Peri-Operative Kinetics of Plasma Mitochondrial DNA Levels during Living Donor Kidney Transplantation

During ischemia and reperfusion injury (IRI), mitochondria may release mitochondrial DNA (mtDNA). mtDNA can serve as a propagator of further injury but in specific settings has anti-inflammatory capacities as well. Therefore, the aim of this study was to study the perioperative dynamics of plasma mtDNA during living donor kidney transplantation (LDKT) and its potential as a marker of graft outcome. Fifty-six donor-recipient couples from the Volatile Anesthetic Protection of Renal Transplants-1 (VAPOR-1) trial were included. Systemic venous, systemic arterial, and renal venous samples were taken at multiple timepoints during and after LDKT. Levels of mtDNA genes changed over time and between vascular compartments. Several donor, recipient, and transplantation-related variables significantly explained the course of mtDNA genes over time. mtDNA genes predicted 1-month and 24-month estimated glomerular filtration rate (eGFR) and acute rejection episodes in the two-year follow-up period. To conclude, mtDNA is released in plasma during the process of LDKT, either from the kidney or from the whole body in response to transplantation. While circulating mtDNA levels positively and negatively predict post-transplantation outcomes, the exact mechanisms and difference between mtDNA genes are not yet understood and need further exploration.</p

Remote ischaemic conditioning and early changes in plasma creatinine as markers of one year kidney graft function-A follow-up of the CONTEXT study

BACKGROUND: Ischaemia-reperfusion injury in kidney transplantation leads to delayed graft function (DGF), which is associated with reduced long term graft function. Remote ischaemic conditioning (RIC) improved early kidney graft function in a porcine model of donation after brain death and was associated with improved long-term cardiac outcome after myocardial ischaemia. This randomised, double-blinded trial evaluated the effect of RIC on kidney graft outcome in the first year, and examined the predictive value of a new measure of initial kidney graft function, i.e. the estimated time to a 50% reduction in plasma creatinine post-transplantation (tCr50). METHODS: A total of 225 patients undergoing deceased donor kidney transplantation were randomised to RIC or a sham procedure performed prior to kidney reperfusion. Up to four repetitive cycles of five minutes of leg ischaemia and five minutes of reperfusion were given. GFR, plasma creatinine, cystatin C and neutrophil gelatinase associated lipocalin (NGAL) were measured at three and twelve months and estimated GFR was calculated using four different equations. Other secondary outcomes were identified from patient files. RESULTS: RIC did not affect GFR or other outcomes when compared to the sham procedure at three or twelve months. tCr50 correlated with one year graft function (p<0.0001 for both mGFR and eGFR estimates). In contrast, DGF i.e. "need of dialysis the first week" did not correlate significantly with one year GFR. CONCLUSION: RIC during deceased donor kidney transplantation did not improve one year outcome. However, t

Remote ischaemic conditioning on recipients of deceased renal transplants, effect on immediate and extended kidney graft function: A multicentre, randomised controlled trial protocol (CONTEXT)

Introduction: Delayed graft function due to ischaemia-reperfusion injury is a frequent complication in deceased donor renal transplantation. Experimental evidence indicates that remote ischaemic conditioning (RIC) provides systemic protection against ischaemia-reperfusion injury in various tissues. Methods and analysis: 'Remote ischaemic conditioning in renal transplantation-effect on immediate and extended kidney graft function' (the CONTEXT study) is an investigator initiated, multicentre, randomised controlled trial investigating whether RIC of the leg of the recipient improves short and long-term graft function following deceased donor kidney transplantation. The study will include 200 kidney transplant recipients of organ donation after brain death and 20 kidney transplant recipients of organ donation after circulatory death. Participants are randomised in a 1:1 design to RIC or sham-RIC (control). RIC consists of four cycles of 5 min occlusion of the thigh by a tourniquet inflated to 250 mm Hg, separated by 5 min of deflation. Primary end point is the time to a 50% reduction from the baseline plasma creatinine, estimated from the changes of plasma creatinine values 30 days post-transplant or 30 days after the last performed dialysis post-transplant. Secondary end points are: need of dialysis post-transplant, measured and estimated-glomerular filtration rate (GFR) at 3 and 12 months after transplantation, patient and renal graft survival, number of rejection episodes in the first year, and changes in biomarkers of acute kidney injury and inflammation in plasma, urine and graft tissue. Ethics and dissemination: The study is approved by the local ethical committees and national data security agencies. Results are expected to be published in 2016

