Incidence of Etiology-specific Hepatocellular Carcinoma: Diverging Trends and Significant Heterogeneity by Race and Ethnicity.

BACKGROUND & AIMS: The main causes of hepatocellular carcinoma (HCC) include chronic hepatitis C and B viral infections (HCV, HBV), nonalcoholic fatty liver disease (NAFLD), and alcohol-related disease (ALD). Etiology-specific HCC incidence rates and temporal trends on a population-basis are needed to improve HCC control and prevention. METHODS: All 14,420 HCC cases from the Florida statewide cancer registry were individually linked to data from the hospital discharge agency and the viral hepatitis department to determine the predominant etiology of each case diagnosed during 2010 to 2018. Age-adjusted incidence rates (AAIRs) were used to assess the intersection between etiology and detailed race-ethnicity. Etiology-specific temporal trends based on diagnosis year were assessed using Joinpoint regression. RESULTS: HCV remains the leading cause of HCC among men, but since 2017 NAFLD-HCC is the leading cause among women. HCV-HCC AAIRs are particularly high among U.S.-born minority men, including Puerto Rican (10.9 per 100,000), African American (8.0 per 100,000), and U.S.-born Mexican American men (7.6 per 100,000). NAFLD is more common among all Hispanics and Filipinos and HBV-HCC among Asian and Haitian black men. HCV-HCC surpasses HBV-HCC in Asian women. ALD-HCC is high among specific Hispanic male groups. Population-based HCV-HCC rates experienced a rapid decline since 2015 (-9.6% annually), whereas ALD-HCC (+6.0%) and NAFLD-HCC (+4.3%) are rising (P < .05). CONCLUSIONS: New direct acting anti-viral drugs have impacted rates of HCV-HCC, offsetting important increases in both ALD- and NAFLD-HCC. Hispanics may be a group of concern because of higher rates for ALD- and NAFLD-HCC. HCC etiology varies remarkably and may warrant specific interventions by detailed race-ethnicity.

Multiple Barriers Impede Screening for Hepatitis Delta: An Internet-Based Survey of Healthcare Providers.

INTRODUCTION: Hepatitis delta virus (HDV) increases risk of cirrhosis and hepatocellular carcinoma in patients with hepatitis B; however, HDV screening rates are low. We assessed providers' perceived barriers to HDV screening and management. METHODS: We distributed an Internet-based survey to members of 3 gastroenterology/hepatology organizations. RESULTS: Most respondents, 69.3%, correctly identified the appropriate HDV screening test. Several reported barriers to HDV care, including uncertainty of screening criteria, 55.5%, and lack of treatment knowledge, 66.7%. DISCUSSION: Our findings highlight the need for increased education regarding HDV care. Education should be combined with standardized approaches that increase ease of HDV screening.

Low Health Literacy, Lack of Knowledge, and Self-Control Hinder Healthy Lifestyles in Diverse Patients with Steatotic Liver Disease.

INTRODUCTION: In parallel with the obesity and diabetes epidemics, steatotic liver disease (SLD) has emerged as a major global public health concern. The mainstay of therapy is counseling on weight loss and increased exercise. However, such lifestyle modifications infrequently lead to success. We aimed to identify barriers to diet and lifestyle modification in patients with SLD. METHODS: Patients with SLD completed a 14-item questionnaire that assigned barriers to healthy eating to three categories: lack of knowledge, lack of self-control, and lack of time, with a higher summary score indicating more perceived barriers. We administered assessments of health literacy and physical activity. We analyzed the data using descriptive statistics and ordinal regression analysis. RESULTS: We included 151 participants with a median age of 64; 54% were female and 68.2% were Hispanic. Median BMI was 31.9 kg/m2. Most respondents, 68.2%, had low health literacy and were either underactive, 29.1% or sedentary, 23.2%. Lack of self-control was the strongest barrier to achieving a healthy lifestyle, followed by lack of knowledge. Lack of time was not significant barrier. Patients with the most significant barriers were more likely to have obesity, low health literacy, and be sedentary. DISCUSSION: Lack of self-control and knowledge are the greatest barriers to adopting a healthy lifestyle in patients with SLD. Future clinical interventions should integrate education that targets various health literacy levels with behavioral approaches to improve a sense of agency.

