Sequential Stem Cell-Kidney Transplantation in Schimke Immuno-osseous Dysplasia.

Lifelong immunosuppression is required for allograft survival after kidney transplantation but may not ultimately prevent allograft loss resulting from chronic rejection. We developed an approach that attempts to abrogate immune rejection and the need for post-transplantation immunosuppression in three patients with Schimke immuno-osseous dysplasia who had both T-cell immunodeficiency and renal failure. Each patient received sequential transplants of αß T-cell-depleted and CD19 B-cell-depleted haploidentical hematopoietic stem cells and a kidney from the same donor. Full donor hematopoietic chimerism and functional ex vivo T-cell tolerance was achieved, and the patients continued to have normal renal function without immunosuppression at 22 to 34 months after kidney transplantation. (Funded by the Kruzn for a Kure Foundation.).

Renal outcome and plasma methylmalonic acid levels after isolated or combined liver or kidney transplantation in patients with methylmalonic acidemia: A multicenter analysis.

BACKGROUND: Methylmalonic acidemia (MMAemia) is characterized by accumulation of methylmalonic acid (MMA) in all body tissues. To minimize disease-related complications, isolated kidney (KTx), liver (LTx) or combined liver-kidney transplantation (LKTx) have been suggested. However, the impact of these different transplant strategies on outcome are unclear. METHODS: In this multicenter retrospective observational study, we compared plasma MMA levels and estimated glomerular filtration rate (eGFR) data of 83 patients. Sixty-eight patients (82%) had a mut0-type MMAemia, one patient had a mut--type MMAemia, and seven (7.3%) had an inherited defect in cobalamin metabolism (cblA- or cblB-type MMAemia). Median observation period was 3.7 years (0-15.1 years). RESULTS: Twenty-six (31%) patients underwent KTx, 24 (29%) LTx and 33 (40%) LKTx. Posttransplant, mean plasma MMA concentration significantly decreased in all three cohorts; but at month 12, plasma MMA in KTx (1372 ± 1101 µmol/L) was 7.8-fold higher than in LTx (176 ± 103 µmol/L; P < 0.001) and 6.4-fold higher than in LKTx (215 ± 110 µmol/L; P < 0.001). Comparable data were observed at month 24. At time of transplantation, mean eGFR in KTx was 18.1 ± 24.3 mL/min/1.73 m2, in LTx 99.8 ± 29.9 mL/min/1.73 m2, and in LKTx 31.5 ± 21.2 mL/min/1.73 m2. At month 12 posttransplant, mean eGFR in KTx (62.3 ± 30.3 mL/min/1.73 m2) was 33.4% lower than in LTx (93.5 ± 18.3 mL/min/1.73 m2; P = 0.0053) and 25.4% lower than in LKTx (83.5 ± 26.9 mL/min/1.73 m2; P = 0.0403). CONCLUSIONS: In patients with isolated MMAemia, LTx and LKTx lead to markedly lower plasma MMA levels during the first 2 years posttransplant than KTx and are associated with a better preservation of kidney function. LTx should therefore be part of the transplant strategy in MMAemia.

Complement-Binding Donor-Specific Anti-HLA Antibodies: Biomarker for Immunologic Risk Stratification in Pediatric Kidney Transplantation Recipients.

Antibody-mediated rejection is a common cause of early kidney allograft loss but the specifics of antibody measurement, therapies and endpoints have not been universally defined. In this retrospective study, we assessed the performance of risk stratification using systematic donor-specific antibody (DSA) monitoring. Included in the study were children who underwent kidney transplantation between January 1, 2010 and March 1, 2018 at Stanford, with at least 12-months follow-up. A total of 233 patients were included with a mean follow-up time of 45 (range, 9-108) months. Median age at transplant was 12.3 years, 46.8% were female, and 76% had a deceased donor transplant. Fifty-two (22%) formed C1q-binding de novo donor-specific antibodies (C1q-dnDSA). After a standardized augmented immunosuppressive protocol was implemented, C1q-dnDSA disappeared in 31 (58.5%). Graft failure occurred in 16 patients at a median of 54 (range, 5-83) months, of whom 14 formed dnDSA. The 14 patients who lost their graft due to rejection, all had persistent C1q-dnDSA. C1q-binding status improved the individual risk assessment, with persistent; C1q binding yielding the strongest independent association of graft failure (hazard ratio, 45.5; 95% confidence interval, 11.7-177.4). C1q-dnDSA is more useful than standard dnDSA as a noninvasive biomarker for identifying patients at the highest risk of graft failure.

