Tackling cancer cell dormancy: Insights from immune models, and transplantation.

Disseminated non-dividing (dormant) cancer cells as well as those in equilibrium with the immune response remain the major challenge for successful treatment of cancer. The equilibrium between disseminated dormant cancer cells and the immune system is reminiscent of states that can occur during infection or allogeneic tissue and cell transplantation. We discuss here the major competing models of how the immune system achieves a self nonself discrimination (pathogen/danger patterns, quorum, and coinhibition/tuning models), and suggest that taking advantage of a combination of the proposed mechanisms in each model may lead to increased efficacy in tackling cancer cell dormancy.

Ovarian tissue damage after grafting: systematic review of strategies to improve follicle outcomes.

Frozen-thawed human ovarian tissue endures large-scale follicle loss in the early post-grafting period, characterized by hypoxia lasting around 7 days. Tissue revascularization occurs progressively through new vessel invasion from the host and neoangiogenesis from the graft. Such reoxygenation kinetics lead to further potential damage caused by oxidative stress. The aim of the present manuscript is to provide a systematic review of proangiogenic growth factors, hormones and various antioxidants administered in the event of ovarian tissue transplantation to protect the follicle pool from depletion by boosting revascularization or decreasing oxidative stress. Although almost all investigated studies revealed an advantage in terms of revascularization and reduction in oxidative stress, far fewer demonstrated a positive impact on follicle survival. As the cascade of events driven by ischaemia after transplantation is a complex process involving numerous players, it appears that acting on specific molecular mechanisms, such as concentrations of proangiogenic growth factors, is not enough to significantly mitigate tissue damage. Strategies exploiting the activated tissue response to ischaemia for tissue healing and remodelling purposes, such as the use of antiapoptotic drugs and adult stem cells, are also discussed in the present review, since they yielded promising results in terms of follicle pool protection.

Detection of Mycoplasma Contamination in Transplanted Retinal Cells by Rapid and Sensitive Polymerase Chain Reaction Test.

Contamination of cells/tissues by infectious pathogens (e.g., fungi, viruses, or bacteria, including mycoplasma) is a major problem in cell-based transplantation. In this study, we tested a polymerase chain reaction (PCR) method to provide rapid, simple, and sensitive detection of mycoplasma contamination in laboratory cultures for clinical use. This mycoplasma PCR system covers the Mycoplasma species (spp.) listed for testing in the 17th revision of the Japanese Pharmacopoeia, and we designed it for use in transplantable retinal cells. Here, we analyzed mycoplasma contamination in induced pluripotent stem cell (iPS cell)-derived transplantable retinal pigment epithelium (RPE) cells. In the spike tests to RPE cells with nine species of class Mollicutes bacteria, including seven Mycoplasma spp. and one of each Acholeplasma spp. and Ureaplasma spp., contamination at the concentration of 100 and 10 CFU/mL were detected with 100% probability in all cases, while 1 CFU/mL had a detection rate of 0-75%. DNA prepared from bacteria species other than class Mollicutes species was not detectable, indicating the specificity of this PCR. While iPS cells and iPS-RPE cells established in our laboratory were all negative by this PCR, some of the commercially available cell lines were positive. Cells for transplantation should never have infection, as once pathogens are implanted into the eyes, they can cause severe intraocular inflammation. Thus, it is imperative to monitor for infections in the transplants, although generally, mycoplasma infection is difficult to detect.

Bacteriophage therapy as a treatment option for transplant infections.

PURPOSE OF REVIEW: Since initial description of the successful use of intravenous bacteriophage therapy in the United States in 2017, there is widespread interest in using bacteriophage therapy for multidrug-resistant (MDR) infections. RECENT FINDINGS: Recent published cases of bacteriophage therapy in transplant candidates and recipients are reviewed highlighting its safety and potential efficacy when used as an adjunct to systemic antibiotics for a variety of clinical indications. An overview of access to bacteriophage therapy in the United States is also provided. SUMMARY: The reviewed cases form the basis for ongoing compassionate use of bacteriophage therapy in transplant candidates and recipients with life-threatening MDR infections until data from clinical trials are available to guide therapy.

Management of transplant patients outside hospital during COVID-19 epidemic: A Chinese experience.