Actionable Solutions to Achieve Health Equity in Chronic Liver Disease.

There are well-described racial and ethnic disparities in the burden of chronic liver diseases. Hispanic persons are at highest risk for developing nonalcoholic fatty liver disease, the fastest growing cause of liver disease. Hepatitis B disproportionately affects persons of Asian or African descent. The highest rates of hepatitis C occur in American Indian and Alaskan Native populations. In addition to disparities in disease burden, there are also marked racial and ethnic disparities in access to treatments, including liver transplantation. Disparities also exist by gender and geography, especially in alcohol-related liver disease. To achieve health equity, we must address the root causes that drive these inequities. Understanding the role that social determinants of health play in the disparate health outcomes that are currently observed is critically important. We must forge and/or strengthen collaborations between patients, community members, other key stakeholders, health care providers, health care institutions, professional societies, and legislative bodies. Herein, we provide a high-level review of current disparities in chronic liver disease and describe actionable strategies that have potential to bridge gaps, improve quality, and promote equity in liver care.

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.

Utility of Commercially Available Quantitative hCG Immunoassays as Tumor Markers in Trophoblastic and Non-Trophoblastic Disease.

BACKGROUND: The use of quantitative human chorionic gonadotropin (hCG) as a tumor marker is widely accepted despite lack of FDA-approval for oncology. Differences in iso- and glycoform recognition among hCG immunoassays is well established, exhibiting wide inter-method variability. Here, we assess the utility of 5 quantitative hCG immunoassays for use as tumor markers in trophoblastic and non-trophoblastic disease. METHODS: Remnant specimens were obtained from 150 patients with gestational trophoblastic disease (GTD), germ cell tumors (GCT), or other malignancies. Specimens were identified by review of results from physician-ordered hCG and tumor marker testing. Five analyzer platforms were used for split specimen analysis of hCG: Abbott Architect Total, Roche cobas STAT, Roche cobas Total, Siemens Dimension Vista Total, and Beckman Access Total. RESULTS: Frequency of elevated hCG concentrations (above reference cutoffs) was highest in GTD (100%), followed by GCT (55% to 57%), and other malignancies (8% to 23%). Overall, the Roche cobas Total detected elevated hCG in the greatest number of specimens (63/150). Detection of elevated hCG in trophoblastic disease was nearly equivalent among all immunoassays (range, 41 to 42/60). CONCLUSIONS: While no immunoassay is likely to be perfect in all clinical situations, results for the 5 hCG immunoassays evaluated suggest that all are adequate for use of hCG as a tumor marker in gestational trophoblastic disease and select germ cell tumors. Further harmonization of hCG methods is needed as serial testing for biochemical tumor monitoring must still be performed using a single method. Additional studies are needed to assess the utility of quantitative hCG as a tumor marker in other malignant disease.

Compound-Specific Behavioral and Enzymatic Resistance to Toxic Milkweed Cardenolides in a Generalist Bumblebee Pollinator.

Plant secondary metabolites that defend leaves from herbivores also occur in floral nectar. While specialist herbivores often have adaptations providing resistance to these compounds in leaves, many social insect pollinators are generalists, and therefore are not expected to be as resistant to such compounds. The milkweeds, Asclepias spp., contain toxic cardenolides in all tissues including floral nectar. We compared the concentrations and identities of cardenolides between tissues of the North American common milkweed Asclepias syriaca, and then studied the effect of the predominant cardenolide in nectar, glycosylated aspecioside, on an abundant pollinator. We show that a generalist bumblebee, Bombus impatiens, a common pollinator in eastern North America, consumes less nectar with experimental addition of ouabain (a standard cardenolide derived from Apocynacid plants native to east Africa) but not with addition of glycosylated aspecioside from milkweeds. At a concentration matching that of the maximum in the natural range, both cardenolides reduced activity levels of bees after four days of consumption, demonstrating toxicity despite variation in behavioral deterrence (i.e., consumption). In vitro enzymatic assays of Na+/K+-ATPase, the target site of cardenolides, showed lower toxicity of the milkweed cardenolide than ouabain for B. impatiens, indicating that the lower deterrence may be due to greater tolerance to glycosylated aspecioside. In contrast, there was no difference between the two cardenolides in toxicity to the Na+/K+-ATPase from a control insect, the fruit fly Drosophila melanogaster. Accordingly, this work reveals that even generalist pollinators such as B. impatiens may have adaptations to reduce the toxicity of specific plant secondary metabolites that occur in nectar, despite visiting flowers from a wide variety of plants over the colony's lifespan.

