Risk factors for renal dysfunction after isolated intestinal transplantation.

INTRODUCTION: Kidney dysfunction is a known complication of intestinal transplantation; however, the rate of development and risk factors for chronic kidney disease (CKD) remain poorly defined. METHODS: This was a single-center retrospective review of isolated adult intestinal allograft recipients from 2011 to 2019. Patients who died or experienced graft loss within 1-year or had a prior transplant were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation at 0-, 6- and 12-months post-transplant, and multivariable linear regression was performed to identify variables associated with adjusted eGFR at 1-year. Independent variables included age, ethnicity, BMI, history of diabetes/hypertension, vasopressor use, TPN and stoma days, urinary or bloodstream infections, intravenous contrast exposure, rejection, concomitant immunosuppression, and time above the therapeutic range of tacrolimus. Variables with a p < .1 in univariate analysis were considered for multivariable modeling. RESULTS: Thirty-three patients were included with a mean age of 43.9 ± 13.0. A mean 42.3% decline in eGFR was observed at 1-year post-transplant, with 15.2% of patients developing new stage 4/5 CKD. Factors associated with a greater decline in adjusted eGFR in the univariate model included increasing age, decreased BMI, stoma days, and vasopressor use. In the adjusted multivariable model patient age (ß = -.77, p < .01) and stoma days (ß = -.06, p < .01) remained significant. Tacrolimus and sirolimus exposure were not associated with decline in eGFR at 1 year. CONCLUSIONS: Renal dysfunction is common following intestinal transplantation. The need for stoma creation should be carefully considered, and reversal should be performed when feasible for renal protection.

Impact of the acuity circle model for liver allocation on multivisceral transplant candidates.

Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018-2020) and post-AC (2020-2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96-74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15-0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.

Candida auris Pan-Drug-Resistant to Four Classes of Antifungal Agents.

Candida auris is an urgent antimicrobial resistance threat due to its global emergence, high mortality, and persistent transmissions. Nearly half of C. auris clinical and surveillance cases in the United States are from the New York and New Jersey Metropolitan area. We performed genome, and drug-resistance analysis of C. auris isolates from a patient who underwent multi-visceral transplantation. Whole-genome comparisons of 19 isolates, collected over 72 days, revealed closed similarity (Average Nucleotide Identity > 0.9996; Aligned Percentage > 0.9764) and a distinct subcluster of NY C. auris South Asia Clade I. All isolates had azole-linked resistance in ERG11(K143R) and CDR1(V704L). Echinocandin resistance first appeared with FKS1(S639Y) mutation and then a unique FKS1(F635C) mutation. Flucytosine-resistant isolates had mutations in FCY1, FUR1, and ADE17. Two pan-drug-resistant C. auris isolates had uracil phosphoribosyltransferase deletion (FUR1[1Δ33]) and the elimination of FUR1 expression, confirmed by a qPCR test developed in this study. Besides ERG11 mutations, four amphotericin B-resistant isolates showed no distinct nonsynonymous variants suggesting unknown genetic elements driving the resistance. Pan-drug-resistant C. auris isolates were not susceptible to two-drug antifungal combinations tested by checkerboard, Etest, and time-kill methods. The fungal population pattern, discerned from SNP phylogenetic analysis, was consistent with in-hospital or inpatient evolution of C. auris isolates circulating locally and not indicative of a recent introduction from elsewhere. The emergence of pan-drug-resistance to four major classes of antifungals in C. auris is alarming. Patients at high risk for drug-resistant C. auris might require novel therapeutic strategies and targeted pre-and/or posttransplant surveillance.

Left lateral segment pediatric liver transplantation: a 25 year experience at Mount Sinai.

