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We aimed to describe our procedure for vascular reconstruction and back table bench preparation for the right lobe live donor allograft. Live donor liver transplantation (LDLT) remains an important option for the expansion of the donor pool. The procedure has been widely used, and its success is dependent on a technically perfect operation with appropriate inflow and outflow of the allograft. Adequate preparation of the right lobe (RL) allograft prior to implantation remains a vital part of the procedure.Our technique of back table vascular reconstruction of the RL allograft has been performed using a hepatic vein patch venoplasty, inferior hepatic vein inclusion, portal vein reconstruction, and segment V and VIII reconstruction for all of our LDLTs.Between March 2009 and January 2020, 321 consecutive adult LDLTs were performed and underwent back table reconstruction with the techniques described. During that time period, no patients had hepatic insufficiency. There was a single thrombosis of a superior mesenteric vein (SMV) to PV jump conduit.Our technique of back table reconstruction of the LDLT right lobe graft remains a crucial part of the operative procedure. Our experience with RL grafts without middle hepatic vein (MHV) and our systematic approach for inflow and outflow reconstruction has yielded excellent results with no technical outflow issues and minimal inflow complications.

PurposeEnhanced B-cell presentation of donor alloantigen relative to presentation of HLA-mismatched reference alloantigen is associated with acute cellular rejection (ACR), when expressed as a ratio called the antigen presenting index (API) in an exploratory cohort of liver and intestine transplant (LT, IT) recipients.MethodsTo test clinical performance, we measured the API using the previously described 6-hour assay in 84 LT and 54 IT with median age 3.3 years (0.05-23.96). Recipients experiencing ACR within 60 days after testing were termed rejectors.ResultsWe first confirmed that B-cell uptake and presentation of alloantigen induced and thus reflected the alloresponse of T-helper cells, which were incubated without and with cytochalasin and primaquine to inhibit antigen uptake and presentation, respectively. Transplant recipients included 76 males and 62 females. Rejectors were tested at median 3.6 days before diagnosis. The API was higher among rejectors compared with non-rejectors (2.2 ± 0.2 vs 0.6 ± 0.04, p-value=1.7E-09). In logistic regression and ROC analysis, API ≥ 1.1 achieved sensitivity, specificity, positive and negative predictive values for predicting ACR in 99 training set samples. Corresponding metrics ranged from 80-88% in 32 independent post-transplant samples, and 73-100% in 20 independent pre-transplant samples. In time-to-event analysis, API ≥ 1,1 predicted higher incidence of late DSA after API measurements in LT (p=0.011) and graft loss in IT recipients (p=0.008), compared with recipients with APIConclusionEnhanced donor antigen presentation by circulating B-cells predicts rejection after liver or intestine transplantation as well as higher incidence of DSA and graft loss late after transplantation

Enteric hyperoxaluria (EH) is a known complication of Roux-en-Y gastric bypass (RYGB) and can lead to nephrolithiasis, oxalate-induced nephropathy, and end-stage renal disease. Recurrent EH-induced renal impairment has been reported after kidney transplantation and may lead to allograft loss. EH occurs in up to one quarter of patients following malabsorption-based bariatric operations. We present a report of medically refractory EH in a renal transplant recipient with allograft dysfunction that was successfully managed with reversal of RYGB. The patient developed renal failure 7 years following gastric bypass requiring renal transplant. Following an uneventful living donor kidney transplant, the patient developed recurrent subacute allograft dysfunction. A diagnosis of oxalate nephropathy was made based on biopsy findings of renal tubular calcium oxalate deposition in conjunction with elevated serum oxalate levels and elevated 24-hr urinary oxalate excretion. Progressive renal failure ensued despite medical management. The patient underwent reversal of her RYGB, which resulted in recovery of allograft function. This report highlights an under-recognized, potentially treatable cause of renal allograft failure in patients with underlying gastrointestinal pathology or history of bariatric surgery and proposes a strategy for management of patients with persistent hyperoxaluria based on a review of the literature.

Adequate perioperative analgesia for pediatric abdominal transplant surgery is essential for patient recovery. However, the risks of commonly used medications such as hepatotoxicity, nephrotoxicity, bleeding concerns, and poor graft results with opioids limit pain management in this population. Thoracic epidural, continuous erector spinae plane, and type-1 quadratus lumborum blocks (QLBs) have been described and utilized in the adult population in this setting. The safety and benefits of regional anesthetic techniques in pediatrics have been widely documented for different types of procedures except pediatric abdominal transplantation, where data remains scarce. Our primary goal was to determine if QLBs provided adequate perioperative analgesia when part of a multimodal approach. Secondary objectives were to examine complications and effects on the intensive care unit (ICU) and hospital stay.We performed a retrospective, observational study of pediatric patients who underwent abdominal transplant surgeries at the University of Pittsburgh Medical Center Children's Hospital of Pittsburgh from January 2015 to July 2021 and received a single injection QLB for pain control. Data collected included: demographics, nerve block characteristics, perioperative opioid consumption, use of non-opioid analgesia, daily pain scores, and hospital and ICU stay.Forty-two patients met the inclusion criteria for our study. Our results suggest that QLBs decrease opioid consumption, facilitate early extubation, prevent reintubation in the ICU, and reduce ICU and hospital stay.QLB is feasible and can be used as a multimodal approach for postoperative pain control in pediatric solid organ transplantation.

