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.
Cellular senescence is characterized by an irreversible cell cycle arrest as well as a pro‐inflammatory phenotype, thought to contribute to aging and age‐related diseases. Neutrophils have essential ...roles in inflammatory responses; however, in certain contexts their abundance is associated with a number of age‐related diseases, including liver disease. The relationship between neutrophils and cellular senescence is not well understood. Here, we show that telomeres in non‐immune cells are highly susceptible to oxidative damage caused by neighboring neutrophils. Neutrophils cause telomere dysfunction both in vitro and ex vivo in a ROS‐dependent manner. In a mouse model of acute liver injury, depletion of neutrophils reduces telomere dysfunction and senescence. Finally, we show that senescent cells mediate the recruitment of neutrophils to the aged liver and propose that this may be a mechanism by which senescence spreads to surrounding cells. Our results suggest that interventions that counteract neutrophil‐induced senescence may be beneficial during aging and age‐related disease.
SYNOPSIS
Whether infiltrating immune cells impact on tissue viability during inflammatory response is poorly characterized. Here, activated neutrophils are shown to induce ROS‐dependent acute senescence in adjacent naïve cells, raising the possibility of intercellular senescence crosstalk during ageing and age‐related pathologies.
Neutrophils induce paracrine senescence in neighbouring cells via ROS‐dependent telomere dysfunction.
Neutrophil clearance prevents senescence and telomere dysfunction in a model of acute liver injury.
Senescent cells recruit neutrophils via the senescence‐associated secretory phenotype (SASP) in the aged liver.
Oxidative damage caused by inflammatory neutrophils contributes to neighbouring cell senescence and liver injury.
Background
Major urological complications (MUCs) after kidney transplantation contribute to patient morbidity and compromise graft function. The majority arise from the vesicoureteric anastomosis and ...present early after transplantation. Ureteric stents have been successfully used to treat such complications. A number of centres have adopted a policy of universal prophylactic stenting, at the time of graft implantation, to reduce the incidence of urine leaks and ureteric stenosis. Stents are associated with specific complications and some centres advocate a policy of only stenting selected anastomoses.
Objectives
To examine the benefits and harms of routine ureteric stenting to prevent urological complications in kidney transplant recipients.
Search methods
We searched the Cochrane Renal Group's Specialised Register (up to 8 January 2013) through contact with the Trials' Search Co‐ordinator using search terms relevant to this review.
Selection criteria
All RCTs and quasi‐RCTs were included in our meta‐analysis.
Data collection and analysis
Four reviewers assessed the studies for quality against four criteria (allocation concealment, blinding, intention‐to‐treat and completeness of follow‐up). The primary outcome was the incidence of MUCs. Further outcomes of interest were graft and patient survival and the incidence of adverse events (urinary tract infection (UTI), haematuria, irritative symptoms, pain and stent migration). Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI).
Main results
Seven RCTs (1154 patients) of low or moderate quality were identified. The incidence of MUCs was significantly reduced (RR 0.24, 95% CI 0.07 to 0.77, P = 0.02, NNT 13) by universal prophylactic stenting. This was dependent on whether the same surgeon performed, or was in attendance, during the operations. Two patients lost their grafts to infective urinary tract complications in the stented group. UTIs, in general, were more common in stented patients (RR 1.49, 95% CI 1.04 to 2.15) unless the patients were prescribed cotrimoxazole 480 mg/d: in which case the incidence was equivalent (RR 0.97, 95% CI 0.71 to 1.33). Stents appeared generally well tolerated, although studies using longer stents (≥ 20 cm) for longer periods (> 6 weeks) had more problems with encrustation and migration.
Authors' conclusions
Routine prophylactic stenting reduces the incidence of MUCs. Studies comparing selective stenting and universal prophylactic stenting, whilst difficult to design and analyse, would address the unresolved quality of life and economic issues.
Prehabilitation prior to surgery for pancreatic cancer: A systematic review Bundred, James R.; Kamarajah, Sivesh K.; Hammond, John S. ...
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... et al.,
September 2020, 2020-09-00, 20200901, Letnik:
20, Številka:
6
Journal Article
Recenzirano
Prehabilitation aims to improve fitness and outcomes of patients undergoing major surgery. This systematic review aimed to appraise current available evidence regarding the role of prehabilitation in ...patients undergoing oncological pancreatic resection.
A systematic literature search of PUBMED, MEDLINE, EMBASE databases identified articles describing prehabilitation programmes before pancreatic resection for malignancy. Data collected included timing of prehabilitation, programme type, duration, adherence and post-operative outcome reporting.
