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Contains fulltext : 229465.pdf (Publisher’s version ) (Closed access) BACKGROUND: Deceased donor kidneys are preserved in cold hypoxic conditions. Providing oxygen during preservation might improve post-transplant outcomes, particularly for kidneys subjected to greater degrees of preservation injury. This study aimed to investigate whether supplemental oxygen during hypothermic machine perfusion (HMP) could improve the outcome of kidneys donated after circulatory death. METHODS: This randomised, double-blind, paired, phase 3 trial was done in 19 European transplant centres. Kidney pairs from donors aged 50 years or older, donated after circulatory death, were eligible if both kidneys were transplanted into two different recipients. One kidney from each donor was randomly assigned using permuted blocks to oxygenated hypothermic machine perfusion (HMPO(2)), the other to HMP without oxygenation. Perfusion was maintained from organ retrieval to implantation. The primary outcome was 12-month estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation in pairs of donated kidneys in which both transplanted kidneys were functioning at the end of follow-up. Safety outcomes were reported for all transplanted kidneys. Intention-to-treat analyses were done. This trial is registered with the ISRCTN Registry, ISRCTN32967929, and is now closed. FINDINGS: Between March 15, 2015, and April 11, 2017, 197 kidney pairs were randomised with 106 pairs transplanted into eligible recipients. 23 kidney pairs were excluded from the primary analysis because of kidney failure or patient death. Mean eGFR at 12 months was 50·5 mL/min per 1·73 m(2) (SD 19·3) in the HMPO(2) group versus 46·7 mL/min per 1·73m(2) (17·1) in HMP (mean difference 3·7 mL/min per 1·73m(2), 95% CI -1·0 to 8·4; p=0·12). Fewer severe complications (Clavien-Dindo grade IIIb or more) were reported in the HMPO(2) group (46 of 417, 11%, 95% CI 8% to 14%) than in the HMP group (76 of 474, 16%, 13% to 20%; p=0·032). Graft failure was lower with HMPO(2) (three [3%] of 106) compared with HMP (11 [10%] of 106; hazard ratio 0·27, 95% CI 0·07 to 0·95; p=0·028). INTERPRETATION: HMPO(2) of kidneys donated after circulatory death is safe and reduces post-transplant complications (grade IIIb or more). The 12-month difference in eGFR between the HMPO(2) and HMP groups was not significant when both kidneys from the same donor were still functioning 1-year post-transplant, but potential beneficial effects of HMPO(2) were suggested by analysis of secondary outcomes. FUNDING: European Commission 7th Framework Programme.

The role of paclitaxel-coated balloons has been established in the coronary and peripheral arterial circulations with recent interest in the use of paclitaxel-coated balloons to improve patency rates following angioplasty of arteriovenous fistulas. To assess the efficacy of paclitaxel-coated angioplasty balloons to prolong the survival time of target lesion primary patency in arteriovenous fistulas, we designed an investigator-led multi-center randomized controlled trial with follow up time variable for a minimum of one year. Patients with an arteriovenous fistula who were undergoing an angioplasty for a clinical indication were included but patients with one or more lesions outside the treatment segment were excluded. Following successful treatment with a high-pressure balloon, 212 patients were randomized. In the intervention arm, the second component was insertion of a paclitaxel-coated balloon. In the control arm, an identical procedure was followed, but using a standard balloon. The primary endpoint was time to loss of clinically driven target lesion primary patency. Primary analysis showed no significant evidence for a difference in time to end of target lesion primary patency between groups: hazard ratio 1.18 with a 95% confidence interval of 0.78 to 1.79. There were no significant differences for any secondary outcomes, including patency outcomes and adverse events. Thus, our study demonstrated no evidence that paclitaxel-coated balloons provide benefit, following standard care high-pressure balloon angioplasty, in the treatment of arteriovenous fistulas. Hence, in view of the benefit suggested by other trials, the role of paclitaxel-coated angioplasty balloons remains uncertain.

