Functional status at listing predicts waitlist and posttransplant mortality in pediatric liver transplant candidates

Functional impairment is associated with mortality in adult liver transplant candidates. This has not been studied in pediatric liver transplant candidates. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to investigate functional status, waitlist mortality, and posttransplant outcomes in children younger than 18 years who were waitlisted in 2006‐2016 for primary liver transplant. Functional status was categorized, by using the Lansky Play‐Performance Scale (LPPS), as normal/good (80‐100), moderately impaired (50‐70), or severely impaired (10‐40) by center assessment. Among 3250 children not listed as Status 1A, 62% had an LPPS score of 80‐100, 25% had a score of 50‐70, and 13% had a score of 10‐40 at listing. Children with an LPPS score of 10‐40 at listing were more likely to die while on the waitlist (standardized hazard ratio 1.85, 95% confidence interval 1.09‐3.13, P = .02) in analyses adjusting for being on a ventilator, breathing support, or dialysis and other illness severity measures. For the 2565 children transplanted, an LPPS score of 10‐40 at listing drastically increased mortality risk by 1 year posttransplant (hazard ratio 5.77, 95% confidence interval 3.05‐10.91, P < .0005). LPPS scores of 10‐40 and 50‐70 both increased the risk of graft loss by 1 year. Functional status is an independent predictor of waitlist and posttransplant mortality in pediatric liver transplant candidates. Validated tools for the assessment of functional status in these children would improve our ability to predict mortality risk—and to appropriately prioritize them for transplant.     

Abdominal lean muscle is associated with lower mortality among kidney waitlist candidates

Morphometric assessments, such as muscle density and body fat distribution, have emerged as strong predictors of cardiovascular risk and postoperative morbidity and mortality. To date, no study has examined morphometric mortality risk prediction among kidney transplant (KT) candidates. KT candidates, waitlisted 2008‐2009, were identified (n=96) and followed to the earliest of transplant, death, or administrative end of study. Morphometric measures, including abdominal adipose tissue, paraspinous and psoas muscle composition, and aortic calcification, were measured from CTs. Risk of waitlist mortality was examined using Cox proportional hazard regression. On adjusted analyses, radiologic measures remained independently and significantly associated with lower waitlist mortality; the addition of radiologic measures significantly improved model predictive ability over models containing traditional risk factors alone (net reclassification index: 0.56, 95% CI: 0.31‐0.75). Higher psoas muscle attenuation (indicative of leaner muscle) was associated with decreased risk of death (aHR: 0.93, 95% CI: 0.91‐0.96, P<.001), and for each unit increase in lean paraspinous volume, there was an associated 2% decreased risk for death (aHR: 0.98, 95% CI: 0.96‐0.99, P=.03). Radiologic measures of lean muscle mass, such as psoas muscle attenuation and paraspinous lean volume, may improve waitlist mortality risk prediction and candidate selection.     

Increasing disparity in waitlist mortality rates with increased model for end-stage liver disease scores for candidates with hepatocellular carcinoma versus candidates without hepatocellular carcinoma

Candidates with hepatocellular carcinoma (HCC) within the Milan criteria (MC) receive standardized Model for End-Stage LIver Disease (MELD) exception points because of the projected risk of tumor expansion beyond the MC. Exception points at listing are meant to be equivalent to a 15% rusj if 90-day mortality, with additional points granted every 3 months, equivalent to a 10% increased morality risk. We analyzed the United Network for Organ Sharing database (January 1, 2005 to May 31, 2009) to compare the 90-day waitlist outcomes of HCC candidates and non-HCC candidates with similar MELD scores. Two hundred fifty-nine HCC candidates (4.1%) who were initially listed with 22 MELD exception points were removed because of death or clinical deterioration within 90 days of listing, whereas 283 non-HCC candidates (11.0%) with initial laboratory MELD scores of 21 to 23 were removed. Ninety-three HCC candidates (4.6%) with 25 exception points (after 3-6 months of waiting) were removed because of death or clinical deterioration within 90 days, whereas 805 non-HCC candidates (17.3%) with laboratory MELD scores of 24 to 26 were removed. Twenty HCC candidates (3.0%) with 28 exception points (after 6-9 months of waiting) were removed for death or clinical deterioration within 90 days, whereas 646 non-HCC candidates (23.6%) with laboratory MELD scores of 27 to 29 were removed. In multivariate logistic regression models, HCC candidates had significantly lower 90-day odds of waitlist removal for death or clinical deterioration (P < 0.001). Over time, the risk of waitlist removal for death or clinical deterioration was unchanged for HCC candidates (P = 0.17), whereas it increased significantly for non-HCC candidates. The current allotment of HCC exception points should be re-evaluated because of the stable risk of waitlist dropout for these candidates.     

