Background
Kidney transplantation is the optimal treatment for end‐stage kidney disease. Retrieval, transport and transplant of kidney grafts causes ischaemia reperfusion injury. The current accepted ...standard is static cold storage (SCS) whereby the kidney is stored on ice after removal from the donor and then removed from the ice box at the time of implantation. However, technology is now available to perfuse or "pump" the kidney during the transport phase or at the recipient centre. This can be done at a variety of temperatures and using different perfusates. The effectiveness of treatment is manifest clinically as delayed graft function (DGF), whereby the kidney fails to produce urine immediately after transplant.
Objectives
To compare hypothermic machine perfusion (HMP) and (sub)normothermic machine perfusion (NMP) with standard SCS.
Search methods
We searched the Cochrane Kidney and Transplant Register of Studies to 18 October 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
Selection criteria
All randomised controlled trials (RCTs) and quasi‐RCTs comparing HMP/NMP versus SCS for deceased donor kidney transplantation were eligible for inclusion. All donor types were included (donor after circulatory (DCD) and brainstem death (DBD), standard and extended/expanded criteria donors). Both paired and unpaired studies were eligible for inclusion.
Data collection and analysis
The results of the literature search were screened and a standard data extraction form was used to collect data. Both of these steps were performed by two independent authors. Dichotomous outcome results were expressed as risk ratio (RR) with 95% confidence intervals (CI). Continuous scales of measurement were expressed as a mean difference (MD). Random effects models were used for data analysis. The primary outcome was incidence of DGF. Secondary outcomes included: one‐year graft survival, incidence of primary non‐function (PNF), DGF duration, long term graft survival, economic implications, graft function, patient survival and incidence of acute rejection.
Main results
No studies reported on NMP, however one ongoing study was identified.
Sixteen studies (2266 participants) comparing HMP with SCS were included; 15 studies could be meta‐analysed. Fourteen studies reported on requirement for dialysis in the first week post‐transplant (DGF incidence); there is high‐certainty evidence that HMP reduces the risk of DGF when compared to SCS (RR 0.77; 95% CI 0.67 to 0.90; P = 0.0006). HMP reduces the risk of DGF in kidneys from DCD donors (7 studies, 772 participants: RR 0.75; 95% CI 0.64 to 0.87; P = 0.0002; high certainty evidence), as well as kidneys from DBD donors (4 studies, 971 participants: RR 0.78, 95% CI 0.65 to 0.93; P = 0.006; high certainty evidence). The number of perfusions required to prevent one episode of DGF (number needed to treat, NNT) was 7.26 and 13.60 in DCD and DBD kidneys respectively. Studies performed in the last decade all used the LifePort machine and confirmed that HMP reduces the incidence of DGF in the modern era (5 studies, 1355 participants: RR 0.77, 95% CI 0.66 to 0.91; P = 0.002; high certainty evidence). Reports of economic analysis suggest that HMP can lead to cost savings in both the North American and European settings.
Two studies reported HMP also improves graft survival however we were not able to meta‐analyse these results. A reduction in incidence of PNF could not be demonstrated. The effect of HMP on our other outcomes (incidence of acute rejection, patient survival, hospital stay, long‐term graft function, duration of DGF) remains uncertain.
Authors' conclusions
HMP is superior to SCS in deceased donor kidney transplantation. This is true for both DBD and DCD kidneys, and remains true in the modern era (studies performed in the last decade). As kidneys from DCD donors have a higher overall DGF rate, fewer perfusions are needed to prevent one episode of DGF (7.26 versus 13.60 in DBD kidneys).
Further studies looking solely at the impact of HMP on DGF incidence are not required. Follow‐up reports detailing long‐term graft survival from participants of the studies already included in this review would be an efficient way to generate further long‐term graft survival data.
Economic analysis, based on the results of this review, would help cement HMP as the standard preservation method in deceased donor kidney transplantation.
RCTs investigating (sub)NMP are required.
American tegumentary leishmaniasis is a vector-borne parasitic disease caused by Leishmania protozoans. Innate immune cells undergo long-term functional reprogramming in response to infection or ...Bacillus Calmette-Guérin (BCG) vaccination via a process called trained immunity, conferring non-specific protection from secondary infections. Here, we demonstrate that monocytes trained with the fungal cell wall component β-glucan confer enhanced protection against infections caused by Leishmania braziliensis through the enhanced production of proinflammatory cytokines. Mechanistically, this augmented immunological response is dependent on increased expression of interleukin 32 (IL-32). Studies performed using a humanized IL-32 transgenic mouse highlight the clinical implications of these findings in vivo. This study represents a definitive characterization of the role of IL-32γ in the trained phenotype induced by β-glucan or BCG, the results of which improve our understanding of the molecular mechanisms governing trained immunity and Leishmania infection control.