BACKGROUND: Outcomes of left lateral segment (LLS) grafts in pediatric recipients were compared between living (LD-LLS) and deceased donor (DD-LLS) grafts. METHODS: 195 LLS grafts (99DD-LLS-96LD-LLS) were analyzed with a median follow-up of 9.1years. The primary endpoints were overall patient/graft survival. RESULTS: LD-LLS grafts were younger (0.9vs.1.4years, p = 0.039), more likely to have a fulminant liver failure (17.9%vs.5.3%,p = 0.002), less likely to have a metabolic disorder (6.3%vs.25.5%,p = 0.002), and less likely to be undergoing retransplantation (5.3% vs.16.2%,p = 0.015). There was a trend toward decreased hepatic artery thrombosis in LD-LLS grafts (6.6% vs. 15.5%,p = 0.054). No differences in the overall biliary complications occurred. The LD-LLS group had prolonged survival compared to the DD-LLS group with 10-year survival rates of 81%, and 74% (p = 0.005), respectively. LD-LLS grafts had longer graft survival compared to DD-LLS grafts (10-year graft survival 85%vs.67%,p = 0.005). Recipient age >1year (HR 2.39,p = 0.026), aortic reconstruction (HR 2.12,p = 0.046) and vascular complication (HR 3.12,p < 0.001) were independent predictors of poor patient survival. Non-biliary liver disease (HR 2.17,p = 0.015), DD-LLS (HR 2.06,p = 0.034) and vascular complication (HR 4.61,p < 0.001) were independent predictors of poor graft survival. CONCLUSION: The use of SLT remains a viable option with excellent long-term outcomes. We show improved graft and patient survival with living donor grafts.

The role of endoscopy in the small intestinal transplant recipient: A review.

Intestinal transplantation (ITx) is the treatment of choice for patients with intestinal failure who have developed life-threatening complications related to long-term parenteral nutrition. Patients may also undergo ITx as part of a combined liver-intestine or multivisceral transplant for a variety of indications, most commonly intestinal failure-associated liver disease or porto-mesenteric thrombosis. Endoscopy plays a critical role in the posttransplant management of these patients, most commonly in the diagnosis and management of rejection, which occurs in up to 30-40% of patients within the first-year posttransplant. With a lack of noninvasive biomarkers to identify the presence of rejection, endoscopy and biopsy remain the gold standard for its diagnosis. Endoscopic evaluation of the graft is also important in the identification of other complications post-ITx, including posttransplant lymphoproliferative disorder, graft-versus-host disease, and enteric infections. Each patient's posttransplant anatomy may be slightly different, making endoscopy sometimes technically challenging and necessitating clear and frequent communication with the surgical team in order to help identify the highest yield approach. Herein, we review the most common pathologies found endoscopically in the post-ITx patient and describe some of the unique challenges the endoscopist faces when evaluating these complex patients.

Tacrolimus time-in-therapeutic range is associated with freedom from acute rejection and graft failure following intestinal transplantation.

BACKGROUND: Trough-adjusted tacrolimus is commonly prescribed following intestinal transplantation to prevent allograft rejection. Despite established practice, there remains limited direct evidence linking tacrolimus levels with improved clinical outcomes. METHODS: This was a single-center review of all adult non-liver containing intestinal allograft recipients from 2011 to 2018. Patients received lymphocyte depleting induction and maintenance immunosuppression consisting of tacrolimus and a corticosteroid taper. Tacrolimus time-in-therapeutic range (TAC-TTR) was calculated for all patients from the date of transplant until 1-year post-transplant using Rosendaal's method. Cox-Proportional hazards modeling was utilized to assess freedom from acute rejection and graft failure stratified by TAC-TTR quartile. RESULTS: 47 patients were included in the review. Mean TAC-TTR for the cohort was 30.2% ± 11.4. Fifteen episodes of acute rejection were observed, 8 of which were severe. Patients in the highest TAC-TTR quartile >36% had a lower incidence of acute rejection and graft failure relative to patients with a TAC-TTR <20%. Cox-Proportional hazards modeling found a 10% decrease in TAC-TTR was associated with an increased hazard for acute rejection (2.03), severe acute rejection (2.19), and graft loss (3.33). CONCLUSION: The results of this study suggest that decreasing TAC-TTR is a risk factor for both acute rejection as well as intestinal allograft failure.

"Stoma or no stoma": First report of intestinal transplantation without stoma.

Recent data suggest that frequent endoscopy and biopsy without evidence of graft dysfunction does not appear to confer survival advantage after intestinal transplantation. After abandoning protocol surveillance, endoscopic examination was decreased significantly at our center. These observations led us to question the need for stoma creation in intestinal transplantation. Herein, we report clinical outcomes of intestinal transplantation without stoma, compared to conventional transplant with stoma. Data analysis was limited to adult intestinal transplantation without liver allograft between 2015 and 2018. We compared patient and graft survival, frequency of endoscopic evaluation, episodes of acute rejection, nutritional therapy, and renal function between "Control group (with stoma)," n = 18 grafts in 16 patients and "Study group (without stoma)," n = 16 grafts in 15 patients. Overall outcome was similar between the 2 groups with respect to graft and patient survival, episodes of acute rejection, and its response to treatment. Nutritional outcomes were similar in both groups. Fewer antidiarrheal medications were required in the study group, but this did not translate into demonstrable gains in preservation of renal function, despite an apparent trend to improvement. Intestinal transplantation without stoma appears to be an acceptable practice model without obvious adverse impact on outcome.

