Delayed referral for liver transplant evaluation worsens outcomes in chronic liver disease patients requiring inpatient transplant evaluation.

BACKGROUND: Indications to refer patients with cirrhosis for liver transplant evaluation (LTE) include hepatic decompensation or a model for end stage liver disease (MELD-Na) score ≥ 15. Few studies have evaluated how delaying referral beyond these criteria affects patient outcomes. AIM: To evaluate clinical characteristics of patients undergoing inpatient LTE and to assess the effects of delayed LTE on patient outcomes (death, transplantation). METHODS: This is a single center retrospective cohort study assessing all patients undergoing inpatient LTE (n = 159) at a large quaternary care and liver transplant center between 10/23/2017-7/31/2021. Delayed referral was defined as having prior indication (decompensation, MELD-Na ≥ 15) for LTE without referral. Early referral was defined as referrals made within 3 mo of having an indication based on practice guidelines. Logistic regression and Cox Hazard Regression were used to evaluate the relationship between delayed referral and patient outcomes. RESULTS: Many patients who require expedited inpatient LTE had delayed referrals. Misconceptions regarding transplant candidacy were a leading cause of delayed referral. Ultimately, delayed referrals negatively affected overall patient outcome and an independent predictor of both death and not receiving a transplant. Delayed referral was associated with a 2.5 hazard risk of death. CONCLUSION: Beyond initial access to an liver transplant (LT) center, delaying LTE increases risk of death and reduces risk of LT in patients with chronic liver disease. There is substantial opportunity to increase the percentage of patients undergoing LTE when first clinically indicated. It is crucial for providers to remain informed about the latest guidelines on liver transplant candidacy and the transplant referral process.

Ex-vivo ureteroscopy, laser lithotripsy, and stone basketing extraction of deceased donor kidney stones during machine perfusion preservation.

The incidence of nephrolithiasis in kidney donors is rare. The timing and treatment of nephrolithiasis in deceased donor kidneys are not well established. While some programs have proposed ex-situ rigid or flexible ureteroscopy treatment before transplantation, we report on two cases of kidney stones in the same deceased donor that we treated by flexible ureteroscopy and laser lithotripsy performed during the storage time on a hypothermic perfusion machine. Two deceased donor kidneys were found to have multiple kidney stones discovered on preprocurement CT imaging. The right kidney had less than five 2-3 mm stones, whereas the left had five to ten 1 mm stones with a single 7 mm stone. Both organs were placed on a hypothermic perfusion machine and maintained at a temperature of 4°C. An ex-vivo flexible ureteroscopy with laser lithotripsy and basket extraction was performed while the kidneys were maintained on Lifeport* perfusion machine. The cold ischemia time was 16.9 and 23.1 h. After 12 months of observational follow-up, neither recipient had nephrolithiasis, UTI, or other urologic complications. The creatinine values now are 1.17 and 2.44 mg/dL (103.4 and 215.7 µmol/L), respectively. Ex-vivo flexible ureteroscopy with laser lithotripsy and stone removal on machine-perfused kidneys appears to be safe and offers a good option to treat graft nephrolithiasis and prevent posttransplant complications. Ureteroscopy serves as a minimally invasive treatment option with direct stone removal. Performing this while on machine perfusion minimizes the ischemic time of the kidney and resultant complications or delays in graft function.

Supervised preoperative walking on increasing early postoperative stamina and mobility in older adults with frailty traits: A pilot and feasibility study.

