Search

Donor–recipient matching is a highly individualized and complex component of solid organ transplantation. Flowcytometry crossmatching (FC-XM) is an integral step in the matching process that is used to detect pre-formed deleterious anti-donor immunoglobulin. Despite high sensitivity in detecting cell-bound immunoglobulin, FC-XM is not able to determine the source or function of immunoglobulins detected. Monoclonal antibody therapeutic agents used in a clinic can interfere with the interpretation of FC-XM. We combined data from the prospectively maintained Antibody Society database and Human Protein Atlas with a comprehensive literature review of PubMed to summarize known FC-XM-interfering antibody therapeutics and identify potential interferers. We identified eight unique FC-XM-interfering antibody therapeutics. Rituximab (anti-CD20) was the most-cited agent. Daratumuab (anti-CD38) was the newest reported agent. We identified 43 unreported antibody therapeutics that may interfere with FC-XM. As antibody therapeutic agents become more common, identifying and mitigating FC-XM interference will likely become an increased focus for transplant centers.

The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013).Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/5 cm and 39.1% in NoDS/5 cm, P 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P 0.001).In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.

OBJECTIVE The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). BACKGROUND LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study. METHODS Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression. RESULTS Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil-lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67). CONCLUSIONS For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.

Substantial technological advances in mechanical circulatory support have caused a shift in the management of end-stage heart failure. From the 1970s through the 1990s, heterotopic heart transplantation was routinely performed in patients in whom orthotopic transplantation was likely to fail. Heterotopic heart transplantation is now performed less often because modern mechanical circulatory assist devices are routinely used as bridges to orthotopic transplantation; regardless, the operation has helped numerous patients who would not otherwise have received adequate allografts. We describe the case of a man with idiopathic nonischemic cardiomyopathy who, at age 17, was given an ABO- and size-matched heterotopic allograft that was a complete human leukocyte antigen mismatch. The graft functioned normally for 20 years until the patient had a myocardial infarction that necessitated placement of a coronary artery stent. Subsequent treatments involved many interventions, including insertion of an intra-aortic balloon pump, medical therapy for heart failure, implantation of a total artificial heart, and, ultimately, orthotopic transplantation. To our knowledge, our patient is the longest surviving recipient of a heterotopic heart transplant, with a remarkable 25-year graft survival despite poor histocompatibility and an almost complete lack of native heart function. The strategies used for his treatment make him a living case study that can add valuable information to the history of cardiac support.

Background The aim of this study is to describe the incidence and impact of reoperation following pediatric liver transplantation, as well as the indications and risk factors for these complications. Methods All primary pediatric liver transplants performed at our institution between January 2012 and September 2016 were reviewed. A reoperative complication was defined as a complication requiring return to the operating room within 30 days or the same hospital admission as the transplant operation, excluding retransplantation. Results Among the 144 pediatric liver transplants performed during the study period, 9% of the recipients required reoperation. The most common indications for reoperation were bleeding and bowel complications. There was no significant difference in the graft survival of patients with a reoperation and those without a reoperation (p = 0.780), but patients with a reoperation had a significantly longer hospital length of stay (median of 39 days vs. 11 days, p = 0.001). Variant donor arterial anatomy, transplant operative time, intraoperative blood loss, transfusion volume of packed red blood cells or cell saver per weight, and transfusion with fresh frozen plasma, platelets, or cryoprecipitate were significantly associated with reoperation upon univariable logistic regression, but none of these risk factors remained statistically significant upon multivariable regression. Conclusion At our institution, reoperation did not significantly impact graft survival. We identified variant donor arterial anatomy, transplant operative time, intraoperative blood loss, transfusion volume of packed red blood cells or cell saver per weight, and transfusion with fresh frozen plasma, platelets, or cryoprecipitate as risk factors for reoperation, although none of these risk factors demonstrated independent association with reoperation in a multivariable model. Type of study Prognosis Study. Level of evidence Level III.

To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC).Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited.Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013).Compared with 747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs 85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P0.001; 4+ LRTs: HR 2.5, P0.001), and unfavorable waitlist alphafetoprotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated patients achieving complete pathologic response (cPR) had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P0.001) compared with both untreated patients (69%; P = 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039), who demonstrated increased recurrence compared with untreated patients in multivariate analysis controlling for pretransplant and pathologic factors (HR 1.32, P = 0.044).Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates.

Low case volume has been associated with poor outcomes in a wide spectrum of procedures. Our objective was to study the association of low case volume and worse outcomes in pediatric heart transplant centers, taking the novel approach of including waitlist outcomes in the analysis. We studied a cohort of 6482 candidates listed in the Organ Procurement and Transplantation Network for pediatric heart transplantation between 2002 and 2014; 4665 (72%) of the candidates underwent transplantation. Candidates were divided into groups according to the average annual transplantation volume of the listing center during the study period: more than 10, six to 10, three to five, or fewer than three transplantations. We used multivariate Cox regression analysis to identify independent risk factors for waitlist and posttransplantation mortality. Of the 6482 candidates, 24% were listed in low-volume centers (fewer than three annual transplantations). Of these listed candidates in low-volume centers, only 36% received a transplant versus 89% in high-volume centers (more than 10 annual transplantations) (p < 0.001). Listing at a low-volume center was the most significant risk factor for waitlist death (hazard ratio [HR] 4.5, 95% confidence interval [CI] 3.5-5.7 in multivariate Cox regression and HR 5.6, CI 4.4-7.3 in multivariate competing risk regression) and was significant for posttransplantation death (HR 1.27, 95% CI 1.0-1.6 in multivariate Cox regression). During the study period, one-fourth of pediatric transplant candidates were listed in low-volume transplant centers. These children had a limited transplantation rate and a much greater risk of dying while on the waitlist.

