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Annals of Surgery Open : Perspectives... Sep 2023We aim to investigate the effects of genetically based HLA matching on patient and graft survival, and acute and chronic rejection after liver transplantation.
OBJECTIVE
We aim to investigate the effects of genetically based HLA matching on patient and graft survival, and acute and chronic rejection after liver transplantation.
BACKGROUND
Liver transplantation is a common treatment for patients with end-stage liver disease. In contrast to most other solid organ transplantations, there is no conclusive evidence supporting human leukocyte antigen (HLA) matching for liver transplantations. With emerging alternatives such as transplantation of bankable (stem) cells, HLA matching becomes feasible, which may decrease the need for immunosuppressive therapy and improve transplantation outcomes.
METHODS
We systematically searched the PubMed, Embase, and Cochrane databases and performed a meta-analysis investigating the effect of genetic HLA matching on liver transplantation outcomes (acute/chronic rejection, graft failure, and mortality).
RESULTS
We included 14 studies with 2682 patients. HLA-C mismatching significantly increased the risk of acute rejection (full mismatching: risk ratio = 1.90, 95% confidence interval = 1.08 to 3.33, = 0.03; partial mismatching: risk ratio = 1.33, 95% confidence interval = 1.07 to 1.66, = 0.01). We did not discern any significant effect of HLA mismatching per locus on acute rejection for HLA-A, -B, -DR, and -DQ, nor on chronic rejection, graft failure, or mortality for HLA-DR, and -DQ.
CONCLUSIONS
We found evidence that genetic HLA-C matching reduces the risk of acute rejection after liver transplantation while matching for other loci does not reduce the risk of acute rejection, chronic rejection, graft failure, or mortality.
PubMed: 37746594
DOI: 10.1097/AS9.0000000000000334 -
Hypertension (Dallas, Tex. : 1979) Nov 2023Masked hypertension (MH) occurs when office blood pressure is normal, but hypertension is confirmed using out-of-office blood pressure measures. Hypertension is a risk... (Meta-Analysis)
Meta-Analysis Review
Masked hypertension (MH) occurs when office blood pressure is normal, but hypertension is confirmed using out-of-office blood pressure measures. Hypertension is a risk factor for subclinical cardiovascular outcomes, including left ventricular hypertrophy, increased left ventricular mass index, carotid intima media thickness, and pulse wave velocity. However, the risk factors for ambulatory blood pressure monitoring defined MH and its association with subclinical cardiovascular outcomes are unclear. A systematic literature search on 9 databases included English publications from 1974 to 2023. Pediatric MH prevalence was stratified by disease comorbidities and compared with the general pediatric population. We also compared the prevalence of left ventricular hypertrophy, and mean differences in left ventricular mass index, carotid intima media thickness, and pulse wave velocity between MH versus normotensive pediatric patients. Of 2199 screened studies, 136 studies (n=28 612; ages 4-25 years) were included. The prevalence of MH in the general pediatric population was 10.4% (95% CI, 8.00-12.80). Compared with the general pediatric population, the risk ratio (RR) of MH was significantly greater in children with coarctation of the aorta (RR, 1.91), solid-organ or stem-cell transplant (RR, 2.34), chronic kidney disease (RR, 2.44), and sickle cell disease (RR, 1.33). MH patients had increased risk of subclinical cardiovascular outcomes compared with normotensive patients, including higher left ventricular mass index (mean difference, 3.86 g/m [95% CI, 2.51-5.22]), left ventricular hypertrophy (odds ratio, 2.44 [95% CI, 1.50-3.96]), and higher pulse wave velocity (mean difference, 0.30 m/s [95% CI, 0.14-0.45]). The prevalence of MH is significantly elevated among children with various comorbidities. Children with MH have evidence of subclinical cardiovascular outcomes, which increases their risk of long-term cardiovascular disease.