Coronavirus disease 2019 (COVID-19) pandemic poses an increasing challenge for transplant community. Aggressive management measures are conductive to improve compliance and to lower the risk of intra-hospital infection. In this Personal Viewpoint essay, we shared experiences about management strategies of transplant patients outside hospital amid the epidemic. With the aid of Cloud Clinic service and telemedicine care, transplant patients could be regularly followed up and get medical consultation online. Furthermore, personal health education and mental health assistance are enrolled in our practice.

Nocardia spp.: A Rare Cause of Pneumonia Globally.

Members of the Nocardia genus are ubiquitous in the environment. These aerobic, gram-positive organisms can lead to life-threatening infection, typically in immunocompromised hosts such as solid organ transplant recipients or those receiving immunosuppressive medications for other reasons. This current review discusses the microbiology of nocardiosis, risk factors for infection, clinical manifestations, methods for diagnosis, and treatment. Nocardiosis primarily affects the lung but may also cause skin and soft tissue infection, cerebral abscess, bloodstream infection, or infection involving other organs. Although rare as a cause of community-acquired pneumonia, Nocardia can have severe morbidity and mortality, particularly in patients with comorbidities or compromised immunity. Early diagnosis and timely initiation of therapy are critical to optimizing patient outcomes. Species identification is important in determining treatment, as is in vitro susceptibility testing. Sulfonamide therapy is usually indicated, although a variety of other antimicrobials may be useful, depending on the species and susceptibility testing. Prolonged therapy is usually indicated, for 6 to 12 months, and in some cases surgical debridement may be required to resolve infection.

Transmission of Eastern Equine Encephalitis Virus From an Organ Donor to 3 Transplant Recipients.

BACKGROUND: In fall 2017, 3 solid organ transplant (SOT) recipients from a common donor developed encephalitis within 1 week of transplantation, prompting suspicion of transplant-transmitted infection. Eastern equine encephalitis virus (EEEV) infection was identified during testing of endomyocardial tissue from the heart recipient. METHODS: We reviewed medical records of the organ donor and transplant recipients and tested serum, whole blood, cerebrospinal fluid, and tissue from the donor and recipients for evidence of EEEV infection by multiple assays. We investigated blood transfusion as a possible source of organ donor infection by testing remaining components and serum specimens from blood donors. We reviewed data from the pretransplant organ donor evaluation and local EEEV surveillance. RESULTS: We found laboratory evidence of recent EEEV infection in all organ recipients and the common donor. Serum collected from the organ donor upon hospital admission tested negative, but subsequent samples obtained prior to organ recovery were positive for EEEV RNA. There was no evidence of EEEV infection among donors of the 8 blood products transfused into the organ donor or in products derived from these donations. Veterinary and mosquito surveillance showed recent EEEV activity in counties nearby the organ donor's county of residence. Neuroinvasive EEEV infection directly contributed to the death of 1 organ recipient and likely contributed to death in another. CONCLUSIONS: Our investigation demonstrated EEEV transmission through SOT. Mosquito-borne transmission of EEEV to the organ donor was the likely source of infection. Clinicians should be aware of EEEV as a cause of transplant-associated encephalitis.

Improving our mechanistic understanding of the indirect effects of CMV infection in transplant recipients.

Cytomegalovirus (CMV) is an immunomodulatory virus that indirectly increases the risk for bacterial, fungal, and viral infections. However, the pathogenesis of this phenomenon is poorly understood. We determined whether inflammatory responses to different Toll-like receptor (TLR) ligands are blunted during CMV infection in solid-organ transplant (SOT) patients. Peripheral blood mononuclear cells from 38 SOT patients with and without CMV were incubated in the presence of various viral, fungal, and bacterial TLR ligands. Cytokines were measured in the supernatant by multiplex enzyme-linked immunosorbent assay. Patients had blunted cytokine responses to bacterial, fungal, and viral ligands during CMV infection when compared to the absence of CMV infection. This was independent of viral load, clinical presentation of CMV infection or immunosuppression, supporting the clinical observation in SOT recipients that CMV infection increases susceptibility to bacterial, fungal, and other viral infections. Moreover, in the absence of CMV infection, patients with subsequent CMV infection had lower cytokines in response to TLR ligands compared to those without subsequent CMV infection, suggesting that inherent differences in patients not directly related to CMV also contribute to this increased susceptibility. In summary, these data provide novel ex vivo evidence to support indirect effects of CMV.

Metagenomic Next-Generation Sequencing for Identification and Quantitation of Transplant-Related DNA Viruses.