Background Advances in critical care prolong survival in children with liver failure, allowing more critically ill children to undergo orthotopic liver transplantation (OLT). In order to justify the use of a scarce donor resource and avoid futile transplants, we sought to determine survival in children who undergo OLT while receiving pre-OLT critical care. Study Design We analyzed 13,723 pediatric OLTs using the United Network for Organ Sharing (UNOS) database from 1987 to 2015, including 6,746 recipients in the Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease (MELD/PELD) era (2002 to 2015). There were 1,816 recipients (26.9%) admitted to the ICU at the time of transplantation. We also analyzed 354 pediatric OLT recipients at our center from 2002 to 2015, one of the largest institutional experiences. Sixty-five recipients (18.3%) were admitted to the ICU at the time of transplantation. Kaplan-Meier, volume threshold, and multivariable analyses were performed. Results Patient survival improved steadily over the study period, (66% 1-year survival in 1987 vs 92% in 2015; p Conclusions This analysis demonstrates that the use of advanced critical care in children and infants with liver failure is justified because OLT can be performed on the sickest children and acceptable outcomes achieved. It is an appropriate use of a scarce donor allograft in a child who would otherwise succumb to a terminal liver disease.

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.

Reports on the long-term outcomes and immunosuppressive regimens of multiorgan transplant patients are limited. Here, we describe a patient with cystic fibrosis complicated by multiorgan failure who was successfully treated with combined liver lung transplant and delayed kidney transplant, resulting in excellent outcomes. Delayed kidney transplant was done to reduce the operative stress of a single procedure, giving time for adequate resuscitation and weaning from vasopressors. Our patient's postoperative course was complicated by post-transplant lymphoproliferative disease, which was successfully treated with rituximab and reduced dosages of immunosuppression.

Kidney transplantation is the treatment of choice in pediatric patients with end-stage renal disease. This population presents technical challenges particularly in those less than 20 kg due to anomalous anatomy, vascular access issues prior to transplantation, and a generally small size for age. Standard allograft outflow is usually achieved utilizing the iliac veins or IVC. When use of the iliocaval system is not feasible, alternative anastomosis must be considered. Herein, we report a case of a pediatric kidney transplantation where successful allograft outflow was achieved using the SMV when he was found to have an atretic IVC intraoperatively. In this setting, use of the portal system was required to achieve adequate allograft outflow. We created a donor iliac graft for added length to anastomose the renal vein with the SMV. In the setting of IVC occlusion with poor drainage, we utilized a patent vessel with larger caliber for outflow to reduce the risk of high venous pressures, allograft failure, venous rotation, and thrombosis. We conclude that the SMV may serve as an alternative outflow tract in the small pediatric patient and provides the vessel caliber needed to reduce the risks of complications.

Summary:. In the fall of 2017, Hurricane Harvey, one of the most costly hurricanes in American history, ravaged the Texas Gulf Coast, interrupting basic sanitation systems to hundreds of thousands of Texas residents. In the aftermath of Hurricane Harvey, our Houston hospitals noted an uptick in the incidence of cases of mucormycosis. Among the most vulnerable and affected have been immunocompromised transplant recipients. Here, we describe the successful management of 2 patients with atypical presentations of mucormycosis, 2 cutaneous infections after liver transplantation. Our comprehensive treatment strategy based upon guidelines and experience included coordinating aggressive surgical and medical therapies. We discuss our approach to surgical management including the extent and frequency of debridement, the methods of assessing disease-free margins, and minimizing the morbidity of radical debridement with temporary coverage and forethought to long-term reconstruction. Additionally, we describe the concurrent medical management, including type, route, and duration of antifungal therapy, minimizing suppression of the innate immune system, and optimizing the wound healing environment through maintaining nutritional status.

Background Hepatitis C virus (HCV) infection is thought to be associated with immune dysfunction. We hypothesized that HCV status would be associated with increased infectious complications in the surgical intensive care unit (SICU). Methods All patients admitted to our SICU between 2008 and 2012 were included. We evaluated 90-day mortality and infectious complications in the SICU. Multivariate logistic regression was performed to identify predictors of infectious complications and 90-day mortality. Results A total of 1,941 patients were included. The HCV-positive group had a higher overall incidence of infectious complications (25% vs 18%), particularly ventilator-associated pneumonia (VAP) and bacteremia. The increased incidences of VAP and bacteremia persisted when cirrhotic patients were excluded. Prolonged intubation (Odds Ratio [OR] = 2.1), abdominal surgery (OR = 1.6), and model for end-stage liver disease ≥ 15 (OR = 1.4) were independent predictors of SICU infectious complications. Conclusions The HCV-positive group had an increased incidence of infectious complications in the SICU, particularly VAP and bacteremia. This effect persisted when cirrhotic patients were excluded.