Topics: Humans; Child; Masked Hypertension; Hypertrophy, Left Ventricular; Blood Pressure Monitoring, Ambulatory; Carotid Intima-Media Thickness; Prevalence; Pulse Wave Analysis; Hypertension; Blood Pressure
PubMed: 37737026
DOI: 10.1161/HYPERTENSIONAHA.123.20967 -
JAMA Network Open Sep 2023Adult trauma centers (ATCs) have been shown to decrease injury mortality and morbidity in major trauma, but a synthesis of evidence for pediatric trauma centers (PTCs)... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Adult trauma centers (ATCs) have been shown to decrease injury mortality and morbidity in major trauma, but a synthesis of evidence for pediatric trauma centers (PTCs) is lacking.
OBJECTIVE
To assess the effectiveness of PTCs compared with ATCs, combined trauma centers (CTCs), or nondesignated hospitals in reducing mortality and morbidity among children admitted to hospitals following trauma.
DATA SOURCES
MEDLINE, Embase, and Web of Science through March 2023.
STUDY SELECTION
Studies comparing PTCs with ATCs, CTCs, or nondesignated hospitals for pediatric trauma populations (aged ≤19 years).
DATA EXTRACTION AND SYNTHESIS
This systematic review and meta-analysis was performed following the Preferred Reporting Items for Systematic Review and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology guidelines. Pairs of reviewers independently extracted data and evaluated risk of bias using the Risk of Bias in Nonrandomized Studies of Interventions tool. A meta-analysis was conducted if more than 2 studies evaluated the same intervention-comparator-outcome and controlled minimally for age and injury severity. Subgroup analyses were planned for age, injury type and severity, trauma center designation level and verification body, country, and year of conduct. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess certainty of evidence.
MAIN OUTCOME(S) AND MEASURE(S)
Primary outcomes were mortality, complications, functional status, discharge destination, and quality of life. Secondary outcomes were resource use and processes of care, including computed tomography (CT) and operative management of blunt solid organ injury (SOI).
RESULTS
A total of 56 studies with 286 051 participants were included overall, and 34 were included in the meta-analysis. When compared with ATCs, PTCs were associated with a 41% lower risk of mortality (OR, 0.59; 95% CI, 0.46-0.76), a 52% lower risk of CT use (OR, 0.48; 95% CI, 0.26-0.89) and a 64% lower risk of operative management for blunt SOI (OR, 0.36; 95% CI, 0.23-0.57). The OR for complications was 0.80 (95% CI, 0.41-1.56). There was no association for mortality for older children (OR, 0.71; 95% CI, 0.47-1.06), and the association was closer to the null when PTCs were compared with CTCs (OR, 0.73; 95% CI, 0.53-0.99). Results remained similar for other subgroup analyses. GRADE certainty of evidence was very low for all outcomes.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, results suggested that PTCs were associated with lower odds of mortality, CT use, and operative management for SOI than ATCs for children admitted to hospitals following trauma, but certainty of evidence was very low. Future studies should strive to address selection and confounding biases.
Topics: Adult; Child; Humans; Adolescent; Trauma Centers; Quality of Life; Hospitalization; Hospitals; Patient Discharge; Observational Studies as Topic
PubMed: 37721752
DOI: 10.1001/jamanetworkopen.2023.34266 -
British Journal of Clinical Pharmacology Feb 2024This study aimed to provide up-to-date information on paediatric population pharmacokinetic models of tacrolimus and to identify factors influencing tacrolimus...
AIMS
This study aimed to provide up-to-date information on paediatric population pharmacokinetic models of tacrolimus and to identify factors influencing tacrolimus pharmacokinetic variability.
METHODS
Systematic searches in the Web of Science, PubMed, Scopus, Science Direct, Cochrane, EMBASE databases and reference lists of articles were conducted from inception to March 2023. All population pharmacokinetic studies of tacrolimus using nonlinear mixed-effect modelling in paediatric solid organ transplant patients were included.