Background and Aims: Frail older adults are more than twice as likely to experience postoperative complications. Preoperative exercise may better prepare these patients through improved stamina and mobility experienced in the days following surgery. We measured the impact of a walking intervention using an activity tracker and coaching on postoperative stamina, and mobility in older adults with frailty traits. Methods: We included patients aged 60+ and scoring 4+ on the Edmonton Frailty Scale. We then randomized patients to intervention versus control stratified by anticipated hospital stay (1 night vs. 2+ night) and baseline stamina (i.e., 6-min walk distance [6MWD]). Intervention patients received an activity tracker and linked smart phone. An athletic trainer (AT) prescribed a daily step count goal and titrated this up after checking in with patients during weekly telephone calls. Controls received general walking recommendations. We then measured postoperative 6MWD 1-3 days after surgery. We also assessed postoperative mobility by measuring steps walked the day after surgery using a thigh-worn monitor. Because many patients could not walk postoperatively, we compared intervention-control difference in both 6MWD and steps using Wilcoxon rank testing and Tobit and ordinal logistic regression adjusting for several patient characteristics. Results: We randomized 104 eligible patients; 80 patients remained for final analysis. There was no difference in intervention versus control postoperative 6MWD (median 72 vs. 74 m Wilcoxon p = 0.54) or postoperative steps taken (median 128 vs. 51 steps Wilcoxon p = 0.76). Analysis adjusting for patient characteristics was consistent with these findings. Conclusion: Our intervention consisting of goal setting with an activity tracker and telephonic coaching by an AT did not appear to improve stamina or mobility measured in the days after surgery. Small sample size limited our ability to examine this impact in subsets defined by surgical specialty or baseline stamina.

Treatment of Acute Graft-versus-Host Disease in Liver Transplant Recipients.

Acute graft-versus-host disease (aGvHD) is a rare complication of liver transplantation associated with high morbidity and mortality. Death typically occurs due to complications related to severe infection, shock, and multiorgan failure. The clinical presentation involves dysfunction of multiple organ systems with overlapping symptoms that often results in a diagnostic delay. As there are a limited number of cases reported in the literature, there are no clear guidelines for treatment. Many different therapeutic measures have been utilized that target various immune system pathways, but steroids remain the first line of therapy. We report on two patients who developed aGvHD after liver transplantation who were treated with ruxolitinib, a novel Janus kinase 1/2 (JAK) inhibitor that has been shown to improve outcomes in steroid refractory cases of aGvHD after allogenic hematopoietic stem cell transplantation. We reviewed the literature to discuss various therapeutic options currently available for aGvHD after liver transplantation.

Outcomes After Stereotactic Body Radiation Therapy as a Bridging Modality to Liver Transplantation for Hepatocellular Carcinoma.

PURPOSE: For patients with hepatocellular carcinoma awaiting liver transplantation (LT), stereotactic body radiation therapy (SBRT) has emerged as a bridging treatment to ensure patients maintain priority status and eligibility per Milan criteria. In this study, we aimed to determine the efficacy and safety of SBRT in such situations. METHODS AND MATERIALS: A retrospective analysis was conducted of the outcomes of 27 patients treated with SBRT who were listed for LT at 1 institution. Among these, 20 patients with 26 tumors went on to LT and were the focus of this study. Operative reports and postoperative charts were evaluated for potential radiation-related complications. The explant pathology findings were correlated with equivalent dose in 2 Gy fractions and tumor size. RESULTS: Median pretreatment tumor size was 3.05 cm. Median total dose of radiation was 50 Gy delivered in 5 fractions. Pathologic complete response (pCR) was achieved in 16 tumors (62%). Median interval from end of SBRT to transplant was 287 days. Of the 21 tumors imaged before transplant, 16 or 76% demonstrated a clinical complete response based on modified Response Evaluation Criteria in Solid Tumors criteria. There was no significant correlation between pCR rate and increasing tumor size (odds ratio [OR], 0.95; 95% confidence interval, 0.595-1.53) or pCR rate and equivalent dose in 2 Gy fractions (OR, 1.03; 95% confidence interval, 0.984-1.07.) No patients experienced radiation-related operative or postoperative complications. Of the 27 patients who were listed for transplant, the dropout rate was 22%. Two of the 5 patients with Child-Pugh score 10 died of liver failure. CONCLUSIONS: These data demonstrate that SBRT as a bridging modality is a feasible option, with a pCR rate comparable to that of other bridging modalities and no additional radiation-related operative or postoperative complications. There was no dose dependence nor size dependence for pCR rate, which may indicate that for the tumor sizes in this study, the radiation doses delivered were sufficiently high.

Transplantation of Renal Allograft After Removal of Renal Cell Carcinoma: Case Report and Review of the Literature.