Liver transplant is a life-saving therapy that can restore quality life for several pediatric liver diseases. However, it is not available to all children who need one. Expertise in medical and surgical management is heterogeneous, and allocation policies are not optimally serving children. Technical variant grafts from both living and deceased donors are underutilized.Several national efforts in pediatric liver transplant to improve access to and outcomes from liver transplant for children have been instituted and include adjustments to allocation policies, UNOS-sponsored collaborative improvement projects, and the emergence of national learning networks to study ongoing challenges in the field the Surgical Working group of the Starzl Network for Excellence in Pediatric Transplantation (SNEPT) discusses key issues and proposes potential solutions to eliminate the persistent wait list mortality that pediatric patients face.A discussion of the factors impacting pediatric patients' access to liver transplant is undertaken, along with a proposal of several measures to ensure equitable access to life-saving liver transplant.Pediatric liver transplant wait list mortality can and should be eliminated. Several measures, including collaborative efforts among centers, could be leveraged to acheive this goal.

Living donor liver transplantation (LDLT) continues to be the primary modality of liver transplantation in Asia, but it accounts for about 5% of all liver transplantations in the US. ABO incompatibility is the primary reason motivated donors are declined. Although kidney paired exchanges are common, liver paired exchange (LPE) is still evolving in the US.This is a retrospective review (between January 1, 2019, and July 31, 2021) of our initial experience with LPE.A total of 10 LPEs (20 LDLTs) were performed during the study period. Seven LPEs were initiated by a nondirected O donor. The other 3 pair sets involved 1 ABO compatible and 1 ABO incompatible pair. Transplantations in a pair set were completed within a mean of 4.8 (range 1-14) days of each other. All 20 donors are doing well with no major complications at 12.7 (range 1-20) months. Seventeen of 20 recipients are alive and have good allograft function. One recipient died in the early postoperative period. Two late deaths of patients with functioning allografts were due to COVID-19 (at 8 months) and peritoneal carcinomatosis and gram-negative sepsis (at 9 months).LPE is feasible in a high-volume LDLT center and is a useful option to increase LDLT by overcoming ABO incompatibility. Nondirected donors can be utilized to initiate an LPE.

The aim of the study was to analyze the long-term outcomes of transplants utilizing ITx donors1 year and to compare these results with older donors.Between January 2007 and December 2019, the primary ITx donors in the Children's Hospital of Pittsburgh of UPMC were retrospectively reviewed. Short- and long-term outcomes of recipients receiving a deceased donor organ from donors1 year were compared with those found in all other recipients.During the study period, there were 89 primary ITx donors, using 30 donors (33.7%) aged1 year. The mean age of their recipients was 1.6 ± 0.7 (0.7-3.2) years. The 30 graft types were isolated intestine (n = 3, 10.0%), liver bowel (n = 20, 66.7%), and multivisceral (n = 7, 23.3%). Technical complications occurred in 12 (40.0%) recipients. Candidates transplanted with intestine allografts from donors1 year of age had shorter wait times (p .001), more liver-inclusive grafts (p .001), and less donor-specific antibodies (DSA) (p = .014). During follow-up, the recipients had less graft loss (p = .018), and more remained alive with graft in place (p = .011). Among children transplanted with such donors, 3-year and graft survival rates were 86.7% and 82.9% compared to 62.8% and 49.9% in the cohort of donors1 year (p = .032 and .011).Donor age1 year was associated with improved graft survival. Optimal utilization of this population for toddler candidates would increase intestine availability, reduce time to transplantation, and potentially improve long-term outcome.

