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Archives of Gynecology and Obstetrics Feb 2024Pre-conceptual comorbidities, an inherent risk of graft loss, rejection during pregnancy, and the postpartum period in women with thoracic lung transplant may predispose... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Pre-conceptual comorbidities, an inherent risk of graft loss, rejection during pregnancy, and the postpartum period in women with thoracic lung transplant may predispose them to increased risk of adverse feto-maternal outcomes. The study aimed to systematically analyze and assess the risk of adverse pregnancy outcomes in women with thoracic organ transplant.
METHODS
MEDLINE, EMBASE, and Cochrane library were searched for publication between January 1990 and June 2020. Risk of bias was assessed using Joanna Briggs critical appraisal tool for case series. The primary outcomes included maternal mortality and pregnancy loss. The secondary outcomes were maternal complications, neonatal complications, and adverse birth outcomes. The analysis was performed using the DerSimonian-Laird random effects model.
RESULTS
Eleven studies captured data from 275 parturient with thoracic organ transplant describing 400 pregnancies. The primary outcomes included maternal mortality {pooled incidence (95% confidence interval) 4.2 (2.5-7.1) at 1 year and 19.5 (15.3-24.5) during follow-up}. Pooled estimates yielded 10.1% (5.6-17.5) and 21.8% (10.9-38.8) risk of rejection and graft dysfunction during and after pregnancy, respectively. Although 67% (60.2-73.2) of pregnancies resulted in live birth, total pregnancy loss and neonatal death occurred in 33.5% (26.7-40.9) and 2.8% (1.4-5.6), respectively. Prematurity and low birth weight were reported in 45.1% (38.5-51.9) and 42.7% (32.8-53.2), respectively.
CONCLUSIONS
Despite pregnancies resulting in nearly 2/3rd of live births, high incidence of pregnancy loss, prematurity and low birth weight remain a cause of concern. Focused pre-conceptual counseling to avoid unplanned pregnancy, especially in women with transplant-related organ dysfunctions and complications, is vital to improve pregnancy outcomes.
PROSPERO NUMBER
CRD42020164020.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Abortion, Spontaneous; Infant, Low Birth Weight; Infant, Premature; Organ Transplantation; Pregnancy Complications; Pregnancy Outcome
PubMed: 37147484
DOI: 10.1007/s00404-023-07065-x -
Annals of the Royal College of Surgeons... Feb 2022Combined heart and liver transplantation (CHLT) is one of the most complex procedures of surgery that has been implemented in the last 35 years. The aim of our... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Combined heart and liver transplantation (CHLT) is one of the most complex procedures of surgery that has been implemented in the last 35 years. The aim of our meta-analysis was to investigate the safety and efficacy of CHLT.
MATERIALS
The meta-analysis was designed according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) and AMSTAR (A MeaSurement Tool to Assess systematic Reviews) recommendations. A literature search was conducted up to April 2020 using the MEDLINE, SCOPUS, ClinicalTrials.gov, Embase™, Cochrane Central Register of Controlled Trials and Google Scholar™ databases.
RESULTS
Our meta-analysis included 16 studies with 860 patients. The mortality rate following CHLT was 14.1%. One and five-year survival rates were 85.3% and 71.4% while the heart and liver rejection rates were 6.1% and 9.1% respectively. The hospital stay was 25.8 days and the intensive care unit stay was 9.9 days. Pooled values were also calculated for cardiopulmonary bypass duration, units of transfused red blood cells and fresh frozen plasma, postoperative infection rate, mechanical ventilation rate and follow-up duration.
CONCLUSIONS
Despite its complexity, CHLT is a safe and effective procedure for the management of lethal diseases that lead to progressive heart and/or liver failure. Nevertheless, there must be strict adherence to the indications for surgery, and future studies should compare CHLT with isolated cardiac and hepatic transplantations.
Topics: Cardiopulmonary Bypass; Heart Transplantation; Humans; Length of Stay; Liver; Liver Transplantation
PubMed: 34482766
DOI: 10.1308/rcsann.2021.0103 -
Artificial Organs Sep 2022This review aims to systematically evaluate the currently available evidence investigating the use of artificial intelligence (AI) and machine learning (ML) in the field... (Review)
Review
BACKGROUND
This review aims to systematically evaluate the currently available evidence investigating the use of artificial intelligence (AI) and machine learning (ML) in the field of cardiac transplantation. Furthermore, based on the challenges identified we aim to provide a series of recommendations and a knowledge base for future research in the field of ML and heart transplantation.
