Characterization of miR-335-5p and miR-335-3p in human osteoarthritic tissues.

OBJECTIVE: We aimed to characterize the expression patterns, gene targets, and functional effects of miR-335-5p and miR-335-3p among seven primary human knee and hip osteoarthritic tissue types. METHODS: We collected synovial fluid, subchondral bone, articular cartilage, synovium, meniscus/labrum, infrapatellar/acetabular fat, anterior cruciate ligament/ligamentum teres, and vastus medialis oblique/quadratus femoris muscle (n = 7-20) from surgical patients with early- or late-stage osteoarthritis (OA) and quantified miR-335-5p and miR-335-3p expression by real-time PCR. Predicted gene targets were measured in knee OA infrapatellar fat following miRNA inhibitor transfection (n = 3), and prioritized gene targets were validated following miRNA inhibitor and mimic transfection (n = 6). Following pathway analyses, we performed Oil-Red-O staining to assess changes in total lipid content in infrapatellar fat. RESULTS: Showing a 227-fold increase in knee OA infrapatellar fat (the highest expressing tissue) versus meniscus (the lowest expressing tissue), miR-335-5p was more abundant than miR-335-3p (92-fold increase). MiR-335-5p showed higher expression across knee tissues versus hip tissues, and in late-stage versus early-stage knee OA fat. Exploring candidate genes, VCAM1 and MMP13 were identified as putative direct targets of miR-335-5p and miR-335-3p, respectively, showing downregulation with miRNA mimic transfection. Exploring candidate pathways, predicted miR-335-5p gene targets were enriched in a canonical adipogenesis network (p = 2.1e - 5). Modulation of miR-335-5p in late-stage knee OA fat showed an inverse relationship to total lipid content. CONCLUSION: Our data suggest both miR-335-5p and miR-335-3p regulate gene targets in late-stage knee OA infrapatellar fat, though miR-335-5p appears to be more prominent, with tissue-, joint-, and stage-specific effects.

Prolonged Enteral Tube Feeding in Infants With a Functional Single Ventricle Is Associated With Adverse Outcomes After Fontan Completion.

OBJECTIVES: To define the baseline characteristics of long-term tube-fed (TF) single ventricle patients, investigate associations between long-term enteral tube feeding and growth, and determine associations with long-term outcomes after Fontan procedure. STUDY DESIGN: We performed a retrospective cohort study of patients in the Australia and New Zealand Fontan Registry undergoing treatment at the Royal Children's Hospital, the Children's Hospital at Westmead, Royal Melbourne Hospital, and Royal Prince Alfred Hospital from 1981 to 2018. Patients were defined as TF or non-tube-fed (NTF) based on enteral tube feeding at the age of 90 days. Feeding groups were compared regarding body mass index (BMI) trajectory, BMI at last follow-up, and long-term incidence of severe Fontan failure. RESULTS: Of 390 patients (56 [14%] TF, 334 [86%] NTF), TF was associated with right ventricular dominance, hypoplastic left heart syndrome, Norwood procedure, increased procedures prior to Fontan, extracardiac conduit Fontan, Fontan fenestration, and atrioventricular valve repair/replacement. TF patients were less likely to be in the higher compared with lowest 0-6 month BMI trajectory (P < .01; P = .03), had lower 6 month weight-for-age z-scores (P < .01) and length-for-age z-scores (P = .01). TF were less likely to be overweight/obese at pediatric follow-up (hazard ratio [HR] = 0.31, 95% CI: 0.12-0.80; P = .02) and more likely to be underweight at adult follow-up (HR = 16.51; 5% CI: 2.70-101.10; P < .01). TF compared with NTF was associated with increased risk of severe Fontan failure (HR = 4.13; 95% CI = 1.65-10.31; P < .01). CONCLUSIONS: Prolonged infant enteral tube feeding is an independent marker of poor growth and adverse clinical outcomes extending long-term post-Fontan procedure.

Liver Cirrhosis After the Fontan Procedure: Impact of Atrioventricular Valve Failure.