Introduction Transient hyperphosphatasemia (TH) is a rare benign condition of elevated serum alkaline phosphatase (AP) levels seen in healthy children. TH has been reported to occur in pediatric solid organ transplants, including kidney transplant patients. Little is known about TH in pediatric kidney transplant patients. Objective To evaluate the incidence and natural history of TH in pediatric kidney transplant patients. Methods A retrospective chart review of patients < 18 years of age who underwent kidney transplantation at the University of Pittsburgh Medical Center (UPMC) Children's Hospital of Pittsburgh between 2008 and 2019 was performed to identify patients with TH, defined as an AP level greater than 1,000 IU/L. Exclusion criteria included repeat kidney transplants or kidney transplant as part of a multiorgan transplant. Results One hundred seventy-six patients underwent a solitary kidney transplant, of which 87 were less than 12 years of age. Eleven patients (6.5%) were found to have TH, all of whom were < 12 years of age (12.8%) (median age: 5 years; range: 1 - 11 years). The median AP level prior to transplant was 183 IU/L (range: 104 - 309 IU/L) and the median peak AP was > 2,300 IU/L (range: 1,227 - 4,912 IU/L). The median time from a kidney transplant to the diagnosis of TH was 0.6 years (range: 0.3 to 7.7 years). The median length of time that TH persisted was 0.5 years (range: 0.2 to 0.9 years). The median estimated glomerular filtration rate (GFR) at the time of diagnosis of TH was 84 mL/min/1.73m2 per the bedside Schwartz equation (range: 45 to 152 mL/min/1.73m2). One patient had variable AP levels over nine months prior to resolution; the other 10 patients had a solitary peak of AP prior to resolution. No patient required treatment of elevated AP levels and the TH resolved spontaneously without intervention. No patients had significant abnormalities of markers of metabolic bone disease or were on active vitamin D, calcium, or phosphorus supplements. Two patients reported bone pain, and one patient was found to have avascular necrosis of the hip. Conclusions TH is a relatively common finding following a pediatric kidney transplant in pre-pubertal children less than 12 years of age. It primarily occurs in the first year following a kidney transplant and usually resolves without recurrence within one year of onset.

The objective of this article is to provide a brief and concise review about the history, indications, surgical technical challenges, post-transplant complications, and overall outcomes of pediatric abdominal organ transplantation (kidney transplant (KT), liver transplant (LT), and intestinal transplant (IT)). Pediatric abdominal organ transplantation (KT, LT, IT) has evolved over the last 50 years to emerge as a successful option for children suffering from end-stage renal disease, end-stage liver disease, liver malignancy, disabling metabolic disease, acute liver failure, and life-threatening intestinal failure. However, pediatric abdominal organ transplantation requires a fundamentally different approach from adult abdominal organ transplantation due to differences in underlying indications for transplant, smaller pediatric recipient size, and various growth stages of childhood. Excellent short-term and good long-term outcomes have been achieved in pediatric KT, LT, and IT recipient when compared with adult counterparts. Further research to develop strategies to induce immunologic tolerance of allografts and diagnose/treat chronic allograft rejection is required in order to continue to improve overall survival of pediatric abdominal organ transplant recipients.

Background Progressive familial intrahepatic cholestasis (PFIC) refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes, resulting in a hepatocellular form of cholestasis. While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause, recent scientific advancements have uncovered multiple specific responsible proteins. The variety of identified defects has resulted in an ever-broadening phenotypic spectrum, ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease. Aim To review current data on defects in bile acid homeostasis, explore the expanding knowledge base of genetic based diseases in this field, and report disease characteristics and management. Methods We conducted a systemic review according to PRISMA guidelines. We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding, diagnosis, and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC. English only articles were accessed in full. The manual search included references of retrieved articles. We extracted data on disease characteristics, associations with other diseases, and treatment. Data was summarized and presented in text, figure, and table format. Results Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults. A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype. Conclusion We present a summary of current advances made in a number of areas relevant to both the classically described FIC1 (ATP8B1), BSEP (ABCB11), and MDR3 (ABCB4) transporter deficiencies, as well as more recently described gene mutations -- TJP2 (TJP2), FXR (NR1H4), MYO5B (MYO5B), and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.

The use of kidneys donated after circulatory death (DCD) provides an invaluable expansion of the organ supply for transplantation. Here we investigated the effect of DCD on fibrotic changes on 1-year post-transplant surveillance kidney allograft biopsy. Recipients of a deceased donor kidney transplant between 2013 and 2017 at a single institution, who survived 1 year and underwent surveillance biopsy, were included in the analysis (n = 333: 87 DCD kidneys, 246 kidneys donated after brain death [DBD]). Banff scores for interstitial fibrosis and tubular atrophy were summed as IFTA and compared between the groups. DCD and DBD groups were comparable for baseline characteristics. Delayed graft function was 39% in DCD vs. 19% in DBD, p = 0.0002. Patient and graft survival were comparable for DCD and DBD cohorts. IFTA scores were higher in DCD compared to DBD (2.43±0.13 vs. 2.01±0.08, p = 0.0054). On multivariate analysis, the odds of IFTA>2 in the DCD group was 2.5x higher (95%CI: 1.35-4.63) than in the DBD group. Within the DCD group, kidneys with IFTA>2 had inferior 5-year graft survival (p = 0.037). In conclusion, compared DBD kidneys, DCD kidneys developed a greater degree of fibrotic changes on 1-year post-transplant surveillance biopsy, which affected graft longevity within the DCD cohort. This article is protected by copyright. All rights reserved.