METHODS
A systematic database search was conducted of original articles that explored the use of ML and/or AI in heart transplantation in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to November 2021.
RESULTS
Our search yielded 237 articles, of which 13 studies were included in this review, featuring 463 850 patients. Three main areas of application were identified: (1) ML for predictive modeling of heart transplantation mortality outcomes; (2) ML in graft failure outcomes; (3) ML to aid imaging in heart transplantation. The results of the included studies suggest that AI and ML are more accurate in predicting graft failure and mortality than traditional scoring systems and conventional regression analysis. Major predictors of graft failure and mortality identified in ML models were: length of hospital stay, immunosuppressive regimen, recipient's age, congenital heart disease, and organ ischemia time. Other potential benefits include analyzing initial lab investigations and imaging, assisting a patient with medication adherence, and creating positive behavioral changes to minimize further cardiovascular risk.
CONCLUSION
ML demonstrated promising applications for improving heart transplantation outcomes and patient-centered care, nevertheless, there remain important limitations relating to implementing AI into everyday surgical practices.
Topics: Artificial Intelligence; Databases, Factual; Heart Transplantation; Humans; Length of Stay; Machine Learning
PubMed: 35719121
DOI: 10.1111/aor.14334 -
Transplant International : Official... Apr 2017Barriers to access and long-term complications remain a challenge in transplantation. Further advancements may be achieved through research priority setting with patient... (Review)
Review
Barriers to access and long-term complications remain a challenge in transplantation. Further advancements may be achieved through research priority setting with patient engagement to strengthen its relevance. We evaluated research priority setting in solid organ transplantation and described stakeholder priorities. Databases were searched to October 2016. We synthesized the findings descriptively. The 28 studies (n = 2071 participants) addressed kidney [9 (32%)], heart [7 (25%)], liver [3 (11%)], lung [1 (4%)], pancreas [1 (4%)], and nonspecified organ transplantation [7 (25%)] using consensus conferences, expert panel meetings, workshops, surveys, focus groups, interviews, and the Delphi technique. Nine (32%) reported patient involvement. The 336 research priorities addressed the following: organ donation [43 priorities (14 studies)]; waitlisting and allocation [43 (10 studies)]; histocompatibility and immunology [31 (8 studies)]; immunosuppression [21 (10 studies)]; graft-related complications [38 (13 studies)]; recipient (non-graft-related) complications [86 (14 studies)]; reproduction [14 (1 study)], psychosocial and lifestyle [49 (7 studies)]; and disparities in access and outcomes [10 (4 studies)]. The priorities identified were broad but only one-third of initiatives engaged patients/caregivers, and details of the process were lacking. Setting research priorities in an explicit manner with patient involvement can guide investment toward the shared priorities of patients and health professionals.
Topics: Biomedical Research; Caregivers; Delphi Technique; Focus Groups; Graft Rejection; Graft Survival; Health Services Accessibility; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Living Donors; Organ Transplantation
PubMed: 28120462
DOI: 10.1111/tri.12924 -
Clinical Transplantation Jun 2021The incidence of melanoma is steadily rising around the world. There is uncertainty about the safety of solid organ transplantation in patients with a prior history of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The incidence of melanoma is steadily rising around the world. There is uncertainty about the safety of solid organ transplantation in patients with a prior history of melanoma.
AIM
To review studies reporting patients with a history of melanoma before solid organ transplantation.
METHODS
Electronic searches of Medline, Embase, and the Cochrane library up to March 2020. All study designs, in any language and without sample size restriction, were eligible for inclusion. Risk of bias was assessed using established tools, and meta-analysis was performed using a random-effects model.
RESULTS
We identified 41 studies reporting 703 100 transplant recipients and 1692 had pre-transplantation melanomas. Risk of death, expressed as a hazard ratio, in patients with pre-transplantation melanoma relative to those without prior melanoma, was 1.32 (95% CI: 1.09-1.59). After transplantation, 13.1% of patients with pre-transplantation melanoma developed new or recurrent melanoma (IQR: 4.8%-18.2%).
CONCLUSIONS
Around 1-in-400 transplant recipients had a prior history of melanoma. This was associated with a greater than 1-in-10 risk of new or recurrent melanoma after transplantation and an increased risk of death. A 5-year waiting time between a melanoma diagnosis and transplantation has been recommended based on historic registry data, but very little additional information is available to justify or revise this.