RESULTS
Of the 21 studies reviewed, 62% developed from liver transplant recipients and 33% from kidney transplant recipients. Most studies used a 1-compartment model to describe tacrolimus pharmacokinetics. Body weight was a significant predictor for tacrolimus volume of distribution (Vd/F). The estimated Vd/F for 1-compartment models ranged from 20 to 1890 L, whereas the peripheral volume of distribution (Vp/F) for 2-compartment models was between 290 and 1520 L. Body weight, days post-transplant, CYP3A5 genotype or haematocrit were frequently reported as significant predictors of tacrolimus clearance. The estimated apparent clearance values range between 0.12 and 2.18 L/h/kg, with inter-individual variability from 13.5 to 110.0%. Only 29% of the studies assessed the generalizability of the models with external validation.
CONCLUSION
This review highlights the potential factors, modelling approaches and validation methods that impact tacrolimus pharmacokinetics in a paediatric population. The clinician could predict tacrolimus clearance based on body weight, CYP3A5 genotype, days post-transplant or haematocrit. Further research is required to determine the relationship between pharmacogenetics and tacrolimus pharmacodynamics in paediatric patients and confirm the applicability of nonlinear kinetics in this population.
Topics: Child; Humans; Body Weight; Cytochrome P-450 CYP3A; Genotype; Immunosuppressive Agents; Kidney Transplantation; Models, Biological; Organ Transplantation; Polymorphism, Single Nucleotide; Tacrolimus; Transplant Recipients
PubMed: 37714740
DOI: 10.1111/bcp.15909 -
Open Forum Infectious Diseases Aug 2023This is a systematic review and meta-analysis of diagnostic test accuracy studies to assess the predictive value of both tuberculin skin test (TST) and interferon-gamma...
BACKGROUND
This is a systematic review and meta-analysis of diagnostic test accuracy studies to assess the predictive value of both tuberculin skin test (TST) and interferon-gamma release assays (IGRA) for active tuberculosis (TB) among solid organ transplantation (SOT) recipients.
METHODS
Medline, Embase, and the CENTRAL databases were searched from 1946 until June 30, 2022. Two independent assessors extracted data from studies. Sensitivity analyses were performed to investigate the effect of studies with high or low risk of bias. Methodological quality of each publication was assessed using QUADAS-2.
RESULTS
A total of 43 studies (36 403 patients) with patients who were screened for latent TB infection (LTBI) and who underwent SOT were included: 18 were comparative and 25 noncomparative (19 TST, 6 QuantiFERON-TB Gold In-Tube [QFT-GIT]). For IGRA tests taken together, positive predictive value (PPV) and negative predictive value (NPV) were 1.2% and 99.6%, respectively. For TST, PPV was 2.13% and NPV was 95.5%. Overall, PPV is higher when TB burden is higher, regardless of test type, although still low in absolute terms. Incidence of active TB was similar between studies using LTBI prophylaxis (mean incidence 1.22%; 95% confidence interval [CI], .2179-2.221) and those not using prophylaxis (mean incidence 1.045%; 95% CI, 0.2731-1.817; = .7717). Strengths of this study include the large number of studies available from multiple different countries; limitations include absence of gold standard for diagnosis of latent TB and low incidence of active TB.
CONCLUSIONS
We found both TST and IGRA had a low PPV and high NPV for the development of active TB posttransplant. Further studies are needed to better understand how to prevent active TB in the SOT population.
PubMed: 37559757
DOI: 10.1093/ofid/ofad324 -
Dermatology Practical & Conceptual Jul 2023Solid organ transplant recipients (SOTR) are at an increased risk for developing keratinocyte carcinomas (KC). Four ultraviolet (UV) modifying factors have been... (Review)
Review
INTRODUCTION
Solid organ transplant recipients (SOTR) are at an increased risk for developing keratinocyte carcinomas (KC). Four ultraviolet (UV) modifying factors have been identified that impact the incidence of KC: Fitzpatrick Skin Type (FST), race, sun exposure, and sun-protective factors.
OBJECTIVES
We conducted a systematic review to summarize the association between UV modifying factors and the incidence of KC in SOTR.
METHODS
We systematically searched PubMed, Scopus, and Web of Science databases, and after screening for inclusion and exclusion criteria, we included 13 studies with 6,910 solid organ transplant recipients in our analysis.
