BACKGROUND:

Pediatric transplantation can be a stressful process for patients and caregivers. Some individuals may experience post-traumatic stress symptoms (PTSS) and post-traumatic growth (PTG) as a result. Although post-traumatic stress disorder (PTSD) has been well-studied in this population, the purpose of the present scoping review is to provide a first synthesis of the existing literature on PTG in pediatric transplant populations.

METHODS:

We conducted a literature search of PsycINFO and Scopus in May 2023. Eligible articles must have included a sample of solid organ transplant (SOT) or stem cell transplant (SCT) recipients under age 18, siblings of recipients, or caregivers; and must have examined PTG.

RESULTS:

Twenty-three studies were identified, and nine studies met inclusion criteria and were included in the review (n = 5 cross sectional; n = 4 qualitative). Cross-sectional studies examined demographic, mental health, and medical correlates of PTG in children and caregivers. PTG was correlated with PTSS among caregivers. Qualitative studies identified themes along each of the five factors of PTG.

CONCLUSION:

Findings overwhelmingly focused on caregiver PTG. Qualitative study findings align with the theoretical model of PTG. Additional research is needed to investigate PTG in siblings of children with a transplant and associations between PTG and medication adherence. This scoping review provides insight into positive change processes following a transplant among children and their caregivers.

BACKGROUND:

Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant immunosuppression for inflammatory bowel disease (IBD) and organ transplant management are limited. This study sought to evaluate the safety of biologic and small molecule therapy for the treatment of IBD among solid organ transplant recipients.

METHODS:

Medline, Embase, and Web of Science databases were systematically searched for studies reporting on safety outcomes associated with the use of biologic and small molecule therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) in patients with IBD postsolid organ transplant (eg, liver, kidney, heart, lung, pancreas). The primary outcome was infectious complications. Secondary outcomes included serious infections, colectomy, and discontinuation of biologic therapy.

RESULTS:

Seven hundred ninety-seven articles were identified for screening, yielding 16 articles for the meta-analyses with information on 163 patients. Antitumor necrosis factor α (Anti-TNFs; infliximab and adalimumab) were used in 8 studies, vedolizumab in 6 studies, and a combination of ustekinumab or vedolizumab and anti-TNFs in 2 studies. Two studies reported outcomes after kidney and cardiac transplant respectively, whereas the rest of the studies included patients with liver transplants. The rates of all infections and serious infections were 20.09 per 100 person-years (100-PY; 95% CI, 12.23-32.99 per 100-PY, I2 = 54%) and 17.39 per 100-PY (95% CI, 11.73-25.78 per 100-PY, I2 = 21%), respectively. The rates of colectomy and biologic medication discontinuation were 12.62 per 100-PY (95% CI, 6.34-25.11 per 100-PY, I2 = 34%) and 19.68 per 100-PY (95% CI, 9.97-38.84 per 100-PY, I2 = 74%), respectively. No cases of venous thromboembolism or death attributable to biologic use were reported.

CONCLUSION:

Biologic therapy is overall well tolerated in patients with solid organ transplant. Long-term studies are needed to better define the role of specific agents in this patient population.

We conducted a systematic review and network meta-analyses evaluating the effects of different intraoperative vasoactive drugs on acute kidney injury (AKI) and other perioperative outcomes in adult liver transplant recipients. We searched multiple electronic databases using words from the "liver transplantation" and "vasoactive drug" domains. We included all randomized controlled trials conducted in adult liver transplant recipients comparing 2 different intravenous vasoactive drugs or 1 against a standard of care that reported AKI, intraoperative blood loss, or any other postoperative outcome. We conducted 4 frequentist network meta-analyses using random effect models, based on the interventions' mechanism of action, and evaluated the quality of evidence (QoE) using Grading of Recommendations, Assessment, Development, and Evaluations recommendations. We included 9 randomized controlled trials comparing different vasopressor drugs (vasoconstrictor or inotrope), 3 comparing a somatostatin infusion (or its analogues) to a standard of care, 11 comparing different vasodilator infusions together or against a standard of care, and 2 comparing vasoconstrictor boluses at graft reperfusion. Intravenous clonidine was associated with shorter duration of mechanical ventilation, intensive care unit, and hospital length of stay (very low QoE), and some vasodilators were associated with lower creatinine level 24 h after surgery (low to very low QoE). Phenylephrine and terlipressin were associated with less intraoperative blood loss when compared with norepinephrine (low and moderate QoE). None of the vasoactive drugs improve any other postoperative outcomes, including AKI. There is still important equipoise regarding the best vasoactive drug to use in liver transplantation for most outcomes. Further studies are required to better inform clinical practice.