Morbidity and mortality of UNOS status 1B cardiac transplant candidates at home.

BACKGROUND: On January 20, 1999, UNOS listing regulations changed, allowing stable patients on inotropic support (Status IB) to be discharged home until cardiac transplant. The outcome, morbidity and cost savings of this new strategy has not been evaluated. METHODS: From 1/20/99 through 1/1/01, 155 patients were classified as UNOS Status 1B at our institution; 64 patients were never discharged and 91 were discharged home. Criteria for discharge were hemodynamic stability on low-dose, single-agent parenteral inotropic infusion, defined as dobutamine at a dose <7.5 microg/kg/min or milrinone <0.5 microg/kg/min. Data on re-admissions were collected prospectively. The frequency of complex ventricular arrhythmias was evaluated in a sub-group discharged with external or internal cardiodefibrillators (n = 38). RESULTS: Total Status I time to transplant for the 91 discharged patients was 139 +/- 91 days, with 87 +/- 67 days spent at home. Inpatient time to transplant was still high, with a mean of 51 +/- 45 days. The in-hospital time was comparable to that of the 64 patients who were never discharged (51 +/- 41 days). Fifty-nine percent of discharged patients were re-admitted, with 37% of patients requiring more than 1 admission. Sixty-six percent of admissions were for worsening heart failure (CHF), and 34% for infection or occlusion of the indwelling intravenous line. No significant arrhythmic events were recorded in the 38 patients who had internal or external cardiodefibrillators. Two patients died suddenly at home. One patient had declined to wear the external cardiodefibrillator. The other patient was not wearing the defibrillator at the time of the event, and in 634 hours of previous monitoring he had had no events. CONCLUSIONS: In UNOS Status 1B patients awaiting cardiac transplant on home inotropic therapy, mortality remains low but the re-admission rate was high. There appeared to be a low incidence of complex ventricular arrhythmias.     

Immune status assessment in adult lung transplant candidates

BackgroundLung transplant recipients have an increased susceptibility to a variety of infections due to immunosuppressive therapy. Current guidelines recommend pneumococcal and other vaccinations, prior to lung transplantation to protect against post-transplant infections, but measurement of the antibody response to vaccination is not advised. Immune status investigation in lung transplant candidates, including the response to pneumococcal polysaccharide vaccination, has not been described.MethodsImmune status investigation, including measurement of immunoglobulins, complement and the response to 23-valent pneumococcal polysaccharide vaccination (23vPPV) was performed in 81 adult lung transplant candidates.ResultsEighteen patients had low IgG levels and 32 patients had low IgG1 and/or IgG2 levels. After vaccination with 23vPPV the median antibody concentration of all serotypes increased significantly. Fifty-two patients had protective IgG-post-vaccination antibody levels to at least 10 serotypes. Twenty-nine patients had an impaired response to 23vPPV.ConclusionsIn conclusion, a significant proportion of our cohort of lung transplant candidates had one or more abnormalities in the immune status. It is likely that these patients have an increased risk for infections after transplantation. Revaccination, including measurement of antibody response, and possibly antibody replacement therapy should be considered to minimize infection risk.     

