The Effect of Interleukin-10 Immunotherapy on Renal Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis of Preclinical Studies.

Renal ischemia-reperfusion is a common cause of acute kidney injury leading to significant morbidity and mortality. There are no effective treatments available in clinical practice. This meta-analysis aims to assess the effect of IL-10 immunotherapy on renal ischemia-reperfusion injury. Medline, Embase, Cochrane-library, Google Scholar and clinicaltrials.gov were searched up to 31 March 2023. Preclinical and clinical interventional studies investigating IL-10 immunotherapy for renal ischemia-reperfusion were eligible for inclusion. The primary endpoint was renal function (serum creatinine) following ischemia-reperfusion. The secondary endpoints included mitochondrial integrity, cellular proliferation, regulated cell death (TUNEL assay), expression of inflammatory cytokines (TNF-α, IL-6 and IL-1ß), M1/M2 macrophage polarization, tissue integrity (tubular injury score), long-term kidney fibrosis (fibrotic area %) and adverse events (pulmonary toxicity, cardiotoxicity hepatotoxicity). The search returned 861 records. From these, 16 full texts were screened and subsequently, seven animal studies, corresponding to a population of 268 mice/rats, were included. Compared to the control treatment, IL-10 immunotherapy reduced serum creatinine more effectively within 24 h of administration (95% CI: -9.177, -5.601, I2 = 22.42%). IL-10 immunotherapy promoted mitochondrial integrity and cellular proliferation and reduced regulated cell death (95% CI: -11.000, -4.184, I2 = 74.94%). It decreased the expression of TNF-α, IL-6 and IL-1ß, led to M2 polarization of the local macrophages, reduced tubular injury score (95% CI: -8.917, -5.755, I2 = 22.71%), and long-term kidney fibrosis (95% CI: -6.963, -3.438, I2 = 0%). No adverse outcomes were captured. In Conclusion, IL-10 immunotherapy safely improves outcomes in animal models of renal ischemia-reperfusion; the translational potential of IL-10 immunotherapy needs to be further investigated in clinical trials.

A Conceptual Framework for Evaluating National Organ Donation and Transplantation Programs.

Conceptual frameworks are valuable resources that can be used to guide the planning, evaluation, and development of healthcare services. However, there are currently no comprehensive frameworks focused on organ donation and transplantation that identify the critical factors underlying a successful national program. To address this knowledge gap, we developed a conceptual framework that takes into account all major domains of influence, including political and societal aspects as well as clinical implementation. The framework was initially constructed based on a targeted review of the relevant medical literature. Feedback provided by a panel of international experts was incorporated into the framework via an iterative process. The final framework features 16 essential domains that are critical for initiating and maintaining a successful program and improving the health of patients with organ failure. Of particular note, these domains are subject to three overarching health system principles: responsiveness, efficiency, and equity. This framework represents a first attempt to develop a whole-system view of the various factors that contribute to the success of a national program. These findings provide a useful tool that can be adapted to any jurisdiction and used to plan, evaluate, and improve organ donation and transplantation programs.

Ten Lessons From the Spanish Model of Organ Donation and Transplantation.

The organ donation and transplantation program in Spain has long been considered the gold standard worldwide. An in-depth understanding of the Spanish program may promote the development and reform of transplant programs in other countries. Here, we present a narrative literature review of the Spanish organ donation and transplantation program supplemented by expert feedback and presented according to a conceptual framework of best practices in the field. Core features of the Spanish program include its three-tiered governing structure, close and collaborative relationships with the media, dedicated professional roles, a comprehensive reimbursement strategy, and intensive tailored training programs for all personnel. Several more sophisticated measures have also been implemented, including those focused on advanced donation after circulatory death (DCD) and expanded criteria for organ donation. The overall program is driven by a culture of research, innovation, and continuous commitment and complemented by successful strategies in prevention of end-stage liver and renal disease. Countries seeking ways to reform their current transplant systems might adopt core features and may ultimately aspire to include the aforementioned sophisticated measures. Countries intent on reforming their transplant system should also introduce programs that support living donation, an area of the Spanish program with potential for further improvement.

Solid Organ Donation and Transplantation in the United Kingdom: Good Governance is Key to Success.

The United Kingdom (UK) supports a highly successful organ donation and transplantation program. While the UK originally had one of the lowest organ donation rates in Europe, sustained reforms have resulted in steady improvement. Of note, the UK nearly doubled its rate of deceased donations between 2008 and 2018. In this report, we present a case study of the UK organ donation and transplantation program as an example of a complete system with sound and inclusive governing structures that are strongly integrated with critical programs focused on training and research. This study was based on an initial targeted review of the literature led by a UK expert that included guidelines, national reports, and academic papers. Feedback solicited from other European experts was incorporated into our findings via an iterative process. Overall, the study highlights the stepwise evolution of the UK program that ultimately became successful largely due to ongoing collaborative efforts carried out at all levels. Centralized coordination of all aspects of the program remains a key driver of improved rates of organ donation and transplantation. The designation and empowerment of expert clinical leadership have helped to maintain focus and promote ongoing quality improvement.