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•Trained immunity induced by β-glucan protects against L. braziliensis infections•β-glucan-induced protection against Leishmania is mediated by IL-32 and IL-1•Bone marrow of IL-32TG mice shows increased responsiveness after β-glucan exposure•IL-32 modulates gene transcription of HSPCs and GMP in BCG-vaccinated subjects
dos Santos et al. describe that trained immunity induced by β-glucan confers protection against L. braziliensis infections. Infection control is associated with IL-32 and IL-1 induction. Genetic variation in the IL-32 gene enhances induction of trained immunity leading to proinflammatory gene transcription in bone marrow hematopoietic stem and progenitor cells.
The melanocortin-1 receptor (MC1R) is one of the key proteins involved in the regulation of melanin production and several polymorphisms have been associated with different phenotypes of skin and ...hair color in human and nonhuman species. Most of the knowledge is centered on more homogeneous populations and studies involving an admixed group of people should be encouraged due to the great importance of understanding the human color variation. This work evaluates the MC1R diversity and the possible impacts of MC1R variants in an admixed sample population of Rio de Janeiro, Brazil, which is a product of Native American, African, and European miscegenation. Sequencing of complete coding region and part of the 3´UTR of MC1R gene identified 31 variants including one insertion and three novel synonymous substitutions in sample population grouped according to skin, hair and eye pigmentation levels. In nonmetric multidimensional scaling analysis (NMDS), three main clusters were identified, in which the Brazilian dark skin group remained in the African cluster whereas the intermediate and the light skin color phenotype in the European one. None gathered with Asians since their immigration to Brazil was a recent event. In silico analyses demonstrated that Cys35Tyr, Ile155Thr and Pro256Ser, found in our population, have a negative effect on receptor function probably due to changes on the receptor structure. Notably, Cys35Tyr mutation could potentially impair agonist binding. Altogether, this work contributes to the understanding of the genetic background of color variation on an admixed population and gives insights into the damaging effects of MC1R variants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
4.
Machine perfusion in liver transplantation Tingle, Samuel J; Tingle, Samuel J; Dobbins, Joseph J ...
Cochrane database of systematic reviews,
09/2023, Letnik:
2023, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Background
Liver transplantation is the only chance of cure for people with end‐stage liver disease and some people with advanced liver cancers or acute liver failure. The increasing prevalence of ...these conditions drives demand and necessitates the increasing use of donated livers which have traditionally been considered suboptimal. Several novel machine perfusion preservation technologies have been developed, which attempt to ameliorate some of the deleterious effects of ischaemia reperfusion injury. Machine perfusion technology aims to improve organ quality, thereby improving outcomes in recipients of suboptimal livers when compared to traditional static cold storage (SCS; ice box).
Objectives
To evaluate the effects of different methods of machine perfusion (including hypothermic oxygenated machine perfusion (HOPE), normothermic machine perfusion (NMP), controlled oxygenated rewarming, and normothermic regional perfusion) versus each other or versus static cold storage (SCS) in people undergoing liver transplantation.
Search methods
We used standard, extensive Cochrane search methods. The latest search date was 10 January 2023.
Selection criteria
We included randomised clinical trials which compared different methods of machine perfusion, either with each other or with SCS. Studies comparing HOPE via both hepatic artery and portal vein, or via portal vein only, were grouped. The protocol detailed that we also planned to include quasi‐randomised studies to assess treatment harms.
Data collection and analysis
We used standard Cochrane methods. Our primary outcomes were 1. overall participant survival, 2. quality of life, and 3. serious adverse events. Secondary outcomes were 4. graft survival, 5. ischaemic biliary complications, 6. primary non‐function of the graft, 7. early allograft function, 8. non‐serious adverse events, 9. transplant utilisation, and 10. transaminase release during the first week post‐transplant. We assessed bias using Cochrane's RoB 2 tool and used GRADE to assess certainty of evidence.
Main results
We included seven randomised trials (1024 transplant recipients from 1301 randomised/included livers). All trials were parallel two‐group trials; four compared HOPE versus SCS, and three compared NMP versus SCS. No trials used normothermic regional perfusion.
