-
The Cochrane Database of Systematic... Sep 2022Non-adherence to immunosuppressant therapy is a significant concern following a solid organ transplant, given its association with graft failure. Adherence to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-adherence to immunosuppressant therapy is a significant concern following a solid organ transplant, given its association with graft failure. Adherence to immunosuppressant therapy is a modifiable patient behaviour, and different approaches to increasing adherence have emerged, including multi-component interventions. There has been limited exploration of the effectiveness of interventions to increase adherence to immunosuppressant therapy.
OBJECTIVES
This review aimed to look at the benefits and harms of using interventions for increasing adherence to immunosuppressant therapies in solid organ transplant recipients, including adults and children with a heart, lung, kidney, liver and pancreas transplant.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 14 October 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were 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), quasi-RCTs, and cluster RCTs examining interventions to increase immunosuppressant adherence following a solid organ transplant (heart, lung, kidney, liver, pancreas) were included. There were no restrictions on language or publication type.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles and abstracts of identified records, evaluated study quality and assessed the quality of the evidence using the GRADE approach. The risk of bias was assessed using the Cochrane tool. The ABC taxonomy for measuring medication adherence provided the analysis framework, and the primary outcomes were immunosuppressant medication initiation, implementation (taking adherence, dosing adherence, timing adherence, drug holidays) and persistence. Secondary outcomes were surrogate markers of adherence, including self-reported adherence, trough concentration levels of immunosuppressant medication, acute graft rejection, graft loss, death, hospital readmission and health-related quality of life (HRQoL). Meta-analysis was conducted where possible, and narrative synthesis was carried out for the remainder of the results.
MAIN RESULTS
Forty studies involving 3896 randomised participants (3718 adults and 178 adolescents) were included. Studies were heterogeneous in terms of the type of intervention and outcomes assessed. The majority of studies (80%) were conducted in kidney transplant recipients. Two studies examined paediatric solid organ transplant recipients. The risk of bias was generally high or unclear, leading to lower certainty in the results. Initiation of immunosuppression was not measured by the included studies. There is uncertain evidence of an association between immunosuppressant medication adherence interventions and the proportion of participants classified as adherent to taking immunosuppressant medication (4 studies, 445 participants: RR 1.09, 95% CI 0.95 to 1.20; I² = 78%). There was very marked heterogeneity in treatment effects between the four studies evaluating taking adherence, which may have been due to the different types of interventions used. There was evidence of increasing dosing adherence in the intervention group (8 studies, 713 participants: RR 1.14, 95% CI 1.03 to 1.26, I² = 61%). There was very marked heterogeneity in treatment effects between the eight studies evaluating dosing adherence, which may have been due to the different types of interventions used. It was uncertain if an intervention to increase immunosuppressant adherence had an effect on timing adherence or drug holidays. There was limited evidence that an intervention to increase immunosuppressant adherence had an effect on persistence. There was limited evidence that an intervention to increase immunosuppressant adherence had an effect on secondary outcomes. For self-reported adherence, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the proportion of participants classified as medically adherent to immunosuppressant therapy (9 studies, 755 participants: RR 1.21, 95% CI 0.99 to 1.49; I² = 74%; very low certainty evidence). Similarly, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the mean adherence score on self-reported adherence measures (5 studies, 471 participants: SMD 0.65, 95% CI -0.31 to 1.60; I² = 96%; very low certainty evidence). For immunosuppressant trough concentration levels, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the proportion of participants who reach target immunosuppressant trough concentration levels (4 studies, 348 participants: RR 0.98, 95% CI 0.68 to 1.40; I² = 40%; very low certainty evidence). It is uncertain whether an intervention to increase adherence to immunosuppressant medication may reduce hospitalisations (5 studies, 460 participants: RR 0.67, 95% CI 0.44 to 1.02; I² = 64%; low certainty evidence). There were limited, low certainty effects on patient-reported health outcomes such as HRQoL. There was no clear evidence to determine the effect of interventions on secondary outcomes, including acute graft rejection, graft loss and death. No harms from intervention participation were reported.
