Reduced Number of Pediatric Orthopedic Trauma Requiring Operative Treatment during COVID-19 Restrictions: A Nationwide Cohort Study

Background and Aims:The coronavirus outbreak significantly changed the need of healthcare services. We hypothesized that the COVID-19 pandemic decreased the frequency of pediatric fracture operations. We also hypothesized that the frequency of emergency pediatric surgical operations decreased as well, as a result of patient-related reasons, such as neglecting or underestimating the symptoms, to avoid hospital admission.Materials and Methods:Nationwide data were individually collected and analyzed in all five tertiary pediatric surgical/trauma centers in Finland. Operations related to fractures, appendicitis, and acute scrotum in children aged above 16 years between March 1 and May 31 from 2017 to 2020 were identified. The monthly frequencies of operations and type of traumas were compared between prepandemic 3 years and 2020.Results:Altogether, 1755 patients were identified in five tertiary hospitals who had an emergency operation during the investigation period. There was a significant decrease (31%, p = 0.03) in trauma operations. It was mostly due to reduction in lower limb trauma operations (32%, p = 0.006). Daycare, school, and organized sports-related injuries decreased significantly during the pandemic. These reductions were observed in March and in April. The frequencies of appendectomies and scrotal explorations remained constant.Conclusion:According to the postulation, a great decrease in the need of trauma operations was observed during the peak of COVID-19 pandemic. In the future, in case similar public restrictions are ordered, the spared resources could be deployed to other clinical areas. However, the need of pediatric surgical emergencies held stable during the COVID-19 restrictions

Lysophosphatidic acid and sphingosine-1-phosphate promote morphogenesis and block invasion of prostate cancer cells in three-dimensional organotypic models

Normal prostate and some malignant prostate cancer (PrCa) cell lines undergo acinar differentiation and form spheroids in three-dimensional (3-D) organotypic culture. Acini formed by PC-3 and PC-3M, less pronounced also in other PrCa cell lines, spontaneously undergo an invasive switch, leading to the disintegration of epithelial structures and the basal lamina, and formation of invadopodia. This demonstrates the highly dynamic nature of epithelial plasticity, balancing epithelial-to-mesenchymal transition against metastable acinar differentiation. This study assessed the role of lipid metabolites on epithelial maturation. PC-3 cells completely failed to form acinar structures in delipidated serum. Adding back lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) rescued acinar morphogenesis and repressed invasion effectively. Blocking LPA receptor 1 (LPAR1) functions by siRNA (small interference RNA) or the specific LPAR1 inhibitor Ki16425 promoted invasion, while silencing of other G-protein-coupled receptors responsive to LPA or S1P mainly caused growth arrest or had no effects. The G-proteins Gα12/13 and Gαi were identified as key mediators of LPA signalling via stimulation of RhoA and Rho kinases ROCK1 and 2, activating Rac1, while inhibition of adenylate cyclase and accumulation of cAMP may be secondary. Interfering with these pathways specifically impeded epithelial polarization in transformed cells. In contrast, blocking the same pathways in non-transformed, normal cells promoted differentiation. We conclude that LPA and LPAR1 effectively promote epithelial maturation and block invasion of PrCa cells in 3-D culture. The analysis of clinical transcriptome data confirmed reduced expression of LPAR1 in a subset of PrCa's. Our study demonstrates a metastasis-suppressor function for LPAR1 and Gα12/13 signalling, regulating cell motility and invasion versus epithelial maturation

Unexpected actions of vitamin D:new perspectives on the regulation of innate and adaptive immunity

Knowledge about the ability of vitamin D to function outside its established role in skeletal homeostasis is not a new phenomenon. Nonclassical immunomodulatory and antiproliferative responses triggered by active 1,25-dihydroxyvitamin D were first reported more than a quarter of a century ago. It is only in recent years, however, that there has been a significant improvement in our understanding of how these nonclassical effects of vitamin D can influence the pathophysiology and possible prevention of human disease. Three particular strands of evidence have been prominent: firstly, population studies have revised our interpretation of normal vitamin D status in humans, suggesting, in turn, that vitamin D insufficiency is a clinical problem of global proportions; secondly, epidemiology has linked vitamin D status with disease susceptibility and/or mortality; and, thirdly, expression of the machinery required to synthesize 1,25-dihydroxyvitamin D in normal human tissue seems to be much more widespread than originally thought. Collectively, these observations suggest that nonclassical metabolism and response to vitamin D might have a significant role in human physiology beyond skeletal and calcium homeostasis. Specific examples of this will be detailed in the current Review, with particular emphasis on the immunomodulatory properties of vitamin D