The National Organ Donation and Transplantation Program in Greece: Gap Analysis and Recommendations for Change.

Greece has fallen far behind many comparable European countries in the field of organ donation and transplantation and has made little progress over the past decade. Despite efforts to improve its organ donation and transplantation program, systemic problems persist. In 2019, the Onassis Foundation commissioned a report to be prepared by the London School of Economics and Political Science that focused on the state of the Greek organ donation and transplantation program and proposed recommendations for its improvement. In this paper, we present our analysis of the Greek organ donation and transplantation program together with an overview of our specific recommendations. The analysis of the Greek program was undertaken in an iterative manner using a conceptual framework of best practices developed specifically for this project. Our findings were further developed via an iterative process with information provided by key Greek stakeholders and comparisons with case studies that featured successful donation and transplantation programs in Croatia, Italy, Portugal, Spain, and the United Kingdom. Because of their overall complexity, we used a systems-level approach to generate comprehensive and far-reaching recommendations to address the difficulties currently experienced by the Greek organ donation and transplantation program.

Organ Donation in Croatia: The Importance of a National Champion, a Comprehensive Plan, and International Collaborations.

The Republic of Croatia is a global leader in organ donation and transplantation despite having fewer resources and more modest healthcare expenditures than other countries in the European Union. The results of an extensive literature review were combined with expert input in an iterative multi-step data collection and evaluation process designed to assess trends in Croatian organ donation and transplantation and identify key elements, policy changes, and drivers of the system that have contributed to its success. Multiple sources of evidence were used in this study, including primary documents, national and international transplantation reports, and insights from critical informants and content experts. The results highlight several key organizational reforms that have substantially improved the performance of the Croatian transplant program. Our findings emphasize the importance of strong central governance led by an empowered national clinical leader acting under the direct auspices of the Ministry of Health and a comprehensive and progressive national plan. The Croatian transplant system is notable for its integrated approach and efficient manner of managing scarce health resources. Collectively, the results suggest that Croatia has become nearly self-sufficient due to its systematic implementation of the guiding principles for organ donation and transplantation.

How to Structure a Successful Organ Donation and Transplantation System in Eight (Not So Easy) Steps: An Italian Case Study.

Valuable information can be obtained from a systematic evaluation of a successful national transplant program. This paper provides an overview of Italy's solid organ transplantation program which is coordinated by the National Transplant Network (Rete Nazionale Trapianti) and The National Transplant Center (Centro Nazionale Trapianti). The analysis is based on a system-level conceptual framework and identifies components of the Italian system that have contributed to improving rates of organ donation and transplantation. A narrative literature review was conducted and the findings were validated iteratively with input from subject matter experts. The results were organized into eight critical steps, including 1) generating legal definitions of living and deceased donation, 2) taking steps to ensure that altruistic donation and transplantation become part of the national culture and a point of pride, 3) seeking out existing examples of successful programs, 4) creating a situation in which it is easy to become a donor, 5) learning from mistakes, 6) working to diminish risk factors that lead to the need for organ donation, 7) increasing the rate of donations and transplantations via innovative strategies and policies, and 8) planning for a system that supports growth.

Lessons From the Portuguese Solid Organ Donation and Transplantation System: Achieving Success Despite Challenging Conditions.

Over the past two decades, Portugal has become one of the world leaders in organ donation and transplantation despite significant financial constraints. This study highlights how Portugal achieved success in organ donation and transplantation and discusses how this information might be used by other countries that are seeking to reform their national programs. To accomplish this goal, we performed a narrative review of relevant academic and grey literature and revised our results after consultation with two national experts. Our findings were then synthesized according to a conceptual framework for organ donation and transplantation programs. Our results revealed several key strategies used by the Portuguese organ donation and transplantation program, including collaboration with Spain and other European nations, a focus on tertiary prevention, and sustained financial commitment. This report also explores how cooperative efforts were facilitated by geographical, governmental, and cultural proximity to Spain, a world leader in organ donation and transplantation. In conclusion, our review of the Portuguese experience provides insight into the development of organ donation and transplantation systems. However, other countries seeking to reform their national transplant systems will need to adapt these policies and practices to align with their unique cultures and contexts.

Enhanced Recovery after Renal Transplantation Decreases Recipients' Urological Complications and Hospital Stay: A Systematic Review and Meta-Analysis.