Infections with DNA viruses are frequent causes of morbidity and mortality in transplant recipients. This study describes the analytical and clinical performance characteristics of the Arc Bio Galileo Pathogen Solution, an all-inclusive metagenomic next-generation sequencing (mNGS) reagent and bioinformatics pipeline that allows the simultaneous quantitation of 10 transplant-related double-stranded DNA (dsDNA) viruses (adenovirus [ADV], BK virus [BKV], cytomegalovirus [CMV], Epstein-Barr virus [EBV], human herpesvirus 6A [HHV-6A], HHV-6B, herpes simplex virus 1 [HSV-1], HSV-2, JC virus [JCV], and varicella-zoster virus [VZV]). The mNGS 95% limit of detection ranged from 14 copies/ml (HHV-6) to 191 copies/ml (BKV), and the lower limit of quantitation ranged from 442 international units (IU)/ml (EBV) to 661 copies/ml (VZV). An evaluation of 50 residual plasma samples with at least one DNA virus detected in prior clinical testing showed a total percent agreement of mNGS and quantitative PCR (qPCR) of 89.2% (306/343), with a κ statistic of 0.725. The positive percent agreement was 84.9% (73/86), and the negative percent agreement was 90.7% (233/257). Furthermore, mNGS detected seven subsequently confirmed coinfections that were not initially requested by qPCR. Passing-Bablok regression revealed a regression line of y = 0.953x + 0.075 (95% confidence interval [CI] of the slope, 0.883 to 1.011; intercept, -0.100 to 0.299), and Bland-Altman analysis (mNGS - qPCR) showed a slight positive bias (0.28 log10 concentration; 95% limits of agreement, -0.62 to 1.18). In conclusion, the mNGS-based Galileo pipeline demonstrates analytical and clinical performance comparable to that of qPCR for transplant-related DNA viruses.

Human ehrlichiosis at a tertiary-care academic medical center: Clinical associations and outcomes of transplant patients and patients with hemophagocytic lymphohistiocytosis.

BACKGROUND: Ehrlichiosis is an acute febrile tick-borne disease which can rarely be a trigger for secondary hemophagocytic lymphohistiocytosis (HLH). METHODS: We reviewed our experience with Ehrlichia infections at a tertiary-care academic medical center. RESULTS: Over 10 years, 157 cases of ehrlichiosis were identified. Ten patients (6.4%) had infection with E. ewingii, 7(4.5%) of whom were transplant patients as compared to 3(1.9%) non-transplant patients (p = .035). Transplant patients were more likely to have leukopenia and elevated creatinine compared to immunocompetent patients; length of hospital stay and early mortality were not different between the two groups. Ten patients met the HLH-2004 diagnosis criteria, which could be an underestimation of HLH occurrence as most patients were not completely evaluated for these criteria. We calculated the H-Score to find the probability of HLH; 25 patients scored high making the occurrence rate of HLH at least 16%. Ehrlichia-induced HLH patients (N = 25) had more anemia, thrombocytopenia, elevated creatinine and AST. Moreover, they had a significantly longer hospital stay (median 9 days) compared to patients without HLH (median 4 days) (p = .006). CONCLUSIONS: Ehrlichia-induced HLH is a potential serious complication with relatively high occurrence rate; patients manifest severe disease with end-organ damage requiring longer hospital stay.

FXR activation alleviates tacrolimus-induced post-transplant diabetes mellitus by regulating renal gluconeogenesis and glucose uptake.