Low dose rabbit antithymocyte globulin is non-inferior to higher dose in low-risk pediatric kidney transplant recipients.

BACKGROUND: Currently, there is no consensus among pediatric kidney transplant centers regarding the use and regimen for immunosuppressive induction therapy. METHODS: In this single center, retrospective cohort study, pediatric kidney transplant recipients transplanted between 1 May 2013 and 1 May 2018 with rabbit antithymocyte globulin (rATG) induction were included. We stratified patients based on immunological risk, with high risk defined as those with repeat transplant, preformed donor specific antibody, current panel-reactive antibodies > 20%, 0 antigen match and/or African-American heritage. Outcome of interest was the incidence of biopsy proven acute rejection by 1 year. RESULTS: A total of 166 patients met inclusion criteria. Age of patients was 12 years (11 mo-21 y), (median, range), 21.5% received a living donor transplant and 50.6% were female. Low-immunologic-risk patients were divided into 2 groups, those who received the lower cumulative rATG dose of ≤ 3.5 mg/kg (n = 52) versus the higher cumulative dose of > 3.5 mg/kg (n = 47). The median total dose in the lower dose group was 3.1 (IQR 0.3) and 4.4 (IQR 0.8) in the higher dose group, P < 0.001. Rejection rate did not differ significantly between the 2 treatment groups (7/52 vs. 6/47). None in the lower dose group developed BK nephropathy versus 3 in the higher dose group. Graft loss due to BK nephropathy occurred in 1 patient in the higher dose group. Graft loss in the whole cohort at 12 months was a rare event (n = 1) with 99.5% graft survival and 100% patient survival. CONCLUSIONS: Reduced rATG dosing (≤ 3.5 mg/kg) when compared to higher dosing (> 3.5 mg/kg) is safe and effective in low-risk pediatric kidney transplant recipients without increasing risk of rejection. A higher resolution version of the Graphical abstract is available as Supplementary information.

Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a fatal disorder characterized by progressive gastrointestinal dysmotility, peripheral neuropathy, leukoencephalopathy, skeletal myopathy, ophthalmoparesis, and ptosis. MNGIE stems from deficient thymidine phosphorylase activity (TP) leading to toxic elevations of plasma thymidine. Hematopoietic stem cell transplant (HSCT) restores TP activity and halts disease progression but has high transplant-related morbidity and mortality. Liver transplant (LT) was reported to restore TP activity in two adult MNGIE patients. We report successful LT in four additional MNGIE patients, including a pediatric patient. Our patients were diagnosed between ages 14 months and 36 years with elevated thymidine levels and biallelic pathogenic variants in TYMP. Two patients presented with progressive gastrointestinal dysmotility, and three demonstrated progressive peripheral neuropathy with two suffering limitations in ambulation. Two patients, including the child, had liver dysfunction and cirrhosis. Following LT, thymidine levels nearly normalized in all four patients and remained low for the duration of follow-up. Disease symptoms stabilized in all patients, with some manifesting improvements, including intestinal function. No patient died, and LT appeared to have a more favorable safety profile than HSCT, especially when liver disease is present. Follow-up studies will need to document the long-term impact of this new approach on disease outcome. Take Home Message: Liver transplantation is effective in stabilizing symptoms and nearly normalizing thymidine levels in patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and may have an improved safety profile over hematopoietic stem cell transplant.

Does liver biopsy accurately measure fibrosis in Fontan-associated liver disease? A comparison of liver biopsy pre-combined heart and liver transplant and liver explant post-transplant.