The objective of this study was to compare enhanced recovery after surgery (ERAS) against traditional perioperative care for renal transplant recipients. Outcome measures included complications, length of stay (LOS), readmission rates, graft and patient survival up to one-year post-transplant. We initially screened Medline, Cochrane, Scopus, Embase and Web of Science databases. We identified 3029 records. From these, 114 full texts were scrutinized for inclusion. Finally, 10 studies were included in the meta-analysis corresponding to 2037 renal transplant recipients. ERAS resulted in lower incidence of urological complications (95CI: 0.276, 0.855) (I2 = 53.08%) compared to traditional perioperative practice. This referred to ureteric stenoses (95CI: 0.186-0.868) (I2 = 0%) and urinary tract infections (95CI: 0.230-0.978) (I2 = 71.55%). ERAS decreased recipients' LOS (95CI: -2.876, -0.835) (I2 = 86.55%). Compared to standard practice, ERAS protocols did not increase unplanned readmissions (95CI:0.800, 1.680) (I2 = 0%). Up to one-year post-transplant, graft survival rates were similar across the ERAS and the control groups (95CI:0.420, 1.722) (I2 = 0%). There was also no difference in recipients' one-year post-transplant survival (95CI:0.162, 3.586) (I2 = 0%). Our results suggest that ERAS protocols can be safely incorporated in the perioperative care of renal transplant recipients, decrease their urological complications and shorten their length of hospital stay without affecting unplanned readmission rates.

Feasibility, Safety and Efficacy of Enhanced Recovery After Living Donor Nephrectomy: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This meta-analysis aims to compare enhanced recovery after surgery (ERAS) vs. standard perioperative practice in the management of living kidney donors. Primary endpoints included mortality, complications, length of stay (LOS) and quality of life after living donor nephrectomy. Medline, Embase, Scopus, Cochrane and Web of Science databases were searched. In total, 3029 records were identified. We then screened 114 full texts. Finally, 11 studies were included in the systematic review corresponding to 813 living donors. Of these, four randomized controlled trials were included in the meta-analysis. ERAS resulted in shorter LOS (95CI: -1.144, -0.078, I2 = 87.622%) and lower incidence of post-operative complications (95CI: 0.158, 0.582, I2 = 0%). This referred to Clavien-Dindo I-II complications (95CI: 0.158, 0.582, I2 = 0%). There was no difference in Clavien-Dindo III-V complications (95CI: 0.061,16.173, I2 = 0%). ERAS donors consumed decreased amounts of narcotics during their hospital stay (95CI: -27.694, -8.605, I2 = 0%). They had less bodily pain (95CI:6.735, 17.07, I2 = 0%) and improved emotional status (95CI: 6.593,13.319, I2 = 75.682%) one month postoperatively. ERAS protocols incorporating multimodal pain control interventions resulted in a mean reduction of 1 day in donors' LOS (95CI: -1.374, -0.763, I2 = 0%). Our results suggest that ERAS protocols result in reduced perioperative morbidity, shorter length of hospital stay and improved quality of life after living donor nephrectomy.

Evaluating trauma care, outcomes and costs in a system in crisis: the necessity of a Greek National Trauma Database.

BACKGROUND: At present there is no organized trauma system in Greece and no national trauma database. The objective of this study was to record and evaluate trauma management at our university hospital and to measure the associated healthcare costs, while laying the foundations for a national database and the organization of regional trauma networks. METHODS: Retrospective study of trauma patients (n=2320) between 2014 and 2015, through our single-center registry. Demographic information, injury patterns, hospital transfer, investigations, interventions, duration of hospitalization, Injury Severity Score (ISS), outcomes, complications and cost were recorded. RESULTS: Road traffic collisions (RTC) accounted for 23.2% of traumas. The proportion of patients who were transferred to the hospital by the National Emergency Medical Services decreased throughout the study (n2015=76/1192 (6.38%), n2014=109/1128 (9.7%)) (p<0.05). 1209 (52.1%) of our trauma patients did not meet the US trauma field triage algorithm criteria. Overtriage of trauma patients to our facility ranged from 90.7% to 96.7%, depending on the criteria used (clinical vs. ISS criteria). Ninety-one (3.9%) of our patients received operative management. Intensive care unit admissions were 21 (0.1%). Seventy-six (3.3%) of our patients had ISS>15 and their mortality was 31.6%. The overall non-salary cost for trauma management was €623 140. 53% of these costs were attributed to RTCs. The cost resulting from the observed overtriage ranged from €121 000 to €315 000. Patients who did not meet the US trauma triage algorithm criteria accounted for 10.5% of total expenses. DISCUSSION: Our results suggest that RTCs pose a significant financial burden. The prehospital triage of trauma patients is ineffective. A reduction of costs could have been achieved if prehospital triage was more effective. LEVEL OF EVIDENCE: Level IV.