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Journal of Tissue Engineering 2019A bioartificial endocrine pancreas is proposed as a future alternative to current treatment options. Patients with insulin-secretion deficiency might benefit. This is... (Review)
Review
A bioartificial endocrine pancreas is proposed as a future alternative to current treatment options. Patients with insulin-secretion deficiency might benefit. This is the first systematic review that provides an overview of scaffold materials and techniques for insulin-secreting cells or cells to be differentiated into insulin-secreting cells. An electronic literature survey was conducted in PubMed/MEDLINE and Web of Science, limited to the past 10 years. A total of 197 articles investigating 60 different materials met the inclusion criteria. The extracted data on materials, cell types, study design, and transplantation sites were plotted into two evidence gap maps. Integral parts of the tissue engineering network such as fabrication technique, extracellular matrix, vascularization, immunoprotection, suitable transplantation sites, and the use of stem cells are highlighted. This systematic review provides an evidence-based structure for future studies. Accumulating evidence shows that scaffold-based tissue engineering can enhance the viability and function or differentiation of insulin-secreting cells both in vitro and in vivo.
PubMed: 31700597
DOI: 10.1177/2041731419884708 -
Transplant Infectious Disease : An... Dec 2022We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) and the risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) and the risk factors involved for an impaired response.
METHODS
We did a systematic review and meta-analysis of studies published up until January 11, 2022, that reported immunogenicity of COVID-19 vaccine among SOT. The study is registered with PROSPERO, number CRD42022300547.
RESULTS
Of the 1527 studies, 112 studies, which involved 15391 SOT and 2844 healthy controls, were included. SOT showed a low humoral response (effect size [ES]: 0.44 [0.40-0.48]) in overall and in control studies (log-Odds-ratio [OR]: -4.46 [-8.10 to -2.35]). The humoral response was highest in liver (ES: 0.67 [0.61-0.74]) followed by heart (ES: 0.45 [0.32-0.59]), kidney (ES: 0.40 [0.36-0.45]), kidney-pancreas (ES: 0.33 [0.13-0.53]), and lung (0.27 [0.17-0.37]). The meta-analysis for standard and booster dose (ES: 0.43 [0.39-0.47] vs. 0.51 [0.43-0.54]) showed a marginal increase of 18% efficacy. SOT with prior infection had higher response (ES: 0.94 [0.92-0.96] vs. ES: 0.40 [0.39-0.41]; p-value < .01). The seroresponse with mRNA-12723 mRNA was highest 0.52 (0.40-0.64). Mycophenolic acid (OR: 1.42 [1.21-1.63]) and Belatacept (OR: 1.89 [1.3-2.49]) had highest risk for nonresponse. SOT had a parallelly decreased cellular response (ES: 0.42 [0.32-0.52]) in overall and control studies (OR: -3.12 [-0.4.12 to -2.13]).
INTERPRETATION
Overall, SOT develops a suboptimal response compared to the general population. Immunosuppression including mycophenolic acid, belatacept, and tacrolimus is associated with decreased response. Booster doses increase the immune response, but further upgradation in vaccination strategy for SOT is required.
