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  • van Gemert JP
  • Ravensbergen SJ
  • Verschuuren EAM
  • Kerstjens HAM
  • Willemse BWM
  • et al.
Transplant Rev (Orlando). 2023 Dec;37(4):100800 doi: 10.1016/j.trre.2023.100800.
BACKGROUND:

There is lack of consensus on non-tuberculous mycobacteria pulmonary disease (NTM-PD) treatment regimen and duration in patient listed for lung transplantation (LTx). We conducted a systematic review on treatment regimen and duration pre- and directly post-LTx, for patients with known NTM-PD pre-LTx. Additionally, we searched for risk factors for NTM disease development post-LTx and for mortality.

METHODS:

Literature was reviewed on PubMed, Embase and the Cochrane Library, for articles published from inception to January 2022. Individual patient data were sought.

RESULTS:

Sixteen studies were included reporting 92 patients. Most frequent used agents were aminoglycosides and macrolides for Mycobacterium abscessus (M. abscessus) and macrolides and tuberculostatic agents for Mycobacterium avium complex (M. avium complex). The median treatment duration pre-LTx was 10 months (IQR 6-17) and 2 months (IQR 2-8) directly post-LTx. Longer treatment duration pre-LTx was observed in children and in patients with M. abscessus. 46% of the patients with NTM-PD pre-LTx developed NTM disease post-LTx, related mortality rate was 10%. Longer treatment duration pre-LTx (p < 0.001) and sputum non-conversion pre-LTx (p = 0.003) were significantly associated with development of NTM-disease post-LTx. Longer treatment duration pre-LTx (p = 0.004), younger age (p < 0.001) and sputum non-conversion (p = 0.044) were risk factors for NTM related death.

CONCLUSIONS:

The median treatment duration pre-LTx was 10 months (IQR 6-17) and 2 months (IQR 2-8) directly post-LTx. Patients with longer treatment duration for NTM-PD pre-LTx and with sputum non-conversion are at risk for NTM disease post-LTx and for NTM-related death. Children were particularly at risk for NTM related death.

  • Annamalai C
  • Kute V
  • Sheridan C
  • Halawa A
Transplant Rev (Orlando). 2023 Dec;37(4):100792 doi: 10.1016/j.trre.2023.100792.
INTRODUCTION:

Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal is the ultimate goal of kidney transplantation, and is made possible by the induction of immunological tolerance. The purpose of this paper is to review the safety and efficacy of immune tolerance induction strategies in living-donor kidney transplantation, both chimerism-based and non-chimerism-based. The impact of these strategies on transplant outcomes, including acute rejection, allograft function and survival, cost, and immune monitoring, will also be discussed.

MATERIALS AND METHODS:

Databases such as PubMed, Scopus, and Web of Science, as well as additional online resources such as EBSCO, were exhaustively searched. Adult living-donor kidney transplant recipients who developed chimerism-based tolerance after concurrent bone marrow or hematopoietic stem cell transplantation or those who received non-chimerism-based, non-hematopoietic cell therapy using mesenchymal stromal cells, dendritic cells, or regulatory T cells were studied between 2000 and 2021. Individual sources of evidence were evaluated critically, and the strength of evidence and risk of bias for each outcome of the transplant tolerance study were assessed.

RESULTS:

From 28,173 citations, 245 studies were retrieved after suitable exclusion and duplicate removal. Of these, 22 studies (2 RCTs, 11 cohort studies, 6 case-control studies, and 3 case reports) explicitly related to both interventions (chimerism- and non-chimerism-based immune tolerance) were used in the final review process and were critically appraised. According to the findings, chimerism-based strategies fostered immunotolerance, allowing for the safe withdrawal of immunosuppressive medications. Cell-based therapy, on the other hand, frequently did not induce tolerance except for minimising immunosuppression. As a result, the rejection rates, renal allograft function, and survival rates could not be directly compared between these two groups. While chimerism-based tolerance protocols posed safety concerns due to myelosuppression, including infections and graft-versus-host disease, cell-based strategies lacked these adverse effects and were largely safe. There was a lack of direct comparisons between HLA-identical and HLA-disparate recipients, and the cost implications were not examined in several of the retrieved studies. Most studies reported successful immunosuppressive weaning lasting at least 3 years (ranging up to 11.4 years in some studies), particularly with chimerism-based therapy, while only a few investigators used immune surveillance techniques. The studies reviewed were often limited by selection, classification, ascertainment, performance, and attrition bias.

