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Therapeutic measures aimed at optimising organ function prior to transplantation-whether by conditioning the donor after determination of brain death or by improving organ preservation after kidney removal-have the potential to enhance outcomes after transplantation. The particular advantage is that, unlike any optimised immunosuppressive therapy, a favourable effect can be achieved without side effects for the organ recipient. In recent years, several such measures have been tested in controlled clinical trials on large patient cohorts following kidney transplantation. Hypothermic pulsatile machine perfusion, in particular, has become the focus of interest, but interventions in the donor prior to organ removal, such as the administration of low-dose dopamine until the start of cold perfusion as an example of conditioning antioxidant therapy and therapeutic donor hypothermia in the intensive care unit after brain death confirmation, have also significantly reduced the frequency of dialysis after transplantation with far less effort and cost. With regard to benefits for graft survival, the database for all procedures is less clear and controversial. The aim of this review article is to re-evaluate the available clinical evidence from large multicentre controlled trials, which have also significantly influenced later meta-analyses, and to assess the significance for use in routine clinical practice.

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Transplantation is the most effective treatment for end-stage chronic kidney disease, as this procedure prolongs and improves the patient's quality of life. One of the key problems is the risk of graft rejection. The purpose of this research was to identify and analyse prognostic factors that will prevent rejection. In particular, the prognostic factors grouped by methods of synthesis, generalisation and statistical processing with calculation and graphical representation of hazard ratio and correlation coefficient were grouped, namely: age of donor and recipient, time of cold kidney ischaemia, duration of preoperative dialysis, body mass index, presence of concomitant diseases (diabetes mellitus, hypertension), primary causes causing transplantation. Several molecular genetic and biochemical prognostic markers (transcription factors, immunocompetent cell signalling and receptors, cytostatin C, creatinine, citrate, lactate, etc.) are annotated. It has been demonstrated that creatinine reduction rate determines the risk of rejection, displaying the dynamics of cystatin C and creatinine changes in the postoperative period. Young recipients who underwent prolonged preoperative dialysis were identified as having the highest risk of rejection. Diabetes and hypertension bear a non-critical but commensurately equal risk of rejection. The survival rate of the graft is better when transplanted from a living donor than from a deceased donor. A correlation between cold ischaemia time, body mass index and the probability of graft failure has been proven, namely, the greater the donor and recipient body mass index and the longer the cold ischaemia time, the lower the chance of successful long-term organ acclimation. The data obtained can be used as prognostic factors for graft accommodation at different intervals after surgery.

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INTRODUCTION: Freezing cold injuries (FCI) are a common risk in extreme cold weather operations. Although the risks have long been recognised, injury occurrences tend to be sparse and geographically distributed, with relatively few cases to study in a systematic way. The first challenge to improve FCI medical management is to develop a common nomenclature for FCI classification. This is critical for the development of meaningful epidemiological reports on the magnitude and severity of FCI, for the standardisation of patient inclusion criteria for treatment studies, and for the development of clinical diagnosis and treatment algorithms. METHODOLOGY: A scoping review of the literature using PubMed and cross-checked with Google Scholar, using search terms related to freezing cold injury and frostbite, highlighted a paucity of published clinical papers and little agreement on classification schemes. RESULTS: A total of 74 papers were identified, and 28 were included in the review. Published reports and studies can be generally grouped into four different classification schemes that are based on (1) injury morphology; (2) signs and symptoms; (3) pathophysiology; and (4) clinical outcome. The nomenclature in the different classification systems is not coherent and the discrete classification limits are not evidence based. CONCLUSIONS: All the classification systems are necessary and relevant to FCI medical management for sustainment of soldier health and performance in cold weather operations and winter warfare. Future FCI reports should clearly characterise the nature of the FCI into existing classification schemes for surveillance (morphology, symptoms, and appearance), identifying risk-factors, clinical guidelines, and agreed inclusion/exclusion criteria for a future treatment trial.