Topics: Humans; Abatacept; COVID-19; COVID-19 Vaccines; Mycophenolic Acid; Organ Transplantation; Transplant Recipients
PubMed: 35924679
DOI: 10.1111/tid.13926 -
Reviews in Cardiovascular Medicine Dec 2020Cardiovascular events are among the most common causes of late death in the transplant recipient (Tx) population. Moreover, major cardiac surgical procedures are more... (Meta-Analysis)
Meta-Analysis
Cardiovascular events are among the most common causes of late death in the transplant recipient (Tx) population. Moreover, major cardiac surgical procedures are more challenging and risky due to immunosuppression and the potential impact on the transplanted organ's functional capacity. We aimed to assess open cardiac surgery safety in abdominal solid organ transplant recipients, comparing the postoperative outcomes with those of nontransplant (N-Tx) patients. Electronic databases of PubMed, EMBASE, and SCOPUS were searched. The endpoints were: overall rate of infectious complications (wound infection, septicemia, pneumonia), cardiovascular and renal events (stroke, cardiac tamponade, acute kidney failure), 30-days, 5-years, and 10-years mortality post-cardiac surgery interventions in patients with and without prior solid organ transplantation. This meta-analysis included five studies. Higher rates of wound infection (Tx vs. N-Tx: OR: 2.03, 95% CI: 1.54 to 2.67, I2 = 0%), septicemia (OR: 3.91, 95% CI: 1.40 to 10.92, I2 = 0%), cardiac tamponade (OR: 1.83, 95% CI: 1.28 to 2.62, I2 = 0%) and kidney failure (OR: 1.70, 95 %CI: 1.44 to 2.02, I2 = 89%) in transplant recipients were reported. No significant differences in pneumonia occurrence (OR: 0.95, 95% CI: 0.71 to 1.27, I2 = 0%) stroke (OR: 0.89, 95% CI: 0.54 to 1.48, I2 = 78%) and 30-day mortality (OR: 1.92, 95% CI: 0.97 to 3.80, I2 = 0%) were observed. Surprisingly, 5-years (OR: 3.74, 95% CI: 2.54 to 5.49, I2 = 0%) and 10-years mortality rates were significantly lower in the N-Tx group (OR: 3.32, 95% CI: 2.35 to 4.69, I2 = 0%). Our study reveals that open cardiac surgery in transplant recipients is associated with worse postoperative outcomes and higher long-term mortality rates.
Topics: Aged; Cardiac Surgical Procedures; Female; Humans; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Pancreas Transplantation; Postoperative Complications; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 33388004
DOI: 10.31083/j.rcm.2020.04.192 -
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 -
Transplantation Reviews (Orlando, Fla.) Dec 2021High quality sleep of sufficient duration is vital to overall health and wellbeing. Self-reported poor quality of sleep, sleep reported as irregular in timing, marked by... (Review)
Review
BACKGROUND
High quality sleep of sufficient duration is vital to overall health and wellbeing. Self-reported poor quality of sleep, sleep reported as irregular in timing, marked by frequent awakenings, or shortened in duration, is common across the solid-organ transplant trajectory.
AIM
This Systematic Review aimed to summarize available literature on rates of self-reported poor quality of sleep among solid organ transplant candidates and recipients.
METHODS
A systematic search of published literature was conducted in PubMed/MEDLINE, Embase, Web of Science, CINHAL, and PsychInfo databases with no date restrictions. Original articles in the English language describing self-reported quality of sleep using standardized questionnaires in adults either waitlisted for, or who received a solid organ transplant (heart, lung, kidney, liver, pancreas, or multi-solid organ) were included.
RESULTS
Of a potential 2054 articles identified, 44 were included (63.6% renal transplant, 20.5% liver transplant, 11.4% lung transplant, and 4.5% included multiple organ transplant populations), with the majority (68.2%) focusing only on post-transplant populations. No included articles focused solely on heart or pancreas transplant populations. On average, the transplant population with the greatest improvement in quality of sleep (reported as poor sleep quality, insomnia, sleep disturbance, or sleep dissatisfaction) from transplant candidacy to post-transplantation were renal transplant (from 53.5% pre, to 38.9% post) followed by liver transplant patients (from 52.8% pre, to 46.3% post), while lung transplant patients remained similar pre- to post-transplantation (55.6% pre, to 52% post). Poor quality of sleep was frequently associated with anxiety and depression, poorer quality of life, restless legs syndrome, and higher comorbidity.
CONCLUSIONS
Reports of poor quality of sleep are highly prevalent across all solid-organ transplant populations, both pre- and post-transplantation. Future studies should assess quality of sleep longitudinally throughout all phases of the transplantation trajectory, with more research focusing on how to optimize sleep in solid organ transplant populations.
Topics: Adult; Humans; Kidney Transplantation; Organ Transplantation; Quality of Life; Self Report; Sleep; Transplant Recipients
PubMed: 34534733
DOI: 10.1016/j.trre.2021.100650 -
Clinical Epigenetics Feb 2022Although kidney transplantation improves patient survival and quality of life, long-term results are hampered by both immune- and non-immune-mediated complications....