Topics: Humans; Melanoma; Organ Transplantation; Proportional Hazards Models; Skin Neoplasms; Transplant Recipients
PubMed: 33720403
DOI: 10.1111/ctr.14287 -
Frontiers in Immunology 2023Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.
METHODS
We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.
RESULTS
In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.
DISCUSSION
We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
Topics: Humans; Graft Rejection; Organ Transplantation; Complement System Proteins; Transplantation, Homologous; HLA Antigens
PubMed: 37849755
DOI: 10.3389/fimmu.2023.1265796 -
Transplantation Reviews (Orlando, Fla.) Oct 2017Solid organ transplant recipients (SOTR) with a pre-transplant malignancy (PTM) have been thought to be at high risk of cancer recurrence. However, recent... (Meta-Analysis)
Meta-Analysis Review
Solid organ transplant recipients (SOTR) with a pre-transplant malignancy (PTM) have been thought to be at high risk of cancer recurrence. However, recent population-based studies report cancer recurrence rates in SOTR similar to those of non-transplant patients. A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library to identify studies reporting cancer recurrence in SOTR with PTM. Quality assessment was performed using a validated tool for assessing the quality of an observational study with no control group designed by the Institute of Health Economics. Overall and site-specific recurrence rates per person-year were pooled using generalized linear random/mixed-effects meta-analysis models and an exact likelihood approach based on a binomial and Poisson distribution. Meta-regressions, subgroup and sensitivity meta-analyses were used to explore sources of heterogeneity. Fifty-seven eligible studies were identified and 39 were included in the meta-analysis. The pooled recurrence rate was 1.6 (95% CI 1.0-2.6) per 100 person-year for all studies, and 1.1 (95% CI 0.5-2.7) when restricted to population-based studies. The recurrence rate was higher for kidney (2.4 per 100 person-year, 95% CI 1.0-5.6) compared with liver (1.0 per 100 person-year, 95% CI 0.4-2.6), and cardiothoracic recipients (1.3 per 100 person-year, 95% CI 0.6-2.7). Time from cancer diagnosis to transplantation (TCT) ≤ 5 years was associated with greater risk of cancer recurrence compared to TCT > 5 years (risk ratio: 2.80, 95% CI 1.12-7.01). In conclusion, the risk of cancer recurrence in recipients with PTM is considerably lower than historic reports used to establish recommendations for listing patients with PTM. Evidence to support minimum cancer remission times before transplantation is limited.
Topics: Cause of Death; Female; Humans; Incidence; Likelihood Functions; Male; Neoplasm Recurrence, Local; Neoplasms; Organ Transplantation; Risk Assessment; Survival Analysis
PubMed: 28867291
DOI: 10.1016/j.trre.2017.08.003 -
Journal of the American Society of... Feb 2024Why are there so few biomarkers accepted by health authorities and implemented in clinical practice, despite the high and growing number of biomaker studies in medical...
SIGNIFICANCE STATEMENT
Why are there so few biomarkers accepted by health authorities and implemented in clinical practice, despite the high and growing number of biomaker studies in medical research ? In this meta-epidemiological study, including 804 studies that were critically appraised by expert reviewers, the authors have identified all prognostic kidney transplant biomarkers and showed overall suboptimal study designs, methods, results, interpretation, reproducible research standards, and transparency. The authors also demonstrated for the first time that the limited number of studies challenged the added value of their candidate biomarkers against standard-of-care routine patient monitoring parameters. Most biomarker studies tended to be single-center, retrospective studies with a small number of patients and clinical events. Less than 5% of the studies performed an external validation. The authors also showed the poor transparency reporting and identified a data beautification phenomenon. These findings suggest that there is much wasted research effort in transplant biomarker medical research and highlight the need to produce more rigorous studies so that more biomarkers may be validated and successfully implemented in clinical practice.
BACKGROUND
Despite the increasing number of biomarker studies published in the transplant literature over the past 20 years, demonstrations of their clinical benefit and their implementation in routine clinical practice are lacking. We hypothesized that suboptimal design, data, methodology, and reporting might contribute to this phenomenon.