OBJECTIVES: Describe clinical characteristics, management, and outcome in a cohort of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) patients. METHODS: We conducted a retrospective chart review of MMIHS patients followed at a large transplant and intestinal rehabilitation center over a period of 17 years. RESULTS: We identified 25 patients with MMIHS (68% girls, 13 transplanted). One transplanted and 1 nontransplanted patient were lost to follow-up. We estimated 100, 100, and 86% for 5-,10-, and 20-year survival, respectively, with only 1 death. Of the 22 patients alive at the time of study (11 transplanted, 11 nontransplanted), median age was 9.2 years (range 2.7–22.9 years). Longest posttransplant follow-up was 16 years. Seventeen patients had available prenatal imaging reports; all showed distended bladder. Eight had genetic testing (5, ACTG2; 2, MYH11; 1, MYL9). Almost all patients had normal growth with median weight z-score −0.77 (interquartile range −1.39 to 0.26), height z score −1.2 (−2.04 to −0.48) and body mass index z-score 0.23 (−0.37 to 0.93) with no statistical difference between transplanted and nontransplanted patients. All nontransplanted patients were on parenteral nutrition with minimal/no feeds, and all except 1 of the transplanted patients were on full enteral feeds. Recent average bilirubin, INR, albumin, and creatinine fell within the reference ranges. CONCLUSIONS: This is the largest single-center case series with the longest duration of follow-up for MMIHS patients. In the current era of improved intestinal rehabilitation and transplantation, MMIHS patients have excellent outcomes in survival, growth, and liver function. This observation contradicts previous reports and should alter counselling and management decisions in these patients at diagnosis.

Liver transplantation is a successful option for inherited metabolic disease yet little is published on the outcome among siblings. We report outcomes of siblings who have undergone liver transplantation for metabolic disease in a single program. Seventy-one siblings (35 males) from 33 individual families underwent liver transplantation since 1982. Outcomes were compared over three consecutive eras. Twenty-eight families had two siblings, four had three siblings, and one had four siblings. In half of families where dates of listing were known, siblings were listed simultaneously. Mean (SD) age at listing for the oldest and second sibling was 13.2 (7.1) and 9.8 (5.7) years, respectively (p < .01). In 18/33 families, the oldest sibling underwent transplantation first. Mean (SD) age at transplant fell from the oldest to second sibling from 12.9 (7.2) to 9.5 (6.3) years, respectively (p < .001). Ten-year patient survival was 83.5% which improved over the eras: era 1 (1982-1994) 65.0%, era 2 (1995-2007) 87.5%, and era 3 (2008-2019) 93.8%: p < .03. Sex, age at transplant, order of transplant, and presence of structural liver disease did not significantly impact survival. When siblings undergo liver transplant for inherited metabolic disease, later siblings are listed and transplanted at a significantly younger age.

Transplantation of kidneys from deceased donors with acute kidney injury (AKI) can expand the donor pool. We investigated the effect of donor AKI on renal function and chronic changes on protocol biopsies at 1-year post-transplant. Donor AKI was defined according to Acute Kidney Injury Network (AKIN) criteria. Between 2013 and 2017, 333 kidneys were transplanted and subsequently biopsied after 1 year. Fifty-three kidneys from AKI donors (AKIN stage I n = 42, stage II n = 8, stage III n = 3) were compared to 280 kidneys from non-AKI donors. At 1-year follow-up, patient and graft survival were comparable. Donor AKI was not predictive of IFTA (Banff interstitial fibrosis plus tubular atrophy scores) at 1-year post-transplant biopsy (2.10 ± 1.28 in AKI, 2.09 ± 1.22 in non-AKI, P = .95). Donor AKI was also not associated with progression of IFTA from 3 to 12 months (P = .69), or inferior glomerular filtration rate (eGFR, P = .94). In a multivariate analysis, the odds of IFTA >2 were comparable between AKI and non-AKI groups. In conclusion, the transplantation of kidneys from donors with predominantly stage I AKI results in comparable function and degree of fibrosis on protocol biopsies 1-year post-transplant. Selected grafts from donors with AKI are a valuable tool for expanding the donor pool for kidney transplantation.

Transplantation of the intestine in children has presented significant challenges even as it has become a standard to treat nutritional failure due to short gut syndrome. These challenges have been addressed in part by significant improvements in short and long-term care. Noteworthy enhancements include reduced need for intestine transplantation, drug-sparing immunosuppressive regimens, immune monitoring, and improved surveillance and management of PTLD and non-adherence.

PURPOSE OF REVIEW The field of intestinal transplantation has shown significant growth and has become the gold standard therapy for patients that suffer from the complications of total parenteral nutrition due to irreversible intestinal failure. In the early years of intestinal transplant, retransplantation was associated with extremely high morbidity and mortality. The purpose of this review is to summarize recent encouraging reports, showing significant improvement in outcomes after intestinal retransplantation. RECENT FINDINGS Recent studies at large volume centers have reported significant progress in patient and graft survival after intestinal retransplantation. Recent literature described the most common indications for retransplantation, surgical techniques, timing of graft enterectomy, immunologic monitoring, and complications. Improvement in outcomes due to advances in immunosuppression management and the importance of liver-containing grafts are also described. SUMMARY Improving early to midterm patient and graft survival has made consideration for intestinal retransplantation even more necessary. Current clinical evidence supports the benefit of intestinal retransplantation in well selected recipients. Initial immunosuppression protocols, technical modifications, proper timing of enterectomy, and improved infectious disease monitoring have contributed to improved outcomes.