Adult intestinal transplantation in the United States.

PURPOSE OF REVIEW: There has been a striking decline in the annual volumes of adult intestinal transplants performed in the United States from a peak in 2008, reaching its lowest volume in 2019. The current review examines the pattern and potential reasons for the decline. RECENT FINDINGS: We observe that while improvements in intestinal rehabilitation may be contributing to some of the decline, movements of key personnel and the paucity of experts in a rarefied field may also be contributing to declining volumes. SUMMARY: We suggest that the decline in volumes of adult intestinal transplants are likely to be multifactorial. At a time of improving transplant outcomes, the indications for intestinal transplant suggested by the Centers for Medicare and Medicaid Services, may be outdated and worthy of revision.

Routine surveillance endoscopy and biopsy after isolated intestinal transplantation-Revisiting the gold standard.

The value of endoscopy and biopsy after intestinal transplantation in the absence of clinical concerns has never been investigated. We examined clinical yield of routine surveillance endoscopy and biopsy (control group, n = 28, Jan 2011 to Jun 2014). Most episodes of acute rejection were diagnosed when there were clinical symptoms or signs such as increased stoma output, fever, or bacteremia, but not by routine surveillance endoscopy and biopsy. The new protocol abandoned routine surveillance. Intestinal allografts were examined only when relevant clinical symptoms and/or signs raised concern for graft dysfunction. We compared outcomes between control and study groups (new protocol, n = 25, Jul 2014 to Dec 2016). Incidence of acute rejection (32% vs 32%), graft salvage rate after acute rejection treatment (78% vs 63%), patient survival (75% vs 88% 1 year, 71% vs 83% 3 years after intestinal transplantation), and graft survival (68% vs 80% 1 year, 61% vs 76% 3 years after intestinal transplantation) were similar between control and study groups. Protocol-driven, routine surveillance endoscopy, and biopsy do not appear to confer any survival advantage to patients or grafts. Endoscopy and biopsy "for cause" without routine surveillance seem to be effective and adequate to monitor intestinal allografts.

Analysis of surgical interruption of the enterohepatic circulation as a treatment for pediatric cholestasis.

To evaluate the efficacy of nontransplant surgery for pediatric cholestasis, 58 clinically diagnosed children, including 20 with Alagille syndrome (ALGS), 16 with familial intrahepatic cholestasis-1 (FIC1), 18 with bile salt export pump (BSEP) disease, and 4 others with low γ-glutamyl transpeptidase disease (levels <100 U/L), were identified across 14 Childhood Liver Disease Research Network (ChiLDReN) centers. Data were collected retrospectively from individuals who collectively had 39 partial external biliary diversions (PEBDs), 11 ileal exclusions (IEs), and seven gallbladder-to-colon (GBC) diversions. Serum total bilirubin decreased after PEBD in FIC1 (8.1 ± 4.0 vs. 2.9 ± 4.1 mg/dL, preoperatively vs. 12-24 months postoperatively, respectively; P = 0.02), but not in ALGS or BSEP. Total serum cholesterol decreased after PEBD in ALGS patients (695 ± 465 vs. 457 ± 319 mg/dL, preoperatively vs. 12-24 months postoperatively, respectively; P = 0.0001). Alanine aminotransferase levels increased in ALGS after PEBD (182 ± 70 vs. 260 ± 73 IU/L, preoperatively vs. 24 months; P = 0.03), but not in FIC1 or BSEP. ALGS, FIC1, and BSEP patients experienced less severely scored pruritus after PEBD (ALGS, 100% vs. 9% severe; FIC1, 64% vs. 10%; BSEP, 50% vs. 20%, preoperatively vs. >24 months postoperatively, respectively; P < 0.001). ALGS patients experienced a trend toward greater freedom from xanthomata after PEBD. There was a trend toward decreased pruritus in FIC1 after IE and GBC. Vitamin K supplementation increased in ALGS after PEBD (33% vs. 77%; P = 0.03). Overall, there were 15 major complications after surgery. Twelve patients (3 ALGS, 3 FIC1, and 6 BSEP) subsequently underwent liver transplantation. CONCLUSION: This was a multicenter analysis of nontransplant surgical approaches to intrahepatic cholestasis. Approaches vary, are well tolerated, and generally, although not uniformly, result in improvement of pruritus and cholestasis. (Hepatology 2017;65:1645-1654).