AUTHORS' CONCLUSIONS
Interventions to increase taking and dosing adherence to immunosuppressant therapy may be effective; however, our findings suggest that current evidence in support of interventions to increase adherence to immunosuppressant therapy is overall of low methodological quality, attributable to small sample sizes, and heterogeneity identified for the types of interventions. Twenty-four studies are currently ongoing or awaiting assessment (3248 proposed participants); therefore, it is possible that findings may change with the inclusion of these large ongoing studies in future updates.
Topics: Adolescent; Adult; Child; Graft Rejection; Humans; Immunosuppressive Agents; Medication Adherence; Organ Transplantation; Transplant Recipients
PubMed: 36094829
DOI: 10.1002/14651858.CD012854.pub2 -
Stem Cell Reviews and Reports Oct 2023The possible beneficial effects of stem cell-derived EV on ischemia-reperfusion injury (IRI) in organ transplantation have been frequently investigated; however, the... (Review)
Review
BACKGROUND
The possible beneficial effects of stem cell-derived EV on ischemia-reperfusion injury (IRI) in organ transplantation have been frequently investigated; however, the source of EV, as well as the methods of isolation and administration vary widely. We conducted a systematic review to summarize current pre-clinical evidence on stem cell-derived EV therapy for IRI of transplantable organs.
METHODS
PubMed, Embase and Web of Science were searched from inception until August 19th, 2022, for studies on stem cell-derived EV therapy for IRI after heart, kidney, liver, pancreas, lung and intestine transplantation. The Systematic Review Center for Laboratory animal Experiments (SYRCLE) guidelines were followed to assess potential risk of bias.
RESULTS
The search yielded 4153 unique articles, of which 96 were retained. We identified 32 studies on cardiac IRI, 38 studies on renal IRI, 21 studies on liver IRI, four studies on lung IRI and one study on intestinal IRI. Most studies used rodent models of transient ischemic injury followed by in situ reperfusion. In all studies, EV therapy was associated with improved outcome albeit to a variable degree. EV-therapy reduced organ injury and improved function while displaying anti-inflammatory-, immunomodulatory- and pro-regenerative properties.
CONCLUSION
A multitude of animal studies support the potential of stem cell-derived EV-therapy to alleviate IRI after solid organ transplantation but suffer from low reporting quality and wide methodological variability. Future studies should focus on determining optimal stem cell source, dosage, and timing of treatment, as well as long-term efficacy in transplant models.
PubMed: 37548807
DOI: 10.1007/s12015-023-10573-7 -
International Journal of Organ... 2020An important aspect of donor management is the optimization of serum sodium levels. (Review)
Review
BACKGROUND
An important aspect of donor management is the optimization of serum sodium levels.
OBJECTIVE
To perform a systematic review to determine the effects of donor sodium levels on heart, lung, kidney, and pancreas graft function, recipient mortality, and to identify the optimal donor serum sodium target.
METHODS
We searched MEDLINE, Cochrane, Guideline databases, and trial registries from 1946 to May 2019 for studies investigating the effects of donor serum sodium levels on transplant outcomes in all non-hepatic organs. A two-step independent review process was used to identify relevant articles based on inclusion/exclusion criteria. We describe the results narratively, assess the risk of bias, and apply GRADE methodology to evaluate the certainty in the evidence.
RESULTS
We included 18 cohort studies in our final analysis (n=28,007). 3 of 4 studies demonstrated an association between donor serum sodium and successful organ transplantation. 5 studies reported no association with graft function, while 6 studies did. 5 studies reported on recipient survival, 3 of which suggested donor sodium is unlikely to be associated with recipient survival. The included studies had serious risk of bias, and the certainty in evidence was deemed to be very low.
CONCLUSION
In low risk of bias studies, donor sodium dysregulation is unlikely to affect kidney graft function or mortality of heart and kidney recipients, but the certainty in the evidence is very low due to inconsistency and imprecision. Further research is required to refine the serum sodium target range, quantify the dose-response curve, and identify organs most vulnerable to sodium dysregulation.
PubMed: 32832039
DOI: No ID Found -
Journal of Diabetes Science and... Jan 2020Pancreas transplantation is currently one of the best treatments proposed in highly selected patients with unstable and brittle type 1 diabetes. The objective of...