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Many risk factors and complications impact the success of liver transplantation, such as ischaemia-reperfusion injury, acute rejection, and primary graft dysfunction. Molecular biomarkers have the potential to accurately diagnose, predict, and monitor injury progression or organ failure. There is a critical opportunity for reliable and non-invasive biomarkers to reduce the organ shortage by enabling i) the assessment of donor organ quality, ii) the monitoring of short- and long-term graft function, and iii) the prediction of acute and chronic disease development. To date, no established molecular biomarkers have been used to guide clinical decision-making in transplantation. In this review, we outline the recent advances in cell-free nucleic acid biomarkers for monitoring graft injury in liver transplant recipients. Prior work in this area can be divided into two categories: biomarker discovery and validation studies. Circulating nucleic acids (CNAs) can be found in the extracellular environment pertaining to different biological fluids such as bile, blood, urine, and perfusate. CNAs that are packaged into extracellular vesicles may facilitate intercellular and interorgan communication. Thus, decoding their biological function, cellular origins and molecular composition is imperative for diagnosing causes of graft injury, guiding immunosuppression and improving overall patient survival. Herein, we discuss the most promising molecular biomarkers, their state of development, and the critical aspects of study design in biomarker research for early detection of post-transplant liver injury. Future advances in biomarker studies are expected to personalise post-transplant therapy, leading to improved patient care and outcomes.

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BACKGROUND AND AIMS: Fluid administration during liver transplant (LT) surgery is controversial. Although adverse outcomes following positive intraoperative fluid balance have been reported, studies presenting the influence of cumulative postoperative fluid balance (CFB) on complications following LT are sparse. Patients with chronic liver disease tend to receive more fluid during and after surgery due to their unique physiological disease state. The aim of this study was to evaluate the influence of 48-hour CFB on the development of acute kidney injury (AKI) and pulmonary complications on day 4 after live donor LT. METHODS: This retrospective study included 230 patients undergoing live donor LT. The effect of CFB on day 2 on AKI and pulmonary complications was analysed. Chi-square test, Fisher's exact test, samples t-test, Mann-Whitney U-test were used. RESULTS: Bivariate analysis showed a lower graft vs recipient weight ratio (GRWR), sepsis (P < 0.001) and a higher 48-hour CFB after surgery significantly increased the development of AKI. For pulmonary complications, higher Model for End- stage Liver Disease-Na(MELD-Na) score, higher peak arterial lactate, higher 48-hour CFB (P = 0.016) and sepsis (P = 0.003) were found to be statistically significant. Upon multivariate analysis, CFB at 48 hours was significantly higher in patients suffering from pulmonary complications, and GRWR and sepsis were significant for AKI. For every one litre increase in CFB on day 2, the odds of pulmonary complications increased by 37%. CONCLUSION: A more positive CFB on day 2 increased the development of pulmonary complications and lower GRWR and sepsis increased the development of AKI.

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BACKGROUND: With ageing population and higher prevalence of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) in older patients, more and more living donor liver transplants (LDLTs) are being considered in this group of patients as eligibility for deceased donor liver transplant is restricted to those aged 65 years and younger. However, the short- and long-term outcomes of this group have not been reported from India, which does not have a robust national health scheme. The aim of this study was to provide guidelines for transplant in this group. METHODS: All patients aged 60 years and older (group 1) who underwent LDLT in our centre between January 2006 and December 2017 were studied. A propensity score-matched group in 1:2 ratio was created with comparable sex and Model for End-Stage Liver Disease score (group 2). The 2 groups were compared for duration of hospital stay, surgical complications, hospital mortality and 1-, 3- and 5-year survival. RESULTS: Group 1 consisted of 207 patients, and group 2 had 414 patients. The number of patients in group 1 gradually increased with time from 4 in 2006 to 33 in 2017 accounting for 15% of total cases. Group 1 had more patients with viral hepatitis, NASH and HCC, and they had a higher 30-day mortality due to cardiorespiratory complications. Although 1- and 3-year survival was similar, the 5-year survival was significantly lower in group 1. CONCLUSION: Five-year survival was lower in the elderly group due to cardiorespiratory complications and recurrence of HCC. Outcomes in the elderly group can be improved with better patient selection and preventing HCC recurrence.

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OBJECTIVES: In transplantation surgery, the ischaemic organ and reperfusion impairment after cold storage remains a considerable risk factor for impaired function and potential failure of the grafted organ. Substantial logistical efforts have been undertaken to reduce the cold ischaemic time because the demand for available transplant organs and the periods of cold ischaemia are increasing. METHODS: Four molecules were investigated (erythropoietin, sildenafil, lazaroid [U74389G], octreotide) in individual intravenous infusions 1 hour before the organ was harvested. This study was performed in 30 healthy landrace/large-white pigs (male; >10 weeks old; average weight, 22 ± 2 kg) in groups of six. The organs were studied at harvest, and at 8 and 24 hours post-harvest. RESULTS: The lazaroid molecule increased malondialdehyde (MDA) levels in the liver and pancreas at 8 hours. Hepatic lazaroid molecules improved liver histology at 8 and 24 hours. For kidneys, erythropoietin had a positive effect at 24 hours post-harvest. For the pancreas, octreotide showed better performance. In the lungs, there was less interstitial oedema with erythropoietin and lazaroid compared with the control group at 8 hours post-harvest. CONCLUSION: All molecules had a positive effect and decreased ischaemia/reperfusion graft injury. Thus, pretreatment before organ harvest has a beneficial role.