BACKGROUND
Although kidney transplantation improves patient survival and quality of life, long-term results are hampered by both immune- and non-immune-mediated complications. Current biomarkers of post-transplant complications, such as allograft rejection, chronic renal allograft dysfunction, and cutaneous squamous cell carcinoma, have a suboptimal predictive value. DNA methylation is an epigenetic modification that directly affects gene expression and plays an important role in processes such as ischemia/reperfusion injury, fibrosis, and alloreactive immune response. Novel techniques can quickly assess the DNA methylation status of multiple loci in different cell types, allowing a deep and interesting study of cells' activity and function. Therefore, DNA methylation has the potential to become an important biomarker for prediction and monitoring in kidney transplantation.
PURPOSE OF THE STUDY
The aim of this study was to evaluate the role of DNA methylation as a potential biomarker of graft survival and complications development in kidney transplantation. MATERIAL AND METHODS: A systematic review of several databases has been conducted. The Newcastle-Ottawa scale and the Jadad scale have been used to assess the risk of bias for observational and randomized studies, respectively.
RESULTS
Twenty articles reporting on DNA methylation as a biomarker for kidney transplantation were included, all using DNA methylation for prediction and monitoring. DNA methylation pattern alterations in cells isolated from different tissues, such as kidney biopsies, urine, and blood, have been associated with ischemia-reperfusion injury and chronic renal allograft dysfunction. These alterations occurred in different and specific loci. DNA methylation status has also proved to be important for immune response modulation, having a crucial role in regulatory T cell definition and activity. Research also focused on a better understanding of the role of this epigenetic modification assessment for regulatory T cells isolation and expansion for future tolerance induction-oriented therapies.
CONCLUSIONS
Studies included in this review are heterogeneous in study design, biological samples, and outcome. More coordinated investigations are needed to affirm DNA methylation as a clinically relevant biomarker important for prevention, monitoring, and intervention.
Topics: Biomarkers; DNA Methylation; Graft Rejection; Humans; Kidney Neoplasms; Kidney Transplantation; Risk Assessment
PubMed: 35130936
DOI: 10.1186/s13148-022-01241-7 -
BioMed Research International 2023Pancreatic trauma is an uncommon injury that occurs usually in a young population and is frequently overlooked and not readily appreciated on initial examination.... (Review)
Review
BACKGROUND
Pancreatic trauma is an uncommon injury that occurs usually in a young population and is frequently overlooked and not readily appreciated on initial examination. Nowadays, the diagnosis and management of pancreatic trauma are still controversial, and there is no gold standard for the treatment. The aim of this study is to describe our experience in the management of blunt pancreatic trauma with a laparoscopic approach and review the literature on laparoscopic management of pancreatic trauma.
METHODS
A systematic literature review was performed, and 40 cases were reported and analysed; 10 cases were excluded because the complete data were not retrievable. We also reported our experience with the case of an 18-year-old male diagnosed with a deep laceration of the pancreas between body and tail, involving the main pancreatic duct, and with a concomitant hematoma. The patient underwent exploratory laparoscopy with abdominal toilet, necrosectomy, and suture of main pancreatic duct; the total blood loss was less than 200 ml, and the total operative time was 180 minutes. The patient recovered uneventfully and was discharged on the 6th postoperative day.
RESULTS
30 patients with pancreatic trauma, 10 adults and 20 pediatrics (mean age 28.2 years and 10.5 years), underwent a total laparoscopic approach: 2 distal pancreatic-splenectomy, 22 spleen-preserving distal pancreatectomy, and 6 laparoscopic drainage. The mean operative time for the adult and pediatric populations was 160.6 and 214.5 minutes, the mean estimated blood loss was 400 ml and 75 ml, and the mean hospital stay was 14.9 and 9 days, respectively.
CONCLUSION
Laparoscopic management for pancreatic trauma can be considered feasible and safe when performed by an experienced laparoscopic pancreatic team, and in such a setting, it can be considered a viable alternative to open surgery, offering the well-known benefits of minimally invasive surgery.