BACKGROUND: Liver cirrhosis is now well recognized as a potential complication after the Fontan procedure, although associated risk factors and optimal timing of liver screening remain unclear. METHODS: All patients who underwent an extracardiac conduit Fontan procedure at The Royal Children's Hospital, Melbourne, were identified using the Australia and New Zealand Fontan Registry. Cirrhosis was diagnosed based on liver biopsy, or a combination of imaging findings and clinical evaluation by a hepatologist. RESULTS: Between 1997 and 2020, 398 patients underwent an extracardiac conduit Fontan procedure at our center, and 276 had ongoing follow-up in Victoria. Ninety-five patients (34%) underwent liver assessment at a mean age of 18.2 ± 6.7 years (11.8 ± 5.5 years post-Fontan). Fifteen patients (16%) were diagnosed with cirrhosis at a mean age of 22.7 ± 5.9 years (14.0 ± 5.2 years post-Fontan). The need for prior or concomitant atrioventricular valve repair or replacement was associated with an increased risk of cirrhosis (univariable hazard ratio [HR] 7.09, 95% confidence interval [CI] 2.13-23.61, P = .001). By multivariable analysis, factors associated with development of cirrhosis were atrioventricular valve failure prior to Fontan (HR 3.27, 95% CI 1.15-9.31, P = .026) and older age at Fontan operation (HR 1.13 per year increase, 95% CI 1.01-1.26, P = .034). The proportion of patients alive, nontransplanted, and without cirrhosis at 10, 15, and 20 years was 93.4% (95% CI 88.4%-98.7%), 79.6% (95% CI 69.7%-90.8%), and 64.6% (95% CI 51.0%-81.9%), respectively. CONCLUSIONS: Early commencement of liver screening should be considered for patients with a history of atrioventricular failure during Fontan palliation.

The Use of Enamel Matrix Derivative during Surgical Therapy for Peri-Implantitis: A Case Series.

Peri-implantitis is a growing concern and currently, there is no agreement on the best method for treating this condition. This study looked at surgical intervention with the use of enamel matrix derivative (EMD) for treating this condition. A cohort of 25 (34 implants) consecutive patients treated with EMD for peri-implantitis was followed for up to 6.4 years. The survival of the implants as well as changes in clinical parameters are reported. Statistical analysis was performed using paired t tests and general estimating equations. The mean length of time implants were followed post-surgery was 3.05 ± 1.53 years. All but two of the treated implants survived in function (94%). Both failed implants were lost in the same patient, who was a heavy smoker. The changes in mean probing depth (1.94 ± 1.18 mm), change in deepest probing depth (3.12 ± 1.45 mm), and reduction in bleeding on probing (73.6 ± 43.9%) according to patient means were all highly significant (p < 0.001 for all changes). When EMD is used during surgical treatment of peri-implantitis, there is a high survival rate of implants and significant improvements in clinical parameters.

Prevalence of irritable bowel syndrome and functional abdominal pain disorders in children with inflammatory bowel disease in remission.

Despite evidence of an increased prevalence of irritable bowel syndrome (IBS) in adults with inflammatory bowel disease (IBD) compared with the general population, the prevalence of IBS in children with IBD is unclear. In this review, we aimed to identify the reported prevalence of IBS or functional abdominal pain disorders (FAPDs) in children with IBD in remission. A search of three databases (MEDLINE, Embase, and PubMed) was performed to identify studies reporting the prevalence of IBS or FAPDs in pediatric patients with IBD in remission. A total of 60 studies were identified, with four eligible studies remaining following abstract screening. In children with IBD in remission, the overall prevalence of IBS ranged between 3.9 and 16.1%, and the overall prevalence of FAPDs ranged between 9.6 and 29.5%. The prevalence of FAPDs in patients in biomarker-based remission was generally higher than those in clinical remission (range 16-22.5% vs 9.6-16.7%, respectively). There is a paucity of literature reporting on the prevalence of IBS or FAPDs in children with IBD in remission. Despite the differences in criteria used to define IBD remission in the included articles, there seems to be an increased overall prevalence of IBS or FAPDs in children with IBD.

The Potential Role of Titanium Allergy in Implant Failure.

Implant bone loss and implant failure are growing concerns. In some cases, a possible factor leading to bone loss may be an allergy to titanium (Ti). In this report, the existing literature on Ti allergy as a factor in implant loss is reviewed, and the current views on its potential role in implant bone loss are discussed. A case report of implant loss and retreatment in a patient with a potential Ti allergy or intolerance is presented and clinically analyzed. The subsequent success of a ceramic implant may support the finding of a Ti allergy or intolerance. Unfortunately, the lack of prospective clinical trials and lack of a reliable test for Ti allergy makes it impossible to clinically verify whether Ti allergy plays a part in implant bone loss.

Body Mass Index Trajectory and Outcome Post Fontan Procedure.