BACKGROUND:

Liver transplantation is a life-saving therapy for end-stage liver disease patients, but acute cellular rejection (ACR) and graft complications remain significant postoperative challenges. Early and accurate diagnosis is crucial for timely intervention and improved patient outcomes, but their diagnosis rely currently on invasive biopsy sampling, thus prompting the search for non-invasive Biomarkers. MicroRNA (miRNA) have emerged as promising biomarkers in various pathological conditions, and their potential utility in diagnosing acute cellular rejection after liver transplantation has gained significant interest.

METHODS:

This systematic review of PubMed, Web of Science, and the ClinicalTrials.gov registry analyzes studies exploring miRNA as biomarkers for ACR and graft dysfunction in liver transplantation (PROSPERO ID CRD42023465278). The Cochrane Collaboration tool for assessing risk of bias was employed. Population data, identified miRNA and their dynamic regulation, as well as event prediction were compared. Data extraction and quality assessment were performed independently by two reviewers.

RESULTS:

Thirteen studies were included in this systematic review. Various investigated miRNAs were upregulated in association with acute cellular rejection, like miR-122, miR-155, miR-181, miR-483-3p, and miR-885-5p, demonstrating great biomarker potential. Additionally, several studies conducted target gene analysis, revealing insights into cellular mechanisms linked to ACR. Moreover, various miRNA were also capable of predicting different organ complications following transplantation, expanding their versatility. Remaining challenges include the standardization of miRNA profiling, the need for functional validation, and the necessity for long-term studies.

CONCLUSION:

The results highlight the potential of miRNA as specific, non-invasive biomarkers for ACR and graft dysfunction following liver transplantation. However, further research is needed to validate these findings and establish standardized diagnostic panels to incorporate them into clinical practice and explore miRNA-based therapies in the future.

BACKGROUND AND AIM:

Domino liver transplantation (DLT) utilizes otherwise discarded livers as donor grafts for another recipients. It is unclear whether DLT has less favorable outcomes compared to deceased donor liver transplantation (DDLT). We aimed to assess the outcomes of DLT compared to DDLT.

METHODS:

MEDLINE, Embase, and Web of Science database were searched to identify studies comparing outcomes after DLT with DDLT. Data were pooled using random-effects modeling, evaluating odds ratios (OR) or mean difference (MD) for outcomes including waiting list time, severe hemorrhage, intensive care unit (ICU), length hospital stay (LOS), rejection, renal, vascular, and biliary events, and recipient survival at 1, 3, 5, and 10 years.

RESULTS:

Five studies were identified including 945 patients (DLT = 409, DDLT = 536). The DLT recipients were older compared to the DDLT group (P = 0.04), and both cohorts were comparable regarding lab MELD, hepatocellular carcinoma, and waitlist time. There were no differences in vascular (OR: 1.60, P = 0.39), renal (OR: 0.62, P = 0.24), biliary (OR: 1.51, P = 0.21), severe hemorrhage (OR: 1.09, P = 0.86), rejection (OR: 0.78, P = 0.51), ICU stay (MD: 0.50, P = 0.21), or LOS (MD: 1.68, P = 0.46) between DLT and DDLT. DLT and DDLT were associated with comparable 1-year (78.9% vs 80.4%; OR: 1.03, P = 0.89), 3-year (56.2% vs 54.1%; OR: 1.35, P = 0.07), and 10-year survival (6.5% vs 8.5%; OR: 0.8, P = 0.67) rates. DLT was associated with higher 5-year survival (41.6% vs 36.4%; OR: 1.70; P = 0.003) compared to DDLT, which was not confirmed at sensitivity analysis.

CONCLUSION:

This meta-analysis of the best available evidence (Level 2a) demonstrated that DLT and DDLT have comparable outcomes. As indications for liver transplantation expand, future high-quality research is encouraged to increase the DLT numbers in clinical practice, serving the growing waiting list candidates, with the caveat of uncertain de novo disease transmission risks.