Female and male Leach's Storm Petrels (Hydrobates leucorhous) pursue different foraging strategies during the incubation period.

Reproduction in procellariiform birds is characterized by a single egg clutch, slow development, a long breeding season and obligate biparental care. Female Leach's Storm Petrels Hydrobates leucorhous, nearly monomorphic members of this order, produce eggs that are between 20 and 25% of adult body weight. We tested whether female foraging behaviour differs from male foraging behaviour during the ~ 44-day incubation period across seven breeding colonies in the Northwest Atlantic. Over six breeding seasons, we used a combination of Global Positioning System and Global Location Sensor devices to measure characteristics of individual foraging trips during the incubation period. Females travelled significantly greater distances and went farther from the breeding colony than did males on individual foraging trips. For both sexes, the longer the foraging trip, the greater the distance. Independent of trip duration, females travelled farther, and spent a greater proportion of their foraging trips prospecting widely as defined by behavioural categories derived from a Hidden Markov Model. For both sexes, trip duration decreased with date. Sex differences in these foraging metrics were apparently not a consequence of morphological differences or spatial segregation. Our data are consistent with the idea that female foraging strategies differed from male foraging strategies during incubation in ways that would be expected if females were still compensating for egg formation.

Clinical, histological and molecular profiling of different stages of alcohol-related liver disease.

OBJECTIVE: Alcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking. DESIGN: Two large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed. RESULTS: Age and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism. CONCLUSIONS: Despite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.

Emerging drugs for the treatment of hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) remains a leading cause of liver-related mortality. Cirrhosis of any etiology is the major risk factor although HCC can develop in its absence in patients with hepatitis B and increasingly in those with nonalcoholic fatty liver disease. When detected at an early stage, curative options include surgical resection, liver transplantation, and/or ablative therapies. Unfortunately, most cases of HCC are recognized at an advanced stage when options are limited and noncurative. However, new systemic therapies with tyrosine kinase inhibitors and immunotherapy have expanded therapeutic options in advanced HCC. Advances in systemic therapy have given patients with advanced HCC hope and prolonged their survival. AREAS COVERED: We discuss recent data and ongoing research efforts to improve the treatment of hepatocellular carcinoma with discussion of current and upcoming systemic therapies combining agents of different classes. EXPERT OPINION: Systemic therapy for HCC is in evolution. The inclusion of immunotherapy to systemic therapy has revolutionized the field of HCC treatment. Identification of the appropriate combination and sequence of systemic therapy coupled with discovery of reliable HCC biomarkers will lead to improved survival and individualized HCC therapy.

Efficacy and Tolerability of a Retinoid Eye Cream for Fine to Moderate Wrinkles of the Periorbital Region.