Identifying a clinically relevant cutoff for height that is associated with a higher risk of waitlist mortality in liver transplant candidates

Height explains a substantial proportion of gender‐based disparity in waitlist mortality among liver transplant candidates. We sought to identify a clinically relevant height cutoff below which waitlist mortality increases significantly. We examined all nonstatus one adult liver transplant candidates from 2010 to 2014. We used a recursive application of the minimum P value approach with univariate competing risk regressions (deceased donor liver transplantation as the competing risk) to detect differences in waitlist mortality with regards to height. Of 69 883 candidates, 36% (24 819) were women and 64% (45 064) were men. Median height for all was 173 cm: 163 cm in women, 178 cm in men. The optimal search method of recursively evaluating smaller height intervals yielded 166 cm as the optimal height cutoff. Using height <166 cm as the cutoff, 72% of women and 9% of men met criteria. Compared to candidates ≥166 cm, “short stature” candidates had higher rates of death/delisting (28% vs 24%) and lower rates of transplantation (38% vs 44%) (P < .01 for both). After adjustment for clinical and demographic characteristics, height <166 cm remained associated with an 8% increased risk of waitlist mortality (95% CI 1.03‐1.14, P < .01). Short candidate height may be a motivation to explore split livers or living donors as accelerated liver transplantation options.     

MELD is MELD is MELD? Transplant center–level variation in waitlist mortality for candidates with the same biological MELD

Recently, model for end-stage liver disease (MELD)-based liver allocation in the United States has been questioned based on concerns that waitlist mortality for a given biologic MELD (bMELD), calculated using laboratory values alone, might be higher at certain centers in certain locations across the country. Therefore, we aimed to quantify the center-level variation in bMELD-predicted mortality risk. Using Scientific Registry of Transplant Recipients (SRTR) data from January 2015 to December 2019, we modeled mortality risk in 33 260 adult, first-time waitlisted candidates from 120 centers using multilevel Poisson regression, adjusting for sex, and time-varying age and bMELD. We calculated a "MELD correction factor" using each center's random intercept and bMELD coefficient. A MELD correction factor of +1 means that center's candidates have a higher-than-average bMELD-predicted mortality risk equivalent to 1 bMELD point. We found that the “MELD correction factor” median (IQR) was 0.03 (−0.47, 0.52), indicating almost no center-level variation. The number of centers with “MELD correction factors” within ±0.5 points, and between ±0.5–± 1, ±1.0–±1.5, and ±1.5–±2.0 points was 62, 41, 13, and 4, respectively. No centers had waitlisted candidates with a higher-than-average bMELD-predicted mortality risk beyond ±2 bMELD points. Given that bMELD similarly predicts waitlist mortality at centers across the country, our results support continued MELD-based prioritization of waitlisted candidates irrespective of center.     

Liver transplantation and waitlist mortality for HCC and non‐HCC candidates following the 2015 HCC exception policy change

Historically, exception points for hepatocellular carcinoma (HCC) led to higher transplant rates and lower waitlist mortality for HCC candidates compared to non‐HCC candidates. As of October 2015, HCC candidates must wait 6 months after initial application to obtain exception points; the impact of this policy remains unstudied. Using 2013‐2017 SRTR data, we identified 39  350 adult, first‐time, active waitlist candidates and compared deceased donor liver transplant (DDLT) rates and waitlist mortality/dropout for HCC versus non‐HCC candidates before (October 8, 2013‐October 7, 2015, prepolicy) and after (October 8, 2015‐October 7, 2017, postpolicy) the policy change using Cox and competing risks regression, respectively. Compared to non‐HCC candidates with the same calculated MELD, HCC candidates had a 3.6‐fold higher rate of DDLT prepolicy (aHR = _3.49 3.69 _3.89) and a 2.2‐fold higher rate of DDLT postpolicy (aHR = _2.09 2.21 _2.34). Compared to non‐HCC candidates with the same allocation priority, HCC candidates had a 37% lower risk of waitlist mortality/dropout prepolicy (asHR = _0.54 0.63 _0.73) and a comparable risk of mortality/dropout postpolicy (asHR = _0.81 0.95 _1.11). Following the policy change, the DDLT advantage for HCC candidates remained, albeit dramatically attenuated, without any substantial increase in waitlist mortality/dropout. In the context of sickest‐first liver allocation, the revised policy seems to have established allocation equity for HCC and non‐HCC candidates.     

