Living donor liver transplant from an HIV-positive mother to her HIV-negative child : opening up new therapeutic options

OBJECTIVE : Transplant a liver from an HIV-positive mother to her HIV-negative child to save the child’s life. DESIGN : A unique case of living donor liver transplantation from an HIV-positive mother to her HIV-negative child in South Africa. Two aspects of this case are ground-breaking. First, it involves living donation by someone who is HIVpositive and second it involves controlled transplant of an organ from an HIV-positive donor into an HIV-negative recipient, with the potential to prevent infection in the recipient. METHODS : Standard surgical procedure for living donor liver transplantation at our centre was followed. HIV-prophylaxis was administered preoperatively. Extensive, ultrasensitive HIV testing, over and above standard diagnostic assays, was undertaken to investigate recipient serostatus and is ongoing. RESULTS : Both mother and child are well, over 1 year posttransplantation. HIV seroconversion in our recipient was detected with serological testing at day 43 posttransplant. However, a decline in HIV antibody titres approaching undetectable levels is now being observed. No plasma, or cell-associated HIV-1 DNA has been detected in the recipient at any time-point since transplant. CONCLUSION : This case potentially opens up a new living liver donor pool which might have clinical relevance in countries where there is a high burden of HIV and a limited number of deceased donor organs or limited access to transplantation. However, our recipient’s HIV status is equivocal at present and additional investigation regarding seroconversion events in this unique profile is ongoing.The South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa.http://journals.lww.com/aidsonlineam2019Medical Virolog

Research into land atmosphere interactions supports the Sustainable Development agenda

Greenhouse gas emissions and land use change - from deforestation, forest degradation and agricultural intensification - are contributing to climate change and biodiversity loss. Important landbased strategies such as planting trees or growing bioenergy crops (with carbon capture and storage) are needed to achieve the goals of the Paris Climate Agreement and to enhance biodiversity. The integrated Land Ecosystems Atmospheric Processes Study (iLEAPS) is an international knowledge-exchange and capacity-building network, specialising in ecosystems and their role in controlling the exchange of water, energy and chemical compounds between the land surface and the atmosphere. We outline priority directions for land-atmosphere interaction research and its contribution to the sustainable development agenda

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure

Shared Medical Appointments and Patient-Centered Experience: a Mixed-Methods Systematic review

Background: Shared medical appointments (SMAs), or group visits, are a healthcare delivery method with the potential to improve chronic disease management and preventive care. In this review, we sought to better understand opportunities, barriers, and limitations to SMAs based on patient experience in the primary care context. Methods: An experienced biomedical librarian conducted literature searches of PubMed, Cochrane Library, PsycINFO, CINAHL, Web of Science, ClinicalTrials.gov, and SSRN for peer-reviewed publications published 1997 or after. We searched grey literature, nonempirical reports, social science publications, and citations from published systematic reviews. The search yielded 1359 papers, including qualitative, quantitative, and mixed method studies. Categorization of the extracted data informed a thematic synthesis. We did not perform a formal meta-analysis. Results: Screening and quality assessment yielded 13 quantitative controlled trials, 11 qualitative papers, and two mixed methods studies that met inclusion criteria. We identified three consistent models of care: cooperative health care clinic (five articles), shared medical appointment / group visit (10 articles) and group prenatal care / CenteringPregnancy® (11 articles). Conclusions: SMAs in a variety of formats are increasingly employed in primary care settings, with no singular gold standard. Accepting and implementing this nontraditional approach by both patients and clinicians can yield measurable improvements in patient trust, patient perception of quality of care and quality of life, and relevant biophysical measurements of clinical parameters. Further refinement of this healthcare delivery model will be best driven by standardizing measures of patient satisfaction and clinical outcomes

Liquid Chromatography–Mass Spectrometry Applications for Quantification of Endogenous Sex Hormones

Liquid chromatography, coupled with tandem mass spectrometry, presents a powerful tool for the quantification of the sex steroid hormones 17-β estradiol, progesterone and testosterone from biological matrices. The importance of accurate quantification with these hormones, even at endogenous levels, has evolved with our understanding of the role these regulators play in human development, fertility and disease risk and manifestation. Routine monitoring of these analytes can be accomplished by immunoassay techniques, which face limitations on specificity and sensitivity, or using gas chromatography–mass spectrometry. LC–MS/MS is growing in capability and acceptance for clinically relevant quantification of sex steroid hormones in biological matrices and is able to overcome many of the limitations of immunoassays. Analyte specificity has improved through the use of novel derivatizing agents, and sensitivity has been refined through the use of high-resolution chromatography and mass spectrometric technology. This review highlights these innovations, among others, in LC–MS/MS steroid hormone analysis captured in the literature over the last decade