When compared with SCS, it was uncertain whether overall participant survival was improved with either HOPE (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.42 to 1.98; P = 0.81, I2 = 0%; 4 trials, 482 recipients; low‐certainty evidence due to imprecision because of low number of events) or NMP (HR 1.08, 95% CI 0.31 to 3.80; P = 0.90; 1 trial, 222 recipients; very low‐certainty evidence due to imprecision and risk of bias).
No trials reported quality of life.
When compared with SCS alone, HOPE was associated with improvement in the following clinically relevant outcomes: graft survival (HR 0.45, 95% CI 0.23 to 0.87; P = 0.02, I2 = 0%; 4 trials, 482 recipients; high‐certainty evidence), serious adverse events in extended criteria DBD liver transplants (OR 0.45, 95% CI 0.22 to 0.91; P = 0.03, I2 = 0%; 2 trials, 156 participants; moderate‐certainty evidence) and clinically significant ischaemic cholangiopathy in recipients of DCD livers (OR 0.31, 95% CI 0.11 to 0.92; P = 0.03; 1 trial, 156 recipients; high‐certainty evidence). In contrast, NMP was not associated with improvement in any of these clinically relevant outcomes. NMP was associated with improved utilisation compared with SCS (one trial found a 50% lower rate of organ discard; P = 0.008), but the reasons underlying this effect are unknown.
We identified 11 ongoing studies investigating machine perfusion technologies.
Authors' conclusions
In situations where the decision has been made to transplant a liver donated after circulatory death or donated following brain death, end‐ischaemic HOPE will provide superior clinically relevant outcomes compared with SCS alone. Specifically, graft survival is improved (high‐certainty evidence), serious adverse events are reduced (moderate‐certainty evidence), and in donors after circulatory death, clinically relevant ischaemic biliary complications are reduced (high‐certainty evidence). There is no good evidence that NMP has the same benefits over SCS in terms of these clinically relevant outcomes. NMP does appear to improve utilisation of grafts that would otherwise be discarded with SCS; however, the reasons for this, and whether this effect is specific to NMP, is not clear. Further studies into NMP viability criteria and utilisation, as well as head‐to‐head trials with other perfusion technologies are needed.
In the setting of donation following circulatory death transplantation, further trials are needed to assess the effect of these ex situ machine perfusion methods against, or in combination with, normothermic regional perfusion.
Background
There remains a lack of consensus on the optimal storage method for deceased donor kidneys. This meta‐analysis compares storage with hypothermic machine perfusion (HMP) vs traditional ...static cold storage (SCS).
Methods
The Cochrane Kidney and Transplant Specialised Register was searched to identify (quasi‐) randomized controlled trials (RCTs) to include in our meta‐analysis. PRISMA guidelines were used to perform and write this review.
Results
There is high‐certainty evidence that HMP reduces the risk of delayed graft function (DGF) when compared to SCS (2138 participants from 14 studies, RR = 0.77; 0.67‐0.90, P = .0006). This benefit is significant in both donation following circulatory death (DCD; 772 patients from seven studies, RR = 0.75; 0.64‐0.87, P = .0002) and donation following brainstem death (DBD) grafts (971 patients from four studies, RR = 0.78; 0.65‐0.93, P = .006). The number of perfusions required to prevent one episode of DGF was 7.26 and 13.60 in DCD and DBD grafts, respectively. There is strong evidence that HMP also improves graft survival in both DBD and DCD grafts, at both 1 and 3 years. Economic analyses suggest HMP is cost‐saving at 1 year compared with SCS.
Conclusion
Hypothermic machine perfusion is superior to SCS in deceased donor renal transplantation. Direct comparisons with normothermic machine perfusion in RCTs are essential to identify optimal preservation methods in kidney transplantation.
Introduction
Reduction in hospital stay, blood loss, postoperative pain and complications are common findings after laparoscopic liver resection, suggesting that the laparoscopic approach may be a ...suitable alternative to open surgery. Some concerns have been raised regarding cost effectiveness of this procedure and potential implications of its large-scale application. Our aim has been to determine cost effectiveness of laparoscopic liver surgery by a case-matched, case–control, intention-to-treat analysis of its costs and short-term clinical outcomes compared with open surgery.