Background Postoperative infection after hand-assisted laparoscopic donor nephrectomy (HALDN) confers significant morbidity to a healthy patient group. Current UK guidelines cite a lack of evidence for routine antibiotic prophylaxis. This trial assessed if a single preoperative antibiotic dose could reduce post HALDN infections. Methods Eligible donors were randomly and blindly allocated to preoperative single-dose intravenous co-amoxiclav or saline. The primary composite endpoint was clinical evidence of any postoperative infection at 30 days, including surgical site infection (SSI), urinary tract infection (UTI), and lower respiratory tract infection (LRTI). Findings In all, 293 participants underwent HALDN (148 antibiotic arm and 145 placebo arm). Among them, 99% (291/293) completed follow-up. The total infection rate was 40.7% (59/145) in the placebo group and 23% (34 of 148) in the antibiotic group (P = 0.001). Superficial SSIs were 20.7% (30/145 patients) in the placebo group versus 10.1% (15/148 patients) in the antibiotic group (P = 0.012). LRTIs were 9% (13/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.046). UTIs were 4.1% (6/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.72).Antibiotic prophylaxis conferred a 17.7% (95% confidence interval 7.2%-28.1%), absolute risk reduction in developing postoperative infection, with 6 donors requiring treatment to prevent 1 infection. Interpretation Single-dose preoperative antibiotic prophylaxis dramatically reduces post-HALDN infection rates, mainly impacting SSIs and LRTIs.

The number of older patients is increasing on the transplant waiting list. Donation after circulatory death (DCD) kidney transplantation has increased, but there remains hesitancy in use of older DCD organs. The aim of this study was to evaluate outcomes of directing older DCD donor kidneys into older recipients. Methods Patients 60 years or older who received transplants from DCD donors 60 years or older, between February 2010 and January 2014, were identified from a prospectively maintained database. Results Over a 4-year period, 88 patients 60 years or older received DCD kidney transplants from donors 60 years or older. Of these 44 (55%) were 60 to 69 years old and 40 (45%) were 70 years or older. Median follow up was 63 months. Patient survival was 95% and 79% at 1 and 5 years, respectively, with a survival in those 70 years and older (69%) compared with those aged 60 to 69 (88%) years (P = .01). Censored for death graft survival was 94% and 80% at 1 and 5 years, respectively. Median estimated glomerular filtration rate at 12 months and 36 months was 36 mL/min (range, 11–70 mL/min) and 39.5 mL/min (range, 11–77 mL/min), respectively. Conclusions Older DCD kidneys, when transplanted into older recipients, result in good patient and graft survival and an acceptable graft function, especially considering their age. This represents a good use of this organ resource.

Importance Continuous hypothermic machine perfusion during organ preservation has a beneficial effect on graft function and survival in kidney transplant when compared with static cold storage (SCS). Objective To compare the effect of short-term oxygenated hypothermic machine perfusion preservation (end-HMPo2) after SCS vs SCS alone on 1-year graft survival in expanded criteria donor kidneys from donors who are brain dead. Design, Setting, and Participants In a prospective, randomized, multicenter trial, kidneys from expanded criteria donors were randomized to either SCS alone or SCS followed by end-HMPo2 prior to implantation with a minimum machine perfusion time of 120 minutes. Kidneys were randomized between January 2015 and May 2018, and analysis began May 2019. Analysis was intention to treat. Interventions On randomization and before implantation, deceased donor kidneys were either kept on SCS or placed on HMPo2. Main Outcome and Measures Primary end point was 1-year graft survival, with delayed graft function, primary nonfunction, acute rejection, estimated glomerular filtration rate, and patient survival as secondary end points. Results Centers in 5 European countries randomized 305 kidneys (median [range] donor age, 64 [50-84] years), of which 262 kidneys (127 [48.5%] in the end-HMPo2 group vs 135 [51.5%] in the SCS group) were successfully transplanted. Median (range) cold ischemia time was 13.2 (5.1-28.7) hours in the end-HMPo2 group and 12.9 (4-29.2) hours in the SCS group; median (range) duration in the end-HMPo2 group was 4.7 (0.8-17.1) hours. One-year graft survival was 92.1% (n = 117) in the end-HMPo2 group vs 93.3% (n = 126) in the SCS group (95% CI, −7.5 to 5.1; P = .71). The secondary end point analysis showed no significant between-group differences for delayed graft function, primary nonfunction, estimated glomerular filtration rate, and acute rejection. Conclusions and Relevance Reconditioning of expanded criteria donor kidneys from donors who are brain dead using end-HMPo2 after SCS does not improve graft survival or function compared with SCS alone. This study is underpowered owing to the high overall graft survival rate, limiting interpretation. Trial Registration isrctn.org Identifier: ISRCTN63852508