CONCLUSIONS:

This review demonstrates that chimerism-based hematopoietic strategies induce immune tolerance, and a substantial number of patients are successfully weaned off immunosuppression. Despite the risk of complications associated with myelosuppression. Non-chimerism-based, non-hematopoietic cell protocols, on the other hand, have been proven to facilitate immunosuppression minimization but seldom elicit immunological tolerance. However, the results of this review must be interpreted with caution because of the non-randomised study design, potential confounding, and small sample size of the included studies. Further validation and refinement of tolerogenic protocols in accordance with local practice preferences is also warranted, with an emphasis on patient selection, cost ramifications, and immunological surveillance based on reliable tolerance assays.

  • O'Connor-Cordova MA
  • Ortega-Macias AG
  • Sancen-Herrera JP
  • Altamirano-Lamarque F
  • Del Toro AV
  • et al.
Transplant Rev (Orlando). 2023 Dec;37(4):100789 doi: 10.1016/j.trre.2023.100789.
CET Conclusion
Reviewer: Reshma Rana Magar, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This systematic review aimed compare the safety, feasibility, and outcomes of RAKT versus OKT. Study selection, quality assessment and data extraction were performed by two independent authors. Nine studies were included, all of which were cohort studies. The authors concluded that RAKT has significantly lower complication rate compared to OKT, without significant differences in terms of intraoperative, perioperative and postoperative outcomes. Heterogeneity was significant for some of the outcomes, which was not explored. Since only observational studies were included, it is possible that the results may have been influenced by selection bias and potential confounders.
Aims: The aim of this study was to compare the outcomes of living donor robotic-assisted kidney transplant (RAKT) versus traditional living donor open kidney transplant (OKT).
Interventions: Electronic databases including PubMed, Scopus, and Cochrane were searched. Study screening, evidence grading and data extraction were performed by two independent reviewers. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for cohort studies.
Participants: 9 studies were included in the review.
Outcomes: Outcomes of interest included intraoperative outcomes (total procedure time, anastomoses time, total ischemia time, rewarming ischemia time, blood loss, blood transfusion and incision length), early postoperative outcomes (surgical site infection, symptomatic lymphocele rate, ileus, overall complications, Clavien-Dindo classification complication rate, hospital readmission rate, visual analogue pain score, creatinine 24 h posttransplant), and follow-up outcomes (patient survival 36 months posttransplant)
Follow Up: N/A
BACKGROUND:

Renal transplant is the standard of care for patients with end-stage renal disease (ESRD). Robotic-assisted kidney transplant (RAKT) has emerged as a safe minimally invasive approach with a lower complication rate than open kidney transplant (OKT). Concerns regarding ischemia times and graft function are still a matter of debate.

METHODS:

Following PRISMA guidelines and PROSPERO registration CRD42023413774, a systematic review was performed in March 2023 on RAKT compared to OKT. Primary outcomes of interest were surgical times, ischemia times, blood loss, complication rates, and graft function. Data were analyzed using R version 4.2.2.

RESULTS:

A total of nine studies comparing living donor RAKT to living donor OKT were included, totaling 1477 patients, out of which 508 underwent RAKT and 969 OKT. RAKT cases were highly selected as depicted in the manuscript. Cumulative analysis showed significantly longer total ischemic time (MD = 16.51; 95% CI = [9.86-23.16]) and rewarming ischemia time (MD = 11.24; 95% CI = [-0.46-22.01]) in RAKT group. No differences were found in total procedure time and time to complete anastomoses. Blood loss and transfusion rate were lower in RAKT group (MD = -53.68; 95% CI = [-89.78; -17.58]) and (RR = 0.29; 95% CI = [0.14; 0.57]), respectively. The meta-analysis revealed a lower rate of surgical site infection (SSI) (RR = 0.31; 95% CI = [0.19-0.52]) and symptomatic lymphocele (RR = 0.16; 95% CI = [0.06-0.43]) in RAKT. No difference in ileus rate was found. Pain scores were significantly lower in the RAKT group (MD = -1.14; 95% CI = [-1.59 - -0.69]; p ≤0.01). No difference in length of stay and hospital readmission were evidenced. Delayed graft function (DGF) and acute rejection rates were not different between interventions groups (RR =1.23; 95% CI = [0.40-3.74]) and (RR =0.96; 95% CI = [0.55-1.70]), respectively. No difference between groups in early graft outcomes are evident.

