Faculty Bibliography

BACKGROUND:Contemporary guidelines emphasize the value of incorporating frailty into clinical decision-making regarding revascularization strategies for coronary artery disease. Yet, there are limited data describing the association between frailty and longer-term mortality among coronary artery bypass grafting (CABG) patients. METHODS:We conducted a retrospective cohort study (2016-2020, 40 VA medical centers) of US veterans nationwide that underwent coronary artery bypass grafting (CABG). Frailty was quantified by the Veterans Administration Frailty Index (VA-FI), which applies the cumulative deficit method to render a proportion of 30 pertinent diagnosis codes. Patients were classified as non-frail (VA-FI ≤ 0.1), pre-frail (0.1 < VA-FI ≤ 0.2), or frail (VA-FI > 0.2). We used Cox proportional hazards models to ascertain the association of frailty with all-cause mortality. Our primary study outcome was 5-year all-cause mortality; the co-primary outcome was days alive and out of the hospital within the first postoperative year. RESULTS:There were 13,554 CABG patients (median 69 years, 79% White, 1.5% women). The mean pre-operative VA-FI was 0.21 (SD: 0.11); 31% were pre-frail (VA-FI: 0.17) and 47% were frail (VA-FI: 0.31). Frail patients were older and had higher co-morbidity burdens than pre-frail and non-frail patients. Compared with non-frail patients (13.0% [11.4, 14.7]), there was a significant association between frail and pre-frail patients and increased cumulative 5-year all-cause mortality (frail: 24.8% [23.3, 26.1]; HR: 1.75 [95% CI 1.54, 2.00]; pre-frail 16.8% [95% CI 15.3, 18.4]; HR 1.2 [1.08,1.34]). Compared with non-frail patients (mean 362[SD 12]), pre-frail (mean 361 [SD 14]; p < 0.01) and frail patients (mean 358[SD 18]; p < 0.01) spent fewer days alive and out of the hospital in the first postoperative year. CONCLUSIONS:Pre-frailty and frailty were prevalent among US veterans undergoing CABG and associated with worse mid-term outcomes. Given the high prevalence of frailty with attendant adverse outcomes, there may be an opportunity to improve outcomes by identifying and mitigating frailty before surgery.

BACKGROUND:Limited data informs cerebral protection during circulatory arrest: this study was designed to identify optimal approaches from a national clinical registry. METHODS:A total of 7830 adults (mean age 63.1, standard deviation 13.1 years) who underwent hemi-arch (n=6891, 88.0%) or total arch (n=939, 12.0%) replacement with hypothermic circulatory arrest between 2014-2016, were identified from The Society of Thoracic Surgeons Database (version 2.81). Aortic dissections were excluded from the analysis. Multivariable logistic regression was used to adjust for 29 baseline and operative variables including demographics, comorbidity, surgery, and nadir temperature, comparing outcomes according to protection strategy. The primary end-point was a composite of 30-day and in-hospital mortality or major permanent neurological complications. RESULTS:C, 22 minutes). In multivariable analysis, deep hypothermia with antegrade (OR 0.65, 95% CI 0.52- 0.81) or retrograde (OR 0.57, 95% CI 0.45- 0.71) perfusion, and moderate hypothermia with antegrade perfusion (OR 0.61, 95% CI 0.46-0-.79) were associated with significant reductions in death and stroke compared to deep hypothermia without cerebral perfusion. Risk reduction was greatest in circulatory arrest >30 minutes. CONCLUSIONS:For patients without dissection and requiring >30 minutes circulatory arrest, optimal cerebral protection strategies are deep hypothermia with either antegrade or retrograde cerebral perfusion; or moderate hypothermia with antegrade cerebral perfusion.

BACKGROUND:Disproportionately high rates of maternal overweight and obesity among the Hispanic population before, during, and after pregnancy pose serious health concerns for both mothers (e.g., preeclampsia, gestational diabetes, weight retention) and children (e.g., elevated lifelong obesity risk). A growing body of evidence implicates environmental exposures (e.g., air pollution, metals) and social stressors (e.g., poverty, violence) in contributing to obesity-related biobehavioral processes, such as physical activity, dietary intake, perceived stress, and cortisol regulation. However, current understanding of the role of environmental exposures and social stressors on obesity-related biobehavioral processes is limited by infrequent, inter-individual measurement, and lack of personal exposure monitoring. METHODS:The "Maternal and Developmental Risks from Environmental and Social Stressors" (MADRES) real-time and personal sampling study examines the within-subject day-level effects of environmental and social stressors on maternal pre- and post-partum obesity-related biobehavioral responses. Among a cohort of 65 low-income, Hispanic women in urban Los Angeles, this study uses innovative personal, real-time data capture strategies (e.g., ecological momentary assessment [EMA], personal exposure monitoring, geolocation monitoring, accelerometry) to repeatedly assess obesity-related processes during the 1st and 3rd trimester, and at 4-6 months postpartum. Day-level effects of environmental exposures and social stressors on women's physical activity, diet, perceived stress and salivary cortisol measured across repeated days will be tested using multilevel modeling. DISCUSSION/CONCLUSIONS:Hispanic women of childbearing age bear a disproportionately high burden of obesity, and this population is also unduly exposed to numerous obesogenic settings. By using innovative real-time data capture strategies, the current study will uncover the daily impacts of environmental and social stressor exposures on women's obesity-related biobehavioral responses, which over time can lead to excessive gestational weight gain, postpartum weight retention and can pose serious consequences for both mother and child. Findings from the real-time and personal sampling study will identify key mechanistic targets for policy, clinical, and programmatic interventions, with the potential for broad-reaching public health impacts.

