In transplant, meaningful international comparisons in organ utilization are needed. This collaborative study between the United Kingdom (UK) and the United States (US) aimed to develop a kidney utilization metric allowing for legitimate intercountry comparisons.Data from the UK and US transplant registries, including all deceased donor kidneys recovered from 2006 to 2017, were analyzed. To identify a potentially comparable kidney utilization rate (UR), several denominators were assessed. We discovered that the proportion of transplanted kidneys from elderly donors in the UK (10.7%) was 18 times greater than that in the US (0.6%). Conversely, en bloc pediatric kidney transplant was more common in the US. Donation after circulatory death utilization has risen in both countries but is twice as prevalent in the UK (39% of transplants) vs the US (20%). In addition, US and UK URs are not directly comparable due to fundamental system differences. However, using a suite of URs revealed practice areas likely to yield the most benefit if improved, such as efforts to increase kidney offer acceptance in the US and to reduce postacceptance discard in the UK. Methods used in this study, including novel intracountry risk-adjusted UR trend logistic regression analyses, can be translated to other international transplant registries in pursuit of further global learning opportunities. K E Y W O R D S clinical research/practice, donors and donation: deceased, donors and donation: donation after brain death (DBD), donors and donation: donation after circulatory death (DCD), kidney transplantation/nephrology, United Network for Organ Sharing (UNOS) S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section.
Improved biomarkers are needed for prostate cancer, as the current gold standards have poor predictive value. Tests for circulating prostate-specific antigen (PSA) levels are susceptible to various noncancer comorbidities in the prostate and do not provide prognostic information, whereas physical biopsies are invasive, must be performed repeatedly, and only sample a fraction of the prostate. Injectable biosensors may provide a new paradigm for prostate cancer biomarkers by querying the status of the prostate via a noninvasive readout. Proteases are an important class of enzymes that play a role in every hallmark of cancer; their activities could be leveraged as biomarkers. We identified a panel of prostate cancer proteases through transcriptomic and proteomic analysis. Using this panel, we developed a nanosensor library that measures protease activity in vitro using fluorescence and in vivo using urinary readouts. In xenograft mouse models, we applied this nanosensor library to classify aggressive prostate cancer and to select predictive substrates. Last, we coformulated a subset of nanosensors with integrin-targeting ligands to increase sensitivity. These targeted nanosensors robustly classified prostate cancer aggressiveness and outperformed PSA. This activity-based nanosensor library could be useful throughout clinical management of prostate cancer, with both diagnostic and prognostic utility.
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