CONCLUSIONS:

Our analysis suggests that RAKT is a minimally invasive, safe, and feasible procedure. It is associated with a lower complication rate and similar intraoperative, perioperative, and postoperative outcomes. Further quality studies are needed to confirm these findings.

  • Herrera S
  • Aguado JM
  • Candel FJ
  • Cordero E
  • Domínguez-Gil B
  • et al.
Transplant Rev (Orlando). 2023 Dec;37(4):100788 doi: 10.1016/j.trre.2023.100788.
  • Haller J
  • Diebold M
  • Leuzinger K
  • Wehmeier C
  • Handschin J
  • et al.
Transplantation. 2023 Dec 1;107(12):2568-2574 doi: 10.1097/TP.0000000000004712.
CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This post-hoc analysis of an RCT investigated the predictive value of urine CXCL10 levels in the diagnosis of BK viral replication. CXCL10 levels were associated with risk of viruria, presence of decoy cells and viraemia. Negative predictive value was high (96%) with an AUC of 0.79, although positive predictive value was low (21%) meaning that the test is not very specific. These findings suggest that urine CXCL10 monitoring may be a useful strategy to rule out significant BK virus infection in transplant recipients. It is worth noting that the investigators selected patients without recent acute rejection episodes, and the test is not specific enough to differentiate between rejection and BK viral infection, meaning that confirmatory tests would be required. The actual clinical benefit of CXCL10 monitoring would need to be confirmed in a prospective RCT.
Aims: This secondary analysis of a randomised controlled trial (RCT) aimed to assess levels of urine CXCL10 at different stages of BK polyomavirus (BKPyV) reactivation and to determine the predictive ability of urine CXCL10 for BKPyV replication.
Interventions: Participants in the original trial were randomly assigned to either the intervention arm where elevated levels of urine CXCL10 indicated the performance of a renal allograft biopsy with therapeutic adaptations based on the result; and the control arm, where the results of the urine CXCL10 analyses was concealed.
Participants: 235 adult kidney transplant recipients from the original trial were included.
Outcomes: The outcomes of interest included urine CXCL10 levels at different stages of BKPyV infection, urine CXCL10 levels at different phases of patients with BKPyV DNAemia and diagnostic performance of urine CXCL10 for detecting BKPyV replication.
Follow Up: 1 year
BACKGROUND:

Urine CXCL10 is a biomarker for renal allograft inflammation induced by rejection, urinary tract infection, or BK polyomavirus (BKPyV) replication. This study aimed to compare urine CXCL10 levels in different stages of BKPyV reactivation and to investigate urine CXCL10 as a biomarker for BKPyV replication.

METHODS:

We included 763 urine samples (235 patients) from an interventional, randomized trial obtained in the context of regular screening for urine CXCL10 levels. All urine samples had a complete urine sediment analysis, no rejection episode noted within 30 d before urine collection, and a urine decoy cell analysis was conducted within ±3 d.

RESULTS:

Urine CXCL10 levels were 2.31 ng/mmol in samples without BKPyV viruria, slightly rose to 4.35 ng/mmol with BKPyV viruria, and then markedly increased to 16.42 ng/mmol when decoy cells were detectable, but still in the absence of BKPyV DNAemia ( P  < 0.001). The highest urine CXCL10 values were observed in samples with BKPyV DNAemia (median 42.59 ng/mmol). The area under the curve of urine CXCL10 levels to detect ≥3 decoy cells was 0.816. At a CXCL10 cutoff of 3 ng/mmol, the negative predictive value was 97%. The area under the curve of urine CXCL10 levels to detect BKPyV DNAemia was 0.882, with a negative predictive value of 99% at a CXCL10 cutoff of 3 ng/mmol.