Topics: Male; Humans; Adult; Child; Adolescent; Pancreas; Pancreatectomy; Pancreatic Diseases; Spleen; Laparoscopy; Abdominal Injuries; Wounds, Nonpenetrating; Pancreatic Neoplasms; Treatment Outcome; Retrospective Studies
PubMed: 37810623
DOI: 10.1155/2023/9296570 -
Scientific Reports Feb 2021Prophylactic drainage after major liver resection remains controversial. This systematic review and meta-analysis evaluate the value of prophylactic drainage after major... (Meta-Analysis)
Meta-Analysis
Prophylactic drainage after major liver resection remains controversial. This systematic review and meta-analysis evaluate the value of prophylactic drainage after major liver resection. PubMed, Web of Science, and Cochrane Central were searched. Postoperative bile leak, bleeding, interventional drainage, wound infection, total complications, and length of hospital stay were the outcomes of interest. Dichotomous outcomes were presented as odds ratios (OR) and for continuous outcomes, weighted mean differences (MDs) were computed by the inverse variance method. Summary effect measures are presented together with their corresponding 95% confidence intervals (CI). The certainty of evidence was evaluated using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach, which was mostly moderate for evaluated outcomes. Three randomized controlled trials and five non-randomized trials including 5,050 patients were included. Bile leakage rate was higher in the drain group (OR: 2.32; 95% CI 1.18-4.55; p = 0.01) and interventional drains were inserted more frequently in this group (OR: 1.53; 95% CI 1.11-2.10; p = 0.009). Total complications were higher (OR: 1.71; 95% CI 1.45-2.03; p < 0.001) and length of hospital stay was longer (MD: 1.01 days; 95% CI 0.47-1.56 days; p < 0.001) in the drain group. The use of prophylactic drainage showed no beneficial effects after major liver resection; however, the definitions and classifications used to report on postoperative complications and surgical complexity are heterogeneous among the published studies. Further well-designed RCTs with large sample sizes are required to conclusively determine the effects of drainage after major liver resection.
Topics: Abdomen; Drainage; Hepatectomy; Humans; Length of Stay; Liver; Pancreas; Postoperative Complications; Time Factors
PubMed: 33542274
DOI: 10.1038/s41598-021-82333-x -
International Journal of Surgery... Nov 2021Although minimally invasive technology has been widely used in hepatectomy, it remains controversial with regards to liver transplantation, especially in donors right... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although minimally invasive technology has been widely used in hepatectomy, it remains controversial with regards to liver transplantation, especially in donors right hepatectomy. Herein, we compared the short-term safety and efficacy of minimally invasive donors right hepatectomy (MIDRH) with open donors right hepatectomy (ODRH).
METHODS
A systematic literature search was carried out using PubMed, Embase, Web of Science and the Cochrane Library database in order to identify comparison studies of MIDRH and ODRH. Next, we obtained the relevant data, and carried out the meta-analysis.
RESULTS
This meta-analysis included 12 studies, which included 1755 cases that underwent donors right hepatectomy. Compared to ODRH, patients that underwent MIDRH had less bleeding (SWD = -0.52, p<0.001), shorter hospital stays (SWD = -0.58, p < 0.001) and lower overall postoperative complications of donors (RR = 0.74, p = 0.008). However, MIDRH was found to be associated with prolonged operative times (SWD = 0.74, p < 0.001), as well as a higher rate of biliary complications in donors (RR = 2.26, p = 0.007) and recipients (RR = 1.69, p < 0.001). There were no statistically significant differences between MIDRH and ODRH in postoperative liver function, rate of major complications and vascular complications of both donors and recipients and overall postoperative complications.
DISCUSSION
MIDRH is superior to ODRH with regards to intraoperative bleeding, postoperative hospital stay and overall donor complications. Although biliary-related complications are higher, it is feasible to develop MIDRH in experienced liver transplant centers. However, higher-quality research is still needed for corroboration.
Topics: Hepatectomy; Humans; Laparoscopy; Length of Stay; Liver Transplantation; Living Donors; Operative Time; Postoperative Complications; Tissue and Organ Harvesting
PubMed: 34688930
DOI: 10.1016/j.ijsu.2021.106152 -
The Cochrane Database of Systematic... Mar 2021Graft thrombosis is a well-recognised complication of solid organ transplantation and is one of the leading causes of graft failure. Currently there are no standardised... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Graft thrombosis is a well-recognised complication of solid organ transplantation and is one of the leading causes of graft failure. Currently there are no standardised protocols for thromboprophylaxis. Many transplant units use unfractionated heparin (UFH) and fractionated heparins (low molecular weight heparin; LMWH) as prophylaxis for thrombosis. Antiplatelet agents such as aspirin are routinely used as prophylaxis of other thrombotic conditions and may have a role in preventing graft thrombosis. However, any pharmacological thromboprophylaxis comes with the theoretical risk of increasing the risk of major blood loss following transplant. This review looks at benefits and harms of thromboprophylaxis in patients undergoing solid organ transplantation.