BACKGROUND: Tacrolimus (FK506)-induced diabetes mellitus is one of the most important factors of post-transplant diabetes mellitus (PTDM). However, the detailed mechanisms underlying PTDM are still unclear. Farnesoid X receptor (FXR) regulates glycolipid metabolism. The objective of this study was to explore whether FXR is involved in the development of tacrolimus-induced diabetes mellitus. METHODS: After C57BL/6J mice were treated with tacrolimus (FK506) for 3 months, the fasting blood glucose levels, body weights, renal morphological alterations, and mRNA expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose transporter 2 (GLUT2) among the control group, the FK506 group and the FK506 + GW4064 (a FXR agonist) group (n = 7) were measured. The intracellular location of peroxisome proliferator activated receptor γ coactivator-1α (PGC1α) and forkhead box O1 (FOXO1) was detected by immunofluorescence. Human renal cortex proximal tubule epithelial cells (HK-2) were treated with 15 µM FK506 or 4 µM FXR agonist (GW4064) for 24, 48 and 72 h, and the expression levels of FXR, gluconeogenesis and glucose uptake, representing the enzymes PEPCK and GLUT2, were detected with real-time PCR and western blot analyses. Finally, the mRNA levels of PEPCK and GLUT2 in HK-2 cells were measured after FXR was upregulated. RESULTS: FK506 significantly inhibited the mRNA and protein levels of FXR at 48 h and 72 h in HK-2 cells (P < 0.05). Meanwhile, FK506 promoted gluconeogenesis and inhibited glucose uptake in HK-2 cells (P < 0.05). However, overexpression of FXR in transfected HK-2 cell lines significantly inhibited gluconeogenesis and promoted glucose uptake (P < 0.05). The FXR agonist GW4064 significantly decreased the fasting blood glucose in mice challenged with FK506 for 3 months (P < 0.05), inhibited gluconeogenesis (P < 0.05) and significantly promoted glucose uptake (P < 0.05). Immunofluorescence staining and western blot analyses further revealed that FXR activation may affect the translocation of PGC1α and FOXO1 from the nucleus to the cytoplasm. CONCLUSIONS: FXR activation may mitigate tacrolimus-induced diabetes mellitus by regulating gluconeogenesis as well as glucose uptake of renal cortex proximal tubule epithelial cells in a PGC1α/FOXO1-dependent manner, which may be a potential therapeutic strategy for the prevention and treatment of PTDM.

Adventitial Activation in the Pathogenesis of Injury-Induced Arterial Remodeling: Potential Implications in Transplant Vasculopathy.

Transplant vasculopathy is one of the major causes of chronic rejection after solid organ transplantation. The pathogenic mechanisms of transplant vasculopathy are still poorly understood. Herein, we summarize current evidence suggesting that activation of the tunica adventitia may be involved in the pathogenesis of transplant vasculopathy. Adventitia is an early responder to various vascular injuries and plays an integral role in eliciting vascular inflammation and remodeling. Accumulation of macrophages in the adventitia promotes the development of vascular remodeling by releasing a variety of paracrine factors that have profound impacts on vascular mural cells. Targeting adventitial macrophages has been shown to be effective for repressing transplantation-induced arterial remodeling in animal models. Adventitia also fosters angiogenesis, and neovascularization of the adventitial layer may facilitate the transport of inflammatory cells through the arterial wall. Further investigations are warranted to clarify whether inhibiting adventitial oxidative stress and/or adventitial neovascularization are better strategies for preventing transplant vasculopathy.

A Protocol to Assess Feasibility, Acceptability, and Usability of Mobile Technology for Symptom Management in Pediatric Transplant Patients.

BACKGROUND: Pediatric blood and marrow transplant (PBMT) patients experience significant symptom distress, and the use of mobile health (mHealth) technologies may enhance symptom management by providing patient-generated health data to foster personalized health strategies. OBJECTIVES: The aim of this study was to present a study protocol to explore feasibility, acceptability, and usability of integrating mHealth technologies to collect and monitor symptom data for PBMT patients. METHODS: An exploratory mixed-methods design is employed for 20 PBMT patients to monitor symptoms using real-time data from two mHealth devices: (a) a self-developed mHealth application and (b) a wearable tracking device. Patient-Reported Outcomes Measurement Information System surveys for fatigue, pain, and sleep disturbance are obtained monthly. Interviews are conducted to obtain further feasibility and usability data. RESULTS: The study began in October 2017; data collection should be completed in 2018. Feasibility and usability results to monitor and record symptom-related data daily via mobile devices will be reported. Patient-Reported Outcomes Measurement Information System surveys and interviews will further explore patients' symptoms and experiences with the mobile devices. DISCUSSION: This study will be among the first to explore the feasibility, acceptability, and usability of integrating multiple mHealth technologies to obtain patient-generated symptom data for the PBMT population. Results will enhance our understanding of how these data present, interact, and cluster together throughout the posttransplant period for these children and lead to symptom management strategies. Results will focus on a high-risk population that potentially stands to benefit from the use of mobile technologies.

[Opportunistic infections by human herpes viruses]. / Opportunistische Infektionen durch humane Herpesviren.