OBJECTIVES: To assess outcomes following liver transplantation for maple syrup urine disease by determining attainment and sustainability of metabolic control and apply an “ideal” outcome composite in long-term survivors. STUDY DESIGN: A single center, retrospective review collected clinical data including branched-chain amino acid (leucine, isoleucine, and valine) levels following liver transplant and determined achievement of an ideal long-term outcome profile of a first allograft stable on immunosuppression monotherapy, normal growth, and absence of common transplant-related sequelae. RESULTS: Of 77 patients meeting inclusion criteria identified, 23 were long-term (≥10-year) survivors and were additionally assessed for ideal outcome attainment. Patient and graft survival were 100% and 99%, respectively, and all patients were on an unrestricted protein intake diet. Although significant variation was noted in mean isoleucine (P < .01) and leucine (P < .05) levels postliver transplantation, no difference was seen in valine (P = .29) and overall clinical impact was likely negligible as metabolic stability was achieved and sustained beyond 3 years postliver transplantation and no metabolic crises were identified. Of 23 long-term survivors with available data, 9 (39%) achieved all composite metrics determined to define “ideal” outcomes in pediatric postliver transplantation populations. CONCLUSIONS: Liver transplant enables long-term metabolic stability for patients with maple syrup urine disease. A combination of experience and improvement in both pre- and postliver transplantation care has enabled excellent survival and minimal comorbidities following transplant.

The field of intestinal transplantation has experienced dramatic growth since the first reported cases 3 decades ago. Improvements in operative technique, donor assessment and immunosuppressive protocols have afforded children who suffer from life-threatening complications of intestinal failure a chance at long-term survival. As experience has grown, newer diseases, with more systemic manifestations have arisen as potential indications for transplant. After discussing the historical developments of intestinal transplant as a backdrop, this review focuses on the specific pre-operative indications for transplant as well as the great success that intestinal rehabilitation has witnessed over the past decade. A detailed discussion of evolution of immunosuppressive strategies is followed a general review of the common infectious complications experienced by children after intestinal transplant as well as the current long- and short-term results, including a section on new research on the quality of life in this challenging population of patients.

Background AKI after pediatric liver transplantation is associated with increased morbidity and mortality. The role of urinary biomarkers for the prediction of AKI in pediatric patients after liver transplantation has not been previously reported. The primary objective of this prospective pilot study was to determine the predictive capabilities of urinary KIM-1, NGAL, TIMP-2, and IGFBP7 for diagnosing AKI. Methods Sixteen children undergoing liver transplantation were enrolled in the study over a 19-month time period. The Kidney Disease Improving Outcomes criteria for urine output and serum creatinine were used to define AKI. Predictive ability was evaluated using the area under the curve obtained by ROC analysis. Results AKI occurred in 6 (37.5%) of the patients between 2 and 4 days after transplant. There were no differences in any of the biomarkers prior to transplant. When obtained within 6 hours after transplant, the area under the ROC curve for predicting AKI was 0.758 (95% CI: 0.458-1.00) for KIM-1, 0.900 (95% CI: 0.724-1.00) for NGAL, and 0.933 (95% CI: 0.812-1.00) for the product of TIMP-2 and IGFBP7 ([TIMP-2]·[IGFBP7]). Conclusions Our results show that both NGAL and [TIMP-2]·[IGFBP7] provide significant discrimination for AKI risk following liver transplant in children. Larger studies are needed to determine the optimal time point for measuring these biomarkers and to validate our findings.