RESULTS
Our review found that lower FST (I-II), white and Latinx populations, lack of regulated sunscreen application, and occupational and residential sun exposure are individual risk factors among solid organ transplant recipients for KC incidence. Although previous studies showed an in-creased SCC:BCC ratio, some studies found a contradictory increased BCC:SCC ratio. Limitations include few research studies that analyze these UV modifying factors and a lack of incorporating both varying immunosuppressant factors and transplantation follow-up times.
CONCLUSIONS
These findings support the need for dermatological advice in increased risk patient demographic populations, lower FST and white and Latinx populations, and subsequently moderating sun exposure and protective factors.
PubMed: 37557127
DOI: 10.5826/dpc.1303a65 -
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 -
The Cochrane Database of Systematic... Aug 2023Prostaglandins are naturally occurring lipids that are synthesised from arachidonic acid. Multiple studies have evaluated the benefits of prostaglandins in reducing... (Review)
Review
BACKGROUND
Prostaglandins are naturally occurring lipids that are synthesised from arachidonic acid. Multiple studies have evaluated the benefits of prostaglandins in reducing ischaemia reperfusion injury after liver transplantation. New studies have been published since the previous review, and hence it was important to update the evidence for this intervention.
OBJECTIVES
To evaluate the benefits and harms of prostaglandins in adults undergoing liver transplantation compared with placebo or standard care.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 27 December 2022.
SELECTION CRITERIA
We included randomised clinical trials evaluating prostaglandins initiated in the perioperative period compared with placebo or standard care for adults undergoing liver transplantation. We included trials irrespective of reported outcomes.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. serious adverse events, and 3. health-related quality of life. Our secondary outcomes were 4. liver retransplantation, 5. early allograft dysfunction, 6. primary non-function of the allograft, 7. acute kidney failure, 8. length of hospital stay, and 9. adverse events considered non-serious. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included 11 randomised clinical trials with 771 adult liver transplant recipients (mean age 47.31 years, male 61.48%), of whom 378 people were randomised to receive prostaglandins and 393 people were randomised to either placebo (272 participants) or standard care (121 participants). All trials were published between 1993 and 2016. Ten trials were conducted in high- and upper-middle-income countries. Prostaglandins may reduce all-cause mortality up to one month (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.61 to 1.23; risk difference (RD) 21 fewer per 1000, 95% CI 63 fewer to 36 more; 11 trials, 771 participants; low-certainty evidence). Prostaglandins may result in little to no difference in serious adverse events (RR 0.92, 95% CI 0.60 to 1.40; RD 81 fewer per 1000, 95% CI 148 fewer to 18 more; 6 trials, 568 participants; low-certainty evidence). None of the included trials reported health-related quality of life. Prostaglandins may result in little to no difference in liver retransplantation (RR 0.98, 95% CI 0.49 to 1.96; RD 1 fewer per 1000, 95% CI 33 fewer to 62 more; 6 trials, 468 participants; low-certainty evidence); early allograft dysfunction (RR 0.62, 95% CI 0.33 to 1.18; RD 137 fewer per 1000, 95% CI 241 fewer to 47 more; 1 trial, 99 participants; low-certainty evidence); primary non-function of the allograft (RR 0.58, 95% CI 0.26 to 1.32; RD 23 fewer per 1000, 95% CI 40 fewer to 16 more; 7 trials, 624 participants; low-certainty evidence); and length of hospital stay (mean difference (MD) -1.15 days, 95% CI -5.44 to 3.14; 4 trials, 369 participants; low-certainty evidence). Prostaglandins may result in a large reduction in the development of acute kidney failure requiring dialysis (RR 0.42, 95% CI 0.24 to 0.73; RD 100 fewer per 1000, 95% CI 132 fewer to 49 fewer; 5 trials, 477 participants; low-certainty evidence). The evidence is very uncertain about the effect of prostaglandins on adverse events considered non-serious (RR 1.19, 95% CI 0.42 to 3.36; RD 225 fewer per 1000, 95% CI 294 fewer to 65 fewer; 4 trials, 329 participants; very low-certainty evidence). Two trials reported receiving funding; one of these was with vested interests. We found one registered ongoing trial.