Infections in immunosuppressed patients represent a particular challenge in the diagnostics and treatment. They often present with atypical and particularly severe courses, for which rapid diagnostics and treatment are decisive for treatment success. Opportunistic infections with human herpes viruses occur not only more frequently in immunocompromised patients compared to healthy people but also represent a special challenge. In the treatment of immunosuppressed patients, e.g. with human immunodeficiency virus infections and patients with solid organ transplantations, infections with herpes simplex virus, varicella zoster virus, Epstein-Barr virus and cytomegalovirus are particularly important. The symtoms are very variable, ranging from asymptomatic detection of viremia to vital life-threatening organ manifestations. This review article describes the most important clinical presentations of these opportunistic infections. Furthermore, the diagnostic, therapeutic and prophylactic strategies for human herpes viruses are summarized.

Thrombotic and hemorrhagic complications during visceral transplantation: risk factors, and association with intraoperative disseminated intravascular coagulation-like thromboelastographic qualities: a single-center retrospective study.

This study describes the risk of thrombotic and hemorrhagic complications, both intraoperatively, and up to 1 month following visceral transplantation. Data from 48 adult visceral transplants performed between 2010 and 2017 were retrospectively studied [32 multivisceral (MVTx); 10 isolated intestine; six modified-MVTx]. Intraoperatively, intracardiac thrombosis (ICT)/pulmonary embolism (PE) occurred in 25%, 0% and 0% of MVTx, isolated intestine and modified MVTx, respectively, and was associated with 50% (4/8) mortality. Preoperative portal vein thrombosis (PVT) was a significant risk factor for ICT/PE (P = 0.0073). Thromboelastography resembling disseminated intravascular coagulation (DIC) (r time <4 mm combined with fibrinolysis or flat-line) was statistically associated with occurrence of ICT/PE (P < 0.0001). Compared to subgroup without ICT/PE, occurrence of ICT/PE was associated with an increased demand for all blood product components both overall, and each surgical stage. Hyperfibrinolysis (56%) was identified as cause of bleeding in MVTx. Incidence of postoperative thrombotic event at 1 month was 25%, 30% and 17% for MVTx, isolated intestine and modified MVTx, respectively. Incidence of postoperative bleeding complications at 1 month was 11%, 20% and 17% for MVTx, isolated intestine and modified MVTx. In conclusion, MVTx recipients with preoperative PVT are at an increased risk of developing intraoperative life-threatening ICT/PE events associated with DIC-like coagulopathy.

Molecular diagnosis of Strongyloides stercoralis among transplant candidates.

Strongyloidiasis can occur without any symptoms or as a potentially fatal hyperinfection or disseminated infection, principally in immunosuppressed patients. Our study aimed to evaluate the application of conventional polymerase chain reaction (cPCR) and real-time PCR (qPCR). Polymerase chain reaction (PCR) and real-time PCR (qPCR) targeting the 18S rRNA gene for detection of Strongyloides stercoralis infection among transplant candidates were applied in stool samples obtained from 150 transplant candidates, preliminarily analyzed by parasitological methods. S. stercoralis larvae were visualized in 15/150 (10.0%) transplant candidates by parasitological methods. DNA from S. stercoralis was amplified in 26/150 (17.3%) and 49/150 (32.7%) stool samples of transplant candidates, using cPCR and qPCR, respectively. The results suggest that molecular methods, especially qPCR, should be used as an additional tool for diagnostic of S. stercoralis infection among transplant candidates.

Preliminary experience on the use of PET/CT in the management of pediatric post-transplant lymphoproliferative disorder.

INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication following prolonged immunosuppression. Contrary to other lymphomas, there is no standardized imaging approach to assess PTLD either at staging or for response to therapy. Positron emission tomography/computed tomography (PET/CT) is an imaging modality that has proven to be useful in lymphoma. However, there is still limited data concerning its use in pediatric PTLD. Our study evaluates the use of PET/CT in pediatric PTLD at our institution. METHODS: To assess the role of PET/CT in pediatric PTLD, we reviewed the pediatric patients with PTLD who had undergone PET/CT at our institution between 2000 and 2016. RESULTS: Nine patients were identified. Six had PET/CT at diagnosis. All lesions seen on CT were identified with PET/CT. Fourteen PET/CTs were done during treatment. Eight PET/CTs were negative, including three where CT showed areas of uncertain significance. In these cases, PET/CT helped us to stop treatment and the patients remain in remission after a long follow-up (mean 74.3 months; range 12.4-180.9 months). PET/CT revealed additional disease in two cases, therefore treatment was intensified. Six biopsies and close follow-up was done to confirm PET/CT results. In one case, PET/CT did not identify central nervous system involvement demonstrated on magnetic resonance imaging. CONCLUSION: PET/CT may have an important role in the staging and follow-up of pediatric PTLD. In our cohort, PET/CT was helpful in staging and assessing treatment response and in clarifying equivocal findings on other imaging modalities.