We aimed to analyse the efficacy of the Thymoglobulin dose used for induction in controlled DCD kidneys, and its initial impact on blood cell and CD3 count, as predictors of efficacy.140 DCD patients who received ATG induction, were analysed. Intended dose was 1.25 mg/kg/day over 5 days, rounded to nearest 25 mg and not exceeding 125 mg/dose. Outcomes included the total dose in relation with rejection, DGF, graft survival, eGFR. The cell count response to ATG was assessed as predictors of outcome.Graft survival, was 96.2%, 92.4%, 85% at 1, 3 and 5 years. Rejection was 7% at 1 year and associated with eGFR at 3 (p = 0.003) and 5 years. ATG dose was not predictive of rejection but was associated with the day5 leucocyte and lymphocyte count (p 0.001) and negatively with DGF (p = 0.05). In 31 patients day3 CD3 count was available and it was associated with rejection (p = 0.002), less DGF (p = 0.09), and 3 years eGFR (p = 0.01).Thymoglobulin provides excellent results in DCD kidneys that do not significantly differ with small dose variations. In higher doses it reduces DGF. Lymphocytes and CD3 count, may be useful surrogate markers of efficacy and outcome.

Background: Postoperative infection following hand assisted laparoscopic donor nephrectomy (HALDN) confers significant morbidity to a healthy patient group. Current UK guidelines cite a lack of evidence for routine antibiotic prophylaxis. This trial assessed if a single preoperative antibiotic dose could reduce post HALDN infections. Methods: Eligible donors were randomly and blindly allocated to preoperative single dose intravenous co-amoxiclav or saline. The primary composite endpoint was clinical evidence of any postoperative infection at 30 days including surgical site infection (SSI), urinary tract infection (UTI) and lower respiratory tract infection (LRTI). The study aimed to detect a 10% or greater reduction in the primary endpoint with 90% power (α 0·05). All analyses were by intention to treat (ITT). Findings: 293 participants underwent HALDN (148 antibiotic arm and 145 placebo arm). 99% (291 of 293) completed follow up. The total infection rate was 40.7% (59 of 145) in the placebo group and 23% (34 of 148) in the antibiotic group (p=0·001). Superficial SSIs were 20·7% (30 of 145 patients) in the placebo group vs 10.1% (15 of 148 patients) in the antibiotic group (p=0·012). LRTIs were 9% (13 of 145) in the placebo group and 3.4% (5 of 148) in the antibiotic group (p=0.046). UTIs were 4.1% (6 of 145) in the placebo group and 3.4% (5 of 148) in the antibiotic group (p=0.72). Reportable adverse events occurred in 22 patients per group (14·7% (antibiotic) vs 15·2% (placebo), p=0·54). Antibiotic prophylaxis conferred a 17.7% (95% CI 7.2–28.1%), absolute risk reduction (ARR) in developing postoperative infection, with 6 donors requiring treatment (NNT) to prevent one infection. Interpretation: Single dose preoperative antibiotic prophylaxis dramatically reduces post HALDN infection rates, mainly impacting SSIs and LRTIs. Trial Registration Number: Trial registration was with the European Union clinical trials register, no 2012-000942-36. Funding Statement: National Institute for Health Research (Project Number PB-PG-1010-23108). Declaration of Interests: We declare the authors have no competing interests. Ethics Approval Statement: Ethical approval for the study was granted by the London Harrow Research Ethics Committee and regulatory approval by the Medicines and Healthcare Products Regulatory Agency (MHRA). All subjects provided written consent.

Hypothermic machine perfusion is effective in improving outcome following kidney transplantation. Molecular analyses of hypothermic machine perfusate (HMP) have the potential to identify biomarkers of organ viability prior to transplantation, offering significant advantages to the transplant surgeon, and leading to a potential increase in the organ donor pool. MicroRNAs are emerging as important biomarkers in the context of kidney injury and transplantation. Recent data demonstrate increased microRNA-21 (miR-21) expression in the kidney following acute kidney injury. This study investigated the potential of miR-21 detected in HMP to act as a sentinel for early kidney transplant outcomes. MiR-21 was found to be readily detectable in HMP by RT-qPCR. Eleven ECD kidneys were maintained on a hypothermic machine perfusion system for a median 627 (range 117-1027) minutes, and evaluation of flow and resistance characteristics suggested stability on the machine from 60 min post-perfusion. MiR-21 quantification at 60 min post-perfusion correlated with eGFR at 6 and 12 months post-transplantation. These data suggest that miR-21 expression in HMP may be predictive of early outcomes following kidney transplantation. In the era of ECD kidneys, a reliable measure of organ quality is urgently needed, and this study suggests miR-21 may be such a marker.