Background Patients with a single ventricle who experience early life growth failure suffer high morbidity and mortality in the perisurgical period. However, long-term implications of poor infant growth, as well as associations between body mass index (BMI) and outcome in adulthood, remain unclear. We aimed to model BMI trajectories of patients with a single ventricle undergoing a Fontan procedure to determine trajectory-based differences in baseline characteristics and long-term clinical outcomes. Methods and Results We performed a retrospective analysis of medical records from patients in the Australia and New Zealand Fontan Registry receiving treatment at the Royal Children's Hospital, The Children's Hospital at Westmead, Royal Melbourne Hospital, and Royal Prince Alfred Hospital from 1981 to 2018. BMI trajectories were modeled in 496 patients using latent class growth analysis from 0 to 6 months, 6 to 60 months, and 5 to 16 years. Trajectories were compared regarding long-term incidence of severe Fontan failure (defined as mortality, heart transplantation, Fontan takedown, or New York Heart Association class III/IV heart failure). Three trajectories were found for male and female subjects at each age group-lower, middle, higher. Subjects in the lower trajectory at 0 to 6 months were more likely to have an atriopulmonary Fontan and experienced increased mortality long term. No association was found between higher BMI trajectory, current BMI, and long-term outcome. Conclusions Poor growth in early life correlates with increased long-term severe Fontan failure. Delineation of distinct BMI trajectories can be used in larger and older cohorts to find optimal BMI targets for patient outcome.

Surveillance of End-Organ Damage in Fontan Patients Prior to Transition to Adult Care: Are We There Yet?

BACKGROUND: Recently published guidelines and consensus statements have outlined recommended screening practices for monitoring of end-organ dysfunction in Fontan patients. We reviewed the current approach to end-organ screening in a local population of Fontan patients at the time of transition to adult care. METHODS: Patient data from the Australia and New Zealand Fontan Registry and patient medical records were used to review investigations performed in Fontan patients transitioned from The Royal Children's Hospital Melbourne to an adult centre between 1 July 2015 and 30 June 2020. RESULTS: A total of 32 patients were referred for transition to an adult centre between 1 July 2015 and 30 June 2020 at a mean age of 18.5±0.7 years (12.7±2.5 years post-Fontan). Liver function tests were performed in 22 patients (69%) within 5 years prior to transition and were abnormal in 15 patients (68%). Liver ultrasound was performed in 13 patients (41%) within 5 years prior to the date of transition, of whom 10 (77%) had abnormal findings (features suggestive of hepatic fibrosis in seven [54%], cirrhosis in two [15%], and portal hypertension in three [23%]). Fourteen (14) patients (44%) had no record of a liver ultrasound being performed between the date of the Fontan procedure and the time of transition to adult care. Hepatocellular carcinoma was diagnosed in one patient at 18 months following transition. A total of 24 patients (75%) had a serum creatinine measured within the 5 years prior to transition, and two (8%) had an estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73 m2. No patient had a urine protein-creatinine ratio measured between the date of the Fontan procedure and the time of transition to adult care. CONCLUSIONS: In this study we have identified that the majority of patients transitioned from a tertiary paediatric centre to an adult centre within the last 5 years did not undergo routine surveillance for end-organ dysfunction. Routine screening for end-organ complications of the Fontan circulation should be incorporated into clinical practice and is an important part of Fontan patient care both pre- and post-transition to adult services.

Treating brain metastases in melanoma: What is the optimal CNS-directed and systemic management?

Treatments for melanoma have significantly advanced with the approval of targeted treatments against the BRAF/MEK pathway and immunotherapy in the form of checkpoint inhibitors. Studies have shown the effectiveness of these treatments against brain metastases. However, the optimum treatment strategy utilising CNS-directed treatments such as stereotactic radiosurgery (SRS) and neurosurgical resection is less clear. Over six years, 70 patients with metastatic melanoma were treated for brain metastases at a tertiary treatment centre. The median overall survival (OS) for all patients was 10.2 months. 51 patients received localised treatment; 7 resection (median OS 10 months), 11 resection and SRS (median OS 17.3 months) and 33 SRS alone (median OS 17.4 months). For patients treated with SRS those who had <2 cm3 treated had a better median OS (20.5 months) compared to those who had >2 cm3 treated (12 months). 69 Patients received systemic treatment. The median OS of patients who did not have CNS-directed treatment was poor (median OS 1.2 months). Patients treated with first line dual immunotherapy had the best median OS (26.7 months), compared to anti-PD-1 (14.1 months), ipilimumab (14.3 months) and kinase inhibitors (10.9 months). Despite advancements in treatment, the development of brain metastases in melanoma is associated with worse outcomes. A combination of CNS-directed and systemic treatment is important to improve survival. Dual immunotherapy appears to be the most effective systemic treatment and the use of SRS improved outcomes. As metastatic melanoma treatments evolve there need to be an ongoing focus to ensure these strategies adequately treat intracranial disease.