Spiritual Diversity, Spiritual Assessment, and Māori End-of-Life Perspectives: Attaining Ka Ea

Copyright © 2020 by the authors. The contemporary world is endowed with increasingly diverse spiritual and cultural perspectives, yet little is known about the spiritual concerns and spiritual resilience of Māori from Aotearoa New Zealand at the end of life. A context is provided for the value of spiritual assessment and identification of spiritual needs or concerns. Spiritual concerns and the desire to attain a state of ka ea (fulfillment, gratitude, or peace) may point to interventions, helping activities, or referrals that guide treatment. We reflect on qualitative findings from the 2017–2020 Pae Herenga study of 61 caregiving families, their helping professionals, and religious/spiritual leaders. We explore essential spiritual values and practices that support kaumātua (older tribal people) who have a life-limiting illness in achieving a sense of satisfaction and fulfilment at the end of life. Three themes emerged: the relational is spiritual, the need to live into the future, and value of spiritual end-of-life care. While some scholars have lamented the lack of culturally appropriate rapid assessment instruments, we suggest that a more open-ended assessment guide is better suited to understand key elements of spiritual diversity and spiritual concerns, particularly the spiritual strengths and resources that lead to well-being and even thriving at life’s end. Finally, learning about spiritual diversity can assist others to reconnect to lost meanings and regain a more holistic and centred view of life

The impact of laws and regulations on the administrative burdens within healthcare

Despite all improvement initiatives such as the national action plan [De-]Regulate Healthcare by the Dutch Ministry of Health, Welfare and Sport in 2018 to create more time for care within the Netherlands, the administrative burden for care workers is still increasing. Managers of healthcare institutes struggle with efficiently implementing government legislations in day-to-day operations. They indicate that the time spent on administrative tasks demanded by municipalities and national authorities is too much. In addition, they also indicate that there is a lack of consistency and uniformity when it comes to the way care workers handle administrative tasks. This way of working causes additional, and often ad hoc, work in the run-up to an audit. It seems that before laws and regulations are effectively implemented, new laws or regulations again demand attention. This looks like a vicious circle, but research to confirm this is not found yet. Therefore, the following research question is formulated: "What is the impact of laws and regulations on the administrative burden with regard to the primary and supportive processes of Dutch long-term care?" An explanatory multiple case study was conducted to answer the research question. Three case studies were carried out during September 2019 to January 2020. Based on these studies, we have concluded that between 29% and 62% of the total perceived administrative burden by long-term care professionals can be related to legislation

Immune Modulatory Effects of Nonsteroidal Anti-inflammatory Drugs in the Perioperative Period and Their Consequence on Postoperative Outcome

Nonsteroidal anti-inflammatory drugs are among the most commonly administered drugs in the perioperative period due to their prominent role in pain management. However, they potentially have perioperative consequences due to immune-modulating effects through the inhibition of prostanoid synthesis, thereby affecting the levels of various cytokines. These effects may have a direct impact on the postoperative outcome of patients since the immune system aims to restore homeostasis and plays an indispensable role in regeneration and repair. By affecting the immune response, consequences can be expected on various organ systems. This narrative review aims to highlight these potential immune system-related consequences, which include systemic inflammatory response syndrome, acute respiratory distress syndrome, immediate and persistent postoperative pain, effects on oncological and neurologic outcome, and wound, anastomotic, and bone healing