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Hepatobiliary Surgery and Nutrition Apr 2023
PubMed: 37124702
DOI: 10.21037/hbsn-23-110 -
Current Opinion in Organ Transplantation Dec 2019Although organ transplantation has become the standard life-saving strategy for patients with end-stage organ failure and those with malignancies, effective and safe... (Review)
Review
PURPOSE OF REVIEW
Although organ transplantation has become the standard life-saving strategy for patients with end-stage organ failure and those with malignancies, effective and safe therapeutic strategies to combat allograft loss remain to be established. With the emerging evidence suggesting the critical role of innate immunity in the mechanism of allograft injury, we summarize the latest understanding of macrophage-neutrophil cross-communication and discuss therapeutic prospects of their targeting in transplant recipients.
RECENT FINDINGS
Macrophages and neutrophils contribute to the pathogenesis of early peritransplant ischemia-reperfusion injury and subsequent allograft rejection immune cascade, primarily by exacerbating inflammatory response and tissue damage. Noteworthy, recent advances enabled to elucidate multifaceted functions of innate immune cells, which are not only deleterious but may also prove graft-protective. Indeed, the efficacy of macrophage polarizing regimens or macrophage-targeted migration have been recognized to create graft-protective local environment. Moreover, novel molecular mechanisms in the neutrophil function have been identified, such as neutrophil extracellular traps, tissue-repairing capability, crosstalk with macrophages and T cells as well as reverse migration into the circulation.
SUMMARY
As efficient strategies to manage allograft rejection and improve transplant outcomes are lacking, newly discovered, and therapeutically attractive innate immune cell functions warrant comprehensive preclinical and clinical attention.
Topics: Graft Rejection; Humans; Immunity, Innate; Reperfusion Injury
PubMed: 31592839
DOI: 10.1097/MOT.0000000000000709 -
BMC Nephrology Dec 2019The effects of Simultaneous Pancreas Kidney Transplantation (SPKT) on Peripheral Vascular Disease (PVD) warrants additional study and more target focus, since little is...
BACKGROUND
The effects of Simultaneous Pancreas Kidney Transplantation (SPKT) on Peripheral Vascular Disease (PVD) warrants additional study and more target focus, since little is known about the mid- and long-term effects on the progression of PVD after transplantation.
METHODS
101 SPKT and 26 Kidney Transplantation Alone (KTA) recipients with insulin-dependent diabetes mellitus (IDDM) were retrospectively evaluated with regard to graft and metabolic outcome. Special subgroup analysis was directed towards the development and progression of peripheral vascular complications (PVC) (amputation, ischemic ulceration, lower extremity angioplasty/ bypass surgery) after transplantation.
RESULTS
The 10-year patient survival was significantly higher in the SPKT group (SPKT: 82% versus KTA 40%; P < 0.001). KTA recipients had a higher prevalence of atherosclerotic risk factors, including coronary artery disease (P < 0.001), higher serum triglyceride levels (P = 0.049), higher systolic (P = 0.03) and diastolic (P = 0.02) blood pressure levels. The incidence of PVD before transplantation was comparable between both groups (P = 0.114). Risk factor adjusted multivariate analysis revealed that patients with SPKT had a significant lower amount (32%) of PVCs (32 PVCs in 21 out of 101 SPKT; P < 0.001) when compared to the KTA patients who developed a significant increase in PVCs to 69% of cases (18 PVCs in 11 out of 26 KTA; P < 0.001). In line mean values of HbA (P < 0.01) and serum triglycerides (P < 0.01) were significantly lower in patients with SPKT > 8 years after transplantation.
CONCLUSION
SPKT favorably slows down development and progression of PVD by maintaining a superior metabolic vascular risk profile in patients with IDDM1.
Topics: Adolescent; Adult; Aged; Child; Diabetes Mellitus; Female; Follow-Up Studies; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Pancreas Transplantation; Peripheral Vascular Diseases; Retrospective Studies; Survival Rate; Treatment Outcome; Young Adult
PubMed: 31815616
DOI: 10.1186/s12882-019-1649-7 -
Pancreas preservation time as a predictor of prolonged hospital stay after pancreas transplantation.The Journal of International Medical... Feb 2021Length of hospital stay is a sensitive indicator of short-term prognosis. In this retrospective study, we investigated how pancreas preservation time affects length of...