Mortality among solid organ waitlist candidates during COVID-19 in the United States

We examined the effects of COVID-19 on solid organ waiting list mortality in the United States and compared effects across patient demographics (e.g., race, age, and sex) and donation service areas. Three separate piecewise exponential survival models estimated for each solid organ the overall, demographic-specific, and donation service area-specific differences in the hazard of waitlist mortality before and after the national emergency declaration on March 13, 2020. Kidney waiting list mortality was higher after than before the national emergency (adjusted hazard ratio [aHR], 1.37; 95% CI, 1.23–1.52). The hazard of waitlist mortality was not significantly different before and after COVID-19 for liver (aHR, 0.94), pancreas (aHR, 1.01), lung (aHR, 1.00), and heart (aHR, 0.94). Kidney candidates had notable variability in differences across donation service areas (aHRs, New York City, 2.52; New Jersey, 1.84; and Michigan, 1.56). The only demographic group with increased waiting list mortality were Blacks versus Whites (aHR, 1.41; 95% CI, 1.07–1.86) for kidney candidates. The first 10 weeks after the declaration of a national emergency had a heterogeneous effect on waitlist mortality rate, varying by geography and ethnicity. This heterogeneity will complicate comparisons of transplant program performance during COVID-19.     

A prognostic model for predicting waiting-list mortality for a total national cohort of adult heart-transplant candidates

BACKGROUND: Current trends in medical management of advanced heart failure and transplant medicine and the enactment of a national transplant law forced a change toward allocation driven by disease severity. OBJECTIVE: The aim of this study was to create a model for predicting waiting-list survival on the basis of simple clinical parameters. METHODS: The clinical profiles of all patients registered for heart transplantation in Germany in 1997 (n=889) were used as a derivation set, and the total German 1998 cohort (n=897) was used as a validation set. The model was validated by the c statistic and by comparison of risk stratified mortality rates. The validated model was fine tuned by the appropriate calibration procedures. The data were first classified into physiologic subscores: an urgency score, a left ventricular heart failure score, a right ventricular heart failure score, and a systemic heart failure score. A stepwise modeling procedure was undertaken using these subscores as factors as well as the recipient's age, ABO blood group, and body surface area. RESULTS: The urgency and the left ventricular subscore were found to be significantly associated with waiting-list mortality. A summary index termed German Transplant Society (GTS) score was then calculated on the basis of seven parameters contained in these two subscores. The GTS score was able to predict waiting-list mortality risks for the 1998 cohort: 1-year mortality before transplantation was 71%, 34%, 11% for the high, medium, and low risk groups, respectively. CONCLUSION: The use of this continuous disease severity index may improve the selection of cardiac transplant candidates.     

Arrhythmogenic mortality in heart-transplant candidates

Abstract  Sudden cardiac death represents a major problem in patients awaiting heart transplantation (HTx). A retrospective analysis of 1019 patients accepted for HTx revealed a high actuarial risk for sudden death accounting to 14 % after 1 year and 20 % after 2 years waiting time. Unterlying disease and hemodynamic characteristics had no predictive value. The use of implantable cardioverteridefibrillator therapy is discussed.     

Clinical judgment versus lung allocation score in predicting lung transplant waitlist mortality

Canadian lung transplant centers currently use a subjective and dichotomous “Status” ranking to prioritize waitlisted patients for lung transplantation. The lung allocation score (LAS) is an objective composite score derived from clinical parameters associated with both waitlist and post-transplant survival. We performed a retrospective cohort study to determine whether clinical judgment (Status) or LAS better predicted waitlist mortality. All adult patients listed for lung transplantation between 2007 and 2012 at three Canadian lung transplant programs were included. Status and LAS were compared in their ability to predict waitlist mortality using Cox proportional hazards models and C-statistics. Status and LAS were available for 1122 patients. Status 2 patients had a higher LAS compared to Status 1 patients (mean 40.8 (4.4) vs 34.6 (12.5), P = .0001). Higher LAS was associated with higher risk of waitlist mortality (HR 1.06 per unit LAS, 95% CI 1.05, 1.07, P < .001). LAS predicted waitlist mortality better than Status (C-statistic 0.689 vs 0.674). Patients classified as Status 2 and LAS ≥ 37 had the worst survival awaiting transplant, HR of 8.94 (95% CI 5.97, 13.37). LAS predicted waitlist mortality better than Status; however, the best predictor of waitlist mortality may be a combination of both LAS and clinical judgment.     