The initial experience with ABO incompatible (ABOi) orthotopic liver transplantations (OLTs) was dismal. In the current study, we investigated whether ABOi pediatric OLTs could achieve acceptable patient outcomes. The option for ABOi transplantation is vital because critically ill children have limited access to donor liver allografts.Kaplan-Meier and multivariate Cox analysis was performed on data collected from 13,179 pediatric OLT recipients in the United Network for Organ Sharing database, including 540 ABOi recipients. We also analyzed 18 pediatric recipients of ABOi OLTs at Texas Children's Hospital. Recipients were divided into 2 groups: transplanted between 1987 to 2002 (remote era) and 2002 to 2013 (modern era).Analysis revealed 4 main points. First, there was a significant (p0.01) improvement in ABOi OLT survival in the modern era. Second, threshold analysis revealed superior outcomes (p0.01) for OLT recipients younger than 2 years of age. Third, survival outcomes for ABOi and ABO-identical OLTs were the same for recipients younger than 2 years: ABOi was 91.8% (1 year) and 88.4% (5 year), and ABO identical was 91.5% (1 year) and 86.7% (5 year) (p = 0.94). Lastly, we found identical OLT results when analyzing our own institutional experience. To date, there has been a 92.9% survival rate in the modern era compared with 75% in the remote era. All recipients younger than 2 years (n = 9) are still alive, compared with 78% of those older than 2 years.This analysis revealed a significant improvement in the survival of ABOi liver transplant recipients in the modern era. Importantly, ABOi liver transplantation can be performed in recipients younger than 2 years of age with equivalent outcomes compared with ABO-identical recipients.

The purposes of this study were to analyze the effects of an ERS on time to transplantation and to describe our center's experience with OLT for HB. Patients who received OLT for HB between 2000 and 2013 were included. Patient and allograft characteristics, chemotherapy regimens, and prior surgical therapies were examined. The interval between diagnosis and OLT prior to and following the institution of an ERS for transplant was compared. Survival and tumor recurrence were analyzed. Nineteen patients received OLT for HB (mean age 33 months). All children received grafts from deceased donors. Two patients underwent prior resections. Tumor recurred in four patients (21.1%). Both patients who received salvage transplants experienced post-OLT recurrence. Three of the four recurrences occurred in spite of adjuvant chemotherapy. There were three deaths: two from metastatic disease. One- and five-yr survivals were 86.1% and 73.8%. After the institution of the ERS, the mean interval between tissue diagnosis and OLT was significantly reduced. Our series of 19 patients demonstrates a 21% recurrence of HB following OLT despite chemotherapy. Five-yr survival reached 73.8%. A system of early referral can effectively reduce times between diagnosis and transplant.

Highlights • Choledochal cysts are congenital biliary tract dilations that may have vague symptoms, making them difficult diagnoses to make. • Cyst resection is the standard of care due to the increased risk of cholangiocarcinoma. • Efficient diagnosis and referral to an experienced hepatobiliary center is crucial., Introduction Choledochal cysts are rare congenital dilations of the biliary tree that can present with non-specific symptoms such as abdominal pain, jaundice, cholelithiasis and pancreatitis. Although most commonly identified in children, they can be found in the adult population. However, because of the non-specific symptoms, this diagnosis may be difficult to make in the adult. A physician therefore must keep this diagnosis within their differential, as it may arise in an unexpected patient population who may present with a convoluted work up. Case presentation In this report, we present the case of a 50-year-old African American woman with recurrent cholelithiasis, cholangitis and eventually obstructive jaundice despite undergoing a laparoscopic cholecystectomy six years prior. Her only work up at that point was a right upper quadrant ultrasound revealing gallbladder sludge, which led to her cholecystectomy. It was the persistence of her symptoms—abdominal pain, cholangitis and obstructive jaundice—previously attributed to chronic cholecystitis and choledocholithiasis that warranted further work up. After multiple physician visits, she was referred to our academic center after an ERCP was performed and she was found to have a dilation of her common bile duct consistent with a choledochal cyst. Furthermore, the ERCP identified multiple bile duct stones within the cyst. This was not identified on her original ultrasound or prior ERCPs. The patient underwent a complete cyst excision with Roux-en-Y hepaticojejunostomy and did well post-operatively. Discussion This report illustrates how choledochal cysts can be an elusive diagnosis, but may present with repeated infections, recurrent biliary stones, and biliary obstruction despite a cholecystectomy. Had she an MRCP prior to her cholecystectomy, she would likely have avoided multiple surgeries, and years of persistent symptoms. Choledochal cysts are associated with an increased risk of biliary malignancy and therefore cyst excision is the standard of care. Conclusion Although rare, physicians need to keep this diagnosis in mind, and be aware of the clinical and imaging findings consistent with a choledochal cyst in order to facilitate appropriate work up, referral and treatment.

