in both rodent and human stromagenic cancers that displays characteristics of senescent fibroblasts and referred to as sCAFs. We show that sCAFs secrete a decoy protein that interferes with cytotoxic activity of activated T effector (Teff) cells. In mouse models for stroma-rich pancreatic cancer, administration of an antibody that blocked the decoy protein resulted in recalibration of the stromal fibroblast by promoted the formation of interferon-licensed-fibroblast cells at the expense of sCAFs. This switch not only enhanced infiltration of tumor-infiltrating T cells but also alleviated their direct suppression resulting in enhanced effector function and tumor regression. Collectively, these results point to the potent immunosuppressive activity of sCAFs mediated by decoy protein as a mechanism by which stroma can promote tumor progression. As stromagenic-cancers are resistance to current therapies, the development of treatments involving blocking of decoy protein may inhibit tumor growth and improve patient survival. Citation Format: Yao Wang, Hara Apostolopoulou, Arjun Sanyal, Hong Sun, Cynthia Sieland, Kavya Gupta, Jiayu Ye, David Gibbs, Paul Wong, Ntranos Vasilis, Sui Huang, James Gardner, Ajay Maker, Thea Tlsty, Anil Bhushan, Tamara Alliston. Restoration of T effector cells function by targeting senescent cancer-associated fibroblast in tumor microenvironment of stroma-rich cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C036.

BACKGROUND: It is unclear whether genetic variants affecting vitamin D metabolism are associated with melanoma prognosis. Two functional missense variants in the vitamin D-binding protein gene (GC), rs7041 and rs4588, determine 3 common haplotypes, Gc1s, Gc1f, and Gc2, of which Gc1f may be associated with decreased all-cause death among melanoma patients based on results of a prior study, but the association of Gc1f with melanoma-specific death is unclear. METHODS: We investigated the association of the Gc1s, Gc1f, and Gc2 haplotypes with melanoma-specific and all-cause death among 4490 individuals with incident, invasive primary melanoma in 2 population-based studies using multivariable Cox-proportional hazards regression. RESULTS: In the pooled analysis of both datasets, the patients with the Gc1f haplotype had a 37% lower risk of melanoma-specific death than the patients without Gc1f (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.47 to 0.83, P = .001), with adjustments for age, sex, study center, first- or higher-order primary melanoma, tumor site, pigmentary phenotypes, and Breslow thickness. Associations were similar in both studies. In pooled analyses stratified by Breslow thickness, the corresponding melanoma-specific death HRs for those patients with the Gc1f haplotype compared with those without Gc1f were 0.89 (95% CI = 0.63 to 1.27) among participants with tumor Breslow thickness equal to or less than 2.0 mm and 0.40 (95% CI = 0.25 to 0.63) among participants with tumor Breslow thickness greater than 2.0 mm (Pinteraction = .003). CONCLUSIONS: Our findings suggest that individuals with the GC haplotype Gc1f may have a lower risk of dying from melanoma-specifically from thicker, higher-risk melanoma-than individuals without this Gc1f haplotype.

PURPOSE: Electric bicycles (e-bikes) achieve higher speeds than pedal bicycles, but few studies have investigated the impact on injury rates specific to the pediatric population. Utilizing the National Electronic Injury Surveillance System (NEISS), we compared rates of pediatric injury for e-bikes, bicycles, and gas-engine bicycles (mopeds) from 2011 to 2020. METHODS: Descriptive and bivariate inferential analyses were performed upon NEISS estimates of e-bike, bicycle, and moped injuries in children aged 2-18 years. Analyses were stratified by patient age and helmet usage. The Mann-Kendall test of trends was used. RESULTS: We identified 3945 e-bike, 23,389 moped, and 2.05 million bicycle injuries. Over time, the incidence of injury increased for e-bikes (Kendalls τ=0.73, p = 0.004), decreased for pedal bicycles (Kendalls τ= - 0.91, p = 0.0003), and did not change for mopeds (Kendalls τ = 0.06, p = 0.85). Males accounted for 82.5 % of e-bike injuries. The age group most commonly affected by e-bike injury (44.3 %) was 10-13 years old. The proportion of injuries requiring hospitalization was significantly higher for e-bikes (11.5 %), compared to moped and bicycle (7.0 and 4.8 %, respectively, p