OBJECTIVES
To assess the benefits and harms of instituting thromboprophylaxis to patients undergoing solid organ transplantation.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 10 November 2020 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
We included all randomised controlled trials (RCTs) and quasi-RCTs designed to examine interventions to prevent thrombosis in solid organ transplant recipients. All donor types were included (donor after circulatory (DCD) and brainstem death (DBD) and live transplantation). There was no upper age limit for recipients in our search.
DATA COLLECTION AND ANALYSIS
The results of the literature search were screened and data collected by two independent authors. Dichotomous outcome results were expressed as risk ratio (RR) with 95% confidence intervals (CI). Random effects models were used for data analysis. Risk of bias was independently assessed by two authors using the risk of bias assessment tool. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
We identified nine studies (712 participants). Seven studies (544 participants) included kidney transplant recipients, and studies included liver transplant recipients. We did not identify any study enrolling heart, lung, pancreas, bowel, or any other solid organ transplant recipient. Selection bias was high or unclear in eight of the nine studies; five studies were at high risk of bias for performance and/or detection bias; while attrition and reporting biases were in general low or unclear. Three studies (180 participants) primarily investigated heparinisation in kidney transplantation. Only two studies reported on graft vessel thrombosis in kidney transplantation (144 participants). These small studies were at high risk of bias in several domains and reported only two graft thromboses between them; it therefore remains unclear whether heparin decreases the risk of early graft thrombosis or non-graft thrombosis (very low certainty). UFH may make little or no difference versus placebo to the rate of major bleeding events in kidney transplantation (3 studies, 155 participants: RR 2.92, 95% CI 0.89 to 9.56; I² = 0%; low certainty evidence). Sensitivity analysis using a fixed-effect model suggested that UFH may increase the risk of haemorrhagic events compared to placebo (RR 3.33, 95% CI 1.04 to 10.67, P = 0.04). Compared to control, any heparin (including LMWH) may make little or no difference to the number of major bleeding events (3 studies, 180 participants: RR 2.70, 95% CI 0.89 to 8.19; I² = 0%; low certainty evidence) and had an unclear effect on risk of readmission to intensive care (3 studies, 180 participants: RR 0.68, 95% CI 0.12 to 3.90, I² = 45%; very low certainty evidence). The effect of heparin on our other outcomes (including death, patient and graft survival, transfusion requirements) remains unclear (very low certainty evidence). Three studies (144 participants) investigated antiplatelet interventions in kidney transplantation: aspirin versus dipyridamole (1), and Lipo-PGE plus low-dose heparin to "control" in patients who had a diagnosis of acute rejection (2). None of these reported on early graft thromboses. The effect of aspirin, dipyridamole and Lipo PGE plus low-dose heparin on any outcomes is unclear (very low certainty evidence). Two studies (168 participants) assessed interventions in liver transplants. One compared warfarin versus aspirin in patients with pre-existing portal vein thrombosis and the other investigated plasmapheresis plus anticoagulation. Both studies were abstract-only publications, had high risk of bias in several domains, and no outcomes could be meta-analysed. Overall, the effect of any of these interventions on any of our outcomes remains unclear with no evidence to guide anti-thrombotic therapy in standard liver transplant recipients (very low certainty evidence).
AUTHORS' CONCLUSIONS
Overall, there is a paucity of research in the field of graft thrombosis prevention. Due to a lack of high quality evidence, it remains unclear whether any therapy is able to reduce the rate of early graft thrombosis in any type of solid organ transplant. UFH may increase the risk of major bleeding in kidney transplant recipients, however this is based on low certainty evidence. There is no evidence from RCTs to guide anti-thrombotic strategies in liver, heart, lung, or other solid organ transplants. Further studies are required in comparing anticoagulants, antiplatelets to placebo in solid organ transplantation. These should focus on outcomes such as early graft thrombosis, major haemorrhagic complications, return to theatre, and patient/graft survival.
Topics: Anticoagulants; Aspirin; Bias; Dipyridamole; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Kidney Transplantation; Liver Transplantation; Placebos; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Thrombosis; Transplant Recipients; Warfarin
PubMed: 33720396
DOI: 10.1002/14651858.CD011557.pub2