The replaced common hepatic artery (RCHA) is an uncommon arterial anomaly that, when present, makes hepatic arterial reconstruction during liver transplantation technically challenging. At our institution, the reconstruction of the recipient RCHA consists of 2 techniques that include either an infrarenal donor iliac artery aortic conduit or a direct donor celiac trunk anastomosis to the proximal RCHA. Our experience demonstrates that the direct anastomosis to the RCHA provides a reliable source of arterial inflow, allows preservation of the recipient arterial anatomy, and minimizes the dissection required to create an infrarenal aortic conduit. Between September 1998 and April 2019, we performed 1782 liver transplants (1230 adults, >18 years; 552 pediatric

Children undergoing liver transplantation are at a significant risk for intraoperative hemorrhage and thrombotic complications, we aim to identify novel risk factors for massive intraoperative blood loss and transfusion in PLT recipients and describe its impact on graft survival and hospital LOS. We reviewed all primary PLTs performed at our institution between September 2007 and September 2016. Data are presented as n (%) or median (interquartile range). EBL was standardized by weight. Massive EBL and MT were defined as greater than the 85th percentile of the cohort. 250 transplantations were performed during the study period. 38 (15%) recipients had massive EBL, and LOS was 31.5 (15-58) days compared to 11 (7-21) days among those without massive EBL (P < 0.001). MT median LOS was 34 (14-59) days compared to 11 (7-21) days among those without MT (P = 0.001). Upon backward stepwise regression, technical variant graft, operative time, and transfusion of FFP, platelet, and/or cryoprecipitate were significant independent risk factors for massive EBL and MT, while admission from home was a protective factor. Recipient weight was a significant independent risk factor for MT alone. Massive EBL and MT were not statistically significant for overall graft survival. MT was, however, a significant risk factor for 30-day graft loss. PLT recipients with massive EBL or MT had significantly longer LOS and increased 30-day graft loss in patients who required MT. We identified longer operative time and technical variant graft were significant independent risk factors for massive EBL and MT, while being admitted from home was a protective factor.

Background The field of transplantation is shifting outcome priorities from 1-year survival to more comprehensive metrics including transplant rate and waitlist mortality. Identifying disenfranchised candidates (high waitlist death risk, low transplantation chance) can be a focus to improve outcomes. Methods Given the waitlist outcomes (continued waiting, death, and transplantation), we aimed to identify factors predicting the likelihood candidates would undergo transplant or death by performing multivariate competing risk analyses of 121 198 candidates in the United Network for Organ Sharing database. We incorporated these probabilities (likelihood of transplantation and waitlist death) into the Transplant Index (TI) to identify disenfranchised candidates (high likelihood of death, low likelihood of transplantation). Results Half of the patients had low incidences of death and transplantation within 90 days (TI-inactive). The remaining were stratified into 10 groups within a predictive index, the TI. Low TI groups (TI 10, 20, 30) had 90-day transplant rates of 50.8%, 41.6%, and 39.8% respectively, and their respective 90-day death rates were 22.8%, 15.1%, and 10.9%. High TI groups (TI 80, 90, >90) had 90-day transplantation rates of 53.7%, 64.3%, and 73.9%, respectively, and 90-day death rates of 5.9%, 6.5%, and 6.7% respectively. As TI increased, the likelihood of transplantation increased and that of death decreased. Low-TI groups represent the disenfranchised candidates. Conclusions The TI identifies disenfranchised candidates on the adult liver transplant waitlist. This is the subgroup that would benefit the most from efforts to increase access to transplantation.

Mesenteric ischemia can be difficult to diagnose without a high degree of suspicion because it presents in a variety of ways. Visceral vascular collaterals between the fore- and midgut often provide protection against ischemia; however, the presence of anatomic variations, such as celiomesenteric trunk, can undermine the expected redundancy. Misdiagnosis can result in prolonged suffering or death, as evidenced in 2 of our patients with celiomesenteric trunk. The first patient with chronic mesenteric ischemia was diagnosed in the clinic and underwent successful surgical correction; the other had overwhelming, acute mesenteric ischemia, which resulted in death. Our cases show that successful diagnosis and management of mesenteric ischemia require astute interpretation of radiologic images.

An index that predicts liver allograft discard can effectively grade allografts and can be used to preferentially allocate marginal allografts to aggressive centers. The aim of this study is to devise an index to predict liver allograft discard using only risk factors available at the time of initial DonorNet offer.Using univariate and multivariate analyses on a training set of 72 297 deceased donors, we identified independent risk factors for liver allograft discard. Multiple imputation was used to account for missing variables.We identified 15 factors as significant predictors of liver allograft discard; the most significant risk factors were: total bilirubin10 mg/dL (odds ratio [OR], 25.23; confidence interval [CI], 17.32-36.77), donation after circulatory death (OR, 14.13; CI, 13.30-15.01), and total bilirubin 5 to 10 mg/dL (OR, 7.57; 95% CI, 6.32-9.05). The resulting Discard Risk Index (DSRI) accurately predicted the risk of liver discard with a C statistic of 0.80. We internally validated the model with a validation set of 37 243 deceased donors and also achieved a 0.80 C statistic. At a DSRI at the 90th percentile, the discard rate was 50% (OR, 32.34; CI, 28.63-36.53), whereas at a DSRI at 10th percentile, only 3% of livers were discarded.The use of the DSRI can help predict liver allograft discard. The DSRI can be used to effectively grade allografts and preferentially allocate marginal allografts to aggressive centers to maximize the donor yield and expedite allocation.