Life expectancy without a transplant for status 1A liver transplant candidates

Status 1A liver transplant candidates are given the highest medical priority for the allocation of deceased donor livers. Organ Procurement and Transplantation Network (OPTN) policy requires physicians to certify that a candidate has a life expectancy without a transplant of less than 7 days for that candidate to be given status 1A. Additionally, candidates receiving status 1A must have one of six medical conditions listed in policy. Using Scientific Registry of Transplant Recipients data from all prevalent liver transplant candidates from 2010 to 2020, we used a bias-corrected Kaplan–Meier model to calculate the survival of status 1A candidates and to determine their life expectancy without a transplant. We found that status 1A candidates have a life expectancy without a transplant of 24 (95% CI 20–46) days—over three times longer than what policy requires for status 1A designation. We repeated the analysis for subgroups of status 1A candidates based on the medical conditions that grant status 1A. We found that none of these subgroups met the life expectancy requirement. Harmonizing OPTN policy with observed data would sustain the integrity of the allocation process.     

Milrinone for long-term pharmacologic support of the status 1 heart transplant candidates

Background. We determined the efficacy of long-term therapy with milrinone alone or in combination with inotropic agents in status 1 heart transplant candidates as a pharmacological support until heart transplantation.

Methods. Hemodynamic and biochemical variables were recorded in 29 status 1 men with symptoms of severe congestive heart failure, who received continuous intravenous milrinone alone (group 1, n = 21) or in combination with inotropic agents (group 2, n = 8) while awaiting heart transplantation.

Results. Symptomatic relief was noted in all patients of both groups without any preoperative deaths. One patient (4.8%) of group 1 died on the second day and 1 patient of group 2 died 16.4 months after transplantation. Although pulmonary capillary wedge pressure (group 1, p = 0.021; group 2, p = 0.0002), mean pulmonary artery pressure (group 1, p = 0.051; group 2, p = 0.004), and pulmonary vascular resistance (group 1, p = 0.0026; group 2, p = 0.056) were reduced by 1 hour after the onset of treatment and maintained unchanged until transplantation, the changes in mean pulmonary artery pressure in group 1 and pulmonary vascular resistance in group 2 were statistically insignificant except in the posttransplantation period.

Conclusions. Long-term therapy with milrinone in combination with inotropic agents is safe and effective when only milrinone infusion is inadequate for pharmacologic support in status 1 candidates.     

Dental health status of liver transplant candidates.

A prerequisite dental evaluation is usually recommended for potential organ transplant candidates. This is based on the premise that untreated dental disease may pose a risk for infection and sepsis, although there is no evidence that this has occurred in organ transplant candidates or recipients. The purpose of this study was to assess the prevalence of dental disease and oral health behaviors in a sample of liver transplant candidates (LTCs). Oral examinations were conducted on 300 LTCs for the presence of gingivitis, dental plaque, dental caries, periodontal disease, edentulism, and xerostomia. The prevalence of these conditions was compared with oral health data from national health surveys and examined for possible associations with most recent dental visit, smoking, and type of liver disease. Significant risk factors for plaque-related gingivitis included intervals of more than 1 yr since the last dental visit (P = 0.004), smoking (P = 0.03), and diuretic therapy (P = 0.005). Dental caries and periodontal disease were also significantly associated with intervals of more than 1 yr since the last dental visit (P = 0.004). LTCs with viral hepatitis or alcoholic cirrhosis had the highest smoking rate (78.8%). Higher rates of edentulism occurred among older LTCs who were less likely to have had a recent dental evaluation (mean 88 months). In conclusion, intervals of more than 1 yr since the last dental visit, smoking, and diuretic therapy appear to be the most significant determinants of dental disease and the need for a pretransplantation dental screening evaluation in LTCs. Edentulous patients should have periodic examinations for oral cancer.     

成年人围手术期血压目标控制研究进展

围手术期低血压经常发生,是外科患者发生术后器官功能不全和死亡的重要促进因素。文章回顾近年来围手术期血压控制水平与器官损伤相关的文献研究,从而为围手术期血压管理目标提供参考以减少术后器官功能不全的发生。目前缺少围手术期血压控制目标的共识,血压控制目标是一个动态管理的过程,不应视为一个固定值。血压目标设定的最终目的是维持器...