Severe acute cellular rejection after intestinal transplantation is associated with poor patient and graft survival.

BACKGROUND: Severe acute cellular rejection (ACR) occurs frequently after intestinal transplantation (ITx). AIM: To evaluate the outcomes and the risk factors for graft failure and mortality in patients with severe ACR after ITx. METHODS: Retrospective study evaluating all ITx recipients who developed severe ACR between 01/2000 and 07/2014. Demographic and histologic data were reviewed. RESULTS: 20/126 (15.9%) ITx recipients developed severe ACR. Of these 20 episodes, 13 were in adults (median age: 47.1). The median (IQR) time from ITx to severe ACR was 206.5 (849) days. All patients received intravenous methylprednisolone and increased doses of tacrolimus. Sixteen (80%) patients did not respond to initial treatment and required thymoglobulin administration. Moreover, 11 (55%) patients required additional immunosuppressive medications. Six (30%) patients required graft enterectomy. Complications related to ACR treatment were the following: 10 (50%) patients developed bacterial infections, four (20%) patients developed cytomegalovirus infection and four (20%) patients developed post-transplant lymphoproliferative disease. At the end of follow-up, only 3/20 (15%) were alive with a functional allograft. The median patient survival time after diagnosis of severe ACR was 400 days (95% CI: 234.0-2613.0). CONCLUSIONS: Severe ACR episodes are associated with high rates of graft loss and complications related to treatment.

The high incidence of severe chronic kidney disease after intestinal transplantation and its impact on patient and graft survival.

INTRODUCTION: Using data from the Scientific Registry of Transplant Recipients (SRTR), cumulative incidence, risk factors for, and impact on survival of severe chronic kidney disease (CKD) in intestinal transplantation (ITx) recipients were assessed. METHODS: First-time adult ITx recipients transplanted in the United States between January 1, 1990 and December 31, 2012 were included. Severe CKD after ITx was defined as: glomerular filtration rate (GFR) <30 mL/min/1.73 m2 , chronic hemodialysis initiation, or kidney transplantation (KTx). Survival analysis and extended Cox model were conducted. RESULTS: The cumulative incidence of severe CKD 1, 5, and 10 years after ITx was 3.2%, 25.1%, and 54.1%, respectively. The following characteristics were significantly associated with severe CKD: female gender (HR 1.34), older age (HR 1.38/10 year increment), catheter-related sepsis (HR 1.58), steroid maintenance immunosuppression (HR 1.50), graft failure (HR 1.76), ACR (HR 1.64), prolonged requirement for IV fluids (HR 2.12) or TPN (HR 1.94), and diabetes (HR 1.54). Individuals with higher GFR at the time of ITx (HR 0.92 for each 10 mL/min/1.73 m2 increment), and those receiving induction therapies (HR 0.47) or tacrolimus (HR 0.52) showed lower hazards of severe CKD. In adjusted analysis, severe CKD was associated with a significantly higher hazard of death (HR 6.20). CONCLUSIONS: The incidence of CKD after ITx is extremely high and its development drastically limits post-transplant survival.

Anesthetic management for intestinal transplantation: A decade of experience.

BACKGROUND: Intestinal transplantation (ITx) is the definitive therapy for patients suffering from intestinal failure. Previously published reports suggest that these cases should be managed perioperatively with the same intensive monitors and techniques as in liver transplantation. METHODS: We retrospectively reviewed the anesthetic management of 67 isolated intestinal, intestinal-pancreas, and intestinal-kidney transplants over the previous decade (2005-2015) in our tertiary care institution. RESULTS: Patients were typically managed with a single arterial line, a single central venous catheter, and rarely intensive modalities such as a pulmonary artery catheter, a transesophageal echocardiography, a second arterial catheter or central venous catheter, a rapid infusion system, a cell salvage device, or viscoelastic testing. Significant hemodynamic derangements were rare, and the rate of postreperfusion syndrome was 8.96%. Our fluid administration type and volume and transfusion type and volume were similar to previous reports in which more intensive anesthetic management was employed. CONCLUSION: We demonstrate that ITx can safely occur without utilizing the intensive resources requisite for a liver transplant.

Pre-emptive Intestinal Transplant: The Surgeon's Point of View.