Stress-induced heart failure, also known as Broken Heart Syndrome or Takotsubo Syndrome, is a phenomenon characterized as rare but well described in the literature, with increasing incidence. While more commonly associated with postmenopausal women with psychiatric disorders, this entity is found in the postoperative patient. The nonischemic cardiogenic shock manifests as biventricular failure with significant decreases in ejection fraction and cardiac function. In a review of over 3000 kidney and liver transplantations over the course of 17 years within two transplant centers, we describe a series of 7 patients with Takotsubo Syndrome after solid organ transplantation. Furthermore, we describe a novel approach of successfully treating the transient, though potentially fatal, cardiogenic shock with a percutaneous ventricular assistance device in two liver transplant patients, while treating one kidney transplant patient medically and the remaining four liver transplant patients with an intra-aortic balloon pump. We describe our experience with Takotsubo’s Syndrome and compare the three modalities of treatment and cardiac augmentation. Our series is novel in introducing the percutaneous ventricular assist device as a more minimally invasive intervention in treating nonischemic heart failure in the solid organ transplant patient, while serving as a comprehensive overview of treatment modalities for stress-induced heart failure.

Objective The aim of this study was to assess improvements in long-term survival after liver transplant by analyzing outcomes in transplant recipients who survived beyond 1 year. Summary of background data Gains in short-term survival following liver transplantation have been gratifying. One-year survival in 1986 was 66% improved to over 92% in 2015. However, little is known about why long-term has not seen similar success. Methods We analyzed 111,568 recipients from 1987 to 2016 using the Kaplan-Meier method for time-to-event analysis and multivariable Cox regression. Results There were no significant gains in unadjusted long-term outcomes among 1-year survivors over the past 30 years. Only the time periods of 1987 to 1990 [hazard ratio (HR) 1.35, confidence interval CI) 1.28-1.42] and 1991 to 1995 (HR 1.17, CI 1.13-1.21) had a minor increase in risk compared with the period 2011 to 2016. Cause of death analysis suggests malignancy after transplantation is a growing problem and preventing recurrent hepatitis C with direct-acting antivirals (DDAs) may only have a limited impact. Furthermore, rejection leading to graft failure and death had a rare occurrence (1.7% of long-term deaths) especially when compared with the sequelae of long-term immunosuppression: malignancy (16.4%), nonrejection graft failure (9.8%), and infection (10.5%) (P Conclusion In stark contrast to short-term survival, there have been no appreciable improvements in long-term survival following liver transplantation among 1-year survivors. Long-term sequelae of immunosuppression, including malignancy and infection, are the most common causes of death. This study highlights the need for better long-term immunosuppression management.

Background The new Model for End-Stage Liver Disease includes serum sodium (MELD-Na). To evaluate its predictive power in non-transplant surgery, we analyzed emergency surgery outcomes of cirrhotic patients, hypothesizing that negative outcomes could be associated with discrete MELD-Na score thresholds. Methods Retrospective chart review was conducted of patients with cirrhosis undergoing emergency surgery at our institution from 2001 to 2013 (n = 85). Risk thresholds and predictors of peri-operative outcomes were identified using univariate and multivariate regression. Results MELD-Na scores of 19, 17, and 12 were identified as predictors of 30-day mortality (OR = 3.44), post-operative complications (OR = 3.08), and discharge to home (inverse relationship, OR = 0.31). Post-operative complications were independent negative predictors of discharge to home (OR = 0.21). Conclusion Although emergency surgery in patients with cirrhosis can be life-saving, knowledge of the significant peri-operative risk should drive decision-making, informed by the increased risk associated with these score thresholds. Further study is needed to establish definitive MELD-Na thresholds.

Risk analysis of cold ischemia time (CIT) in liver transplantation has largely focused on patient and graft survival. Posttransplant length of stay is a sensitive marker of morbidity and cost. We hypothesize that CIT is a risk factor for posttransplant prolonged length of stay (PLOS) and aim to conduct an hour-by-hour analysis of CIT and PLOS. We retrospectively reviewed all adult, first-time liver transplants between March 2002 and September 2016 in the United Network for Organ Sharing database. The 67,426 recipients were categorized by hourly CIT increments. Multivariate logistic regression of PLOS (defined as >30 days), CIT groups, and an extensive list of confounding variables was performed. Linear regression between length of stay and CIT as continuous variables was also performed. CIT 1-6 hours was protective against PLOS, whereas CIT >7 hours was associated with increased odds for PLOS. The lowest odds for PLOS were observed with 1-2 hours (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.45-0.92) and 2-3 hours (OR, 0.65; 95% CI, 0.55-0.78) of CIT. OR for PLOS steadily increased with increasing CIT, reaching the greatest odds for PLOS with 13-14 hours (OR, 2.05; 95% CI, 1.57-2.67) and 15-16 hours (OR, 2.06; 95% CI, 1.27-3.33) of CIT. Linear regression revealed a positive correlation between length of stay and CIT with a correlation coefficient of +0.35 (P < 0.001). In conclusion, post-liver transplant length of stay is sensitive to CIT, with a substantial increase in the odds of PLOS observed with nearly every additional hour of cold ischemia. We conclude that CIT should be minimized to protect against the morbidity and cost associated with posttransplant PLOS. Liver Transplantation 24 762-768 2018 AASLD.