The accuracy of liver biopsy to stage fibrosis due to Fontan-associated liver disease (FALD) remains unclear. We compared the results of biopsy pre-combined heart and liver transplantation (CHLT) to the results of whole liver explant. Liver biopsy and explants from 15 Fontan patients (ages 16-49, median 28 years) were retrospectively reviewed. Staging was as follows: stage 0: no fibrosis, stage 1: pericellular fibrosis, stage 2: bridging fibrosis, and stage 3: regenerative nodules. There is no stage 4. Clinical characteristics including Model of End-stage Liver Disease eXcluding INR and Varices, Ascites, Splenomegaly, and Thrombocytopenia (VAST) scores were collected, and descriptive statistics and Mann-Whitney U tests were used to analyze the data. All patients had biopsies with at least bridging fibrosis, and all had nodularity on explant; transjugular biopsy never overestimated fibrosis. Explant showed higher-grade fibrosis (stage 3) than pre-CHLT biopsy (stage 2) in 6 of 15 patients and equal grade of fibrosis (stage 3) in 9 of 15 patients. Though clinical characteristics varied significantly, VAST score was ≥2 in all but two patients. Transjugular liver biopsy does not overestimate and can underestimate fibrosis in Fontan patients undergoing CHLT, likely due to the patchy nature of fibrosis in FALD.

Ureterostomy as an alternative to ileal conduits in pediatric kidney transplantation.

INTRODUCTION: Urinary diversion in pediatric renal transplant candidates with bladders not amenable to primary reconstruction can be achieved by pre-transplant ileal conduit creation. We performed cutaneous ureterostomies to limit pre-transplant surgery, protect the peritoneum for dialysis, transplant patients sooner, and preserve ureter length for future surgical reconstruction. METHODS: We compared four pediatric transplant recipients with ureterostomies to four recipients with ileal conduits from 2009 to 2017. RESULTS: All patients with ileal conduits developed at least one urinary tract infection (UTI) within 1 year of transplant and three of four patients had recurrent UTIs within the first year. Two patients required ileal conduit revisions for redundant conduits and recurrent UTIs. Of the four ureterostomy patients, two patients had UTIs within one year of transplant. Two patients developed ureterostomy strictures requiring revision at the fascial level; one was associated with a UTI. CONCLUSION: In our small case series, ureterostomy allowed for a single operative intervention with preservation of ureter length for later reconstruction. Ureterostomy is safe and recurrent UTI may be lower in the ureterostomy group. Long-term evaluation of ureterostomy for urinary diversion in pediatric kidney transplant is warranted.

Acute kidney injury and chronic kidney disease after combined heart-liver transplant in patients with congenital heart disease: A retrospective case series.

Although it is known that children undergoing heart transplantation are at increased risk for both AKI and CKD, renal function following CHLT remains understudied. All pediatric CHLT patients from 2006 to 2019 were included. The prevalence of AKI in the first 7 post-operative days, renal recovery at 30 post-operative days, and CKD were ascertained. AKI was defined as an increase in creatinine greater than 1.5 times baseline, and CKD, as an eCrCl less than 90 mL/min/1.73 m2 . The need for RRT was also analyzed. 10 patients were included, with an average age of 20 years and an average listing time of 130 days. Preoperatively, the median eCrCl was 91.12 mL/min/m2 (IQR 70.51, 127.75 min/mL/m2 ). 5 (50%) patients had CKD, with 4 at stage 2 and 1 at stage 3. AKI occurred post-operatively in 3 of 9 (33%) patients: 2 at stage 1 and 1 at stage 2. 2 (67%) resolved by 7 days. Of the 5 patients who reached their 1-year follow-up, 1 (20%) had stage 3 CKD. Among 2 patients, neither had CKD at 5 years. One patient required RRT 2 weeks after CHLT. Despite an increased prevalence of preoperative CKD, patients undergoing CHLT have a lower AKI prevalence than those receiving an isolated heart or liver transplant. Of those with AKI, early renal recovery is common, although at 1 year CKD remains present in 20%. Among long-term survivors, normal renal function is achievable.