CONCLUSIONS:

Urine CXCL10 levels are already significantly elevated in BKPyV viruria (especially with decoy cell shedding) and further increase with BKPyV DNAemia. Low urine CXCL10 values can rule out the presence of ≥3 decoy cells and BKPyV DNAemia with high certainty.

  • Duarsa GWK
  • Sugianto R
  • Yusari IGAAA
  • Tirtayasa PMW
  • Situmorang GR
  • et al.
Methods X. 2023 Dec;11:102250 doi: 10.1016/j.mex.2023.102250.

The systematic review and meta-analysis were conducted for COVID-19 infections in kidney transplant patients. Recent research on this topic was still scarce and limited meta-analysis research discussion, specific to some risks or treatment in kidney transplantation patients with COVID-19 infection. Therefore, this article demonstrated the fundamental steps to conducting systematic review and meta-analysis studies to derive a pooled estimate of predictor factors of worse outcomes in kidney transplant patients with positive for the SARS-CoV- 2 test•PICOT Framework to determine the research scope•PRISMA strategy for study selection•Forest Plot for meta-analysis study.

  • Azegami T
  • Kounoue N
  • Sofue T
  • Yazawa M
  • Tsujita M
  • et al.
Ren Fail. 2023 Dec;45(1):2169618 doi: 10.1080/0886022X.2023.2169618.
BACKGROUND:

Pre-emptive kidney transplantation (PEKT), i.e., transplantation performed before initiation of maintenance dialysis, is considered an ideal renal replacement therapy because there is no exposure to long-term dialysis therapy. Therefore, we summarized advantages/disadvantages of PEKT to assist in deciding whether kidney transplantation should be performed pre-emptively.

METHODS:

This study was registered with PROSPERO, CRD42021269163. Observational studies comparing clinical outcomes between PEKT and non-PEKT were included; those involving only pediatric recipients or simultaneous multi-organ transplantations were excluded. The PubMed/MEDLINE, Cochrane Library, and Ichushi-Web databases were searched on 1 August 2021. Studies were pooled using the generic inverse-variance method with random effects model, and risk of bias was assessed using ROBINS-I.

RESULTS:

Seventy-six studies were included in the systematic review (sample size, 23-121,853; enrollment year, 1968-2019). PEKT patients had lower all-cause mortality (adjusted HR: 0.78 [95% CI 0.66-0.92]), and lower death-censored graft failure (0.81 [0.67-0.98]). Unadjusted RRs for the following outcomes were comparable between the two patient groups: cardiovascular disease, 0.90 (0.58-1.40); biopsy-proven acute rejection, 0.75 (0.55-1.03); cytomegalovirus infection, 1.04 (0.85-1.29); and urinary tract infection, 0.89 (0.61-1.29). Mean differences in post-transplant QOL score were comparable in both groups. The certainty of evidence for mortality and graft failure was moderate and that for other outcomes was very low following the GRADE classification.

CONCLUSIONS:

The present meta-analysis shows the potential benefits of PEKT, especially regarding patient and graft survival, and therefore PEKT is recommended for adults with end-stage kidney disease.

  • Farhadian N
  • Farhadian M
  • Zamanian MH
  • Taghadosi M
  • Vaziri S
Immunopharmacol Immunotoxicol. 2023 Dec;45(4):402-408 doi: 10.1080/08923973.2022.2160733.