Pre-emptive transplantation is a well-established practice for certain types of end-organ failure such as in the use of kidney transplantation. For irreversible intestinal failure, total parenteral nutrition (TPN) remains the gold standard, due to the suboptimal long-term results of intestinal transplantation. As such, the only role for pre-emptive transplantation, if at all, will be for patients identified to be at high risk of complications and mortality while on definitive long-term TPN. In these patients, the timing of early listing and transplantation could become life-saving, taking into account that mortality on the waiting list is still the highest for intestinal candidates. The development of simulation models or pre-transplant scoring systems could help in selecting patients based on potential outcome on TPN or with transplantation, and recent reports from high-volume centers identify few underlying pathologic conditions and some TPN complications as at higher risk of increased morbidity and mortality. A pre-emptive transplant could be used as a rehabilitative procedure in a well-selected case-by-case scenario, among TPN patients at risk of liver failure, repeated central line infections, mesenteric infarction, short bowel syndrome (SBS) <50 cm or with end stoma, congenital mucosal disease, desmoid tumors: These conditions must be carefully evaluated, not to underestimate the clinical stage nor to over-estimate the impact of a temporary situation. At the present time, diseases with a variable and unpredictable course, such as intestinal dysmotility disorders, or quality of life and financial issues are still far from being considered as indications for a pre-emptive transplant.

Comparative incidence of rejection occurring in small intestinal and colonic mucosal biopsies of patients undergoing intestinal transplantation.

AIMS: To compare the diagnosis of acute cellular rejection (ACR) based on biopsies (Bx) performed simultaneously in the small bowel (SB) and colonic grafts (paired Bx) after intestinal transplantation (ITx). METHODS AND RESULTS: Retrospective study including all ITx with colon at Mount Sinai Hospital between 2009 and 2014. Paired Bx were reviewed blindly by two experienced gastrointestinal (GI) pathologists and were graded based on the VIII International Small Bowel Transplant Symposium Consensus criteria, with minor modifications for evaluation of colon biopsies. Each Bx was classified as negative or positive for ACR. Cohen's kappa statistic was used to quantify the interpathologist agreement and the agreement between SB and colonic Bx for the diagnosis of ACR. Fifteen patients underwent 51 paired Bx. The strength of agreement for the grade of ACR in the SB biopsies (kappa = 0.62) and the colonic biopsies (kappa = 0.65) was good. The inter-rater agreement was better for Bx negative for ACR and for higher grades of ACR. Overall, 74.5% of paired Bx were concordant for the presence or absence of ACR. The strength of agreement for the presence or absence of ACR between the SB and colonic Bx (kappa = 0.44) was moderate. Two cases of severe ACR were restricted to the SB allograft. CONCLUSIONS: Paired Bx in the SB and the colon are usually in agreement regarding the presence or the absence of ACR. However, colonic Bx alone may not suffice to exclude ACR following ITx. With minor modifications, the histopathological criteria of the SB may be adaptable to the colonic allograft.

Roux-en-Y intussusception after pediatric liver transplant - A case report.

Small bowel obstruction in a pediatric patient following liver transplant often results from adhesions, hernias, or post-transplant lymphoproliferative disease. Here, we present an unusual and previously unreported entity - Roux-en-Y intussusception in an eight-yr-old female several years after liver transplantation. Although a rare complication, Roux-en-Y intussusception should be considered as a potential etiology in the patient presenting with bowel obstruction, with specific attention to acute presentation accompanying jaundice.

Epstein-Barr virus-associated smooth muscle tumors in children following solid organ transplantation: a review.

EBV-SMT are a rare entity following organ transplantation. Given the rarity of the tumor, there is no standard approach to diagnosis and treatment. A literature search identified 28 reported cases of EBV-SMT in addition to our own experience with one case. The aim of this review is to summarize the existing data regarding pathogenesis, diagnosis, and treatment.

Balloon-occluded retrograde transvenous obliteration for recurrent fundal gastric variceal bleeding in an adolescent.

Gastric variceal bleeding is associated with high morbidity and mortality. Balloon-occluded retrograde transvenous obliteration is a relatively new treatment used to control bleeding gastric varices that involves transvenous sclerosis of gastric varices through a spontaneous gastrorenal shunt. Here, we report on a 14-yr-old patient that underwent balloon-occluded retrograde transvenous obliteration for refractory bleeding fundal varices in the setting of esophageal varices and cirrhosis, which did not respond to medical management or endoscopic injection. This case report serves as a reminder that balloon-occluded retrograde transvenous obliteration can successfully control fundal variceal bleeding in pediatric patients and may serve as a bridge to liver transplantation.