Mesenchymal liver hamartomas are benign tumors that can cause life-threatening abdominal distension and carry a risk for malignant transformation. In this case report, we describe a 13-month-old male with Beckwith–Wiedemann Syndrome (BWS) who presented with multiple mesenchymal liver hamartomas causing severe intra-abdominal mass effect. Imaging revealed six large multi-locular cystic lesions, ranging from 3.8 to 8.9 cm in diameter. The large size and spread of the tumors necessitated liver transplantation for complete removal. The patient successfully underwent cadaveric piggyback liver transplantation at 25 months of age. He was alive at 16-month follow-up without evidence of tumor recurrence or graft rejection. Histological examination of the hepatic masses revealed mucinous epithelial lining and abundant hepatocytes in varying stages of differentiation, supporting the diagnosis of mesenchymal hamartoma. To the best of our knowledge, this is the first reported case of liver transplantation in a patient with BWS as definitive treatment for unresectable mesenchymal liver hamartoma.

Prolonged high fat feeding is associated with myocardial contractile dysfunction in rodents. However, epidemiological data do not necessarily support the concept that fat-enriched diets adversely affect cardiac function in humans. When fed in an ad libitum manner, laboratory rodents consume chow throughout the day. In contrast, humans typically consume food only during the awake phase. Discrepancies between rodent and human feeding behaviors led us to hypothesize that the time of day at which dietary lipids are consumed significantly influences myocardial adaptation. In order to better mimic feeding behavior in humans, mice were fed (either a control or high fat diet) only during the 12-hour dark phase (i.e., no food was provided during the light phase). We report that compared to dark phase restricted control diet fed mice, mice fed a high fat diet during the dark phase exhibit: 1) essentially normal body weight gain and energy balance; 2) increased fatty acid oxidation at whole body, as well as skeletal and cardiac muscle (in the presence of insulin and/or at high workloads) levels; 3) induction of fatty acid responsive genes, including genes promoting triglyceride turnover in the heart; 4) no evidence of cardiac hypertrophy; and 5) persistence/improvement of myocardial contractile function, as assessed ex vivo. These data are consistent with the hypothesis that ingestion of dietary fat only during the more active/awake period allows adequate metabolic adaptation, thereby preserving myocardial contractile function. This article is part of a Special Issue entitled "Focus on cardiac metabolism".

Careful management of immunosuppression is paramount to prevent acute rejection in kidney transplantation. We studied a cohort of 139,875 kidney transplant recipients from the Organ Procurement and Transplantation Network (OPTN) database between 2002 and 2013. We confirmed the analysis with a cohort of 35,277 who received thymoglobulin induction with tacrolimus maintenance, and a third cohort of 12,161 recipients who received basiliximab induction with tacrolimus maintenance. We performed multivariate logistic regression analyses on data from all three cohorts and identified independent risk factors for treated acute rejection at 1 year. Recipient age was a robust risk factor for rejection in all three cohorts in a dose response pattern. Young age (18-25 years) was among the strongest risk factors for rejection in all three cohorts; thymoglobulin cohort: OR 1.87 (1.59-2.19); basiliximab cohort: OR 2.41 (1.89-3.05); and inclusive cohort: OR 1.97 (1.83-2.12). The opposite was true for old age (65-69 years); thymoglobulin cohort: OR 0.69 (0.59-0.81); basiliximab cohort: OR 0.77 (0.62-0.96); and inclusive cohort: OR 0.75 (0.70-0.80). This study is unique because it is the largest and most comprehensive multivariate analysis that demonstrates recipient age is a robust risk factor for acute rejection in an inverse dose response pattern.

Background Careful management of induction and maintenance of immunosuppression is paramount to prevent acute rejection in liver transplantation. A methodical analysis of risk factors for acute cellular rejection may provide a more comprehensive method to profile the immunologic risk of candidates. Methods Using registry data from the Organ Procurement and Transplantation Network (OPTN), we identified 42,508 adult recipients who underwent orthotopic liver transplant (OLT) between 2002 and 2013. We excluded recipients with a blank entry for treated rejection. We analyzed this all inclusive cohort in addition to a subset of 27,493 patients with just tacrolimus immunosuppression. Multivariate logistic regression was used on both cohorts and identified independent risk factors for treated acute rejection at one year. Results Recipient age (reference group was 40 to 60 years) was a dominant risk factor for rejection in both cohorts and had a dose response relationship. The strongest risk factors in the inclusive cohort were: age 18–25 (OR 2.20), age 26–29 (OR 2.03), and primary biliary cholangitis (OR 1.55). The most protective factors were age 70 and older (OR 0.68), and age 65–69 (OR 0.70). The rates of rejection had a similar pattern. Conclusions Although prior studies have suggested age as a risk factor for rejection in liver transplantation, this is the first study of national-level data to demonstrate a robust dose dependent relationship between age and risk for rejection at one year. Clinicians should place significant weight on recipient age when they assess their recipients for the immunologic risk of rejection.