OBJECTIVE
Length of hospital stay is a sensitive indicator of short-term prognosis. In this retrospective study, we investigated how pancreas preservation time affects length of hospital stay after pancreas transplantation.
METHODS
Patients receiving pancreas transplantation (1998.7-2018.6) were identified from the Scientific Registry of Transplant Recipients database and grouped according to pancreas preservation time. We analyzed the relationship of pancreas preservation time with graft and patient survival and prolonged length of stay (PLOS; i.e., hospital stay ≥20 days).
RESULTS
We included 18,099 pancreas transplants in the survival analysis. Pancreas preservation time >20 hours had a significantly higher risk of graft failure than 8 to 12 hours. Pancreas preservation time was not significantly associated with patient survival. We included 17,567 pancreas transplants in the analysis for PLOS. Compared with 8 to 12 hours, pancreas preservation time >12 hours had a significantly higher PLOS risk, which increased with increased pancreas preservation time. In simultaneous pancreas-kidney transplantation, we also found that pancreas preservation time was positively associated with PLOS risk with pancreas preservation time >12 hours.
CONCLUSION
Pancreas preservation time is a sensitive predictor of PLOS. Transplant centers should minimize pancreas preservation time to optimize patient outcomes.
Topics: Graft Survival; Humans; Kidney Transplantation; Length of Stay; Pancreas; Pancreas Transplantation; Retrospective Studies; Treatment Outcome
PubMed: 33626941
DOI: 10.1177/0300060520987059 -
Journal of Nephrology Sep 2022Transplant nephropathology is a highly specialized field of pathology comprising both the evaluation of organ donor biopsy for organ allocation and post-transplant graft... (Review)
Review
BACKGROUND
Transplant nephropathology is a highly specialized field of pathology comprising both the evaluation of organ donor biopsy for organ allocation and post-transplant graft biopsy for assessment of rejection or graft damage. The introduction of digital pathology with whole-slide imaging (WSI) in clinical research, trials and practice has catalyzed the application of artificial intelligence (AI) for histopathology, with development of novel machine-learning models for tissue interrogation and discovery. We aimed to review the literature for studies specifically applying AI algorithms to WSI-digitized pre-implantation kidney biopsy.
METHODS
A systematic search was carried out in the electronic databases PubMed-MEDLINE and Embase until 25th September, 2021 with a combination of the key terms "kidney", "biopsy", "transplantation" and "artificial intelligence" and their aliases. Studies dealing with the application of AI algorithms coupled with WSI in pre-implantation kidney biopsies were included. The main theme addressed was detection and quantification of tissue components. Extracted data were: author, year and country of the study, type of biopsy features investigated, number of cases, type of algorithm deployed, main results of the study in terms of diagnostic outcome, and the main limitations of the study.
RESULTS
Of 5761 retrieved articles, 7 met our inclusion criteria. All studies focused largely on AI-based detection and classification of glomerular structures and to a lesser extent on tubular and vascular structures. Performance of AI algorithms was excellent and promising.
CONCLUSION
All studies highlighted the importance of expert pathologist annotation to reliably train models and the need to acknowledge clinical nuances of the pre-implantation setting. Close cooperation between computer scientists and practicing as well as expert renal pathologists is needed, helping to refine the performance of AI-based models for routine pre-implantation kidney biopsy clinical practice.