INTRODUCTION: The periorbital region is susceptible to premature skin aging and among the first areas to manifest age-related changes. Retinoids are highly effective but can be irritating, limiting use in this vulnerable area. A hydrating formulation comprised of a double-conjugated retinoid/alpha hydroxy acid (lactic acid; AHARet-EM) has been developed to address photoaging of the periorbital area. This study evaluated the efficacy, tolerability, and subject satisfaction of nightly application of AHARet-EM, and a regimen that included application of a peptide-rich eye cream (InF-E; AM) and AHARet-EM (PM). DESIGN: A 12-week, dual-center, open-label study evaluated nightly application of AHARet-EM in subjects 35 to 65 years of age with fine to moderate lines/wrinkles in the periorbital area (3-7 score based on the Fitzpatrick Classification Wrinkle Scale [FCWS]). A subset of subjects applied AHARet-EM (PM) and InF-E (AM). Investigator assessments at baseline and weeks 4, 8, and 12 were based on the 9-point FCWS for lines/wrinkles (1 [Fine Wrinkles] to 9 [Deep Wrinkles]) and a 6-point scale (0 [None] to 5 [Severe]) for texture, erythema, and under-eye darkness, puffiness, and dryness. Subject satisfaction and adverse events (AEs) were captured over 12 weeks. RESULTS: Twenty-six subjects, Fitzpatrick skin type III-VI, completed the study. Subjects applying AHARet-EM (n=16) demonstrated significant improvements from baseline at week 12 in the appearance of lines/wrinkles (33%; P<.0001), texture (37%, P<.0001), erythema (37%, P=.004), under-eye darkness (41%; P<.001), puffiness (55%, P<.0001) and dryness (94%, P<.0001). Significant improvements from baseline were demonstrated in subjects using the AM/PM regimen (n=10) at week 12 in the appearance of texture (33%; P=.002), erythema (68%; P=.001), under-eye darkness (32%; P=.007), puffiness (64%; P=.01) and dryness (90%; P<.0001). No AEs occurred related/possibly related to use of the study products. High levels of subject satisfaction were reported over 12 weeks. CONCLUSION: Nightly application of a hydrating, double-conjugated retinoid eye cream demonstrated significant improvements in the appearance of lines/wrinkles, under-eye darkness, puffiness, and dryness of the periorbital area at week 12. Morning application of a peptide-rich eye cream afforded additional benefits. The study products were non-irritating, and subjects reported high levels of satisfaction throughout the study. J Drugs Dermatol. 2022;21(9):932-937. doi:10.36849/JDD.6815.

Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: An international registry study.

BACKGROUND & AIMS: Chronic liver disease (CLD) and cirrhosis are associated with immune dysregulation, leading to concerns that affected patients may be at risk of adverse outcomes following SARS-CoV-2 infection. We aimed to determine the impact of COVID-19 on patients with pre-existing liver disease, which currently remains ill-defined. METHODS: Between 25th March and 8th July 2020, data on 745 patients with CLD and SARS-CoV-2 (including 386 with and 359 without cirrhosis) were collected by 2 international registries and compared to data on non-CLD patients with SARS-CoV-2 from a UK hospital network. RESULTS: Mortality was 32% in patients with cirrhosis compared to 8% in those without (p <0.001). Mortality in patients with cirrhosis increased according to Child-Pugh class (A [19%], B [35%], C [51%]) and the main cause of death was from respiratory failure (71%). After adjusting for baseline characteristics, factors associated with death in the total CLD cohort were age (odds ratio [OR] 1.02; 1.01-1.04), Child-Pugh A (OR 1.90; 1.03-3.52), B (OR 4.14; 2.4-7.65), or C (OR 9.32; 4.80-18.08) cirrhosis and alcohol-related liver disease (OR 1.79; 1.03-3.13). Compared to patients without CLD (n = 620), propensity-score-matched analysis revealed significant increases in mortality in those with Child-Pugh B (+20.0% [8.8%-31.3%]) and C (+38.1% [27.1%-49.2%]) cirrhosis. Acute hepatic decompensation occurred in 46% of patients with cirrhosis, of whom 21% had no respiratory symptoms. Half of those with hepatic decompensation had acute-on-chronic liver failure. CONCLUSIONS: In the largest such cohort to date, we demonstrate that baseline liver disease stage and alcohol-related liver disease are independent risk factors for death from COVID-19. These data have important implications for the risk stratification of patients with CLD across the globe during the COVID-19 pandemic. LAY SUMMARY: This international registry study demonstrates that patients with cirrhosis are at increased risk of death from COVID-19. Mortality from COVID-19 was particularly high among patients with more advanced cirrhosis and those with alcohol-related liver disease.

