Global Kidney Exchange: Analysis and Background Papers from the Perspective of the Right to Health

Global Kidney Exchange (GKE) is a program aimed at facilitating trans-national kidney donation. Although its proponents aim at reducing the unmet demand of kidneys in the United States through the trans-nationalization of kidney exchange programs, the World Health Organization (WHO) and The Transplantation Society (TTS) have expressed concerns about its potential effect on black markets of organs and transnational organ trafficking, as well as on low- or middle-income countries health systems. For GKE to be implemented, it would need to be permitted to operate in at least some low- or middle-income countries. What are the right to health implications of GKE’s implementation? With the aim of answering this question, the eighteen University of Denver students in the First Year Seminar course I taught in autumn 2017 with the title “The Right to Health in Theory and Practice”, identified and researched the different aspects that would affect this issue, and produced the analysis we present in this report. Based on our analysis, the potential right to health implications of GKE are: First, the program may improve timely access to organ donation primarily to patients with health insurance in the United States. Second, a large-scale implementation of the program may have a positive impact on health costs savings, which potentially could benefit the United States health system. Third, on a global health level, the program relies on existing health inequalities among countries in terms of funding, human resources, and health system strengthening, and it is likely to exacerbate those inequalities. Fourth, the program has the potential of negatively affecting the efforts that low- and middle-income countries are already doing to address end-stage renal failure, including the improvement of their own organ donation systems. Finally, given what we have learned about the current situation of organ trafficking, it is easy to think that GKE would unintentionally end up being linked to chains of organ trade. The only way how a program like GKE could have a positive impact from a right to health perspective is if it establishes local partnerships that have the effect of decreasing health inequalities. Additionally, we identified some issues of concern that are beyond the level of influence of local authorities: the unmet demand of kidneys in high-income countries is a reality that incentivizes organ trade and transplant tourism, and this is a problem in need of solutions; transnational organ trafficking as well as human trafficking with the purpose of organ donation are problems that need more visibility; for a global exchange of organs to be implemented, it would need to rely on supranational or transnational regulation and oversight; and the global epidemic of chronic kidney disease needs to be addressed through a public health perspective that emphasizes prevention

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Holographic Cell Differentiation in Mixed-Species Populations

Survival rates for most cancers have increased steadily over the past few decades as new technologies have led to better treatment outcomes. However, this process often relies heavily on the detection of cancer in its earliest stages, before symptoms occur or a tumor is visible in a CT or MR image. This is particularly true for diseases such as pancreatic cancer that exhibit almost no symptoms until very late stages and have extremely low survival rates as a result. Even some commonly treatable diseases, such as breast cancer, become far more problematic in later stages. As such, any efforts to improve cancer treatment further will inevitably require the detection of so-called micro-cancer, small clusters of cancer cells that are often manifest as metastatic circulating tumor cells (CTCs). Fortunately, cancerous cells typically exhibit a morphology that is highly distinct from healthy cells, allowing their detection using visible and infrared light that interacts strongly with objects on the scale of a few microns (due to a wavelength of ~500-900 nm)

Community Visioning for Marysville, Kansas: A three-part study comprised of a housing conditions inventory, city-wide brownfield redevelopment concepts, and ideas for transforming the Union Pacific Depot site into a regional destination

The Marysville Chamber of Commerce and Visitor’s Center and the City of Marysville collaborated with Kansas State University’s Department of Landscape Architecture and Regional & Community Planning (LARCP) and K-State’s Technical Assistance to Brownfields (TAB) for the spring and fall semesters in 2019. The intent of the collaboration was threefold: to document housing assets in the community, generate a set of strategic urban design ideas, and develop site planning alternatives for the Union Pacific Depot brownfield site. The effort was co-led by Associate Professor Blake Belanger and Assistant Professor Susmita Rishi. Professor Rishi and her students conducted a housing conditions inventory as part of PLAN650 Housing and Development Programs in the spring semester of 2019. She directed a different group of students to develop a set of urban design strategies in the fall semester of 2019 in PLAN640 Urban Design and Development Seminar. Also, during fall 2019, Professor Belanger led a group of students in LAR442 Site Research and Design Studio to develop design alternatives for the historic Union Pacific Train Depot site and adjacent parcels. Students shared their findings of PLAN640 and LAR442 in a public exhibit and open house on November 6, 2019. The agreement was mutually beneficial. Marysville leaders and decision-makers received fresh ideas, and students had the opportunity to work with external collaborators on a community engagement project. The City of Marysville funded the housing inventory during Phase 1 of the project and K-State TAB funded Phase 2 through an Environmental Protection Agency (EPA) Small Community Technical Assistance Grant (SCTAG) from the Kansas Department of Health and Environment (KDHE). In addition to the student work, Sustainable Strategies DC prepared a Resource Roadmap and TAB provided a summary of the November 6, 2019 public open house. In total, the contributors included 2 professors, 57 students, and 2 professionals

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure.People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window).Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p Background Methods Findings Interpretation Funding</p