Aim/background Domino liver transplantation (DLT) using liver allografts from patients with metabolic disorders enhances organ utilization. Short- and long-term course and outcome of these patients can impact the decision to offer this procedure to patients, especially those with diseases that can potentially be cured with liver transplant. We reviewed the outcomes of DLT from maple syrup urine disease (MSUD) patients in our large academic pediatric and adult transplant program. Methods All patients receiving DLT were analyzed retrospectively with a minimum of one-year follow-up period for patient and donor characteristics, early and late postoperative complications and patient and graft survival with their MSUD donors in terms of age, weight, MELD/PELD scores, cold ischemia time, postoperative leucine levels, and peak ALT (alanine aminotransferase) levels during the first 48 postoperative hours. Results Between 2006 and May 2019, 21 patients underwent domino liver transplantation with live donor allografts from MSUD patients. Four patients transplanted for different metabolic diseases are focus of a separate report. Seventeen patients with minimum one-year follow-up period are reported herein. The indications were primary sclerosing cholangitis (PSC, n = 4), congenital hepatic fibrosis (CHF, n = 2), alpha-1 antitrypsin deficiency (A-1 ATD, n = 2), progressive familial intrahepatic cholestasis (PFIC, n = 2), cystic fibrosis (n = 1), primary biliary cirrhosis (PBC, n = 1), neonatal hepatitis (n = 1), embryonal sarcoma (n = 1), Caroli disease (n = 1), hepatocellular carcinoma (HCC, n = 1), and chronic rejection after liver transplantations for PSC (n = 1). All patients and grafts survived at median follow-up of 6.4 years (range 1.2-12.9 years). Median domino recipient age was 16.2 years (range 0.6-64.6 years) and median MSUD recipient age was 17.6 years (range 4.8-32.1 years). There were no vascular complications during the early postoperative period, one patient had portal vein thrombosis 3 years after DLT and a meso-Rex bypass was successfully performed. Small for size syndrome (SFSS) occurred in reduced left lobe DLT recipient and was managed successfully with conservative management. Biliary stricture developed in 2 patients and was resolved by stenting. Comparison between DLT and MSUD recipients' peak postoperative ALT results and PELD/MELD scores showed lower levels in DLT group (P-value Conclusions Patient and graft survival in DLT from MSUD donors was excellent at short- and long-term follow-up. Metabolic functions have been normal in all recipients on a normal unrestricted protein diet. Ischemia preservation injury based on peak ALT was significantly decreased in DLT recipients. Domino transplantation from pediatric and adult recipients with selected metabolic diseases should be increasingly considered as an excellent option and alternative to deceased donor transplantation, thereby expanding the living donor pool. This, to date, is the largest world experience in DLT utilizing livers from patients with MSUD.

The aim of this study was to compare outcomes between living donor liver transplant (LDLT) and deceased donor liver transplant (DDLT) at a single center to demonstrate the advantages of LDLT and provide justification for the increased utilization and application of this procedure.LDLT comprises a very small percentage of all liver transplants performed in the United States, this despite its advantages and a shortage of the availability of deceased donor organs.A retrospective review of all adult LDLT (n = 245) and DDLT (n = 592) performed at a single center over 10 years (2009-2019), comparing survival outcomes by Kaplan-Meier analysis and comparing other measures of outcome such as recovery times, complications, costs, and resource utilization.Patient survival outcomes were superior in LDLT recipients (3-year 86% vs 80%, P = 0.03). Other outcomes demonstrated shorter length of hospital stay (11 vs 13 days, P = 0.03), less likelihood of intraoperative blood transfusion (52% vs 78%, P0.01), and less likelihood of need for posttransplant dialysis (1.6% vs 7.4%, P0.01). Early reoperation and biliary/vascular complication rates were similar. Hospital costs related to the transplant were 29.5% lower for LDLT. Complications in living donors were acceptable with no early or late deaths, 3-month reoperation rate of 3.1%, and overall complication rate of 19.5%. Given its advantages, we have expanded LDLT-in 2018, LDLT comprised 53.6% of our transplants (national average 4.8%), and our transplant rate increased from 44.8 (rate per 100-person years) in 2015 to 87.5 in 2018.LDLT offers advantages over DDLT including superior outcomes and less resource utilization. The time has come to change the paradigm of how LDLT is utilized in this country.

Cell-mediated immunity to CMV, if known, could improve antiviral drug therapy in at-risk children and young adults with LT and IT. Host immunity has been measured with CMV-specific T cells, which express IFNγ, but not those which express CD154, a possible substitute for IFNγ. CMV-specific CD154+ T cells and their subsets were measured with flow cytometry after stimulating PBL from recipient blood samples with an overlapping peptide mix of CMV-pp65 antigen for up to 6 hours. CMV-specific CD154+ T cells co-expressed IFNγ in PBL from three healthy adults and averaged 3.8% (95% CI 3.2%-4.4%) in 40 healthy adults. CMV-specific T cells were significantly lower in 19 CMV DNAemic LT or IT recipients, compared with 126 non-DNAemic recipients, 1.3% (95% CI 0.8-1.7) vs 4.1 (95% CI 3.6-4.6, P < .001). All T-cell subsets demonstrated similar between-group differences. In logistic regression analysis of 46 training set samples, 12 with DNAemia, all obtained between days 0 and 60 from transplant, CMV-specific T-cell frequencies ≥1.7% predicted freedom from DNAemia with NPV of 93%. Sensitivity, specificity, and PPV were 83%, 74%, and 53%, respectively. Test performance was replicated in 99 validation samples. In 32 of 46 training set samples, all from seronegative recipients, one of 19 recipients with CMV-specific T-cell frequencies ≥1.7% experienced DNAemia, compared with 8 of 13 recipients with frequencies