The relationship between sarcopenia and prognosis in solid organ transplantation recipients (SOTr) remains unverified. We aimed to quantify the prevalence of pretransplant sarcopenia and its effect on patient and graft survival in SOTr. We used PubMed, EMBASE, Cochrane Library and Web of Science to search relevant studies published in English (from inception to December 31, 2021). Prospective and retrospective cohort studies that reported the prevalence of sarcopenia before transplant or the association between sarcopenia and clinical outcomes in SOTr were included. Primary outcomes were the prevalence of sarcopenia and its impact on patient and graft survival. Secondary outcomes included perioperative complications, acute rejection, length of hospital stay, length of intensive care unit stay (ICU LOS) and early readmission. Thirty-nine studies involving 5792 patients were included. Pooled prevalence of sarcopenia amongst SOTr candidates was 40 % (95 % confidence interval [CI]: 34%-47 % and I2 = 97 %). Sarcopenia was associated with increased risk of death (hazard ratio [HR] = 1.87, 95 % CI: 1.46-2.41 and I2 = 60 %), poor graft survival (HR = 1.71, 95 % CI: 1.16-2.54 and I2 = 57 %) and increased liver graft loss (HR = 1.43, 95 % CI: 1.03-1.99 and I2 = 38 %). Patients with sarcopenia demonstrated increased incidence of perioperative complications (risk ratio [RR] = 1.34, 95 % CI: 1.17-1.53 and I2 = 40 %), long ICU LOS (mean difference = 2.31 days, 95 % CI: 0.58-4.04 and I2 = 97 %) and decreased risk of acute rejection (RR = 0.61, 95 % CI: 0.42-0.89 and I2 = 0 %). In Conclusion, sarcopenia is prevalent in SOTr candidates and associated with death and graft loss. Identifying sarcopenia before transplantation and intervening may improve long-term outcomes.

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.

BACKGROUND:

Rescue liver transplantation (LT) is the only life-saving option for posthepatectomy liver failure (PHLF) whenever it is deemed as irreversible and likely to be fatal. The goals were to perform a qualitative systematic review of rescue LT for PHLF and a survey among various international LT experts.

METHODS:

A literature search was performed from 2000 to 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Population, Intervention, Comparison, Outcome framework, and to this, the authors' experience was added. The international online open survey included 6 cases of PHLF extracted from the literature and submitted to 976 LT experts. The primary outcome was whether experts would consider rescue LT for each case. Interrater agreement among experts was calculated using the free-marginal multirater kappa methodology.

RESULTS:

The review included 40 patients. Post-LT mortality occurred in 8 (20%) cases (7/28 with proven cancer and 1/12 with benign disease). In the long term, 6 of 21 (28.6%) survivors with cancer died of recurrence (median = 38 mo) and 15 (71.4%) were alive with no recurrence (median = 111 mo). All 11 survivors with benign disease were alive and well (median = 39 mo). In the international survey among experts in LT, the percentage agreement to consider rescue LT was 28%-98%, higher for benign than for malignant disease ( P = 0.011). Interrater agreement for the primary endpoint was low, expected 5-y survival >50% being the strongest independent predictor to consider LT.

CONCLUSIONS:

Rescue LT for PHLF may achieve good results in selected patients. Considerable inconsistencies of decision-making exist among LT experts when considering LT for PHLF.

BACKGROUND:

Of nearly 90 hand and 50 face transplant recipients, only five have received a cross-sex vascularized composite allotransplantation (CS-VCA). CS-VCA has the potential to expand the donor pool and has been proven anatomically feasible and ethically acceptable in previous studies. However, there is a lack of immunologic data. This study evaluated the immunologic feasibility of CS-VCA through analysis of the solid organ transplant literature, given the paucity of CS-VCA data. The authors hypothesize that rates of acute rejection (AR) and graft survival (GS) in CS versus same-sex (SS) solid organ transplantation are similar.

METHODS:

A systematic review and meta-analysis were performed. Studies comparing GS or AR episodes in CS and SS adult kidney (KT) and liver transplant (LT) populations were included. Odds ratios were calculated for overall GS and AR for all SS and CS transplant combinations [male-to-female (MTF), female-to-male, and overall].

RESULTS:

A total of 693 articles were initially identified with 25 included in the meta-analysis. No significant difference in GS was noted between SS-KT versus CS-KT [OR, 1.04 (95% CI, 1.00 to 1.07); P = 0.07), SS-KT versus MTF-KT [OR, 0.97 (95% CI, 0.90 to 1.04); P = 0.41), and SS-LT versus MTF-LT [OR, 0.95 (95% CI, 0.91 to 1.00); P = 0.05). No significant difference in AR was noted between SS-KT versus MTF-KT [OR, 0.99 (95% CI, 0.96 to 1.02); P = 0.57), SS-LT versus CS-LT [OR, 0.78 (95% CI, 0.53 to 1.16); P = 0.22], or SS-LT versus female-to-male LT [OR, 1.03 (95% CI, 0.95 to 1.12); P = 0.47]. For the remaining pairings, GS was significantly increased and AR was significantly decreased in the SS transplants.

CONCLUSIONS:

Published data suggest immunologic feasibility of CS-KT and CS-LT with the potential for generalization to the VCA population.

CLINICAL RELEVANCE STATEMENT:

In theory, CS-VCA could expand the potential donor pool, ultimately leading to decreased wait times for recipients and improve the likelihood of establishing a immunologically favorable donor-recipient match.