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Ischaemia impairs organ quality during preservation in a time-dependent manner, due to a lack of oxygen supply. Its impact on pancreas and islet transplantation outcome has been demonstrated by a correlation between cold ischaemia time and poor islet isolation efficiency. Our goal in the present study was to improve pancreas and islet quality using a novel natural oxygen carrier (M101, 2 g/L), which has been proven safe and efficient in other clinical applications, including kidney transplantation, and for several pre-clinical transplantation models. When M101 was added to the preservation solution of rat pancreas during ischaemia, a decrease in oxidative stress (ROS), necrosis (HMGB1), and cellular stress pathway (p38 MAPK)activity was observed. Freshly isolated islets had improved function when M101 was injected in the pancreas. Additionally, human pancreases exposed to M101 for 3 hours had an increase in complex 1 mitochondrial activity, as well as activation of AKT activity, a cell survival marker. Insulin secretion was also up-regulated for isolated islets. In summary, these results demonstrate a positive effect of the oxygen carrier M101 on rat and human pancreas during preservation, with an overall improvement in post-isolation islet quality.

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BACKGROUND: The Australian kidney paired donation program adopted the principles of within-chain simultaneous live donor surgery and of organ transport, with the requirement of keeping cold ischemia time (CIT) to <12 h. Whether these principles could be adhered to and what impact on transplant outcome they might have is unknown. METHODS: We evaluated the logistic challenges and outcomes of the first 100 kidney transplants performed in the Australian kidney paired donation program. RESULTS: Within 4 years, 17 donor surgeons at 12 centres were involved in 37 chain exchange surgeries. Sixteen kidneys were transplanted at the same hospital and 84 required transport to the recipient hospital. Mean (±SD) within chain anaesthetic induction time variability was 8 ± 18 min and mean individual surgeon operating time was 115 ± 44 min. In two cases, delays during donor surgery resulted in increased CIT by 1 h because of deferred transport. CIT was 2.6 ± 0.6 h for non-shipped and 6.8 ± 2.8 h for shipped kidneys, four kidneys had CIT of 12-14 h. Immediate allograft function was observed in 85% of recipients, with no difference between shipped and non-shipped kidneys. There were only two cases of delayed graft function requiring temporary dialysis; both had CIT <7 h. There was no difference in serum creatinine at 1 month between non-shipped and shipped kidneys (105 ± 26 versus 112 ± 50 µmol/L) and allograft survival at 1 year was 97%. CONCLUSION: The study provided a favourable audit of kidney transplant activity, despite challenges of simultaneous surgery, organ transport coordination and prolonged CIT. The decision to ship donor kidneys rather than the donor was demonstrated to be feasible and safe.

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To assess the impact of shipping distance and cold ischaemia time (CIT) of shipped organs in a kidney paired donation (KPD) programme, we evaluated the outcomes of the initial 100 kidney transplants performed in the Australian KPD programme. In a 44-month period, 12 centres were involved in fifteen 2-way, twenty 3-way, one 4-way and one 6-way exchanges. Sixteen kidneys were transplanted at the same hospital (CIT 2.6 ± 0.6 h) and 84 required transport to the recipient hospital (CIT 6.8 ± 2.8 h). A spontaneous fall in serum creatinine by at least 10% within 24 h was observed in 85% of recipients, with no difference between nonshipped and shipped kidneys. There were two cases of transient delayed graft function requiring dialysis and patient and graft survival at 1 year were 99% and 97%, respectively. There was no difference in recipients of nonshipped compared with shipped kidneys with regard to serum creatinine at 1 month (mean difference (MD) 7.3 µmol/l, 95% CI -20.2 to 34.8, P = 0.59), 1-year graft survival (MD 3.9%, 95% CI -5.4 to 13.2, P = 0.41) or patient survival (MD -2.4%, 95% CI -10.0 to 5.2, P = 0.54). Despite prolonged CIT for interstate exchanges, the programme's decision to ship donor kidneys rather than the donor appears to be safe.

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Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient's quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.

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