Background Severe geographic inequities in liver transplantation have persisted for years. Previous investigators have demonstrated 90-day transplant rates varying from 14% to 82% and death rates varying from 18% to 86%. The aim of this analysis was to utilize a robust multivariate analysis to investigate whether geographic inequities affected the length of stay after liver transplantation. Methods We conducted a unique Kaplan-Meier analysis with the event being discharge from the hospital and length of stay as the time to the event, using a cohort of 66 674 recipients listed in the UNOS database from 2002 to 2016. Multivariate Cox regression using 43 covariates was used for time-to-event analysis. Results Region 9 (0.82; CI 0.79-0.85), Region 2 (0.85; CI 0.83-0.88), and Region 10 (0.96; CI 0.93-0.99) were statistically significant factors for prolonged hospital stay. The following covariates were the most significant factors for prolonged hospital stay: serum sodium >150 mEq/L (0.70; CI 0.62-0.78), ICU admission (0.77; CI 0.74-0.80), hospital admission (0.81; 0.79-0.83), region 9 (0.82; CI 0.79-0.85), and ventilator dependence (0.82; CI 0.76-0.88). Conclusion In this analysis, we demonstrate regional disparities in hospital length of stay that are significant in robust multivariable Cox regression analysis. We hope the transplant community will take immediate measures to correct geographic inequities.

Background Excess caloric intake is strongly associated with the development of increased adiposity, glucose intolerance, insulin resistance, dyslipidemia, and hyperleptinemia (i.e., the cardiometabolic syndrome). Research efforts have focused attention primarily on the quality (i.e., nutritional content) and/or quantity of ingested calories as potential causes for diet-induced pathology. Despite growing acceptance that biological rhythms profoundly influence energy homeostasis, little is known regarding how the timing of nutrient ingestion influences development of common metabolic diseases. Objective To test the hypothesis that the time of day at which dietary fat is consumed significantly influences multiple cardiometabolic syndrome parameters. Results We report that mice fed either low or high fat diets in a contiguous fashion during the 12 hour awake/active period adjust both food intake and energy expenditure appropriately, such that metabolic parameters are maintained within a normal physiologic range. In contrast, fluctuation in dietary composition during the active period (as occurs in humans) markedly influences whole body metabolic homeostasis. Mice fed a high fat meal at the beginning of the active period retain metabolic flexibility in response to dietary challenges later in the active period (as revealed by indirect calorimetry). Conversely, consumption of high fat meal at the end of the active phase leads to increased weight gain, adiposity, glucose intolerance, hyperinsulinemia, hypertriglyceridemia, and hyperleptinemia (i.e., cardiometabolic syndrome) in mice. The latter perturbations in energy/metabolic homeostasis are independent of daily total or fat-derived calories. Conclusions The time-of-day at which carbohydrate versus fat is consumed markedly influences multiple cardiometabolic syndrome parameters.

An index to predict hospital length of stay after liver transplantation could address unmet clinical needs. Length of stay is an important surrogate for hospital costs and efforts to limit stays can preserve our healthcare resources. Here, we devised a scoring system that predicts hospital length of stay following liver transplantation. We used univariate and multivariate analyses on 73,635 adult liver transplant recipient data and identified independent recipient and donor risk factors for prolonged hospital stay (> 30 days). Multiple imputation was used to account for missing variables. We identified 22 factors as significant predictors of prolonged hospital stay, including the most significant risk factors: Intensive Care Unit (ICU) admission (OR 1.75, CI 1.58-1.95) and previous transplant (OR 1.60, CI 1.47-1.75). The Length of Stay (LOS) index assigns weighted risk points to each significant factors in a scoring system to predict prolonged hospital stay after liver transplantation with a c-statistic of 0.75. The LOS index demonstrated good discrimination across the entire population, dividing the cohort into tertiles, which had odds ratios of 2.25 (CI 2.06-2.46) and 7.90 (7.29-8.56) for prolonged hospital stay (> 30 days). The LOS index utilizes 22 significant donor and recipient factors to accurately predict hospital length of stay following liver transplantation. The index further demonstrates the basis for a clear clinical recommendation to mitigate risk of long hospitalization by minimizing cold ischemia time. This article is protected by copyright. All rights reserved.

