Recent Publications by CFE Educators

BACKGROUND

Accurate prediction of outcome among liver transplant candidates with hepatocellular carcinoma (HCC) remains challenging. We developed a prediction model for waitlist dropout among liver transplant candidates with HCC.

METHODS

The study included 18,920 adult liver transplant candidates in the United States listed with a diagnosis of HCC, with data provided by the Organ Procurement and Transplantation Network. The primary outcomes were 3-, 6-, and 12-month waitlist dropout, defined as removal from the liver transplant waitlist due to death or clinical deterioration.

RESULTS

Using 1,181 unique variables, the random forest model and Spearman's correlation analyses converged on 12 predictive features involving 5 variables, including AFP (maximum and average), largest tumor size (minimum, average, and most recent), bilirubin (minimum and average), INR (minimum and average), and ascites (maximum, average, and most recent). The final Cox proportional hazards model had a concordance statistic of 0.74 in the validation set. An online calculator was created for clinical use and can be found at: http://hcclivercalc.cloudmedxhealth.com/.

CONCLUSION

In summary, a simple, interpretable 5-variable model predicted 3-, 6-, and 12-month waitlist dropout among patients with HCC. This prediction can be used to appropriately prioritize patients with HCC and their imminent need for transplant.

Under current United Network for Organ Sharing (UNOS) policy, patients with hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP) levels ≥1000 ng/mL are required to show a reduction in AFP level to 500 ng/mL before liver transplantation (LT). However, effects of AFP reduction on post-LT HCC outcomes among patients with HCC with moderately elevated AFP levels between 100 and 1000 ng/mL are unclear. Adults in the UNOS registry who underwent LTs from January 2005 to September 2015 with initial AFP levels of 100 to 999 ng/mL at listing for Model for End-Stage Liver Disease exceptions were included. Primary predictor was AFP level at LT, categorized as 100, 100 to 499, or ≥500 ng/mL, and patients with only 1 recorded pre-LT AFP value (AFP 1-value). Survival was compared using the Kaplan-Meier curve method. Factors associated with post-LT survival and HCC recurrence were assessed in a multivariable Cox regression model. Among 1766 included patients, 50.2% had AFP 1-value, followed by 24.7%, 18.9%, and 6.2% with AFP levels 100, 100 to 499, and ≥500 ng/mL, respectively. The 5-year post-LT survival rate was lowest in the AFP ≥500 category, at 56.1%, compared with 72.7%, 70.4%, and 65.6% in the AFP 100, 100 to 499 ng/mL, and AFP 1-value categories, respectively. In multivariable analysis, AFP ≥500 ng/mL at LT was associated with a greater risk of post-LT death (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.1-2.1) and HCC recurrence (HR, 1.9; 95% CI, 1.1-3.1) when compared with the AFP 100 ng/mL category; other significant variables included donor risk index, age, race/ethnicity, Child-Turcotte-Pugh class, and tumor diameter. Among AFP levels ≥500 ng/mL at LT, 40.4% had AFP levels ≥1000, but no difference in post-LT survival or recurrence was seen between those patients with AFP levels or ≥1000 ng/mL. Mandating AFP 500 ng/mL at LT for all patients, not only for those with initial AFP levels ≥1000 ng/mL, may improve post-LT outcomes and can be considered in future UNOS policy.

BACKGROUND

Older adults are increasingly admitted to the ICU, and those with disabilities, dementia, frailty, and multimorbidity are vulnerable to adverse outcomes. Little is known about how pre-existing geriatric conditions have changed over time.

RESEARCH QUESTION

How have changes in disability, dementia, frailty, and multimorbidity in older adults admitted to the ICU changed from 1998 through 2015?

STUDY DESIGN AND METHODS

Medicare-linked Health and Retirement Survey (HRS) data identifying patients 65 years of age and older admitted to an ICU between 1998 and 2015. ICU admission was the unit of analysis. Year of ICU admission was the exposure. Disability, dementia, frailty, and multimorbidity were identified based on responses to HRS surveys before ICU admission. Disability represented the need for assistance with ≥ 1 activity of daily living. Dementia used cognitive and functional measures. Frailty included deficits in ≥ 2 domains (physical, nutritive, cognitive, or sensory function). Multimorbidity represented ≥ 3 self-reported chronic diseases. Time trends in geriatric conditions were modeled as a function of year of ICU admission and were adjusted for age, sex, race or ethnicity, and proxy interview status.

RESULTS

Across 6,084 ICU patients, age at admission increased from 77.6 years (95% CI, 76.7-78.4 years) in 1998 to 78.7 years (95% CI, 77.5-79.8 years) in 2015 (P  .001 for trend). The adjusted proportion of ICU admissions with pre-existing disability rose from 15.5% (95% CI, 12.1%-18.8%) in 1998 to 24.0% (95% CI, 18.5%-29.6%) in 2015 (P = .001). Rates of dementia did not change significantly (P = .21). Frailty increased from 36.6% (95% CI, 30.9%-42.3%) in 1998 to 45.0% (95% CI, 39.7%-50.2%) in 2015 (P = .04); multimorbidity rose from 54.4% (95% CI, 49.2%-59.7%) in 1998 to 71.8% (95% CI, 66.3%-77.2%) in 2015 (P  .001).

INTERPRETATION

Rates of pre-existing disability, frailty, and multimorbidity in older adults admitted to ICUs increased over time. Geriatric principles need to be deeply integrated into the ICU setting.