Racial and Ethnic Disparities in Barriers to Care in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of death in patients with cirrhosis and has a rising mortality rate in the United States.1 Racial and ethnic minorities experience a disproportionate burden of HCC, including higher incidence rates, more late-stage diagnoses, and worse survival.2,3 These disparities are complex in nature and can be attributed to many proximal, intermediate, and distal determinants, such as health literacy and behaviors, social support, social needs, social determinants of health, and access to health care.4 Prior studies have identified racial and ethnic differences in clinical factors, including receipt of HCC surveillance and tumor stage5; however, few studies have examined differences in patient-reported barriers that may partly explain observed disparities. Understanding these data is essential to inform interventions to address and mitigate disparities. Therefore, we described patient-reported barriers to medical care and examined differences in barriers by race and ethnicity in a large, diverse population of patients newly diagnosed with HCC.

Dynamic Changes in Ultrasound Quality for Hepatocellular Carcinoma Screening in Patients With Cirrhosis.

BACKGROUND & AIMS: Identifying patients in whom ultrasound may be inadequate to exclude the presence of hepatocellular carcinoma (HCC) can inform interventions to improve screening effectiveness. We aimed to characterize correlates of suboptimal ultrasound quality and changes in ultrasound quality over time in patients with cirrhosis undergoing HCC screening. METHODS: We performed a retrospective cohort study of patients with cirrhosis who underwent ultrasound examination at 2 large health systems between July 2016 and July 2019. Exam adequacy was graded by radiologists using the LI-RADS Visualization Score (A, B, C); we evaluated changes in visualization over time among patients with >1 ultrasound exams. We performed multivariable logistic regression to identify characteristics associated with limited ultrasound visualization (scores B or C). RESULTS: Of 2053 cirrhosis patients, 1685 (82.1%) had ultrasounds with score A, 262 (12.8%) had score B, and 106 (5.2%) had score C. Limited visualization was associated with alcohol-related or nonalcoholic fatty liver disease cirrhosis and presence of class II-III obesity. Among 1546 patients with >1 ultrasounds, 1129 (73.0%) had the same visualization score on follow-up (1046 score A, 60 score B, 23 score C). However, 255 (19.6%) of 1301 with score A at baseline had limited visualization when repeated (230 score B, 25 score C), and 130 (53.1%) of 245 patients with baseline limited visualization had good visualization when repeated. CONCLUSIONS: Nearly 1 in 5 patients with cirrhosis had moderately-severely limited ultrasound visualization for HCC nodules, particularly those with obesity or alcohol-related or nonalcoholic fatty liver disease cirrhosis. Ultrasound quality can change between exams, including improvement in many patients with limited visualization.

Musculoskeletal Injuries Are Commonly Reported Among Gastroenterology Trainees: Results of a National Survey.

BACKGROUND: Endoscopy-related musculoskeletal injuries are increasingly recognized among gastroenterologists. While injury rates and risk factors have been studied among practicing gastroenterologists, little is known about rates among trainees during fellowship. AIMS: This study analyzes the prevalence of endoscopy-related overuse injuries and risk factors for injuries among a national sample of gastroenterology (GI) fellows. We also surveyed GI fellowship program directors and fellows about perceptions of overuse injuries during GI training. METHODS: We distributed a 29-item electronic survey to GI fellows at accredited programs in the USA in April 2016. Survey items included demographic information, questions pertaining to injuries, and level of agreement on the importance of ergonomics training in GI fellowship. Additionally, we distributed a 7-item electronic survey to fellowship program directors evaluating perception of overuse injuries and prevention during fellowship training. Fisher's exact test determined factors associated with sustaining an injury. RESULTS: An estimated 1509 fellows received the survey. Eleven percent (n = 165) of gastroenterology fellows completed the survey. Twenty percent reported having a musculoskeletal injury. Female gender was the only factor associated with a higher rate of reported injury (p < 0.01). The most common injuries reported were thumb and other hand-related pain (n = 28 [64%]). CONCLUSIONS: Musculoskeletal injuries may affect up to 20% of GI fellows. Female fellows more frequently report injuries and may be at particularly high risk which has not been found in previously reported surveys of practicing gastroenterologists. Standardized curricula on ergonomic considerations and injury prevention are needed to enhance GI fellowship training and reduce injury rates.