Readmission Rates and Associated Outcomes for Alcoholic Hepatitis: A Nationwide Cohort Study.

BACKGROUND/AIMS: Alcoholic hepatitis (AH) can lead to sudden and severe hepatic decompensation necessitating recurrent hospitalizations. We evaluated the trends, predictors, and healthcare cost burden of AH-related readmissions in the USA. METHODS: Utilizing the National Readmissions Database 2010-2014, we performed a retrospective longitudinal analysis to identify the index readmission with AH for up to 90 days after discharge. Annual trends of 30- and 90-day AH-related readmissions were calculated. Predictors of 30- and 90-day readmission were determined by multivariate logistic regression. Annual healthcare cost burden associated with AH-linked readmissions was estimated. RESULTS: Of the 21,572 (unweighted: 50,769) AH-related hospitalizations, 4917 (22.8%) and 7890 (36.6%) were readmitted in 30 and 90 day, respectively, with rates that were statistically unchanged from 2010 to 2014. Predictors of 30-day readmissions included female gender, hepatitis C virus infection, cirrhosis, ascites, acute kidney injury, urinary tract infection, history of bariatric surgery, chronic pancreatitis, and high medical comorbidity index. Acute pancreatitis and palliative care consultation were associated with a lower risk of 30-day readmission. Predictors of 90-day readmission were similar to risk factors for 30-day readmission. From 2010 to 2014, the annual cost (and total hospitalization days) burden increased in 2014 to $164 million (22,244 days) and $321 million (42,772 days) for 30- and 90-day AH-related readmissions, respectively. CONCLUSION: Despite relatively stable trends in AH-related readmission, the total LOS and cost has been rising. A target-directed approach with a focus on high-risk subpopulations may help understand the unique challenges associated with the rising cost of AH-related readmissions.

HSP70-Mediated NLRP3 Inflammasome Suppression Underlies Reversal of Acute Kidney Injury Following Extracellular Vesicle and Focused Ultrasound Combination Therapy.

Acute kidney injury (AKI) is the abrupt loss of renal function, for which only supportive therapies exist. Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) have been shown to be therapeutically effective in treating AKI by spurring endogenous cell proliferation and survival while suppressing inflammation. Pre-treating kidneys with pulsed focused ultrasound (pFUS) has also been shown to enhance MSC therapy for AKI, but its role in MSC-derived EV therapy remains unexplored. Using a mouse model of cisplatin-induced AKI, we show that combination therapy with pFUS and EVs restores physiological and molecular markers of kidney function, more so than either alone. Both pFUS and EVs downregulate heat shock protein 70 (HSP70), the NLRP3 inflammasome, and its downstream pro-inflammatory cytokines IL-1ß and IL-18, all of which are highly upregulated in AKI. In vitro knockdown studies suggest that HSP70 is a positive regulator of the NLRP3 inflammasome. Our study therefore demonstrates the ability of pFUS to enhance EV therapy for AKI and provides further mechanistic understanding of their anti-inflammatory and regenerative effects.

Impact of Pretransplant Donor BK Viruria in Kidney Transplant Recipients.

BACKGROUND: BK virus (BKV) is a significant cause of nephropathy in kidney transplantation. The goal of this study was to characterize the course and source of BKV in kidney transplant recipients. METHODS: We prospectively collected pretransplant plasma and urine samples from living and deceased kidney donors and performed BKV polymerase chain reaction (PCR) and immunoglobulin G (IgG) testing on pretransplant and serially collected posttransplant samples in kidney transplant recipients. RESULTS: Among deceased donors, 8.1% (17/208) had detectable BKV DNA in urine prior to organ procurement. BK viruria was observed in 15.4% (6/39) of living donors and 8.5% (4/47) of deceased donors of recipients at our institution (P = .50). BKV VP1 sequencing revealed identical virus between donor-recipient pairs to suggest donor transmission of virus. Recipients of BK viruric donors were more likely to develop BK viruria (66.6% vs 7.8%; P < .001) and viremia (66.6% vs 8.9%; P < .001) with a shorter time to onset (log-rank test, P < .001). Though donor BKV IgG titers were higher in recipients who developed BK viremia, pretransplant donor, recipient, and combined donor/recipient serology status was not associated with BK viremia (P = .31, P = .75, and P = .51, respectively). CONCLUSIONS: Donor BK viruria is associated with early BK viruria and viremia in kidney transplant recipients. BKV PCR testing of donor urine may be useful in identifying recipients at risk for BKV complications.