Purpose: Solid organ transplant recipients (SOTR) have a high risk for severe COVID-19 infection; hence it is necessary to find alternative treatment strategies to protect these patients from the complications caused by the severe progression of the disease. This study aimed to determine the effectiveness of sotrovimab among SOTR with COVID-19.Materials and methods: A systematic literature search was conducted with relevant keywords to find studies that reported clinical outcomes regarding sotrovimab administration in SOTR outpatients with confirmed COVID-19 infection, who had mild-to-moderate symptoms.Results: Of 796 records found by a systematic search, only 14 met the inclusion criteria for reporting in a systematic review and only 6 enrolled in a meta-analysis. This meta-analysis indicated that SOTR outpatients with mild to moderate COVID-19 who received sotrovimab had lower likelihood of all-cause hospitalization (OR: 0.29, CI: 0.16, 0.52, p < 0.001), ICU admission (OR: 0.17, CI: 0.05, 0.64, p = 0.009) and mortality (OR: 0.15, CI: 0.03, 0.64, p = 0.010) within 30 days of drug infusion compared to controls.Conclusions: Our findings confirm that monoclonal antibody therapy with sotrovimab in SOTR is associated with better outcomes and consequently a reduced risk of disease progression in this high-risk population.

  • Pennington KM
  • Martin MJ
  • Murad MH
  • Sanborn D
  • Saddoughi SA
  • et al.
BACKGROUND:

Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The objective of this study was to identify risk factors for the development of fungal infections within the first year following solid organ transplant.

METHODS:

We searched for eligible articles through February 3, 2023. Studies published after January 1, 2001, that pertained to risk factors for development of invasive fungal infections in solid organ transplant were reviewed for inclusion. Of 3087 articles screened, 58 were included. Meta-analysis was conducted using a random-effects model to evaluate individual risk factors for the primary outcome of any invasive fungal infections and invasive candidiasis or invasive aspergillosis (when possible) within 1 y posttransplant.

RESULTS:

We found 3 variables with a high certainty of evidence and strong associations (relative effect estimate ≥ 2) to any early invasive fungal infections across all solid organ transplant groups: reoperation (odds ratio [OR], 2.92; confidence interval [CI], 1.79-4.75), posttransplant renal replacement therapy (OR, 2.91; CI, 1.87-4.51), and cytomegalovirus disease (OR, 2.97; CI, 1.78-4.94). Both posttransplant renal replacement therapy (OR, 3.36; CI, 1.78-6.34) and posttransplant cytomegalovirus disease (OR, 2.81; CI, 1.47-5.36) increased the odds of early posttransplant invasive aspergillosis. No individual variables could be pooled across groups for invasive candidiasis.

CONCLUSIONS:

Several common risk factors exist for the development of any invasive fungal infections in solid organ transplant recipients. Additional risk factors for invasive candidiasis and aspergillosis may be unique to the pathogen, transplanted organ, or both.

  • You P
  • Gao RY
  • Han YZ
  • Zhang XK
  • Li WX
  • et al.
Surg Infect (Larchmt). 2023 Nov 10; doi: 10.1089/sur.2023.206.

Background: Post-operative infection remains a major cause of morbidity and mortality in adults early after liver transplantation (LT). Procalcitonin (PCT) may be a good test method for early diagnosis of post-operative infection and determining its severity. This study was performed to assess the diagnostic accuracy of PCT as a biomarker for infection after LT. Patients and Methods: A meta-analysis and systematic review was conducted for studies reporting diagnostic performance of PCT for infection in adults after LT. Observational studies were evaluated for their reporting of diagnostic accuracy, relevance, and quality. Results: Ten eligible studies assessing 730 patients were included in this meta-analysis and systematic review summarizing the diagnostic value of PCT for post-operative infection in adult liver transplantation. Pooled sensitivity and specificity with corresponding 95% confidence interval were 69% (95% confidence interval [CI], 54-81; heterogeneity I2 = 82.4%) and 88% (95% CI, 82-92; I2 = 52.7%), respectively. The diagnostic odd ratio (DOR) was 16 (95% CI, 10-25; I2 = 76.4%). The summary receiver operator characteristic (SROC) of PCT for post-operative infection was 0.88. There was a wide range of variability in the cutoff values, ranging from 0.22 to 42.80 ng/mL. Heterogeneity was reduced by excluding studies that focused on pediatric LT recipients. Conclusions: Procalcitonin is a moderately accurate diagnostic marker for post-operative infection in adult LT. Additionally, the diagnostic performance can be improved by combining it with other inflammatory biomarkers. This article provides the research direction for post-operative infection control.