BACKGROUND:Limited data exist with regard to treatment outcomes in Asian Americans with chronic hepatitis C (CHC). We evaluated sofosbuvir (SOF)-based regimens in a national cohort of Asian Americans. METHODS:Eligible Asian Americans patients with CHC who had posttreatment follow-up of 24 weeks for SOF -based therapies from December 2013 to June 2017 were enrolled from 11 sites across the United States. The primary endpoint was sustained virologic response (SVR) rates at posttreatment weeks 12 and 24. Secondary endpoints were to evaluate safety by tolerability and adverse events (AEs). RESULTS:Among 231 patients screened, 186 were enrolled. At baseline, 31% (57/186) patients were cirrhotic, 34% (63/186) were treatment experienced. Most of the subjects (42%, 79/186) received ledispavir/SOF therapy. The overall SVR12 was 95%, ranging from 86% in genotype (GT) 1b on SOF+ribavirin to 100% in GT 1b patients on ledipasvir/SOF at subgroup analyses. SVR12 was significantly lower in cirrhotic than in noncirrhotic patients [88% (50/57) vs. 98% (126/129), P<0.01]. Stratified by GT, SVR12 were: 96% (43/45) in GT 1a; 93% (67/72) in GT 1b; 100% (23/23) in GT 2; 90% (19/21) in GT 3; 100% (1/1) in GT 4; 83% (5/6) in GT 5; and 100% (16/16) in GT 6. Cirrhotic patients with treatment failure were primarily GT 1, (GT 1a, n=2; GT 1b, n=4) with 1 GT 5 (n=1). Patients tolerated the treatment without serious AEs. Late relapse occurred in 1 patient after achieving SVR12. CONCLUSIONS:In Asian Americans with CHC, SOF-based regimens were well tolerated without serious AEs and could achieve high SVR12 regardless of hepatitis C viral infection GT.

BACKGROUND AND AIMS/OBJECTIVE:The management of chronic hepatitis B patients is not well characterized in real-world practice. We compared baseline characteristics of CHB patients on entecavir, the frequency of on-treatment monitoring, and the effectiveness of ETV treatment between academic and community practices. METHODS:Treatment-naïve CHB patients ≥18 years old, treated with ETV for ≥12 months from 2005 to 2013, in 26 community and academic practices throughout the USA were retrospectively evaluated. RESULTS:Of 841 patients enrolled, 658 (65% male, 83% Asian, median age 47, 9% with cirrhosis) met inclusion criteria. Half of the patients (52%) were from community practices. A lower percentage of patients in community practices had cirrhosis or liver cancer (5 vs. 14%). Community practices more often treated patients with baseline ALT < 2 × ULN. Over a median follow-up of 4 years, community practices were more likely to discontinue ETV with less frequent laboratory monitoring compared to academic practices. The 5-year cumulative probability of ALT normalization was greater among patients treated in community practices (70 vs. 50%, p < 0.001), but the 5-year cumulative probability of undetectable HBV DNA was lower (45 vs. 70%, p < 0.001) than those treated in academic practices. CONCLUSION/CONCLUSIONS:Academic practices saw CHB patients with more advanced liver disease, more often followed AASLD guidelines, and monitored patients on ETV treatment more frequently than community practices. While patients in community practices were less likely to achieve undetectable HBV DNA and more likely to achieve ALT normalization, the rates of HBeAg loss and seroconversion as well as HBsAg loss were similar.

OBJECTIVES: Data from the United States are lacking regarding the impact of entecavir (ETV) on the risk of hepatocellular carcinoma (HCC). Our aim is to determine whether treatment with ETV is associated with a reduced HCC risk by calculating the expected HCC incidence based on the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model and comparing it with the observed HCC incidence. METHODS: The incidence of HCC in US patients treated with ETV between 2005 and 2013 in a retrospective cohort was obtained. The predicted HCC incidence was calculated using the REACH-B model. The standardized incidence ratios (SIRs) were calculated as a ratio of observed over predicted HCC cases. RESULTS: Of 841 patients, 646 (65% male, 84% Asian, median age 47 years, 36% hepatitis B e antigen positive, 9.4% with cirrhosis) met the inclusion criteria. Over a median follow-up of 4 years, 17 (2.6%) cases of HCC were diagnosed, including 8 out of 61 (13.1%) patients with cirrhosis and 9 out of 585 (1.5%) without cirrhosis. Compared with those without HCC, the 17 patients with HCC were older at 53 years vs. 47 years and more likely to have cirrhosis at 47.1% vs. 8.4%. Among patients without cirrhosis, the observed HCC incidence was significantly lower than predicted by the fourth year (SIR, 0.37; 95% confidence interval: 0.166-0.82). A sensitivity analysis that comprised all patients, including those with cirrhosis, showed that at the maximum follow-up time of 8.2 years, a significantly lower than predicted HCC incidence was noted with an SIR of 0.56 (95% confidence interval: 0.35-0.905). CONCLUSIONS: Based on the REACH-B model, long-term ETV therapy was associated with a lower than predicted HCC incidence. However, the risk of HCC persisted, and careful HCC surveillance remains warranted despite the anti-viral treatment.Am J Gastroenterol advance online publication, 21 June 2016; doi:10.1038/ajg.2016.257.