Short-term outcomes of en bloc combined heart and liver transplantation in the failing Fontan.

Patients with failing Fontan physiology and liver cirrhosis are being considered for combined heart and liver transplantation. We performed a retrospective review of our experience with en bloc combined heart and liver transplantation in Fontan patients > 10 years old from 2006 to 18 per Institutional Review Board approval. Six females and 3 males (median age 20.7, range 14.2-41.3 years) underwent en bloc combined heart and liver transplantation. Indications for heart transplant included ventricular dysfunction, atrioventricular valve regurgitation, arrhythmia, and/or lymphatic abnormalities. Indication for liver transplant included portal hypertension and cirrhosis. Median Fontan/single ventricular end-diastolic pressure was 18/12 mm Hg, respectively. Median Model for End-Stage Liver Disease excluding International Normalized Ratio score was 10 (7-26), eight patients had a varices, ascites, splenomegaly, thrombocytopenia score of ≥ 2, and all patients had cirrhosis. Median cardiopulmonary bypass and donor ischemic times were 262 (178-307) and 287 (227-396) minutes, respectively. Median intensive care and hospital stay were 19 (5-96) and 29 (13-197) days, respectively. Survival was 100%, and rejection was 0% at 30 days and 1 year post-transplant. En bloc combined heart and liver transplantation is an acceptable treatment in the failing Fontan patient with liver cirrhosis.

Two infants with bilateral renal agenesis who were bridged by chronic peritoneal dialysis to kidney transplantation.

Bilateral renal agenesis is associated with severe oligohydramnios and was considered incompatible with postnatal life due to severe pulmonary hypoplasia. The use of renal replacement therapy was limited by significant morbidity and mortality associated with dialysis in very young infants with major pulmonary pathology. In the United States, there is a tremendous controversy about whether or not the use of prenatal amniotic fluid infusions provides a benefit to fetuses with bilateral renal agenesis. One of the critical issues identified is that there are, as yet, no children reported who had achieved long-term survival. Previous reports all indicated these children died shortly after birth or after unsuccessful peritoneal dialysis. We present two infants with a prenatal diagnosis of bilateral renal agenesis whose mothers elected to undergo prenatal amnioinfusions. One was born at 28 weeks with a birthweight of 1230 g and the other born at 34 weeks with a birthweight of 1940 g. We present the details of both cases, with initial management on chronic peritoneal dialysis, which started shortly after birth, as a bridge to living related kidney transplants.

Prenatal treatment of ornithine transcarbamylase deficiency.