Twenty-eight years of intestinal transplantation in Paris: experience of the oldest European center.

Our aim was to describe our achievements in pediatric intestinal transplantation (ITx) and define areas for improvement. After a period (1987-1990) of nine isolated small bowel transplants (SBTx) where only one patient survived with her graft, 110 ITx were performed on 101 children from 1994 to 2014: 60 SBTx, 45 liver-small bowel, four multivisceral (three with kidneys), and one modified multivisceral. Indications were short bowel syndrome (36), motility disorders (30), congenital enteropathies (34), and others (1). Induction treatment was introduced in 2000. Patient/graft survival with a liver-containing graft or SBTx was, respectively, 60/41% and 46/11% at 18 years. Recently, graft survival at 5/10 years was 44% and 31% for liver-containing graft and 57% and 44% for SBTx. Late graft loss occurred in 13 patients, and 7 of 10 retransplanted patients died. The main causes of death and graft loss were sepsis and rejection. Among the 55 currently living patients, 21 had a liver-containing graft, 19 a SBTx (17 after induction), and 15 were on parenteral nutrition. ITx remains a difficult procedure, and retransplantation even more so. Over the long term, graft loss was due to rejection, over-immunosuppression was not a significant problem. Multicenter studies on immunosuppression and microbiota are urgently needed.

Severe chronic norovirus diarrheal disease in transplant recipients: Clinical features of an under-recognized syndrome.

BACKGROUND: Norovirus (NV) infection has been reported as a cause of severe chronic diarrhea in transplant recipients, but this entity remains under-recognized in clinical practice, leading to diagnostic delays. Transplant clinicians should become familiar with this syndrome in order to facilitate early detection and management. METHODS: Demographic, clinical, and outcomes variables were summarized from a series of transplant recipients with positive stool NV reverse transcription polymerase chain reaction (RT-PCR) assays at Johns Hopkins in 2013-2014. Factors associated with longer duration of symptoms were compared using random forest analysis. RESULTS: Thirty-one of 193 (16%) transplant recipients who were tested for NV had positive stool RT-PCRs. Symptoms included diarrhea (100%), nausea/vomiting (58%), abdominal pain (52%), and wasting (35%). Acute kidney injury occurred in 23%, and persisted in 21% after 6 months. Median duration of diarrheal symptoms was 4 months (range, <1-20) and 11/31 (35.4%) patients had relapses after improvement. Wasting, incompatible kidney transplant status, and plasmapheresis were associated with longer diarrhea durations. Treatments included nitazoxanide (in 74%), reduction of immunosuppression (58%), and intravenous immunoglobulin (32%). Six patients died, but no deaths were attributed to NV. CONCLUSIONS: It is important for clinicians to recognize that NV can cause severe chronic diarrhea in transplant recipients. In this series, receipt of a human leukocyte antigen- and/or blood type-incompatible kidney transplant, and plasmapheresis were associated with longer symptom duration.

Transition readiness, adolescent responsibility, and executive functioning among pediatric transplant recipients: Caregivers' perspectives.

This study aimed both to evaluate caregivers' perspectives of EF and transition readiness among adolescent transplant recipients and to examine the indirect effects of adolescent responsibility and parent involvement across domains of EF. Fifty-seven caregivers of adolescent solid organ transplant recipients participated in this study and completed measures of adolescent EF, transition readiness, responsibility in healthcare behavior, and parent involvement. Bootstrapping procedures were used to test indirect effects. Caregiver report of adolescent EF was significantly related to transition readiness among transplant recipients. Significant indirect effects were found for adolescent responsibility but not parent involvement. No significant differences were found between metacognitive and behavioral regulation domains of EF in the association with transition readiness. Assessment of adolescent EF skills may help guide the development of individualized transition readiness guidelines to promote successful gains in self-management abilities as well as eventual transfer to adult medical services.