Pediatric recipients of intestinal transplants have a high incidence of PTLD, but the impact of specific induction immunosuppression agents is unclear. In this single-center retrospective review from 2000 to 2017, we describe the incidence, characteristics, and outcomes of PTLD after primary intestinal transplantation in 173 children with or without liver, after induction with rATG, alemtuzumab, or anti-IL-2R agents. Thirty cases of PTLD occurred among 28 children, 28 EBV+ and 2 EBV-. Although not statistically significant, the PTLD incidence was higher after isolated intestinal transplant compared with liver-inclusive allograft (19.3% vs 13.3%, P = .393) and after induction with anti-IL-2R antibody and alemtuzumab compared with rATG (28.6% and 27.3% vs 13.3%, P = .076). The 30 PTLD cases included 13 monomorphic PTLD, 13 polymorphic PTLD, one spindle cell, one Burkitt lymphoma, and two cases too necrotic to classify. After reduction of immunosuppression, management was based on disease histology and extent. Resection with or without rituximab was used for polymorphic tumors and limited disease extent, whereas chemotherapy was used for diffuse disease. Of the 28 patients, 11 recovered with functioning allografts (39.3%), 10 recovered after enterectomy (35.7%), and seven patients died (25%), three due to PTLD and four due to other causes. All who died of progressive PTLD had received chemotherapy, highlighting the mortality of PTLD, toxicity of treatment and need for novel agents. Alemtuzumab is no longer used for induction at our center.

Indications for liver transplantation (LT) in metabolic disease are evolving. We reviewed the US experience with primary LT for metabolic disease in the Scientific Registry for Transplant Recipients (October 1987 to June 2017) to determine the following: temporal changes in indications, longterm outcomes, and factors predicting survival. Patients were grouped by the presence of structural liver disease (SLD) and whether the defect was confined to the liver. There were 5996 patients who underwent LT for metabolic disease, 2354 (39.3%) being children. LT for metabolic disease increased in children but not in adults. Children experienced a 6-fold increase in LT for metabolic disease without SLD. Indications for LT remained stable in adults. Living donor liver transplantation increased between era 1 and era 3 from 5.6% to 7.6% in children and 0% to 4.5% in adults. Patient and graft survival improved with time. The latest 5-year patient survival rates were 94.5% and 81.5% in children and adults, respectively. Outcomes were worse in adults and in those with extrahepatic disease (P

Pediatric intestinal transplantation has moved from the theoretic to an actual therapy for children with irreversible intestinal failure who are suffering from complications of total parenteral nutrition. Owing to significant advancement in the management of intestinal failure and prevention of parenteral nutrition-related complications that have led to reduction in incidence of parenteral nutrition-associated liver disease and have improved intestinal adaptation, the indications for intestinal transplantation are evolving. Long-term outcomes have improved, but challenges in long-term graft function owing to chronic rejection and immunosuppressant-related complications remain the major opportunities for improvement.

Background The prevalence of atrial fibrillation (AF) in patients undergoing renal (RT) or liver transplantation (LT) has increased during the last decades. Yet, there is still uncertainty on the association between AF and patient and graft survival. Methods Multiple electronic databases were searched using various combinations of keywords and MeSH terms pertinent to the exposure (AF), and outcomes (graft and patient survival). Randomized or quasi-randomized controlled studies, cohort and case-control studies on adults with documented AF undergoing RT or LT were included. The quality of studies was assessed using the Newcastle-Ottawa Assessment Scale. When appropriate, data on the primary and secondary outcomes were pooled in a meta-analysis using the random-effect model. The Odds ratio was used for patients undergoing LT and the hazard ratio was used for patients who underwent renal transplantation. Results A total of 50,362 publications were identified. Six studies, with a total of 136,331 patients, satisfied the inclusion criteria. LT was performed on 2861 patients and RT was performed on 133,470 recipients. Overall, AF affected 6652 (4.8%) transplant recipients. Among them, 153 received a LT and 6499 underwent RT. The OR for mortality after LT was 2.375 (95% CI; 1.532–3.682) (P = 0.000) in AF(+) recipients and the HR was 1.859 (95% CI; 1.031–3.354) (P = 0.039) after RT. The OR for graft loss in AF(+) after LT r was 1.088 (95% CI; 0.311–3.804) (P = 0.894) and the HR for graft loss was 1.632 (95% CI; 1.200–2.218) (P = 0.002) after RT. Conclusions To the best of our knowledge, this is the first systematic review and meta-analysis to explore the association between AF and patient and graft survival after RT or LT. Our findings suggest that the presence of AF is associated with inferior patient survival. For renal transplant recipients, AF is also associated with inferior graft survival.