PURPOSE OF STUDY: Patients with neonatal urea cycle defects (UCDs) typically experience severe hyperammonemia during the first days of life, which results in serious neurological injury or death. Long-term prognosis despite optimal pharmacological and dietary therapy is still poor. The combination of intravenous sodium phenylacetate and sodium benzoate (Ammonul®) can eliminate nitrogen waste independent of the urea cycle. We report attempts to improve outcomes for males with severe ornithine transcarbamylase deficiency (OTCD), a severe X-linked condition, via prenatal intravenous administration of Ammonul and arginine to heterozygous carrier females of OTCD during labor. METHODS USED: Two heterozygote OTCD mothers carrying male fetuses with a prenatal diagnosis of OTCD received intravenous Ammonul, arginine and dextrose-containing fluids shortly before birth. Maintenance Ammonul and arginine infusions and high-caloric enteral nutrition were started immediately after birth. Ammonul metabolites were measured in umbilical cord blood and the blood of the newborn immediately after delivery. Serial ammonia and biochemical analyses were performed following delivery. SUMMARY OF RESULTS: Therapeutic concentrations of Ammonul metabolites were detected in umbilical cord and neonatal blood samples. Plasma ammonia and glutamine levels in the postnatal period were within the normal range. Peak ammonia levels in the first 24-48h were 53mcmol/l and 62mcmol/l respectively. The boys did not experience neurological sequelae secondary to hyperammonemia and received liver transplantation at ages 3months and 5months. The patients show normal development at ages 7 and 3years. CONCLUSION: Prenatal treatment of mothers who harbor severe OTCD mutations and carry affected male fetuses with intravenous Ammonul and arginine, followed by immediate institution of maintenance infusions after delivery, results in therapeutic levels of benzoate and phenylacetate in the newborn at delivery and, in conjunction with high-caloric enteral nutrition, prevents acute hyperammonemia and neurological decompensation. Following initial medical management, early liver transplantation may improve developmental outcome.

Structured Reporting of Multiphasic CT for Hepatocellular Carcinoma: Effect on Staging and Suitability for Transplant.

OBJECTIVE: The purpose of this study is to evaluate whether use of a standardized radiology report template would improve the ability of liver transplant surgeons to diagnose stage T2 hepatocellular carcinoma (HCC) and determine patient suitability to undergo orthotopic liver transplant (OLT). MATERIALS AND METHODS: In this retrospective study, a standardized template was devised, and its use was mandated for reporting of liver CT findings for patients with cirrhosis and HCC. Two surgeons analyzed 200 reports (100 before and 100 after template implementation) for descriptions of cirrhosis, portal hypertension, lesion enhancement characteristics, tumor thrombus, portal and superior mesenteric vein patency, and Organ Procurement Transplantation Network (OPTN) class. Ability to determine Milan criteria and surgeon satisfaction were also assessed. Data obtained before and after template implementation were statistically analyzed using the Cochran-Mantel-Haenszel test. RESULTS: Template implementation increased the percentage of reports documenting the presence or absence of portal hypertension (74% to 88% for surgeon 1 and 86% to 87% for surgeon 2; p = 0.042); lesion number (76% to 88% for surgeon 2 [no change for surgeon 1]; p = 0.038), size (95% to 96% for surgeon 1 and 82% to 93% for surgeon 2; p = 0.03), and enhancement (93% to 94% for surgeon 1 and 80% to 91% for surgeon 2; p = 0.049); presence of tumor thrombus (10% to 57% for surgeon 1 and 31% to 63% for surgeon 2; p < 0.001); and OPTN class (8% to 82% for surgeon 1 and 2% to 81% for surgeon 2; p < 0.001). The surgeons were significantly more able to determine the presence of T2 disease and qualification for exception points after implementation of the template (increasing from 80% to 94%; p = 0.025). Satisfaction with reports also improved (p < 0.0001). CONCLUSION: The reporting template improved determination of patient suitability to undergo transplant according to the Milan criteria.

When does vesicoureteral reflux in pediatric kidney transplant patients need treatment?

PURPOSE: The treatment of VUR in children with UTI has changed significantly, due to studies showing that antibiotic prophylaxis does not decrease renal scarring. As children with kidney transplants are at higher risk for UTI, we investigated if select patients with renal transplant VUR could be managed without surgery. MATERIALS AND METHODS: A total of 18 patients with VUR into their renal grafts were identified, and 319 patients underwent transplantation from 2006 to 2016. The cause for the detection of the VUR, treatment, and graft function was reviewed. RESULTS: Six boys and 12 girls were identified, 13 of whom had grade 3 or 4 VUR into the renal graft. Nine patients presented with hydronephrosis or abnormal renal biopsy: eight were successfully managed with antibiotic prophylaxis and bladder training, one developed UTI and underwent Dx/HA subureteric injection. Nine patients presented with recurrent febrile UTI, only one was successfully managed without surgery. Only 2 of 9 (22%) patients who underwent Dx/HA injection had resolution of their reflux. Of the remaining seven, five required open ureteral reimplantation (two for obstruction), one lost the graft due to rejection, and one had significant hydronephrosis. eGFR was similar between the hydronephrosis, UTI, and abnormal renal biopsy groups at all times. CONCLUSION: Patients with transplant VUR and recurrent febrile UTI are more likely to require surgical therapy, but the complication and failure rate for Dx/HA injection is significant. Patients with transplant VUR without febrile UTI can be successfully managed with bladder training and temporary antibiotic prophylaxis.