METHODS
We formed a consortium of experts in systematic reviews, nephrologists, methodologists, and epidemiologists. A systematic literature search was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Library between January 1, 2005, and November 12, 2022 (PROSPERO ID: CRD42020154747). All English language, original studies investigating the association between a biomarker and kidney allograft outcome were included. The final set of publications was assessed by expert reviewers. After data collection, two independent reviewers randomly evaluated the inconsistencies for 30% of the references for each reviewer. If more than 5% of inconsistencies were observed for one given reviewer, a re-evaluation was conducted for all the references of the reviewer. The biomarkers were categorized according to their type and the biological milieu from which they were measured. The study characteristics related to the design, methods, results, and their interpretation were assessed, as well as reproducible research practices and transparency indicators.
RESULTS
A total of 7372 publications were screened and 804 studies met the inclusion criteria. A total of 1143 biomarkers were assessed among the included studies from blood ( n =821, 71.8%), intragraft ( n =169, 14.8%), or urine ( n =81, 7.1%) compartments. The number of studies significantly increased, with a median, yearly number of 31.5 studies (interquartile range [IQR], 23.8-35.5) between 2005 and 2012 and 57.5 (IQR, 53.3-59.8) between 2013 and 2022 ( P < 0.001). A total of 655 studies (81.5%) were retrospective, while 595 (74.0%) used data from a single center. The median number of patients included was 232 (IQR, 96-629) with a median follow-up post-transplant of 4.8 years (IQR, 3.0-6.2). Only 4.7% of studies were externally validated. A total of 346 studies (43.0%) did not adjust their biomarker for key prognostic factors, while only 3.1% of studies adjusted the biomarker for standard-of-care patient monitoring factors. Data sharing, code sharing, and registration occurred in 8.8%, 1.1%, and 4.6% of studies, respectively. A total of 158 studies (20.0%) emphasized the clinical relevance of the biomarker, despite the reported nonsignificant association of the biomarker with the outcome measure. A total of 288 studies assessed rejection as an outcome. We showed that these rejection studies shared the same characteristics as other studies.
CONCLUSIONS
Biomarker studies in kidney transplantation lack validation, rigorous design and methodology, accurate interpretation, and transparency. Higher standards are needed in biomarker research to prove the clinical utility and support clinical use.
Topics: Humans; Biomarkers; Kidney Transplantation; Prognosis; Retrospective Studies; Systematic Reviews as Topic
PubMed: 38053242
DOI: 10.1681/ASN.0000000000000260 -
The Cochrane Database of Systematic... Sep 2023Liver transplantation is the only chance of cure for people with end-stage liver disease and some people with advanced liver cancers or acute liver failure. The... (Review)
Review
BACKGROUND
Liver transplantation is the only chance of cure for people with end-stage liver disease and some people with advanced liver cancers or acute liver failure. The increasing prevalence of these conditions drives demand and necessitates the increasing use of donated livers which have traditionally been considered suboptimal. Several novel machine perfusion preservation technologies have been developed, which attempt to ameliorate some of the deleterious effects of ischaemia reperfusion injury. Machine perfusion technology aims to improve organ quality, thereby improving outcomes in recipients of suboptimal livers when compared to traditional static cold storage (SCS; ice box).
OBJECTIVES
To evaluate the effects of different methods of machine perfusion (including hypothermic oxygenated machine perfusion (HOPE), normothermic machine perfusion (NMP), controlled oxygenated rewarming, and normothermic regional perfusion) versus each other or versus static cold storage (SCS) in people undergoing liver transplantation.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 10 January 2023.
SELECTION CRITERIA
We included randomised clinical trials which compared different methods of machine perfusion, either with each other or with SCS. Studies comparing HOPE via both hepatic artery and portal vein, or via portal vein only, were grouped. The protocol detailed that we also planned to include quasi-randomised studies to assess treatment harms.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. overall participant survival, 2. quality of life, and 3. serious adverse events. Secondary outcomes were 4. graft survival, 5. ischaemic biliary complications, 6. primary non-function of the graft, 7. early allograft function, 8. non-serious adverse events, 9. transplant utilisation, and 10. transaminase release during the first week post-transplant. We assessed bias using Cochrane's RoB 2 tool and used GRADE to assess certainty of evidence.