The health benefits of pomegranate consumption have recently received considerable scientific focus, with most studies examining fruit and/or juice consumption. Pomegranate seed oil (POMo) is a rich source of 9-cis, 11-trans conjugate linolenic acid (CLA), which may offset the side-effects associated with weight gain. Male, wild-type CD-1 mice were divided into one of three groups (twenty per group): high-fat (HF), HF+seed oil (HF+POMo) or lean control (LN). In HF and HF+POMo, mice were provided access ad libitum to a high-fat chow (60 % of energy from fat). HF+POMo was supplemented with 61·79 mg POMo/d. LN consumed a restricted low-fat (10 % of energy from fat) chow to maintain body weight within 5 % of initial weight. Plasma was analysed for biomarkers associated with cholesterol profile (total cholesterol, HDL and TAG), glucose sensitivity (glucose and insulin), adipose tissue accumulation (leptin and adiponectin) and systemic low-grade inflammation (C-reactive protein and haptoglobin). The key findings of this study were that weight gain was associated with an increase in biomarkers of cholesterol profile, glucose sensitivity, adipose tissue accumulation and systemic low-grade inflammation (P P

Carbohydrate consumption during strenuous aerobic exercise reportedly minimizes post-exercise suppression of the innate immune system. One of the most common measurements of innate immunity is natural killer cell activity (NKCA). It is not known whether actual carbohydrate consumption or merely the knowledge of carbohydrate consumption mediates alteration in NKCA. The purpose of the present investigation was to determine if knowledge of carbohydrate beverage could result in alteration of RPE and NKCA, independent of actual carbohydrate intake. We recruited 11 male and female endurance athletes and randomly assigned them to either a correct or false knowledge of carbohydrate intake, such that in the false group, subjects were informed that they were receiving the carbohydrate beverage (CHO), but actually received a placebo (PLA) beverage. CHO and PLA beverages were matched to be similar in taste and appearance. Subjects completed 60 min of cycle ergometry (74% of VO2 peak). Venous blood samples were collected before (PRE), immediately after (POST), and 2 h after (2H) exercise and used to determine plasma glucose concentration, leukocyte total and differential counts, and NKCA. Data were statistically analyzed using a 3-factor analysis of variance (ANOVA) (p < 0.05). We did not find a significant effect of knowledge of drink type on leukocyte count, leukocyte differential, or NKCA. Drink type did not significantly alter leukocyte total, differential counts, or NKCA. There was a significant effect of exercise on NKCA. Knowledge of drink type does not alter innate immunity following exercise as assessed by leukocyte counts and NKCA.

Sensenbrenner syndrome, or cranioectodermal dysplasia, is a rare heterogeneic autosomal recessive disorder, affecting ~1 of 1 000 000 live births. The syndrome usually manifests within the first year of life and can present with progressive liver and renal involvement. For all Sensenbrenner patients, renal and liver diseases are the main contributors of morbidity and mortality. In this report, we present the case of a 7-year-old boy with congenital liver disease progressing to liver failure secondary to Sensenbrenner syndrome. For this patient, evidence of liver dysfunction was evident from 2 months of age and progressed to frank cirrhosis and severe portal hypertension with multiple episodes of life-threatening variceal bleeding by age 6. This report illustrates the capability of orthotopic liver transplantation as a viable therapy for those pediatric patients suffering from severe liver failure secondary to a congenital ciliopathy, such as Sensenbrenner syndrome. In fact, early emphasis should be placed on the renal and liver involvement associated with Sensenbrenner syndrome with particular consideration for early referral for transplantation in cases with severe disease. Although the condition is rare, clinicians should be aware of it and its association with fatal liver disease to facilitate appropriate evaluation and referral.

Drowning, a common cause of death in the pediatric population, is a potentially large donor pool for OLT. Anecdotally, transplant centers have deemed these organs high risk over concerns for infection and graft dysfunction. We theorized drowned donor liver allografts do not portend worse outcomes and therefore should not be excluded from the donation pool. We reviewed our single-center experience of pediatric OLTs between 1988 and 2015 and identified 33 drowned donor recipients. These OLTs were matched 1:2 to head trauma donor OLTs from our center. A chart review assessed postoperative peak AST and ALT, incidence of HAT, graft and recipient survival. Recipient survival at one year between patients with drowned donor vs head trauma donor allografts was not statistically significant (94% vs 97%, P=.63). HAT incidence was 6.1% in the drowned donor group vs 7.6% in the control group (P=.78). Mean postoperative peak AST and ALT was 683 U/L and 450 U/L for drowned donors vs 1119 U/L and 828 U/L in the matched cohort. These results suggest drowned donor liver allografts do not portend worse outcomes in comparison with those procured from head trauma donors.

Portosystemic shunts can serve as a bridge to liver transplantation in patients with end-stage liver disease by providing portal decompression to treat life-threatening variceal bleeding and prevent recurrent episodes until an organ becomes available. The conventional TIPS procedure, however, is technically challenging to perform in infants due to the small size of their intrahepatic vasculature. We report two cases of emergent creation of portosystemic shunts as a bridge to liver transplantation in infants with life-threatening variceal bleeding using a conventional TIPS technique in the first case and a percutaneous DIPS technique in the other. Both procedures were successful at reducing the portosystemic pressure gradient and preventing further variceal bleeds until a liver transplant could be performed. The novel percutaneous DIPS procedure is a valuable alternative to the conventional TIPS in infants, as it is better suited for small or challenging intrahepatic vascular anatomy.