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

Acute Lymphoblastic Leukemia in Children and Adults: A Review of the Differences in Biology, Treatment, and Prognosis

This paper analyzes the difference between Acute Lymphoblastic Leukemia (ALL) in adults and children. Specifically, it discusses the biological differences in cancer subtypes seen between these two groups, how they affect the possible treatment options, and how these differences play a role in the disparity in prognostic outcomes. In addition, this paper also examines how the age differences play a role in risk management for Acute Lymphoblastic Leukemia

A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children.

BACKGROUND: The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)ssaV(-)) ZH9 with two independently attenuating deletions. Studies in healthy adults demonstrated immunogenicity and an acceptable safety profile. OBJECTIVES: We conducted a randomised placebo controlled, single-blind trial to evaluate the safety and immunogenicity of M01ZH09 in healthy Vietnamese children aged 5 to 14 years. METHODS: Subjects were randomly assigned to receive either a nominal dose of 5x10(9) CFU of M01ZH09 or placebo and were followed up for 28 days. The primary safety outcome was the proportion of subjects with any adverse event attributed to M01ZH09. The primary immunogenicity endpoint was the proportion of subjects who showed a positive immune response to M01ZH09 in the Salmonella Typhi lipopolysaccharide (LPS) specific serum IgA and IgG ELISA. PRINCIPAL FINDINGS: One hundred and fifty-one children were enrolled, 101 subjects received M01ZH09 and 50 subjects received placebo. An intention to treat analysis was conducted. There were no serious adverse events and no bacteraemias. In the M01ZH09 group, 26 (26%; 95% CI, 18-5%) of 101 subjects experienced adverse events compared to 11 (22%; 95% CI, 12-36%) of 50 subjects in the placebo group (odds ratio (OR) [95%CI] = 1.23 [0.550-2.747]; p = 0.691). Faecal shedding of S. Typhi (Ty2 aroC(-)ssaV(-)) ZH9 was detected in 51 (51%; 95% CI, 41-61%) of 100 M01ZH09 subjects. No shedding was detected beyond day 3. A positive immune response, defined as 70% increase (1.7 fold change) in LPS specific serum IgG (day 14 or 28) and/or 50% increase (1.5 fold change) in LPS specific serum IgA (day 7 or 14) from baseline was detected in 98 (97%; 95% CI, 92-99%) of 101 M01ZH09 recipients and 8 (16%; 95% CI, 7-29%) of 50 placebo recipients. Twenty-eight (100%; 95% CI, 88-100%) of 28 vaccine recipients who were evaluated in the LPS specific IgA ELISPOT assay showed a positive response compared to none of the 14 placebo recipients tested. CONCLUSIONS: This was the first phase II trial of a novel oral candidate typhoid vaccine in children in an endemic country. M01ZH09 had an appropriate safety profile and was immunogenic in children. TRIAL REGISTRATION: Controlled-trials.com ISRCTN91111837

Positron emission tomography and functional characterization of a complete ​PBR/​TSPO knockout

The evolutionarily conserved peripheral benzodiazepine receptor (PBR), or 18-kDa translocator protein (TSPO), is thought to be essential for cholesterol transport and steroidogenesis, and thus life. TSPO has been proposed as a biomarker of neuroinflammation and a new drug target in neurological diseases ranging from Alzheimer’s disease to anxiety. Here we show that global C57BL/6-Tspotm1GuWu(GuwiyangWurra)-knockout mice are viable with normal growth, lifespan, cholesterol transport, blood pregnenolone concentration, protoporphyrin IX metabolism, fertility and behaviour. However, while the activation of microglia after neuronal injury appears to be unimpaired, microglia from GuwiyangWurraTSPO knockouts produce significantly less ATP, suggesting reduced metabolic activity. Using the isoquinoline PK11195, the ligand originally used for the pharmacological and structural characterization of the PBR/TSPO, and the imidazopyridines CLINDE and PBR111, we demonstrate the utility of GuwiyangWurraTSPO knockouts to provide robust data on drug specificity and selectivity, both in vitro and in vivo, as well as the mechanism of action of putative TSPO-targeting drugs