HCV testing: Order and completion rates among baby boomers obtaining care from seven health systems in Florida, 2015-2017.

Many U.S. residents infected with hepatitis C virus (HCV) are baby boomers (born 1945-1965), who remain undiagnosed. Past CDC and USPSTF guidelines recommended one-time HCV testing for all baby boomers, with newer guidelines recommending universal screening for all adults. This retrospective cohort study examined electronic medical records for patient visits from 2015 to 2017 within the OneFlorida Data Trust and University of South Florida Health system. We assessed percentages of HCV tests ordered and completed across four age groups (those born before 1945, 1945-1965, 1966-1985, and after 1985). In 2019, we used logistic regression to examine factors associated with HCV test ordering and completion among baby boomers, including age, race, sex, number of primary care visits, HIV status, hepatitis diagnosis, and liver cancer history. All age groups had low rates of HCV test orders. 4.4% of baby boomers had a test ordered in 2015, and 6.7% in 2016. Of those, 94.5% and 89.7% completed testing, respectively. All other races/ethnicities had lower likelihood of testing completion than Whites (Blacks (aOR 0.82, 95%, CI 0.75-0.91); Asians (0.69, 0.52-0.92); Hispanics (0.29, 0.26-0.32)), although test orders were higher for Asians (1.48, 1.37-1.61) and Blacks (1.78, 1.73-1.82). Tests ordered (11.42, 10.94-11.92) and completed (2.25, 1.94-2.60) were more likely among those with hepatitis history. Test orders were more likely for HIV-positive patients (3.68, 3.45-3.93), but completion was less likely (0.67, 0.57-0.78). Interventions are needed to increase testing rates so that HCV infections are treated early, mitigating HCV-related morbidity and mortality, especially related to liver cancer.

A Case of Dubin-Johnson Syndrome Presenting as Neonatal Cholestasis With Paucity of Interlobular Bile Ducts.

Dubin-Johnson syndrome (DJS) is a rare autosomal recessive disorder that typically manifests in young adulthood as jaundice with conjugated hyperbilirubinemia. We report a case presenting as neonatal cholestasis with the unexpected histologic finding of paucity of interlobular bile ducts, a feature that is not typically seen in DJS. The diagnosis was confirmed by absent canalicular multidrug-resistance-associated protein 2 (MRP2) immunohistochemical staining on liver biopsy tissue and molecular genetic testing that demonstrated heterozygous mutations in the ATP-Binding Cassette Subfamily C Member 2 (ABCC2) gene, including a novel missense mutation. This report describes a case of DJS with atypical clinicopathologic findings and suggests that DJS should be considered in patients with neonatal cholestasis and bile duct paucity.

A mixed-methods approach to understanding perceptions of hepatitis B and hepatocellular carcinoma among ethnically diverse Black communities in South Florida.

PURPOSE: Hepatitis B (HBV), the leading cause of hepatocellular carcinoma (HCC), disproportionately affects minorities. Compared to other races, Blacks more often present with advanced HCC and have decreased survival. We observed higher HBV-associated HCC rates among Blacks than reported nationally. In our center, Haitian Blacks had the highest rates of HBV-associated HCC and shorter survival compared to other Blacks. We investigated knowledge and perceptions regarding HBV and HCC among Blacks born in the United States or Haiti. METHODS: Using community partnerships, participants were recruited via word of mouth, email, social media or from Hepatology clinic. Focus groups were conducted in Haitian Creole or English and stratified by birthplace, gender and infection status. Discussions were audio-recorded and transcribed verbatim. A constant comparative method was used for data analysis; themes are based on conversational details. RESULTS: There were 55 participants; 49% were male and 27% had chronic HBV. Only 42% of Haitian Blacks knew about HBV prior to participation vs. 78% of African Americans, p 0.03. Both groups expressed that fear, mistrust of the medical establishment, denial and stigma might compel persons to avoid seeking care. Both groups attributed higher rates of late stage HCC diagnosis in Blacks to inadequate financial resources and education. Those with HBV reported confusion regarding their infection and suboptimal communication with healthcare providers. CONCLUSIONS: In two communities disproportionately affected by HBV, misconceptions about disease transmission, stigma, low health literacy and decreased access to care may limit detection for HBV. Culturally relevant community-based interventions are needed to increase HBV detection.