Six studies, including 193 patients were included in the final analysis. Three studies included patients undergoing neoadjuvant therapy followed by resection and 3 studies included patients undergoing upfront resection. Time from diagnosis to surgery ranged between 2 and 22 weeks across all studies. Two studies reported a professionally supervised exercise programme, and four described unsupervised programmes. Exercise programmes varied from 5 days to 6 months in duration. Adherence to exercise programmes was better with supervised programmes (99% reaching weekly activity goal vs 85%) and patients not undergoing neoadjuvant therapy (90% reaching weekly activity goal vs 82%). All studies reported improvement in muscle mass or markers of muscle function following prehabilitation. Two studies reported the impact of Prehabilitation on postoperative outcomes and Prehabilitation was associated with lower delayed gastric emptying and a shorter hospital stay with no impact on other postoperative outcomes.
Early evidence demonstrates that Prehabilitation programmes may improve postoperative outcomes following pancreatic surgery. However current Prehabilitaton programmes for patients undergoing pancreatic resection report diverse exercise regimens with no consensus regarding timing or length of Prehabilitation, warranting a need for standardisation of Prehabilitation programmes in pancreatic surgery.
Background
Waiting lists for kidney transplantation continue to grow and live organ donation has become more important as the number of brain stem dead cadaveric organ donors continues to fall. The ...major disincentive to potential kidney donors is the pain and morbidity associated with open surgery.
Objectives
To identify the benefits and harms of using laparoscopic compared to open nephrectomy techniques to recover kidneys from live organ donors.
Search methods
We searched the online databases CENTRAL (in The Cochrane Library 2010, Issue 2), MEDLINE (January 1966 to January 2010) and EMBASE (January 1980 to January 2010) and handsearched textbooks and reference lists.
Selection criteria
Randomised controlled trials comparing laparoscopic donor nephrectomy (LDN) with open donor nephrectomy (ODN).
Data collection and analysis
Two review authors independently screened titles and s for eligibility, assessed study quality, and extracted data. We contacted study authors for additional information where necessary.
Main results
Six studies were identified that randomised 596 live kidney donors to either LDN or ODN arms. All studies were assessed as having low or unclear risk of bias for selection bias, allocation bias, incomplete outcome data and selective reporting bias. Four of six studies had high risk of bias for blinding. Various different combinations of techniques were used in each study, resulting in heterogeneity in the results. The conversion rate from LDN to ODN ranged from 1% to 1.8%. LDN was generally found to be associated with reduced analgesia use, shorter hospital stay, and faster return to normal physical functioning. The extracted kidney was exposed to longer warm ischaemia periods (2 to 17 minutes) with no associated short‐term consequences. ODN was associated with shorter duration of procedure. For those outcomes that could be meta‐analysed there were no significant differences between LDN or ODN for perioperative complications (RR 0.87, 95% CI 0.47 to 4.59), reoperations (RR 0.57, 95% CI 0.09 to 3.64), early graft loss (RR 0.31, 95% CI 0.06 to 1.48), delayed graft function (RR 1.09, 95% CI 0.52 to 2.30), acute rejection (RR 1.41, 95 % CI 0.87 to 2.27), ureteric complications (RR 1.51, 95% CI 0.69 to 3.31), kidney function at one year (SMD 0.15, 95% CI ‐0.11 to 0.41) or graft loss at one year (RR 0.76, 95% CI 0.15 to 3.85).
Authors' conclusions
LDN is associated with less pain compared with open surgery; however, there are equivalent numbers of complications and occurrences of perioperative events that require further intervention. Kidneys obtained using LDN procedures were exposed to longer warm ischaemia periods than ODN‐acquired grafts, although this has not been reported as being associated with short‐term consequences.
Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation after circulatory death (DCD) ...donors have been used to increase transplant rates, but these organs are susceptible to cold ischemic injury in the storage period before transplantation, the clinical consequence of which is high rates of delayed graft function (DGF). Normothermic machine perfusion (NMP) is an emerging technique that circulates a warmed, oxygenated red-cell-based perfusate through the kidney to maintain near-physiological conditions. We conducted a randomized controlled trial to compare the outcome of DCD kidney transplants after conventional static cold storage (SCS) alone or SCS plus 1-h NMP. A total of 338 kidneys were randomly allocated to SCS (n = 168) or NMP (n = 170), and 277 kidneys were included in the final intention-to-treat analysis. The primary endpoint was DGF, defined as the requirement for dialysis in the first 7 d after transplant. The rate of DGF was 82 of 135 (60.7%) in NMP kidneys versus 83 of 142 (58.5%) in SCS kidneys (adjusted odds ratio (95% confidence interval) 1.13 (0.69-1.84); P = 0.624). NMP was not associated with any increase in transplant thrombosis, infectious complications or any other adverse events. A 1-h period of NMP at the end of SCS did not reduce the rate of DGF in DCD kidneys. NMP was demonstrated to be feasible, safe and suitable for clinical application. Trial registration number: ISRCTN15821205 .