INTRODUCTION
Pancreas transplantation is currently one of the best treatments proposed in highly selected patients with unstable and brittle type 1 diabetes. The objective of pancreas transplantation is to restore normoglycemia and avoid the occurrence of complications associated with diabetes. Graft pancreatitis and thrombosis, arising from ischemia reperfusion injuries, are major causes of graft loss in the postoperative period. Ex situ perfusion, in hypothermic or normothermic settings, allowed to improve ischemic reperfusion injury in other organ transplantations (kidney, liver, or lung). The development of pancreatic graft perfusion techniques would limit these ischemic reperfusion injuries.
OBJECTIVE
Evaluation of the safety and feasibility of ex situ perfusion of pancreas for whole-organ transplantation.
METHODS
English literature about pancreas perfusion was analyzed using electronic database Medline via PubMed (1950-2018). Exclusion criteria were studies that did not specify the technical aspects of machine perfusion and studies focused only on pancreas perfusion for islet isolation.
RESULTS
Hypothermic machine perfusion for pancreas preservation has been evaluated in nine studies and normothermic machine perfusion in ten studies. We evaluated machine perfusion model, types of experimental model, anatomy, perfusion parameters, flushing and perfusion solution, length of perfusion, and comparison between static cold storage and perfusion.
CONCLUSIONS
This review compared ex vivo machine perfusion of experimental pancreas for whole-organ transplantation. Pancreas perfusion is feasible and could be a helpful tool to evaluate pancreas prior to transplantation. Pancreas perfusion (in hypothermic or normothermic settings) could reduce ischemic reperfusion injuries, and maybe could avoid pancreas thrombosis and reduce morbidity of pancreas transplantation.
Topics: Feasibility Studies; Humans; Pancreas; Pancreas Transplantation; Perfusion
PubMed: 31409133
DOI: 10.1177/1932296819869312 -
Liver International : Official Journal... Mar 2024To systematically review the literature for reports on Wolcott-Rallison syndrome, focusing on the spectrum and natural history, genotype-phenotype correlations, patient...
BACKGROUND AND AIMS
To systematically review the literature for reports on Wolcott-Rallison syndrome, focusing on the spectrum and natural history, genotype-phenotype correlations, patient and native liver survival, and long-term outcomes.
METHODS
PubMed, Livio, Google Scholar, Scopus and Web of Science databases were searched. Data on genotype, phenotype, therapy, cause of death and follow-up were extracted. Survival and correlation analyses were performed.
RESULTS
Sixty-two studies with 159 patients met the inclusion criteria and additional 30 WRS individuals were collected by personal contact. The median age of presentation was 2.5 months (IQR 2) and of death was 36 months (IQR 50.75). The most frequent clinical feature was neonatal diabetes in all patients, followed by liver impairment in 73%, impaired growth in 72%, skeletal abnormalities in 59.8%, the nervous system in 37.6%, the kidney in 35.4%, insufficient haematopoiesis in 34.4%, hypothyroidism in 14.8% and exocrine pancreas insufficiency in 10.6%. Episodes of acute liver failure were frequently reported. Liver transplantation was performed in six, combined liver-pancreas in one and combined liver-pancreas-kidney transplantation in two individuals. Patient survival was significantly better in the transplant cohort (p = .0057). One-, five- and ten-year patient survival rates were 89.4%, 65.5% and 53.1%, respectively. Liver failure was reported as the leading cause of death in 17.9% of cases. Overall survival was better in individuals with missense mutations (p = .013).
CONCLUSION
Wolcott-Rallison syndrome has variable clinical courses. Overall survival is better in individuals with missense mutations. Liver- or multi-organ transplantation is a feasible treatment option to improve survival.
Topics: Infant, Newborn; Humans; Infant; Follow-Up Studies; Diabetes Mellitus, Type 1; Osteochondrodysplasias; Diabetes Mellitus; eIF-2 Kinase; Epiphyses
PubMed: 38230874
DOI: 10.1111/liv.15834 -
Internal Medicine Journal Sep 2022Increased recipient and donor age are associated with worse solid organ pancreas transplant outcomes. However, donor and recipient age criteria vary between...
BACKGROUND
Increased recipient and donor age are associated with worse solid organ pancreas transplant outcomes. However, donor and recipient age criteria vary between jurisdictions. We systematically reviewed studies reporting the association between transplanting older recipients and donors beyond current Transplantation Society of Australia and New Zealand (TSANZ) limits with solid pancreas transplant outcomes.