The association between etiology of hepatocellular carcinoma and race-ethnicity in Florida.

BACKGROUND AND AIM: The incidence of hepatocellular carcinoma (HCC) has risen considerably in the US since 1980. The main causes include metabolic disorders (NAFLD, diabetes, obesity, metabolic syndrome), alcohol-related disease (ALD) and hepatitis C and B virus infections (HCV, HBV). Etiology-specific HCC incidence rates by detailed race-ethnicity are needed to improve HCC control and prevention efforts. METHODS: All HCC cases diagnosed in Florida during 2014-2015 were linked to statewide hospital discharge data to determine etiology. Age-specific and age-adjusted rates were used to assess the intersection between etiology and detailed racial-ethnicities, including White, African American, Afro-Caribbean, Asian, Cuban, Puerto Rican and Continental Hispanic (Mexican, South and Central American). RESULTS: Of 3666 HCC cases, 2594 matched with discharge data. HCV was the leading cause of HCC among men and women (50% and 43% respectively), followed by metabolic disorders (25% and 37%) and ALD (16% and 9%). Puerto Rican and African American men had the highest HCV-HCC rates, 7.9 and 6.3 per 100 000 respectively. Age-specific rates for HCV-HCC peaked among baby boomers (those born in 1945-1965). Metabolic-HCC rates were highest among populations above age 70 and among Continental Hispanics. Afro-Caribbean men had high rates of HBV-HCC, whereas Puerto Rican men had high ALD-HCC. CONCLUSIONS: HCC etiology is associated with specific race/ethnicity. While HCV-related HCC rates are projected to decrease soon, HCC will continue to affect Hispanics disproportionately, based on higher rates of metabolic-HCC (and ALD-HCC) among Continental Hispanics, who demographically represent 80% of all US Hispanics. Multifaceted approaches for HCC control and prevention are needed.

Knowledge and Perceptions of Hepatitis B and Hepatocellular Carcinoma Screening Guidelines Among Trainees: A Tale of Three Centers.

BACKGROUND: Hepatitis B (HBV), the leading cause of hepatocellular carcinoma (HCC) worldwide, disproportionately affects minorities in the USA. Undiagnosed HBV precludes HCC screening and contributes to late-stage cancer presentation and decreased survival. Barriers to HBV and HCC screening include lack of insurance and limited diffusion of guidelines. We aimed to assess knowledge about HBV and HCC screening indications and explore barriers to screening. METHODS: We surveyed trainees from the University of Miami/Jackson Memorial Hospitals, Palmetto General Hospital, and Mount Sinai Medical Center. We assessed knowledge using clinical vignettes. We performed bivariate and Chi-squared analyses. RESULTS: There were 183 respondents; median age was 31 and 52% were male. The sample was 35% Hispanic, 29% White, 18% Asian, and 9% Black. Training department was Internal Medicine, 71%; Family Medicine, 11%; Infectious Diseases, 6%; or Gastroenterology, 7%. Only 59% correctly estimated national HBV prevalence; 25% correctly estimated global prevalence. In vignettes with behavioral risk factors, trainees correctly advised screening, 63-96%. However, when the risk factor was the birthplace, correct responses ranged from 33 to 53%. Overall, 45% chose an incorrect combination of HBV screening tests. Perceived barriers to screening included limited expertise in screening of immigrants and limited patient education. Respondents were more likely to recommend HCC screening in cirrhotic patients versus non-cirrhotic HBV patients. Key barriers to HCC screening included uncertainty about HCC guidelines and patient financial barriers. CONCLUSIONS: Knowledge of HBV and HCC screening recommendations is suboptimal among trainees. Efforts to broadly disseminate HBV and HCC guidelines through targeted educational interventions are needed.