AUTHORS' CONCLUSIONS
Eleven trials evaluated prostaglandins in adult liver transplanted recipients. Based on low-certainty evidence, prostaglandins may reduce all-cause mortality up to one month; may cause little to no difference in serious adverse events, liver retransplantation, early allograft dysfunction, primary non-function of the allograft, and length of hospital stay; and may have a large reduction in the development of acute kidney injury requiring dialysis. We do not know the effect of prostaglandins on adverse events considered non-serious. We lack adequately powered, high-quality trials evaluating the effects of prostaglandins for people undergoing liver transplantation.
Topics: Adult; Humans; Male; Middle Aged; Liver; Prostaglandins; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 37540003
DOI: 10.1002/14651858.CD006006.pub3 -
International Journal of Dermatology Sep 2023Melanoma transmitted through organ transplantation is an increasingly reported event. Immunosuppression increases the risk of melanoma; however, transmission of... (Review)
Review
Melanoma transmitted through organ transplantation is an increasingly reported event. Immunosuppression increases the risk of melanoma; however, transmission of malignancy from transplanted organs is a distinct etiology of melanoma occurrence. The risk of transmission of melanoma from an organ donor with melanoma has yet to be determined. The authors aimed to investigate this phenomenon by reviewing the outcomes of patients that received organs from donors with melanoma. A systematic literature review was conducted with emphasis on identifying organ donors with known histories of melanoma and reported information regarding recipients of their organs. The databases PubMed, MEDLINE, Embase, and JBI EBP were searched in January 2023. Search terms included "melanoma," terms for solid organs, "donor," "transplant," "transmission," and their variations as well as terms related to temporal relations. Inclusion criteria were articles that stated outcomes in organ recipients from donors that had a diagnosis of melanoma either pretransplant or postmortem. Reference lists of selected articles were hand searched for further studies. A total of 232 articles were identified from the search parameters. After applying inclusion and exclusion criteria, 13 articles were selected. Hand searching the references of these articles yielded four additional articles. Of the 75 organ recipients that received organs from donors with known melanoma, 43 developed melanoma. While a definitive quantitative risk cannot be ascertained based on our review, the numerous reported cases of melanoma in organ recipients from donors that have melanoma should still be considered by clinicians.
Topics: Humans; Melanoma; Organ Transplantation; Tissue Donors; Immunosuppression Therapy
PubMed: 37537648
DOI: 10.1111/ijd.16797 -
Vaccines Jun 2023Solid organ transplant (SOT) recipients are at increased risk of COVID-19 infection because of their suppressed immunity. The available data show that COVID-19 vaccines... (Review)
Review
Solid organ transplant (SOT) recipients are at increased risk of COVID-19 infection because of their suppressed immunity. The available data show that COVID-19 vaccines are less effective in SOT recipients. We aimed to assess the cellular and humoral immunogenicity with an increasing the number of doses of COVID-19 vaccines in SOT recipients and to identify factors affecting vaccine response in this population. A systematic review and meta-analysis were conducted to identify ongoing and completed studies of humoral and cellular immunity following COVID-19 vaccines in SOT recipients. The search retrieved 278 results with 45 duplicates, and 43 records did not match the inclusion criteria. After title and abstract screening, we retained 189 records, and 135 records were excluded. The reasons for exclusion involved studies with immunocompromised patients (non-transplant recipients), dialysis patients, and individuals who had already recovered from SARS-CoV-2 infection. After full-text reading, 55 observational studies and randomized clinical trials (RCTs) were included. The proportion of responders appeared higher after the third, fourth, and fifth doses. The risk factors for non-response included older age and the use of mycophenolate mofetil, corticosteroids, and other immunosuppressants. This systematic review and meta-analysis demonstrates the immunogenicity following different doses of COVID-19 vaccines among SOT patients. Due to the low immunogenicity of vaccines, additional strategies to improve vaccine response may be necessary.
PubMed: 37514982
DOI: 10.3390/vaccines11071166