Association between ultrasound quality and test performance for HCC surveillance in patients with cirrhosis: a retrospective cohort study.

BACKGROUND: Ultrasound visualisation is limited in approximately 20% of patients with cirrhosis undergoing hepatocellular carcinoma (HCC) surveillance; however, it is unknown if impaired visualisation directly impacts test performance. We aimed to evaluate the association between ultrasound visualisation and surveillance test performance. METHODS: We performed a retrospective cohort study among patients with cirrhosis, with or without HCC, who underwent ultrasound-based surveillance at two large health systems between July 2016 and July 2019. Ultrasound visualisation assessment was recorded by interpreting radiologists using the ultrasound LI-RADS Visualisation score. We performed logistic regression analyses to evaluate the association between ultrasound visualisation and diagnostic test performance. We assessed sensitivity for HCC detection among ultrasounds performed in the year prior to HCC diagnoses and specificity using ultrasounds in those without HCC. RESULTS: Among 186 patients with HCC, severely limited visualisation (Vis Score C) on ultrasound prior to HCC diagnosis was associated with increased odds of false-negative results, that is lower sensitivity (OR 7.94, 95% CI 1.23-51.16) in multivariable analysis. Ultrasound sensitivity with visualisation scores A or B exceeded 75%, compared to only 27.3% with visualisation score C. Among 2052 cirrhosis patients without HCC, moderate visualisation limitations (Vis score B) were associated with increased odds of false-positive results (OR 1.60, 1.13-2.27), although specificity exceeded 95% across all visualisation scores. CONCLUSIONS: Impaired ultrasound visualisation is associated with worse surveillance test performance. Alternative blood-based biomarkers and imaging strategies are needed for patients at risk for ultrasound-based surveillance failure.

Computational Redesign of Acyl-ACP Thioesterase with Improved Selectivity toward Medium-Chain-Length Fatty Acids.

Enzyme and metabolic engineering offer the potential to develop biocatalysts for converting natural resources into a wide range of chemicals. To broaden the scope of potential products beyond natural metabolites, methods of engineering enzymes to accept alternative substrates and/or perform novel chemistries must be developed. DNA synthesis can create large libraries of enzyme-coding sequences, but most biochemistries lack a simple assay to screen for promising enzyme variants. Our solution to this challenge is structure-guided mutagenesis in which optimization algorithms select the best sequences from libraries based on specified criteria (i.e. binding selectivity). Here, we demonstrate this approach by identifying medium-chain (C6-C12) acyl-ACP thioesterases through structure-guided mutagenesis. Medium-chain fatty acids, products of thioesterase-catalyzed hydrolysis, are limited in natural abundance compared to long-chain fatty acids; the limited supply leads to high costs of C6-C10 oleochemicals such as fatty alcohols, amines, and esters. Here, we applied computational tools to tune substrate binding to the highly-active 'TesA thioesterase in Escherichia coli. We used the IPRO algorithm to design thioesterase variants with enhanced C12- or C8-specificity while maintaining high activity. After four rounds of structure-guided mutagenesis, we identified three thioesterases with enhanced production of dodecanoic acid (C12) and twenty-seven thioesterases with enhanced production of octanoic acid (C8). The top variants reached up to 49% C12 and 50% C8 while exceeding native levels of total free fatty acids. A comparably sized library created by random mutagenesis failed to identify promising mutants. The chain length-preference of 'TesA and the best mutant were confirmed in vitro using acyl-CoA substrates. Molecular dynamics simulations, confirmed by resolved crystal structures, of 'TesA variants suggest that hydrophobic forces govern 'TesA substrate specificity. We expect that the design rules we uncovered and the thioesterase variants identified will be useful to metabolic engineering projects aimed at sustainable production of medium-chain oleochemicals.