Background & aimsElements of field cancerization, including atrophic gastritis, metaplasia, and dysplasia, promote gastric cancer development in association with chronic inflammation. However, it remains unclear how stroma changes during carcinogenesis and how the stroma contributes to progression of gastric preneoplasia. Here we investigated heterogeneity of fibroblasts, one of the most important elements in the stroma, and their roles in neoplastic transformation of metaplasia.MethodsWe used single-cell transcriptomics to evaluate the cellular heterogeneity of mucosal cells from patients with gastric cancer. Tissue sections from the same cohort and tissue microarrays were used to identify the geographical distribution of distinct fibroblast subsets. We further evaluated the role of fibroblasts from pathologic mucosa in dysplastic progression of metaplastic cells using patient-derived metaplastic gastroids and fibroblasts.ResultsWe identified 4 subsets of fibroblasts within stromal cells defined by the differential expression of PDGFRA, FBLN2, ACTA2, or PDGFRB. Each subset was distributed distinctively throughout stomach tissues with different proportions at each pathologic stage. The PDGFRα+ subset expanded in metaplasia and cancer compared with normal, maintaining a close proximity with the epithelial compartment. Co-culture of metaplasia- or cancer-derived fibroblasts with gastroids showing the characteristics of spasmolytic polypeptide-expressing metaplasia-induced disordered growth, loss of metaplastic markers, and increases in markers of dysplasia. Culture of metaplastic gastroids with conditioned media from metaplasia- or cancer-derived fibroblasts also promoted dysplastic transition.ConclusionsThese findings indicate that fibroblast associations with metaplastic epithelial cells can facilitate direct transition of metaplastic spasmolytic polypeptide-expressing metaplasia cell lineages into dysplastic lineages.

Esophageal adenocarcinoma arises from Barrett's esophagus, a precancerous metaplastic replacement of squamous by columnar epithelium in response to chronic inflammation. Multi-omics profiling, integrating single-cell transcriptomics, extracellular matrix proteomics, tissue-mechanics and spatial proteomics of 64 samples from 12 patients' paths of progression from squamous epithelium through metaplasia, dysplasia to adenocarcinoma, revealed shared and patient-specific progression characteristics. The classic metaplastic replacement of epithelial cells was paralleled by metaplastic changes in stromal cells, ECM and tissue stiffness. Strikingly, this change in tissue state at metaplasia was already accompanied by appearance of fibroblasts with characteristics of carcinoma-associated fibroblasts and of an NK cell-associated immunosuppressive microenvironment. Thus, Barrett's esophagus progresses as a coordinated multi-component system, supporting treatment paradigms that go beyond targeting cancerous cells to incorporating stromal reprogramming.

The demand for high-resolution imaging, and high sample throughputs in LA-ICP-MS experiments has led to developing rapid-response ablation cells with low dispersion. These cells can achieve short transient signals called single pulse responses (SPRs), whose width is in the single-digit millisecond range at 1% of the maximum. However, coupled with ICP-Q-MS, recording those short signals poses a problem due to the sequential measurement of selected m/z ratios. If more than one m/z ratio is targeted, the time resolution of quadrupole detection systems is insufficient for accurately determining short SPRs. This work focuses on utilizing rapid response ablation cells for the analysis of multiple elements with quadrupole-based detection systems in the SPR mode. To achieve this, an ArF-excimer laser equipped with a rapid-response ablation chamber is coupled to an ICP-MS with a short settling time of 0.2 ms and below. The two naturally occurring Ag-isotopes were analyzed in the NIST SRM 612 to optimize the dwell times for ideal data acquisition. The data shows that the ratio of the dwell time and the settling time, plays a crucial role. With the optimized parameters, the natural ratio of 107Ag and 109Ag within a 10 ms FW0.01M transient signal could be determined. This concept of LA-ICP-MS was then applied for depth profiling analysis of Al-doped SiC, a wide bandgap semiconductor. This procedure acquired depth profiles on 30 different sample locations in approximately 2 minutes with an exceptional depth resolution of 55 nm. [ABSTRACT FROM AUTHOR]