Background: Recent studies have reported a significant decrease in wound problems and hospital stay in obese patients undergoing renal transplantation by robotic-assisted minimally invasive techniques with no difference in graft function. Objective: Due to the lack of cost-benefit studies on the use of robotic-assisted renal transplantation versus open surgical procedure, the primary aim of our study is to develop a Markov model to analyze the cost-benefit of robotic surgery versus open traditional surgery in obese patients in need of a renal transplant. Methods: Electronic searches will be conducted to identify studies comparing open renal transplantation versus robotic-assisted renal transplantation. Costs associated with the two surgical techniques will incorporate the expenses of the resources used for the operations. A decision analysis model will be developed to simulate a randomized controlled trial comparing three interventional arms: (1) continuation of renal replacement therapy for patients who are considered non-suitable candidates for renal transplantation due to obesity, (2) transplant recipients undergoing open transplant surgery, and (3) transplant patients undergoing robotic-assisted renal transplantation. TreeAge Pro 2017 R1 TreeAge Software, Williamstown, MA, USA) will be used to create a Markov model and microsimulation will be used to compare costs and benefits for the two competing surgical interventions. Results: The model will simulate a randomized controlled trial of adult obese patients affected by end-stage renal disease undergoing renal transplantation. The absorbing state of the model will be patients' death from any cause. By choosing death as the absorbing state, we will be able simulate the population of renal transplant recipients from the day of their randomization to transplant surgery or continuation on renal replacement therapy to their death and perform sensitivity analysis around patients' age at the time of randomization to determine if age is a critical variable for cost-benefit analysis or cost-effectiveness analysis comparing renal replacement therapy, robotic-assisted surgery or open renal transplant surgery. After running the model, one of the three competing strategies will result as the most cost-beneficial or cost-effective under common circumstances. To assess the robustness of the results of the model, a multivariable probabilistic sensitivity analysis will be performed by modifying the mean values and confidence intervals of key parameters with the main intent of assessing if the winning strategy is sensitive to rigorous and plausible variations of those values. Conclusions: After running the model, one of the three competing strategies will result as the most cost-beneficial or cost-effective under common circumstances. To assess the robustness of the results of the model, a multivariable probabilistic sensitivity analysis will be performed by modifying the mean values and confidence intervals of key parameters with the main intent of assessing if the winning strategy is sensitive to rigorous and plausible variations of those values. [JMIR Res Protoc 2018;7(3):e74]

BACKGROUND Recent studies have reported a significant decrease in wound problems and hospital stay in obese patients undergoing renal transplantation by robotic-assisted minimally invasive techniques with no difference in graft function. OBJECTIVE Due to the lack of cost-benefit studies on the use of robotic-assisted renal transplantation versus open surgical procedure, the primary aim of our study is to develop a Markov model to analyze the cost-benefit of robotic surgery versus open traditional surgery in obese patients in need of a renal transplant. METHODS Electronic searches will be conducted to identify studies comparing open renal transplantation versus robotic-assisted renal transplantation. Costs associated with the two surgical techniques will incorporate the expenses of the resources used for the operations. A decision analysis model will be developed to simulate a randomized controlled trial comparing three interventional arms: (1) continuation of renal replacement therapy for patients who are considered non-suitable candidates for renal transplantation due to obesity, (2) transplant recipients undergoing open transplant surgery, and (3) transplant patients undergoing robotic-assisted renal transplantation. TreeAge Pro 2017 R1 TreeAge Software, Williamstown, MA, USA) will be used to create a Markov model and microsimulation will be used to compare costs and benefits for the two competing surgical interventions. RESULTS The model will simulate a randomized controlled trial of adult obese patients affected by end-stage renal disease undergoing renal transplantation. The absorbing state of the model will be patients' death from any cause. By choosing death as the absorbing state, we will be able simulate the population of renal transplant recipients from the day of their randomization to transplant surgery or continuation on renal replacement therapy to their death and perform sensitivity analysis around patients' age at the time of randomization to determine if age is a critical variable for cost-benefit analysis or cost-effectiveness analysis comparing renal replacement therapy, robotic-assisted surgery or open renal transplant surgery. After running the model, one of the three competing strategies will result as the most cost-beneficial or cost-effective under common circumstances. To assess the robustness of the results of the model, a multivariable probabilistic sensitivity analysis will be performed by modifying the mean values and confidence intervals of key parameters with the main intent of assessing if the winning strategy is sensitive to rigorous and plausible variations of those values. CONCLUSIONS After running the model, one of the three competing strategies will result as the most cost-beneficial or cost-effective under common circumstances. To assess the robustness of the results of the model, a multivariable probabilistic sensitivity analysis will be performed by modifying the mean values and confidence intervals of key parameters with the main intent of assessing if the winning strategy is sensitive to rigorous and plausible variations of those values.

Insulinoma is a rare pancreatic neuroendocrine tumor that is usually described as benign, sporadic, and very small (

GVHD as a complication of SOT presents both a diagnostic and therapeutic challenge. Typically affecting the skin, gastrointestinal tract, and liver, GVHD occurs when donor lymphocytes engrafted in recipient tissues are activated by host antigen-presenting cells resulting in cytokine release and donor cell-mediated cytotoxicity to host tissue. Here, we describe a 5-year-old girl who developed fatal, refractory GVHD after isolated intestinal transplantation when recipient immune cells failed to repopulate the allograft in the setting of CMV viremia. Persistence of the donor immune cells in the allograft mucosa, rather than engraftment in the recipient bone marrow, likely perpetuated this refractory GVHD. Early diagnosis and intervention are critical to reduce morbidity and mortality. Thus, periodic monitoring of peripheral blood and allograft mucosal chimerism with sensitive detection methods may allow early detection and potentially curative enterectomy in similar cases of refractory GVHD.