Transarterial chemoembolization in children to treat unresectable hepatocellular carcinoma.

Children with unresectable HCC have a dismal prognosis and few approved treatment options. TACE is an effective treatment option for adults with HCC, but experience in children is very limited. Retrospective analysis was performed of 8 patients aged 4-17 years (4 male, mean 12.5 years) who underwent TACE for unresectable HCC. Response to TACE was evaluated by change in AFP, RECIST and tumor volume, PRETEXT, and transplantation eligibility by UCSF and Milan criteria. Post-procedure mean follow-up was 8.2 years. Mean overall change in tumor volume for the 8 patients was 51%. Percent change in AFP ranged from a decrease of 100% to an increase of 89.3%, with a mean change of -49.6%. Two patients did not undergo resection or transplantation and died of progressive disease. Six patients underwent orthotopic liver transplantation with mean first TACE-to-transplant interval of 141 days (range 11-514). Following transplantation, 5 patients were alive at the end of the follow-up period and one died of recurrent disease. Based on our initial experience, TACE for children with unresectable HCC appears to be a safe and effective method for managing hepatic tumor burden and for downstaging and bridging to liver transplantation.

Fatal Emmonsia sp. Infection and Fungemia after Orthotopic Liver Transplantation.

We report a fatal case of disseminated Emmonsia sp. infection in a 55-year-old man who received an orthotopic liver transplant. The patient had pneumonia and fungemia, and multisystem organ failure developed. As human habitats and the number of immunocompromised patients increase, physicians must be aware of this emerging fungal infection.

Stereotactic body radiotherapy for pediatric hepatocellular carcinoma with central biliary obstruction.

Here, we present the case of a pediatric patient with newly diagnosed hepatocellular carcinoma causing central biliary obstruction and persistently elevated bilirubin of 3.0-4.3 mg/dl despite placement of bilateral internal-external biliary drains. The tumor was not resectable, and the patient was not a candidate for liver transplant due to nodal disease, for chemotherapy due to hyperbilirubinemia, or for local therapies aside from stereotactic body radiotherapy (SBRT). In this report, we discuss the successful use of SBRT in the management of this patient, and its role in allowing the patient to become a candidate for additional therapies.

Cysteamine in renal transplantation: A report of two patients with nephropathic cystinosis and the successful re-initiation of cysteamine therapy during the immediate post-transplant period.

Nephropathic cystinosis is a rare disorder causing the accumulation of intracellular cystine crystals in tissues. The damage to the proximal tubules of the kidneys results in Fanconi syndrome, and patients with cystinosis experience the progression of chronic kidney disease, resulting in the need for kidney transplantation. Treatment of cystinosis with cysteamine has proven to be effective; however, it has many gastrointestinal side effects that are concerning for transplant specialists during the immediate post-transplant period. Transplant specialists routinely discontinue cysteamine therapy for up to six weeks to ensure proper immunosuppressant absorption. This practice is worrisome because it communicates the acceptability of lapses of cysteamine treatment to patients. It may be better to re-initiate cysteamine therapy shortly after transplantation while the patient is followed more closely by the transplant team. This report presents two pediatric patients with nephropathic cystinosis who successfully restarted cysteamine therapy in the immediate post-transplant period without issue in regard to immunosuppression absorption or gastrointestinal side effects. These cases challenge current practice of discontinuing cysteamine therapy during kidney transplantation, and immediate re-initiation of cysteamine therapy in cystinosis patients post-transplant should be considered.