Topics: Algorithms; Artificial Intelligence; Biopsy; Humans; Intelligence; Kidney
PubMed: 35441256
DOI: 10.1007/s40620-022-01327-8 -
Cellular Immunology May 2020The gastrointestinal (GI) tract microbiota is an environmental factor that regulates host immunity in allo-transplantation (allo-Tx). It is required for the development... (Review)
Review
The gastrointestinal (GI) tract microbiota is an environmental factor that regulates host immunity in allo-transplantation (allo-Tx). It is required for the development of resistance against pathogens and the stabilization of mucosa-associated lymphoid tissue. The gut-microbiota axis may also precipitate allograft rejection by producing metabolites that activate host cell-mediated and humoral immunity. Here, we discuss new insights into microbial immunomodulation, highlighting ongoing attempts to affect commensal colonization in an attempt to ameliorate allograft rejection cascade. Recent progress on the use of antibiotics to modulate GI microbiota diversity and innate-adaptive immune interface are discussed. Our focus on the microbiota's influence of endoplasmic reticulum (ER) stress and autophagy signaling through hepatic EP4/CHOP/LC3B platforms reveals a novel molecular pathway and potential biomarkers determining the progression of allo-Tx damage. Understanding and harnessing the potential of microbiome/bacteriophage therapies may offer safe and effective means for personalized treatment to reduce risks of infections and immunosuppression in allo-Tx.
Topics: Animals; Gastrointestinal Microbiome; Humans; Organ Transplantation
PubMed: 32139071
DOI: 10.1016/j.cellimm.2020.104080 -
Scientific Reports Oct 2021Theoretically, pancreas transplant alone in uremic (PTAU) patients could also be one of the options for those waiting for both pancreas and kidney grafts, but it has... (Clinical Trial)
Clinical Trial
Theoretically, pancreas transplant alone in uremic (PTAU) patients could also be one of the options for those waiting for both pancreas and kidney grafts, but it has never been reported. There were 160 cases of pancreas transplant in this study, including 16% PTAU. The 5-year patient survival was 66.2% after PTAU, 94.5% after SPK, 95.8% after PAK, and 95.4% after PTA. Rejection of pancreas graft was significantly lower in PTAU group (3.8%), followed by 16.7% in pancreas after kidney transplant (PAK), 29.8% in simultaneous pancreas and kidney transplant (SPK) and 37.0% in pancreas transplant alone (PTA). Fasting blood sugar and serum HbA1c levels after PTAU were not significantly different from those by other subgroups. The 5-year death-censored pancreas graft survival was 100% after PTAU and PAK, and 97.0% after SPK and 77.9% after PTA. However, the 5-year death-uncensored pancreas graft survival was 67.0% after PTAU, 100% after PAK, 91.3% after SPK, and 74.0% after PTA. The superior graft survival in the PTAU group was achieved only if deaths with a functioning graft were censored. In conclusion, given the inferior patient survival outcome, PTAU is still not recommended unless SPK and PAK is not available. Although PTAU could be a treatment option for patients with diabetes complicated by end-stage renal disease (ESRD) in terms of surgical risks, endocrine function, and immunological and graft survival outcomes, modification of the organ allocation policies to prioritize SPK transplant in eligible patients should be the prime goal.
Topics: Adolescent; Adult; Diabetes Complications; Disease-Free Survival; Female; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Pancreas Transplantation; Survival Rate; Uremia
PubMed: 34702876
DOI: 10.1038/s41598-021-00621-y -
American Journal of Transplantation :... Aug 2022Enteric drainage in pancreas transplantation is complicated by an enteric leak in 5%-8%, frequently necessitating pancreatectomy. Pancreatic salvage outcomes are not...
Enteric drainage in pancreas transplantation is complicated by an enteric leak in 5%-8%, frequently necessitating pancreatectomy. Pancreatic salvage outcomes are not well studied. Risk factors for enteric leak were examined and outcomes of attempted graft salvage were compared to immediate pancreatectomy. Pancreas transplants performed between 1995 and 2018 were reviewed. Donor, recipient, and organ variables including demographics, donor type, ischemic time, kidney donor profile index, and pancreas donor risk index were analyzed. Among 1153 patients, 33 experienced enteric leaks (2.9%). Donors of allografts that developed leak were older (37.9y vs. 29.0y, p = .001), had higher KDPI (37% vs. 24%, p < .001), higher pancreas donor risk index (1.83 vs. 1.32, p < .001), and longer cold ischemic time (16.5 vs. 14.8 h, p = .03). Intra-abdominal abscess and higher blood loss decreased the chance of successful salvage. Enteric leak increased 6-month graft loss risk (HR 13.9[CI 8.5-22.9], p < .001). However, 50% (n = 12) of allografts undergoing attempted salvage survived long-term. After 6 months of pancreas graft survival, salvage and non-leak groups had similar 5-year graft survival (82.5% vs. 81.5%) and mortality (90.9% vs. 93.5%). Enteric leaks remain a challenging complication. Pancreatic allograft salvage can be attempted in suitable patients and accomplished in 50% of cases without significantly increased graft failure or mortality risk.