Correlation between tumor voxel dose response matrix and tumor biomarker profile in patients with head and neck squamous cell carcinoma.

BACKGROUND: We have developed a novel imaging analysis procedure that is highly predictive of local failure after chemoradiation in head and neck cancer. In this study we investigated whether any pretreatment biomarkers correlated with key imaging parameters. METHODS: Pretreatment biopsy material was available for 28 patients entered into an institutional trial of adaptive radiotherapy in which FDG-PET images were collected weekly during treatment. The biopsies were immunohistochemically stained for CD44, EGFR, GLUT1, ALDH1, Ki-67 and p53 and quantified using image analysis. Expression levels were correlated with previously derived imaging parameters, the pretreatment SUVmax and the dose response matrix (DRM). RESULTS: The different parameters of the SUVmax and DRM did not correlate with each other. We observed a positive and highly significant (p = 0.0088) correlation between CD44 expression and volume of tumor with a DRM greater than 0.8. We found no correlation between any DRM parameter and GLUT1, p53, Ki-67 and EGFR or ALDH1. GLUT1 expression did correlate with the maximum SUV0 and the volume of tumor with an SUV0 greater than 20. CONCLUSIONS: The pretreatment SUVmax and DRM are independent imaging parameters that combine to predict local recurrence. The significant correlation between CD44 expression, a known cancer stem cell (CSC) marker, and volume of tumor with a DRM greater than 0.8 is consistent with concept that specific foci of cells are responsible for tumor recurrence and that CSCs may be randomly distributed in tumors in specific niches. Dose painting these small areas may lead to improved tumor control.

Cross-sectional assessment of haemostatic profile and hepatic dysfunction in Fontan patients.

BACKGROUND: Fontan-associated liver disease is accompanied by a hypercoagulable state. While hepatic dysfunction in Fontan patients is common, its relationship with haemostatic changes and clinical outcomes in this patient population remains unclear. OBJECTIVE: To correlate liver dysfunction and haemostatic profiles with clinical outcomes in the Fontan population. PATIENTS/METHODS: Patients were enrolled in a multicentre, cross-sectional study in Australia and New Zealand. Hepatic structure and function were assessed using serum-based calculations (Fibrotest and model for end-stage liver disease excluding international normalised ratio scores). Haemostatic profiles were assessed by Thrombin Generation. Platelet function was assessed via Platelet Factor 4 (PF4) and P-selectin (P-SEL). Clinical outcomes were obtained from the Australian and New Zealand Fontan Registry. RESULTS: Seventy-three patients participated in the study (mean age 18.9±8.5 years with a mean of 13.5±6.9 years post-Fontan). The Endogenous Thrombin Potential (ETP) for patients who suffered thrombotic events (TE) (1366.4±66.2 nM/min) was higher compared with patients with major bleeding events (1011.1±138.4 nM/min) (p=0.03). Except for a negative correlation between Fibrotest-score and PF4 (p=0.045), PF4 and P-SEL concentrations did not correlate with markers of hepatic dysfunction or structural abnormality. CONCLUSIONS: Increased ETP is associated with TE during clinical follow-up after Fontan. This study reinforces that hepatic dysfunction may contribute to the derangement of coagulation factors, impacting the individual risk of haemostatic complications for the Fontan population.

Bone loss around implants-is it metallosis?

Most would agree that the etiology of dental implant failure is related to oral biofilm. At present one group of scientists and clinicians feel that biofilm is solely responsible for bone loss around the devices. However, there is strong evidence that particles and ions of titanium released into the surrounding tissues by the action of biofilm and/or mechanical forces, a process termed metallosis, can be responsible for bone loss around some dental implants. These findings are reinforced by similar responses found around failed metal on metal joint prostheses. Both possible etiologies are discussed in detail in this commentary.

Mammalian cell response and bacterial adhesion on titanium healing abutments: effect of multiple implantation and sterilization cycles.