During the breaking test of a high voltage circuit breaker, a canted spring contact connecting the busbars of the switchgear melted. This event provided a good opportunity to test the reliability of finite element (FE) temperature rise calculations based on a transient coupled thermal-electromagnetic (EM) model. To properly include the Joule-losses at the tiny contact points in a time-varying ANSYS FE analysis, we had to devise a unique method of contact resistance modelling. The paper shortly describes this method and shares our experience we obtained from the case study of canted spring contact temperature rise.

BackgroundSocioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases, including renal failure, and often poorer outcomes for patients with such conditions. The aim of this study was to investigate the effect of deprivation on peritonitis episodes following peritoneal dialysis (PD)-catheter insertion.MethodsThe Welsh Index of Multiple Deprivation (WIMD) was used to assess the influence of socioeconomic deprivation on outcomes following 233 consecutive first PD-catheter insertions from a single institution in the United Kingdom, performed between 2010 and 2015. The primary outcome measure was the presence of peritonitis episodes.ResultsPeritoneal dialysis catheters were inserted in 243 patients, of which data were available for 233. Fifty-four patients experienced at least 1 episode of peritonitis. Overall, more patients in the most deprived group (vs least deprived) experienced peritonitis, although this was not statistically significant. When analyzing the severity of the peritonitis, within the ‘Education’ domain of the WIMD, significantly more patients from the most deprived group (compared with the least deprived group) experienced ‘2 or more peritonitis’ episodes ( p = 0.04) and were hospitalized for antibiotics ( p = 0.02).ConclusionThis study has shown that patients who live in more ‘educationally’ deprived areas are more likely to have multiple episodes of peritonitis requiring hospital admission following PD-catheter insertions.

Introduction: The first renal transplantation was completed in 1991 at the University of Debrecen. In 2013 Hungary joined Eurotransplant. Aim: The authors retrospectively compared the trends. Method: Comparison between Period A (from January 1, 2008 to August 31, 2013) and Period B (from September 1, 2013 to October 22, 2015). Results: The proportion of living transplants rose from 3.5% to 9.1 %. During period B over 25% of utilized donors were over 60 years of age. Recipients with body mass index above 30 kg/m2 increased from 12% to 31%. Prevalence of diabetes among recipients rose twofold. Uretero-neocystostomy was used during period A (99%) while in period B end to side uretero-ureteral anastomosis has also gained popularity (68%). In 2013 the authors introduced routine use of induction treatment. Acute rejection rate decreased from 34% to 8%. The rate of surgical complications did not change. Acute bacterial infections decreased from 41% to 33%. Cumulative renal allograft 1, 3 and 5 year survival rates were 86.6%, 85% and 82.7% in group A vs. projected rates 88%, 84% and 84% in group B, respectively. Conclusions: Despite the growing proportion of expanded criteria donors, the authors were able to maintain a low incidence of delayed graft function and a favorable graft survival. Since 2013 the authors introduced treatments for acute humoral rejection according to international standards. Orv. Hetil., 2016, 157(24), 925–937.

Background Reasons for declining kidney donors are older age, with or without, hypertension, kidney dysfunction, and diabetes. Implantation of both kidneys into a single recipient from such donors may improve their acceptability and outcome. Methods Patients who underwent dual kidney transplantation (DKT) between June 2010 and May 2014 were identified from a prospectively maintained database. Single kidney transplantations (SKT) with matching donor criteria were also identified. Donors considered for DKT were the following: DBDs >70 years of age with diabetes and/or hypertension; DCDs >65 years of age with diabetes and/or hypertension; and DCDs >70 years of age. Results Over a 4-year period, 34 patients underwent adult DKT, and 51, with matching donor criteria, underwent SKT. The median estimated glomerular filtration rate (eGFR) at 12 and 36 months of DKT was 49 (range, 5–79) and 42 (range, 15–85) mL/min compared with SKT of 35 (range, 10–65) and 32 (range, 6–65), respectively. The 1-year graft survival for DKT and SKT was 88% and 96% ( P = .52), and patient survival was 94% and 98%, respectively ( P = .12). Median hospital stay, intensive care unit admission, and wound complications were more frequent in the DKT group. Conclusions Graft function following DKT is significantly better compared with matched criteria SKT; graft and patient survival are similar. There is an increased rate of complications following DKT, with longer hospital stay and ICU admission.

