The term vasculogenic mimicry (VM) refers to the capacity of certain cancer cells to form fluid-conducting structures within a tumor in an endothelial cell (EC)-free manner. Ever since its first report by Maniotis in 1999, the existence of VM has been an extremely contentious issue. The overwhelming consensus of the literature suggests that VM is frequently observed in highly aggressive tumors and correlates to lower patient survival. While the presence of VM in vivo in animal and patient tumors are claimed upon the strong positive staining for glycoproteins (Periodic Acid Schiff, PAS), it is by no means universally accepted. More controversial still is the existence of an in vitro model of VM that principally divides the scientific community. Original reports demonstrated that channels or tubes occur in cancer cell monolayers in vitro when cultured in matrigel and that these structures may support fluid movement. However, several years later many papers emerged stating that connections formed between cancer cells grown on matrigel represented VM. We speculate that this became accepted by the cancer research community and now the vast majority of the scientific literature reports both presence and mechanisms of VM based on intercellular connections, not the presence of fluid conducting tubes. In this opinion paper, we call upon evidence from an exhaustive review of the literature and original data to argue that the majority of in vitro studies presented as VM do not correspond to this phenomenon. Furthermore, we raise doubts on the validity of concluding the presence of VM in patient samples and animal models based solely on the presence of PAS+ staining. We outline the requirement for new biomarkers of VM and present criteria by which VM should be defined in vitro and in vivo .

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Introduction The need for beds and health personnel to treat coronavirus (COVID- 19) patients has led to the suspension of many elective sur-geries in Chile, including knee arthroplasties. This study aims to determine the incidence of knee arthroplasty in 2020, reflecting the effect of the COVID- 19 pandemic, and estimate the cost and time it would take to recover the waiting list prior to March 2020. Methods A cross- sectional study was designed. We analyzed databases from The Department of Statistics and Health Information databases from Chile for 2019 and 2020, identifying patients with surgical discharges associated with knee arthroplasty codes. We estimated the time it would take to recover the surgeries unperformed in 2020 by simulating a monthly workload increase from the 2019 baseline. The costs of knee arthroplasty paid by the National Health Fund to institutions were estimated by diagnosis-related groups. Results We found that the incidence rate of knee arthroplasty in 2020 decreased by 64% compared with 2019. The impact was higher in the public system (68%) and the National Health Found (63%). A simulated increase in knee arthroplasty productivity by 30% would allow recovering the postponed knee arthroplasty surgeries in 27 months, at a monthly cost to the public system of 318 million Chilean pesos (378 thousand US dollars). Conclusions The incidence rate of knee arthroplasty during 2020 decreased by 64%, revealing the extensive waiting line for people with knee osteoarthritis. An increase between 20- 40% in productivity compared with 2019 would allow recovering the unperformed surgeries in 20 to 41 months, at a monthly cost to the public network between 210 and 425 million Chilean pesos (250 to 506 thousand US dollars).

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