OBJECTIVE: Multiple implantations of the implant healing abutment (IHA) could adversely impact its surface properties in vivo. Furthermore, the effect of sterilization and reuse of the IHA on soft tissue viability and bacterial contamination has not been extensively studied. The goal of this study was to perform an in vitro analysis of mammalian cell viability and bacterial adhesion on the surfaces of retrieved IHA after single and multiple implantations and repetitive cycles of sterilization. MATERIALS AND METHODS: IHA surface morphology was studied using optical microscopy. Cell viability of gingival fibroblasts (HGF-1) and oral keratinocytes (HOKg) in indirect contact with IHAs was assessed for 3 and 7 days. Immersion in bacterial culture was performed with a polyculture of Streptococcus species for 3 days and Streptococcus species with Fusobacterium nucleatum for 7 days. RESULTS: IHAs exhibited signs of surface damage even after a single exposure to the oral cavity. Fibroblasts did not show a significant preference towards control IHAs over used IHAs, whereas keratinocytes exhibited a significant decrease in viability when exposed to IHAs after multiple implantation cycles as compared with controls. Adherent bacterial count increased with increasing number of IHA implantations for both polycultures. CONCLUSIONS: Reusing of IHAs in vivo promoted surface degradation in addition to adversely impacting host cell viability and oral bacterial attachment in vitro. These findings show IHA reuse might potentially affect its clinical performance. CLINICAL RELEVANCE: Careful consideration should be taken when reusing IHAs in patients because this practice can result in permanent surface changes that might affect soft tissue integration during the healing period and promote bacterial colonization.

Dacomitinib and gedatolisib in combination with fractionated radiation in head and neck cancer.

BACKGROUND AND PURPOSE: There has been little success targeting individual genes in combination with radiation in head and neck cancer. In this study we investigated whether targeting two key pathways simultaneously might be more effective. MATERIALS AND METHODS: We studied the effect of combining dacomitinib (pan-HER, irreversible inhibitor) and gedatolisib (dual PI3K/MTOR inhibitor) with radiation in well characterized, low passage xenograft models of HNSCC in vitro and in vivo. RESULTS: Dacomitinib showed differential growth inhibition in vitro that correlated to EGFR expression whilst gedatolisib was effective in both cell lines. Neither agent radiosensitized the cell lines in vitro. In vivo studies demonstrated that dacomitinib was an effective agent alone and in combination with radiation whilst the addition of gedatolisib did not enhance the effect of these two modalities despite inhibiting phosphorylation of key genes in the PI3K/MTOR pathway. CONCLUSIONS: Our results showed that combining two drugs with radiation provided no added benefit compared to the single most active drug. Dacomitinib deserves more investigation as a radiation sensitizing agent in HNSCC.

Acute and Chronic Kidney Disease Following Congenital Heart Surgery: A Review.

BACKGROUND: There is an increasing prevalence of chronic kidney disease in the population of adults currently living with congenital heart disease. A considerable proportion of children who undergo congenital heart surgery experience postoperative acute kidney injury. Whether there is an association between acute kidney injury after cardiac surgery in childhood and development of chronic kidney disease is unclear. METHODS: Three electronic databases were searched to capture relevant studies exploring the relationship between acute kidney injury after congenital heart surgery in children and progression to chronic kidney disease. RESULTS: A literature search identified a total of 212 research articles, 7 of which were selected for in-depth review. CONCLUSIONS: There is a likely association between acute kidney injury in children undergoing congenital heart surgery and progression to chronic kidney disease. Research should be developed to mitigate factors contributing to postoperative acute kidney injury in neonates, infants, and children undergoing cardiac surgery. Better targeted follow-up protocols to monitor renal function in children undergoing cardiac surgery should be implemented. A universal definition for acute kidney injury and chronic kidney disease is needed to improve detection and research in this field.

Effects of multiple implantations of titanium healing abutments: Surface characteristics and microbial colonization.

OBJECTIVE: Very few studies have investigated dental implant components involved in the early stage of healing, especially the implant healing abutment (IHA), despite its vital role in soft tissue contouring and shaping after implant placement. Although these components are labelled by the manufacturer for "single-use only," it is a common clinical practice to clean, sterilize, and reuse them. METHODS: In the present study, IHAs after single and multiple implantations were retrieved as per standard procedures, and biological material isolated from the surface was subjected to 16S rRNA sequence analysis. The microbiome analysis was followed by cleaning and sterilization in order to replicate clinical sterilization techniques. Following sterilization, retrievals were subjected to surface characterization with optical and scanning electron microscopy to investigate surface features, and electrochemical testing was performed to evaluate corrosion behavior. RESULTS: The microbiota was comprised of early colonizers including Streptococcus species and secondary anaerobic colonizers such as Fusobacterium, Capnocytophaga, and Prevotella species. The surface analysis revealed that irrespective of the cleaning and sterilization techniques, the pristine, homogeneous surface of the new, unused IHAs could not be restored. Both single and multiple-use IHAs had severe surface changes including discoloration, major abrasions, biological contamination, and the IHA retrievals exhibited higher corrosion rate as compared to control specimens. SIGNIFICANCE: Reusing IHAs multiple times may not be a prudent practice as the microbial colonization and surface changes caused by using this component multiple times may affect the performance of IHAs in soft tissue healing.