In situ cell differentiation monitoring of Catharanthus roseus suspension culture processes by NIR spectroscopy.

Plant suspension culture is attracting interest as a promising platform to produce biological medicines due to the absence of virus, prions or DNA related to mammals during the production process. However, the heterogenic plant cell proliferation nature is particularly challenging for establishing industrial processes based on innovative approaches currently used, particularly in the animal cell culture industry. In this context, while Process Analytical Technology (PAT) tools have been used to monitor classical parameters such as biomass dry weight, its use in cells heterogeneity has received limited attention. Therefore, the feasibility of in situ monitoring of cell differentiation in plant cell suspensions employing NIR spectroscopy and chemometrics was investigated. Off-line measurements of cell heterogeneity in term of cell differentiation and in-line NIR spectra captured in 3 L bioreactor cultures were employed to generate calibration models. Then models were tested to estimate the population distribution of parenchyma, collenchyma and sclerenchyma cells during Catharanthus roseus suspension cultures. Results have proven in situ NIR spectroscopy as a capable PAT tool to monitor differentiated cells accurately and in real-time. These results are the starting point to follow-up PAT systems so that plant cell culture heterogeneity may be better understood and controlled in biopharmaceutical plant cell cultures.

Phase 2 study of pembrolizumab and circulating biomarkers to predict anticancer response in advanced, unresectable hepatocellular carcinoma.

BACKGROUND: Checkpoint inhibitors have shown modest activity in patients with advanced hepatocellular carcinoma (HCC). Herein, the authors report a prospective single-institution clinical/translational phase 2 study of pembrolizumab in patients with advanced HCC and circulating biomarkers closely related to response. METHODS: Pembrolizumab was administered at a dose of 200 mg intravenously every 3 weeks among patients who may have developed disease progression while receiving, were intolerant of, or refused sorafenib. The circulating levels of cytokines, chemokines, programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and PD-L2 were correlated with response, tumor PD-L1 expression, and other clinicopathological features. RESULTS: A total of 29 patients were treated and 28 patients were evaluable for response. The most common laboratory grade 3/4 adverse events were increases in aspartate aminotransferase and/or alanine aminotransferase and serum bilirubin, which for the most part were reversible. In terms of efficacy, one patient achieved a complete response and 8 patients achieved partial responses for an overall response rate of 32%. Four other patients had stable disease. The median progression-free survival was 4.5 months and the median overall survival was 13 months. Response did not correlate with prior sorafenib therapy, PD-L1 tumor staining, or a prior history of hepatitis. Correlative studies revealed that high baseline plasma TGF-ß levels (≥200 pg/mL) significantly correlated with poor treatment outcomes after pembrolizumab. Tumor PD-L1 and plasma PD-L1/PD-1 levels were associated with plasma IFN-γ or IL-10. CONCLUSIONS: Pembrolizumab was found to demonstrate activity in patients with advanced HCC. Toxicity generally was tolerable and reversible. A set of immunological markers in blood plasma as well as PD-L1 staining indicated that baseline TGF-ß could be a predictive biomarker for response to pembrolizumab.

Structural Interventions to Reduce and Eliminate Health Disparities.

Health disparities research in the United States over the past 2 decades has yielded considerable progress and contributed to a developing evidence base for interventions that tackle disparities in health status and access to care. However, health disparity interventions have focused primarily on individual and interpersonal factors, which are often limited in their ability to yield sustained improvements. Health disparities emerge and persist through complex mechanisms that include socioeconomic, environmental, and system-level factors. To accelerate the reduction of health disparities and yield enduring health outcomes requires broader approaches that intervene upon these structural determinants. Although an increasing number of innovative programs and policies have been deployed to address structural determinants, few explicitly focused on their impact on minority health and health disparities. Rigorously evaluated, evidence-based structural interventions are needed to address multilevel structural determinants that systemically lead to and perpetuate social and health inequities. This article highlights examples of structural interventions that have yielded health benefits, discusses challenges and opportunities for accelerating improvements in minority health, and proposes recommendations to foster the development of structural interventions likely to advance health disparities research.