Topics: Graft Survival; Humans; Kidney Transplantation; Pancreas Transplantation; Postoperative Complications; Retrospective Studies
PubMed: 35593379
DOI: 10.1111/ajt.17094 -
Nefrologia 2023Graft outcomes in pancreas transplantation have improved in recent decades, but data are mainly derived from registries or prospective single-centre studies. This large...
INTRODUCTION AND OBJECTIVES
Graft outcomes in pancreas transplantation have improved in recent decades, but data are mainly derived from registries or prospective single-centre studies. This large epidemiological study was undertaken to investigate the impact of clinical and demographic factors on graft and patient survival in pancreas transplant recipients in Spain, and to provide robust, country-wide, practice-based data to complement registry findings.
PATIENTS AND METHODS
We conducted a retrospective, longitudinal, epidemiological study to assess risk factors impacting patient and graft survival in pancreas transplant recipients in eight centres in Spain. All patients transplanted between 1 January 2008 and 31 December 2012 were included; data were collected until 31 December 2015. The Kaplan-Meier method was used for all time-to-event analyses, including patient survival, graft survival, acute rejection, and BPAR. For graft survival analysis, in cases of death with functioning graft, patients were censored without any event on the date of death. For acute rejection and BPAR, patients were censored without any event on the date of death or graft loss. Univariable and multivariable analyses (Cox proportional hazards model) were conducted to assess the association between baseline clinical and demographic characteristics and patient/graft survival.
RESULTS
Data were included for 241 (80.1%) simultaneous pancreas-kidney transplants, 56 (18.6%) pancreas-after-kidney transplants and 4 (1.3%) pancreas transplants alone. Mean±standard deviation time from diagnosis until transplantation was 26.1±7.5 years. Nineteen patients died, mainly due to infections (n=10); the remaining 282 patients (93.7%) survived from transplantation until the end of the study. Among 55 patients (18.3%) with pancreas graft loss, the main reasons were vascular thrombosis (n=19), chronic rejection (n=10), acute rejection (n=6) and death with a functioning graft (n=5). The overall rate of vascular-related death was 1.3% at 5 years post transplant. Univariable analysis showed that patient age and weight, donor age, previous kidney transplantation, previous cardiovascular events and need for insulin more than 48h post transplantation were significantly associated with pancreas graft survival. Of these, in multivariable analyses pancreas graft survival was inferior in patients who had received a previous kidney transplant prior to pancreas transplantation (log-rank test, p=0.0002). Glucose metabolism, renal function and cardiovascular risk factors were generally stable following transplantation.
CONCLUSIONS
The results of this multicentre study highlight the excellent patient and graft outcomes following pancreas transplantation, with a notably low incidence of cardiovascular events.
Topics: Humans; Graft Survival; Pancreas Transplantation; Retrospective Studies; Prospective Studies; Pancreas; Cardiovascular Diseases
PubMed: 36494288
DOI: 10.1016/j.nefroe.2022.11.019 -
Journal of Clinical Medicine Apr 2021Enhanced recovery after surgery (ERAS) initially started in the early 2000s as a series of protocols to improve the perioperative care of surgical patients. They aimed... (Review)
Review
Enhanced recovery after surgery (ERAS) initially started in the early 2000s as a series of protocols to improve the perioperative care of surgical patients. They aimed to increase patient satisfaction while reducing postoperative complications and postoperative length of stay. Despite these protocols being widely adopted in many fields of surgery, they are yet to be adopted in pancreatic transplantation: a high-risk surgery with often prolonged length of postoperative stay and high rate of complications. We have analysed the literature in pancreatic and transplantation surgery to identify the necessary preoperative, intra-operative and postoperative components of an ERAS pathway in pancreas transplantation.
PubMed: 33915899
DOI: 10.3390/jcm10071418