COVID-19 hospitalization rate in children across a private hospital network in the United States: COVID-19 hospitalization rate in children.

OBJECTIVES: There are limited studies with varying results evaluating the rate of hospitalizations of pediatric patients tested for COVID-19 in the United States. More information in the pediatric COVID-19 literature is needed. The objective of this study was to describe the rates of positive tests, hospitalization, severe disease, and mortality for COVID-19 in children. MATERIAL AND METHODS: We performed a retrospective analysis of data collected from a data warehouse from 184 hospitals across the United States. All cases of pediatric patients who were tested for COVID-19 were analyzed for test positivity, hospitalization, severe disease, and mortality. A separate subgroup analysis for ages < 1 year, 1-4 years, 5-8 years, 9-14 years, and 15-17 years was performed. RESULTS: Of 24,781 patient encounters, we found a test positivity rate of 11.15% (95% CI: 10.76-11.55). There were 142 admissions out of the 2,709 symptomatic patients, 5.24% (95% CI: 4.43-6.15) admission rate. Of those admitted, we found that 54.93% (78/142) were admitted to the PICU, but only 22 of the 142 admissions, 15.49% (95% CI: 9.97-22.51), were determined to have severe COVID-19 disease. One patient died during the study period giving an overall pediatric mortality rate of 0.04% (95% CI: 0.00-0.21). CONCLUSION: In our sample, we found a test positivity rate of 11.15%. We also report a 5.24% hospitalization rate with 15.49% of admitted patients with severe disease. Lastly, we also report a very low mortality rate of 0.04% of all patients who tested positive for COVID-19.

Differential Contribution of Pancreatic Fibroblast Subsets to the Pancreatic Cancer Stroma.

BACKGROUND & AIMS: Although the healthy pancreas consists mostly of epithelial cells, pancreatic cancer and the precursor lesions known as pancreatic intraepithelial neoplasia, are characterized by an extensive accumulation of fibroinflammatory stroma that includes a substantial and heterogeneous fibroblast population. The cellular origin of fibroblasts within the stroma has not been determined. Here, we show that the Gli1 and Hoxb6 markers label distinct fibroblast populations in the healthy mouse pancreas. We then set out to determine whether these distinct fibroblast populations expanded during carcinogenesis. METHODS: We developed genetically engineered models using a dual-recombinase approach that allowed us to induce pancreatic cancer formation through codon-optimized Flp recombinase-driven epithelial recombination of Kirsten rat sarcoma viral oncogene homolog while labeling Gli1+ or Hoxb6+ fibroblasts in an inducible manner. By using these models, we lineage-traced these 2 fibroblast populations during the process of carcinogenesis. RESULTS: Although in the healthy pancreas Gli1+ fibroblasts and Hoxb6+ fibroblasts are present in similar numbers, they contribute differently to the stroma in carcinogenesis. Namely, Gli1+ fibroblasts expand dramatically, whereas Hoxb6+ cells do not. CONCLUSIONS: Fibroblasts present in the healthy pancreas expand during carcinogenesis, but with a different prevalence for different subtypes. Here, we compared Gli1+ and Hoxb6+ fibroblasts and found only Gli1+ expanded to contribute to the stroma during pancreatic carcinogenesis.

Pancreatic HIF2α Stabilization Leads to Chronic Pancreatitis and Predisposes to Mucinous Cystic Neoplasm.

BACKGROUND & AIMS: Tissue hypoxia controls cell differentiation in the embryonic pancreas, and promotes tumor growth in pancreatic cancer. The cellular response to hypoxia is controlled by the hypoxia-inducible factor (HIF) proteins, including HIF2α. Previous studies of HIF action in the pancreas have relied on loss-of-function mouse models, and the effects of HIF2α expression in the pancreas have remained undefined. METHODS: We developed several transgenic mouse models based on the expression of an oxygen-stable form of HIF2α, or indirect stabilization of HIF proteins though deletion of von Hippel-Lindau, thus preventing HIF degradation. Furthermore, we crossed both sets of animals into mice expressing oncogenic KrasG12D in the pancreas. RESULTS: We show that HIF2α is not expressed in the normal human pancreas, however, it is up-regulated in human chronic pancreatitis. Deletion of von Hippel-Lindau or stabilization of HIF2α in mouse pancreata led to the development of chronic pancreatitis. Importantly, pancreatic HIF1α stabilization did not disrupt the pancreatic parenchyma, indicating that the chronic pancreatitis phenotype is specific to HIF2α. In the presence of oncogenic Kras, HIF2α stabilization drove the formation of cysts resembling mucinous cystic neoplasm (MCN) in humans. Mechanistically, we show that the pancreatitis phenotype is linked to expression of multiple inflammatory cytokines and activation of the unfolded protein response. Conversely, MCN formation is linked to activation of Wnt signaling, a feature of human MCN. CONCLUSIONS: We show that pancreatic HIF2α stabilization disrupts pancreatic homeostasis, leading to chronic pancreatitis, and, in the context of oncogenic Kras, MCN formation. These findings provide new mouse models of both chronic pancreatitis and MCN, as well as illustrate the importance of hypoxia signaling in the pancreas.

Comparison of ultrasound-measured properties of the common carotid artery to tobacco smoke exposure in a cohort of Indonesian patients.

BACKGROUND: The purpose of this study was to use point-of-care ultrasound (POCUS) to investigate the relationship between tobacco smoke exposure and the characteristics of the common carotid artery (CCA). The effect of both primary and secondary smoking on CCA properties was evaluated. METHODS: We performed a prospective cross-sectional study across 20 primary care clinics in Bandung, West Java, Indonesia in July 2016. Point of care ultrasound was performed on a convenience sample of Indonesian patients presenting to clinic. The CCA wall stiffness and carotid intima-media thickness (CIMT) were measured during diastole and systole. These measurements were correlated with smoke exposure and cardiovascular disease. RESULTS: We enrolled 663 patients in the study, with 426 patients enrolled in the smoking category and 237 patients enrolled in the second-hand smoke category. There was an overall positive correlation with the measured lifestyle factors and the ultrasound-measured variables in the group of individuals who smoked. For all variables, age seemed to contribute the most out of all of the lifestyle factors for the positive changes in CIMT and CCA wall stiffness. CONCLUSION: Our data yielded correlations between CCA properties and cardiovascular risk, as well as between CIMT and arterial stiffness. We were also able to demonstrate an increase in thickness of the CIMT in patients who have been exposed by tobacco through the use of ultrasound. Further large scale studies comparing patients with multiple cardiac risk factors need to be performed to confirm the utility of ultrasound findings of cardiovascular disease and stroke.