Low Dose Brain Irradiation Reduces Amyloid-ß and Tau in 3xTg-AD Mice.

We have previously reported that low doses of external beam ionizing irradiation reduced amyloid-ß (Aß) plaques and improved cognition in APP/PS1 mice. In this study we investigated the effects of radiation in an age-matched series of 3xTg-AD mice. Mice were hemibrain-irradiated with 5 fractions of 2 Gy and sacrificed 8 weeks after the end of treatment. Aß and tau were assessed using immunohistochemistry and quantified using image analysis with Definiens Tissue Studio. We observed a significant reduction in Aß plaque burden and tau staining; these two parameters were significantly correlated. This preliminary data is further support that low doses of radiation may be beneficial in Alzheimer's disease.

Laser identification of residual microislands of calculus and their removal with chelation.

BACKGROUND: During videoscope-assisted minimally invasive surgery which uses a high magnification videoscope to treat periodontal defects, small areas resembling calculus are detected remaining on root surfaces following scaling. These are clinically termed microislands of calculus, which are removed by the use of a chelating agent. This material has not been verified as calculus and the ability of a chelating agent to remove calculus has not been proven. The purpose of this ex vivo study is to verify if the material is calculus and to determine if calculus is removed with a chelating agent. METHODS: Extracted teeth (n = 22) with heavy calculus on root surfaces were selected. A 5-mm2 area containing calculus was scribed on each root. Digital videoscope images were made of the marked areas using only white light and also with only a 655-nm diode laser that causes calculus to fluoresce. The marked areas were root planed until no calculus was visible with 3.5× surgical loupes. Digital images were again made. The test area was then burnished with a chelating agent (EDTA) for 30 seconds and images again made. Using the images, the percentage of the marked root surface containing calculus was calculated. RESULTS: Calculus remained on the roots surfaces after they were judged to be clean using 3.5× loupe magnification. Remaining calculus was reduced after burnishing for 30 seconds with EDTA. CONCLUSIONS: Calculus remains on root surfaces judged to be calculus free using surgical loupes for visualization. Small areas of calculus are reduced or eliminated with a chelating agent.

Fontan-associated nephropathy: Predictors and outcomes.

BACKGROUND: Nephropathy is a known complication of the Fontan circulation, but its determinants have not been identified and patient outcomes are also still unknown. METHODS: The Australia and New Zealand Fontan Registry was used to identify those who underwent Fontan operation before and survived beyond 16-years-old with an intact Fontan circulation. Serum creatinine values were collected for each patient between 16 and 25 years and at recent follow-up. The Modification of Diet in Renal Disease (MDRD) equation was used to calculate eGFR. Patient outcomes were obtained from the Registry. Fontan failure was defined as death, transplantation, plastic bronchitis, protein losing enteropathy, Fontan takedown and NYHA class III-IV. RESULTS: Serum creatinine measurements were available for 328 patients. Renal dysfunction was defined as eGFR <90 mL/min/1.72m2. Renal dysfunction was present in 67/328 (20%) and 3/328 (1%) patients had an eGFR <60 mL/min/1.72m2. The 10-year survival and 10-year freedom from death and transplantation were the same, 96% (95% CI: 0.9-1) for those with renal dysfunction, and 89% (0.83-0.95; p = 0.1) and 87% (95% CI: 0.81-0.94; p = 0.05) for patients without dysfunction. The 10-year freedom from failure were also similar, 83% (95% CI: 0.70-0.97) for those without renal dysfunction vs 80% (95% CI: 0.74-0.89; p = 0.84). There was no change in mean eGFR for the renal dysfunction group over a mean of 8 ± 5.5 years. CONCLUSION: By the time they reach adulthood, 20% of patients with a Fontan circulation have renal dysfunction by eGFR calculation. Over the course of one decade, Fontan-associated nephropathy appears well tolerated.