AIMS
To review current outcomes of solid pancreas transplantation in recipients and donors over the TSANZ reference ages.
METHODS
Studies comparing transplant outcomes between a reference-age and an older-age donor (>45 years) or recipient (≥50 years) cohort for solid pancreas transplantation were included. Primary outcomes were pancreas/kidney graft and patient survival at 1 and 5 years. Secondary outcomes were post-transplant complications (graft thrombosis, acute rejection and relaparotomy rates).
RESULTS
Eleven studies were included (two studies assessing solid pancreas outcomes between older vs reference-aged donors and nine studies assessing outcomes between older vs reference-aged recipients). Seven of 11 studies were judged to be at high risk of bias. Primary and secondary outcomes were not significantly different between recipient age groups in nine studies. A sensitivity analysis of older versus reference-aged studies excluding studies at high risk of bias also showed non-inferior primary and secondary outcomes at 1 year. Two studies comparing outcomes by donor age showed worse graft survival but non-inferior patient survival with older donors.
CONCLUSION
Increased donor or recipient age alone should not absolutely contraindicate solid pancreas transplantation, especially if other risk predictors are minimised.
Topics: Aged; Graft Survival; Humans; Kidney Transplantation; Pancreas Transplantation; Retrospective Studies; Tissue Donors; Transplant Recipients; Treatment Outcome
PubMed: 34338407
DOI: 10.1111/imj.15464 -
Journal of Clinical Medicine Feb 2023Pancreatic resections for malignant or benign diseases are associated with major morbidity and changes in physiology. To reduce perioperative complications and enhance... (Review)
Review
INTRODUCTION
Pancreatic resections for malignant or benign diseases are associated with major morbidity and changes in physiology. To reduce perioperative complications and enhance recovery, many types of perioperative medical management have been introduced. The aim of this study was to provide an evidence-based overview on the best perioperative drug treatment.
METHODS
The electronic bibliographic databases Medline, Embase, CENTRAL, and Web of Science were systematically searched for randomized controlled trials (RCT) evaluating perioperative drug treatments in pancreatic surgery. The investigated drugs were somatostatin analogues, steroids, pancreatic enzyme replacement therapy (PERT), prokinetic therapy, antidiabetic drugs, and proton pump inhibitors (PPI). Targeted outcomes in each drug category were meta-analyzed.
RESULTS
A total of 49 RCT were included. The analysis of somatostatin analogues showed a significantly lower incidence of postoperative pancreatic fistula (POPF) in the somatostatin group compared to the control group (OR 0.58, 95% CI: 0.45 to 0.74). The comparison of glucocorticoids versus placebo showed significantly less POPF in the glucocorticoid group (OR 0.22, 95% CI: 0.07 to 0.77). There was no significant difference in DGE when erythromycin was compared to placebo (OR 0.33, 95% CI: 0.08 to 1.30). The other investigated drug regimens could only be analyzed qualitatively.
CONCLUSION
This systematic review provides a comprehensive overview on perioperative drug treatment in pancreatic surgery. Some often-prescribed perioperative drug treatments lack high quality evidence and further research is needed.
PubMed: 36902534
DOI: 10.3390/jcm12051750 -
Surgery Jan 2015Laparoscopic distal pancreatectomy is regarded as a feasible and safe surgical alternative to open distal pancreatectomy for lesions of the pancreatic tail and body. The... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Laparoscopic distal pancreatectomy is regarded as a feasible and safe surgical alternative to open distal pancreatectomy for lesions of the pancreatic tail and body. The aim of the present systematic review was to provide recommendations for clinical practice and research on the basis of surgical morbidity, such as pancreas fistula, delayed gastric empting, safety, and clinical significance of laparoscopic versus open distal pancreatectomy for malignant and nonmalignant diseases of the pancreas.
METHODS
A systematic literature search (MEDLINE) was performed to identify all types of studies comparing laparoscopic distal pancreatectomy and open distal pancreatectomy. Random effects meta-analyses were calculated after critical appraisal of the included studies and presented as odds ratios or mean differences each with corresponding 95% confidence intervals.
RESULTS
A total of 4,148 citations were retrieved initially; available data of 29 observational studies (3,701 patients overall) were included in the meta-analyses. Five systematic reviews on the same topic were found and critically appraised. Meta-analyses showed superiority of laparoscopic distal pancreatectomy in terms of blood loss, time to first oral intake, and hospital stay. All other parameters of operative morbidity and safety showed no difference. Data on oncologic radicality and effectiveness are limited.