Background
Kidney transplantation is the treatment of choice for patients with end‐stage kidney disease. In a previous review we concluded that the routine use of ureteric stents in kidney ...transplantation reduces the incidence of major urological complications (MUC). Unfortunately, this reduction appears to lead to a concomitant rise in urinary tract infections (UTI). For kidney recipients UTI is now the commonest post‐transplant complication. This represents a considerable risk to the immunosuppressed transplant recipient, particularly in the era of increased immunologically challenging transplants. There are a number of different approaches taken when considering ureteric stenting and these are associated with differing degrees of morbidity and hospital cost.
Objectives
This review aimed to look at the benefits and harms of early versus late removal of the ureteric stent in kidney transplant recipients.
Search methods
We searched the Cochrane Kidney and Transplant Specialised Register up to 27 March 2017 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register Search Portal and ClinicalTrials.gov.
Selection criteria
All RCTs and quasi‐RCTs were included in our meta‐analysis. We included recipients of kidney transplants regardless of demography (adults or children) or the type of stent used.
Data collection and analysis
Two authors reviewed the identified studies to ascertain if they met inclusion criteria. We designated removal of a ureteric stent before the third postoperative week (< day 15) or during the index transplant admission as "early" removal. The studies were assessed for quality using the risk of bias tool. The primary outcome of interest was the incidence of MUC. Further outcomes of interest were the incidence of UTI, idiosyncratic stent‐related complications, hospital‐related costs and adverse events. A subgroup analysis was performed examining the difference in complications reported depending on the type of ureteric stent used; bladder indwelling (BI) versus per‐urethral (PU). Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) with 95% confidence intervals (CI).
Main results
Five studies (1127 patients) were included in our analysis. Generally the risk of bias of the included studies was judged low or unclear; they addressed the research question and utilised a prospective randomised design. It is uncertain whether early stent removal verus late stent removal improved the incidence of MUC (5 studies, 1127 participants: RR 1.87, 95% CI 0.61 to 5.71; I2 = 21%; low certainty evidence). The incidence of UTI may be reduced in the early stent removal group (5 studies, 1127 participants: RR 0.49 95% CI 0.30 to 0.81; I2 = 59%; moderate certainty evidence). This possible reduction in the UTI incidence was only apparent if a BI stent was used, (3 studies, 539 participants, RR 0.45 95% CI 0.29 to 0.70; I2 = 13%; moderate certainty evidence). However, if an externalised PU stent was used there was no discernible difference in UTI incidence between the early and late group (2 studies, 588 participants: RR 0.60 95% CI 0.17, 2.03; I2 = 83%; low certainty evidence). Data on health economics and quality of life outcomes were lacking.
Authors' conclusions
Early removal of ureteric stents following kidney transplantation may reduce the incidence of UTI while it uncertain if there is a higher risk of MUC. BI stents are the optimum method for achieving this benefit.
Background
Chemotherapy-associated liver injury is a major cause for concern when treating patients with colorectal liver metastases. The aim of this review was to determine the pathological effect ...of specific chemotherapy regimens on the hepatic parenchyma as well as on surgical morbidity, mortality and overall survival.
Methods
A systematic review of the published literature and a meta-analysis were performed. For each of the variables under consideration, the effects of different chemotherapy regimens were determined by calculation of relative risks by a random-effects model.
Results
Hepatic parenchymal injury is regimen specific, with oxaliplatin-based regimens being associated with grade 2 or greater sinusoidal injury (number needed to harm 8; 95 % confidence interval CI 6.4–13.6), whereas irinotecan-based regimens associated with steatohepatitis (number needed to harm 12; 95 % CI 7.8–26). The use of bevacizumab alongside FOLFOX reduces the risk of grade 2 or greater sinusoidal injury (relative risk 0.34; 95 % CI 0.15–0.75).
Conclusions
Chemotherapy before resection of colorectal liver metastases is associated with an increased risk of regimen-specific liver injury. This liver injury may have implications for the functional reserve of the liver for patients undergoing major hepatectomy for colorectal liver metastases.
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.
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