With the rising incidence of end-stage renal disease in the United States, patients needing renal transplants are waiting longer for increasingly scarce grafts. Formerly, the general practice was to avoid organs with tumors for transplant because of the risk of malignancy transmission to the recipient. However, with comprehensive donor selection and a small-sized primary tumor, the positive outcomes of transplant outweigh the risks of transmission after a partial nephrectomy. In our case, a 31-year-old woman, the daughter of the recipient, underwent a laparoscopic nephrectomy with an existing 8-mm tumor later confirmed as renal cell carcinoma. An ex vivo tumor enucleation was performed before the allograft was transplanted into the 69-year-old patient with endstage renal disease. At last follow-up, graft function has remained excellent with no evidence of local recurrence or metastasis in both the donor and recipient. Here, we describe our case and perform a literature review on the incidence and management of renal allografts with incidentally detected renal cell carcinoma during transplant.

Liver transplant evaluation for fulminant liver failure due to acute hepatitis A infection: Case series and literature review.

Hepatitis A virus can cause liver damage ranging from mild illness to fulminant hepatic failure, constituting 0.35% of all cases of fulminant liver failure. While rates of spontaneous remission are higher for hepatitis A, recent outbreaks attributable to vaccine shortages in highly populated urban cities plagued by insufficient affordable housing and inaccessible sanitation, and changes in the epidemiology of viral strains have resulted in increased hospitalizations and deaths. While the prognosis for patients with FHF has improved since the introduction of transplantation, the decision to transplant is often difficult to reach. We present five patients with HAV and subsequent FHF, one of whom successfully received a liver transplant. We have reviewed all published cases of HAV FHF in the literature and report ten patients, seven of whom received liver transplantation. There are few predictive models that attempt to distinguish between fulminant hepatitis A and spontaneous recovery. Patients found to have positive hepatitis A IgM, encephalopathy, worsening LFT's and coagulation should be monitored closely and referred to transplant centers urgently for management.

Candida auris outbreak involving liver transplant recipients in a surgical intensive care unit.

Candida auris is a yeast that is difficult to eradicate and has caused outbreaks in health care facilities. We report a cluster of 5 patients in 1 intensive care unit who were colonized or infected in 2017. The initial 2 patients were recipients of liver transplants who had cultures that grew C auris within 3 days of each other in June 2017 (days 43 and 30 posttransplant). Subsequent screening cultures identified 2 additional patients with C auris colonization. Respiratory and urine cultures from a fifth patient yielded C auris. All isolates were fluconazole resistant but susceptible to echinocandins. Whole genome sequencing showed the strains were clonal, suggesting in-hospital transmission, and related but distinct from New York/New Jersey strains, consistent with a separate introduction. However, no source or contact was found. Two of the 5 patients died. C auris infection likely contributed to 1 patient death by infecting a vascular aneurysm at the graft anastomosis. Strict infection control precautions were initiated to control the outbreak. Our experience reveals that although severe disease from C auris can occur in transplant recipients, outbreaks can be controlled using recommended infection control practices. We have had no further patients infected with C auris to date.

Impact of recipient functional status on 1-year liver transplant outcomes.

BACKGROUND: The Karnofsky Performance Status (KPS) scale has been widely validated for clinical practice for over 60 years. AIM: To examine the extent to which poor pre-transplant functional status, assessed using the KPS scale, is associated with increased risk of mortality and/or graft failure at 1-year post-transplantation. METHODS: This study included 38278 United States adults who underwent first, non-urgent, liver-only transplantation from 2005 to 2014 (Scientific Registry of Transplant Recipients). Functional impairment/disability was categorized as severe, moderate, or none/normal. Analyses were conducted using multivariable-adjusted Cox survival regression models. RESULTS: The median age was 56 years, 31% were women, median pre-transplant Model for End-Stage for Liver Disease score was 18. Functional impairment was present in 70%; one-quarter of the sample was severely disabled. After controlling for key recipient and donor factors, moderately and severely disabled patients had a 1-year mortality rate of 1.32 [confidence interval (CI): 1.21-1.44] and 1.73 (95%CI: 1.56-1.91) compared to patients with no impairment, respectively. Subjects with moderate and severe disability also had a multivariable-adjusted 1-year graft failure rate of 1.13 (CI: 1.02-1.24) and 1.16 (CI: 1.02-1.31), respectively. CONCLUSION: Pre-transplant functional status is a useful prognostic indicator for 1-year post-transplant patient and graft survival.