MAIN RESULTS
We included seven randomised trials (1024 transplant recipients from 1301 randomised/included livers). All trials were parallel two-group trials; four compared HOPE versus SCS, and three compared NMP versus SCS. No trials used normothermic regional perfusion. When compared with SCS, it was uncertain whether overall participant survival was improved with either HOPE (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.42 to 1.98; P = 0.81, I = 0%; 4 trials, 482 recipients; low-certainty evidence due to imprecision because of low number of events) or NMP (HR 1.08, 95% CI 0.31 to 3.80; P = 0.90; 1 trial, 222 recipients; very low-certainty evidence due to imprecision and risk of bias). No trials reported quality of life. When compared with SCS alone, HOPE was associated with improvement in the following clinically relevant outcomes: graft survival (HR 0.45, 95% CI 0.23 to 0.87; P = 0.02, I = 0%; 4 trials, 482 recipients; high-certainty evidence), serious adverse events in extended criteria DBD liver transplants (OR 0.45, 95% CI 0.22 to 0.91; P = 0.03, I = 0%; 2 trials, 156 participants; moderate-certainty evidence) and clinically significant ischaemic cholangiopathy in recipients of DCD livers (OR 0.31, 95% CI 0.11 to 0.92; P = 0.03; 1 trial, 156 recipients; high-certainty evidence). In contrast, NMP was not associated with improvement in any of these clinically relevant outcomes. NMP was associated with improved utilisation compared with SCS (one trial found a 50% lower rate of organ discard; P = 0.008), but the reasons underlying this effect are unknown. We identified 11 ongoing studies investigating machine perfusion technologies.
AUTHORS' CONCLUSIONS
In situations where the decision has been made to transplant a liver donated after circulatory death or donated following brain death, end-ischaemic HOPE will provide superior clinically relevant outcomes compared with SCS alone. Specifically, graft survival is improved (high-certainty evidence), serious adverse events are reduced (moderate-certainty evidence), and in donors after circulatory death, clinically relevant ischaemic biliary complications are reduced (high-certainty evidence). There is no good evidence that NMP has the same benefits over SCS in terms of these clinically relevant outcomes. NMP does appear to improve utilisation of grafts that would otherwise be discarded with SCS; however, the reasons for this, and whether this effect is specific to NMP, is not clear. Further studies into NMP viability criteria and utilisation, as well as head-to-head trials with other perfusion technologies are needed. In the setting of donation following circulatory death transplantation, further trials are needed to assess the effect of these ex situ machine perfusion methods against, or in combination with, normothermic regional perfusion.
Topics: Humans; Liver Transplantation; Quality of Life; Perfusion; End Stage Liver Disease
PubMed: 37698189
DOI: 10.1002/14651858.CD014685.pub2 -
Nephrology, Dialysis, Transplantation :... Aug 2015The prevalence of obesity is increasing globally and is associated with chronic kidney disease and premature mortality. However, the impact of recipient obesity on... (Review)
Review
BACKGROUND
The prevalence of obesity is increasing globally and is associated with chronic kidney disease and premature mortality. However, the impact of recipient obesity on kidney transplant outcomes remains unclear. This study aimed to investigate the association between recipient obesity and mortality, death-censored graft loss and delayed graft function (DGF) following kidney transplantation.
METHODS
A systematic review and meta-analysis was conducted using Medline, Embase and the Cochrane Library. Observational studies or randomized controlled trials investigating the association between recipient obesity at transplantation and mortality, death-censored graft loss and DGF were included. Obesity was defined as a body mass index (BMI) of ≥30 kg/m(2). Obese recipients were compared with those with a normal BMI (18.5-24.9 kg/m(2)). Pooled estimates of hazard ratios (HRs) for patient mortality or death-censored graft loss and odds ratios (ORs) for DGF were calculated.
RESULTS
Seventeen studies including 138 081 patients were analysed. After adjustment, there was no significant difference in mortality risk in obese recipients [HR = 1.24, 95% confidence interval (CI) = 0.90-1.70, studies = 5, n = 83 416]. However, obesity was associated with an increased risk of death-censored graft loss (HR = 1.06, 95% CI = 1.01-1.12, studies = 5, n = 83 416) and an increased likelihood of DGF (OR = 1.68, 95% CI = 1.39-2.03, studies = 4, n = 28 847).
CONCLUSIONS
Despite having a much higher likelihood of DGF, obese transplant recipients have only a slightly increased risk of graft loss and experience similar survival to recipients with normal BMI.
Topics: Body Mass Index; Delayed Graft Function; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Obesity; Risk Factors; Survival Rate; Transplant Recipients; Treatment Outcome
PubMed: 26044837
DOI: 10.1093/ndt/gfv214