Methods
Laparoscopic liver segmentectomies and bisegmentectomies performed at Ninewells Hospital and Medical School between 2005 and 2007 were considered. Resections involving more than two Couinaud segments, or involving any synchronous procedure, were excluded. An operation-magnitude-matched control group was identified amongst open liver resections performed between 2004 and 2007. Hospital costs were obtained from the
Scottish Health Service Costs Book
(ISD Scotland) and average national costs were calculated. Cost of theatre time, disposable surgical devices, hospital stay, and high-dependency unit (HDU) and intensive care unit (ICU) usage were the main endpoints for comparison. Secondary endpoints were morbidity and mortality. Statistical analysis was performed with Student’s
t
-test,
χ
2
and Fisher exact test as most appropriate.
Results
Twenty-five laparoscopic liver resections were considered, including atypical resection, segmentectomy and bisegmentectomy, and they were compared to 25 matching open resections. The two groups were homogeneous by age, sex, coexistent morbidity, magnitude of resection, prevalence of liver cirrhosis and indications. Operative time (
p
< 0.03), blood loss (
p
< 0.0001), Pringle manoeuvre (
p
< 0.03), hospital stay (
p
< 0.003) and postoperative complications (
p
< 0.002) were significantly reduced in the laparoscopic group. Overall hospital cost was significantly lower in the laparoscopic group by an average of £2,571 (
p
< 0.04).
Conclusions
Laparoscopic liver segmentectomy and bisegmentectomy are feasible, safe and cost effective compared to similar open resections. Large-scale application of laparoscopic liver surgery could translate into significant savings to hospitals and health care programmes.
The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of ...admission.
To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type.
Secondary
analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model.
A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio OR, 0.95; 89% credible interval CrI, 0.66-10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56-1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50-0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65-0.97; probability of benefit, 0.97).
There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment. Clinical trial registered with www.clinicaltrials.gov (NCT02875873).
This is a protocol for a Cochrane Review (intervention). The objectives are as follows:
To perform pairwise comparisons and network meta‐analyses to assess the effects of static cold storage and ...different methods of machine perfusion (including hypothermic oxygenated machine perfusion, normothermic machine perfusion, controlled oxygenated rewarming, and normothermic regional perfusion) in people undergoing liver transplantation.
Ionic liquids are a diverse range of charged chemicals with low volatility and often liquids at ambient temperatures. This characteristic has in part lead to them being considered ...environmentally-friendly replacements for existing volatile solvents. However, methylimidazolium ionic liquids are slow to break down in the environment and a recent study at Newcastle detected 1 octyl 3 methylimidazolium (M8OI) – an 8 carbon variant methylimidazolium ionic liquid - in soils in close proximity to a landfill site. The current M8OI toxicity database in cultured mammalian cells, in experimental animal studies and in model indicators of environmental impact are reviewed. Selected analytical data from the Newcastle study suggest the soils in close proximity to the landfill site, an urban soil lacking overt contamination, had variable levels of M8OI. The potential for M8OI - or a structurally related ionic liquid – to trigger primary biliary cholangitis (PBC), an autoimmune liver disease thought to be triggered by an unknown agent(s) in the environment, is reviewed.
•“Ionic liquids” defines a diverse range of chemicals proposed as green chemicals.•There are limited data in mammalian systems regarding their potential toxicity.•The ionic liquid M8OI has been found at high levels in the environment.•M8OI inhibits mitochondrial function and induces mammalian cell apoptosis.•M8OI is metabolised to a lipoic acid mimetic and may be a hazard trigger for PBC.
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•A new tetrameric ligand (TBTP) was synthesized using click chemistry strategy.•Copper(II) with TBTP form 1-D coordination polymer.•1-D coordination polymers present antiferromagnetic ...behavior.•Oxidation of aniline to azobenzene is catalyzed by the 1D coordination polymer.
A novel tetrameric tetraO-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-pentaerythritol (TBTP) has been synthesized using click chemistry strategy. TBTP was characterized and used as ligand to form new Cu(II) complexes, forming 1-D coordination polymers. Two square planar complexes were characterized by single-crystal X-ray diffraction, presenting formula Cu(TBTP)Cu(NO3)4 (1) and Cu(TBTP)(NO3)2 (2). In both structures, a cationic 1-D coordination polymer (CP) has been formed. The CP contain a 1:1 Cu(II)/TBTP ratio with four neutral triazole groups coordinating the Cu(II) center, forming a CuN bonds ranging 1.988(2)–2.001(2) Å. The study of the magnetic properties of compounds 1 and 2 pointed to an antiferromagnetic behavior for both compounds, defined by inter- and intra-chain dipolar interactions among their metallic centers. In addition, the complex 1 was found to be an efficient catalyst for selective oxidation of aniline to azobenzene under mild reaction conditions.
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