Association Between Sarcopenia and Functional Status in Liver Transplant Patients.

OBJECTIVES: A growing body of evidence shows that frailty and functional performance predict liver transplant outcomes. The Organ Procurement and Transplant Network uses the Karnofsky Performance Status scale to adjust for transplant center case mix in assessing quality measures. This study explores the strength of the relationship between Karnofsky Performance Status scores and objective measures of frailty. MATERIALS AND METHODS: This observational study includes 136 adult, first-time liver transplant recipients at UMass Memorial (2006-2015) who had 2 abdominal computed tomography scans available (at ≤ 90 days pretransplant and ≥ 7 days before that). We analyzed the relationship between Karnofsky Performance Status and muscle wasting using absolute and change in psoas muscle size and quality pretransplant. RESULTS: The mean age was 55 years, mean Model for End-Stage Liver Disease was 22, and 34% of patients were women. In the study group, 50% of patients had sarcopenia pretransplant and 71.3% demonstrated declined lean psoas area at an average rate of 11% per month. Patients who experienced muscle wasting at a rate of ≥ 1% per month had 2.83 times the risk (95% confidence interval, 1.18-6.80) of being severely impaired/disabled pretransplant. The risk increased by 2.32-fold (95% confidence interval, 1.44-3.75) for every standard deviation decrease in pretransplant lean psoas area. CONCLUSIONS: Provider-assessed physical health status moderately correlates with objective measures of frailty.

Single-Center Experience With Liver Transplant Using Donors With Very High Transaminase Levels.

OBJECTIVES: Elevation of transaminases has been used as a marker of hepatic ischemic injury and as a crucial parameter for liver graft assessment. However, analysis of serum transaminases has limitations regarding the quantitative assessment of liver necrosis and is not a reliable predictor of outcomes. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all liver transplants (N = 238) performed at the UMass Memorial Medical Center from 2009 to 2013. RESULTS: Fourteen liver grafts showed high peak aminotransferases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at > 1000 U/L. This high aminotransferase group was compared with 224 donors with low transaminase levels (ALT/AST < 1000 U/L). The high transaminase donors had a median peak AST level of 3216 U/L (range, 1823-13?030 U/L) and ALT level of 2677 U/L (range, 812-7080 U/L). The high transaminase donors showed higher levels of lactate dehydrogenase, international normalized ratio, total bilirubin, and gamma-glutamyltransferase compared with low transaminase donors; however, only lactate dehydrogenase results reached statistical significance. None of the grafts from the high transaminase donors showed primary nonfunction. Three-year graft and patient survival rates were similar in both groups (75% vs 80% [P = .48] and 72% vs 82% [P = .33], respectively). In an analysis of the discard rate of livers over a 10-year period in the United States using the Scientific Registry of Transplant Recipients database, the discard rate of livers with high aminotransferase levels was 69.14% compared with 22.23% for livers with low transaminase levels. CONCLUSIONS: Liver grafts from donors with high transaminase levels can lead to clinical results that are similar to liver grafts from donors who had lower peak transaminase levels.

Bipolar Sealing Device Use in Pancreas Graft Preparation: A Novel Tieless Backtable Surgery Technique.

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Successful Renal Transplantation after Presumed Cyanide Toxicity Treated with Hydroxocobalamin and Review of the Literature.