CONCLUSION
Laparoscopic distal pancreatectomy seems to be a safe and effective alternative to open distal pancreatectomy. No more nonrandomized trials are needed within this context. A large, randomized trial is warranted and should focus on oncologic effectiveness, defined end points, and cost-effectiveness.
Topics: Humans; Laparoscopy; Pancreatectomy; Pancreatic Neoplasms; Randomized Controlled Trials as Topic
PubMed: 25482464
DOI: 10.1016/j.surg.2014.06.081 -
Transplantation Reviews (Orlando, Fla.) Jan 2016Pancreas or pancreatic islet transplantation is an important treatment option for insulin-dependent diabetes and its complications. However, as the pancreas is... (Review)
Review
Pancreas or pancreatic islet transplantation is an important treatment option for insulin-dependent diabetes and its complications. However, as the pancreas is particularly susceptible to ischaemic-reperfusion injury, the criteria for pancreas and islet donation are especially strict. With a chronic shortage of donors, one critical challenge is to maximise organ availability and expand the donor pool. To achieve that, continuous improvement in organ preservation is required, with the aims of reducing ischaemia-reperfusion injury, prolong preservation time and improve graft function. Static cold storage, the only method used in clinical pancreas and islet cell transplant currently, has likely reached its plateau. Machine perfusion, hypothermic or normothermic, could hold the key to improving donor pancreas quality as well as quantity available for transplant. This article reviews the literature on experimental models of pancreas machine perfusion, examines the benefits of machine perfusion, the technical aspects and their clinical implications.
Topics: Extracorporeal Circulation; Humans; Islets of Langerhans Transplantation; Organ Preservation
PubMed: 26253243
DOI: 10.1016/j.trre.2015.06.002 -
Experimental and Clinical... May 2021Induction immunosuppression for simultaneous pancreas-kidney transplant has helped reduce graft loss due to early rejection. Both thymoglobulin and interleukin 2... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Induction immunosuppression for simultaneous pancreas-kidney transplant has helped reduce graft loss due to early rejection. Both thymoglobulin and interleukin 2 receptor antagonists are the most commonly used induction agents; however, some high-volume centers prefer alemtuzumab.Thisnetwork meta-analysis aimedto compare differentinductionregimens for simultaneouspancreaskidney transplantin terms ofbothpancreas and patient graft survival, as well to assess acute rejection.
MATERIALS AND METHODS
A systematic review was conducted to identify randomized clinical trials up to October 31, 2019, that examined induction regimens for simultaneous pancreas-kidney transplant. Study characteristics, postoperative data (patient, pancreas, and kidney graft survival), complications (eg, bleeding), infection rates, and malignancy rates were extracted. We compared all regimens using randomeffects network meta-analyses to maintain randomization within trials.
RESULTS
This study identified 7 randomized clinical trials that involved 536 patients, which reported 5 induction regimens. These regimens included antithymocyte globulin (97 patients), alemtuzumab (42 patients), 2 doses (113 patients) or 5 doses (164 patients) of daclizumab, and no induction therapy (120 patients). In the network meta-analysis, a regimen with 2 doses of daclizumab was consistently ranked first for patient survival and kidney and pancreas graft survival. In contrast, alemtuzumab was ranked best for acute rejection (both pancreas and kidney). Rates of majorinfection (ie, cytomegalovirus) and malignancy were reported in 3 studies, precluding a reliable analysis.
CONCLUSIONS
Daclizumab with 2 doses, given before simultaneous pancreas-kidney transplant, was associated with the best rates of patient and graft survival. Despite the recent withdrawal of daclizumab, an alternative anti-interleukin 2 induction regimen (basiliximab) has demonstrated promising results in nonrandomized series, warranting that further highquality large-scale randomized clinical trials are still needed.
Topics: Alemtuzumab; Daclizumab; Humans; Immunosuppression Therapy; Kidney Transplantation; Neoplasms; Network Meta-Analysis; Pancreas Transplantation; Randomized Controlled Trials as Topic
PubMed: 34053419
DOI: 10.6002/ect.2020.0231