Background: Niemann-Pick’s type B (NP-B) disease is a rare, autosomal recessive visceral storage disorder related to a lysosomal accumulation of sphingomyelin, which is caused by mutations in the sphingomyelinase gene, SMPD1.Case report: We present a boy who had normal early development, but from one year of age, he showed progressive manifestations of hepatosplenomegaly, somatomotor retardation and cardiopulmonary dysfunction. The activity of the sphingomyelinase enzyme was very low in his fibroblasts. He died at 17 years of age from cardio-respiratory insufficiency. Gross pathology and histology of the internal organs were compatible with Niemann-Pick’s disease. His brain and spinal cord displayed no signs of storage disease, confirming the subtype of NP-B. Unexpectedly, however, significant accumulation of iron was seen in the substantia nigra, subthalamic nuclei, putamen, globus pallidus and some cortical regions accompanied by axonal spheroids. Brain iron accumulation is the hallmark of a disease group termed neurodegeneration with brain iron accumulation (NBIA). Sequencing of the known NBIA disease genes was unsuccessful in the proband’s DNA isolated from formalin-fixed, paraffin-embedded blocks, but both asymptomatic parents were heterozygous carriers of the same c19orf12 deletion.Conclusions: This case initially raised the question as to whether two rare autosomal recessive disorders, NP-B and a subtype of NBIA could have co-occurred in our patient, or the lipid dysmetabolism due to sphingomyelinase deficiency caused secondary brain iron accumulation. Genetic analyses in the parents suggested the former possibility by identifying a c19orf12 gene deletion known to underlie in homozygous state Mitochondrial Membrane Protein Associated Neurodegeneration.

Recent clinical trials with non-competitive and competitive N-methyl-D-aspartate (NMDA) receptor antagonists in patients with stroke have shown that these patients develop more adverse effects, particularly psychomimetic effects such as hallucinations and agitation, than normal volunteers at equivalent doses. We therefore examined whether such increased adverse effect potential of NMDA antagonists also occurs in a rat model of permanent focal ischemia. For this purpose, the right middle cerebral artery was occluded under halothane anesthesia, and behavioral alterations in response to the non-competitive NMDA antagonist, MK-801 (dizocilpine), were recorded after recovery from anesthesia. Behavioral alterations in ischemic rats were compared with those in sham-lesioned rats in a blinded fashion. MK-801 (0.4 mg/kg) induced psychomimetic-like stereotyped behaviors which were about twice as intense in ischemic than in non-ischemic rats. A similar trend for enhanced adverse effects was seen with the competitive NMDA antagonist CGS 19755 (Selfotel). Although more NMDA antagonists have to be tested to draw definite conclusions, the present data may indicate that enhanced sensitivity of stroke patients to adverse effects of NMDA antagonists can be predicted by use of a focal ischemia model in rats, thus allowing use of this model for developing novel cytoprotective strategies targeted to minimize glutamatergic excitotoxicity with reduced adverse effect potential.

The purpose of this paper is to document the preformance characteristics and capabilities of the radar section of a, 5-4GHz Microwave Active Spectrometer system. The system will provide ground truth data for radar remote sensing (6° and its dependence on look angle and polarization) and should be able to test the propozition of Auer /1/ to utilize the microwave ellipsometry for radar remote sensing. It is especially designed to measure the electromagnetic properties of natural surfaces at relative low frequencies and with all possible polarizations. Data collected from various fields have been analysed for the dependence of the scattering ring coefficient on soil moisture, vegetation height and ground relief respectively frequency, polarization and look angle.

The evidence to date suggests that vaping is not a safe alternative to smoking tobacco. This, coupled with the worrying trend of young nonsmokers being attracted to vaping, raises fears of yet another generation suffering from chronic lung disease and other acute and chronic health conditions. Finally, due to the insufficient regulations in several countries, up-to-date data on the prevalence of e-cigarette use and studies on the health's implications of their use are urgently needed to inform policy at a national and international level (ie, European Union). Pediatricians are typically on the front line for identifying emerging risks for children and adolescents ; therefore, they may effectively help increase awareness about the potential danger of vaping on health. Information on the use of vaping devices should be implemented worldwide and included in public health information and prevention programs.