We report two cases of successful renal transplantation with allografts from donors who suffered anoxic brain injury as the primary cause of death from house fires. Each was treated prophylactically with hydroxocobalamin (Cyanokit) for suspected cyanide toxicity. During organ procurement, gross examination was notable for deep discoloration of the parenchymal tissues. Approximately 6 and 18 months after transplantation, both recipients have excellent renal graft function and remain independent from hemodialysis (HD). Hydroxocobalamin is the antidote for suspected acute cyanide toxicity. While largely tolerated by the recipient, there is concern over the potential functional implications of the associated side effects of dramatic tissue discoloration and development of oxalate crystals. Furthermore, difficulties performing hemodialysis in patients treated with hydroxocobalamin have been reported due to discoloration of the effluent fluid impacting the colorimetric sensor, causing false alarms and repetitive interruptions. As such, many transplant centers in the United States (US) continue to reject these organs. We seek to highlight two cases of successful transplantation following donor administration of hydroxocobalamin (Cyanokit) and present the first documented case of successful perioperative intermittent hemodialysis following transplantation of an allograft exposed to hydroxocobalamin. Furthermore, we emphasize the importance of optimal organ utilization and caution against unnecessary refusal.

Functional status predicts postoperative mortality after liver transplantation.

BACKGROUND: Frail patients are more vulnerable to perioperative stressors of liver transplantation (LT). Program Specific Reports, used in transplant center auditing, risk-adjust for frailty using the Karnofsky Performance Status (KPS) scale. We evaluate the extent to which functional impairment/disability is associated with increased risk of postoperative death. METHODS: We included 24 505 first-time LT recipients from the Scientific Registry of Transplant Recipients (2006-2011). We categorized patients as Severe, Moderate, or Normal function/disability using the KPS scale and evaluated risk of 30- and 90-day mortality. Analyses took potential center-specific differences in KPS measurement protocols into account using hierarchal logistic modeling. RESULTS: Over one-quarter of our population was Severely impaired/disabled, and 30.5% had no functional limitations. Severely and Moderately impaired/disabled patients had 2.56 (95% CI 1.91-3.44) and 1.40 (95% CI 1.10-1.78) times the odds of 30-day mortality, respectively, after adjusting for key recipient and donor factors. Estimates remained consistent regardless of Model for End-Stage Liver Disease score, medical condition, or clustering analyses by center. Technical/operative complications and multiorgan failure/hemorrhage were more common causes of death among more Severely disabled patients than in higher functioning groups. CONCLUSIONS: Pre-transplant functional status, assessed using the KPS scale, is a reliable predictor of post-LT mortality in the United States.

Decade-Long Trends in Liver Transplant Waitlist Removal Due to Illness Severity: The Impact of Centers for Medicare and Medicaid Services Policy.

BACKGROUND: The central tenet of liver transplant organ allocation is to prioritize the sickest patients first. However, a 2007 Centers for Medicare and Medicaid Services regulatory policy, Conditions of Participation (COP), which mandates publically reported transplant center performance assessment and outcomes-based auditing, critically altered waitlist management and clinical decision making. We examine the extent to which COP implementation is associated with increased removal of the "sickest" patients from the liver transplant waitlist. STUDY DESIGN: This study included 90,765 adult (aged 18 years and older) deceased donor liver transplant candidates listed at 102 transplant centers from April 2002 through December 2012 (Scientific Registry of Transplant Recipients). We quantified the effect of COP implementation on trends in waitlist removal due to illness severity and 1-year post-transplant mortality using interrupted time series segmented Poisson regression analysis. RESULTS: We observed increasing trends in delisting due to illness severity in the setting of comparable demographic and clinical characteristics. Delisting abruptly increased by 16% at the time of COP implementation, and likelihood of being delisted continued to increase by 3% per quarter thereafter, without attenuation (p < 0.001). Results remained consistent after stratifying on key variables (ie, Model for End-Stage Liver Disease and age). The COP did not significantly impact 1-year post-transplant mortality (p = 0.38). CONCLUSIONS: Although the 2007 Centers for Medicare and Medicaid Services COP policy was a quality initiative designed to improve patient outcomes, in reality, it failed to show beneficial effects in the liver transplant population. Patients who could potentially benefit from transplantation are increasingly being denied this lifesaving procedure while transplant mortality rates remain unaffected. Policy makers and clinicians should strive to balance candidate and recipient needs from a population-benefit perspective when designing performance metrics and during clinical decision making for patients on the waitlist.