Alcohol-related Disease Research Articles

Effect of gibberellic acid treatment and alternating temperature on breaking physiological dormancy and germination inPenthorum chinensePursh (Penthoraceae)

Penthorum chinense(Penthoraceae) is a threatened South Korean medicinal plant used to treat alcohol-related diseases and prepare cosmetics in traditional Chinese medicine. Wetlands, the native habitat of this plant, have been decreasing owing to damage caused by landisation and urban development in recent years. In this study, we considered the effect of temperature and gibberellic acid treatment onP. chinenseseed germination to improve conservation outcomes of the species. The optimum germination temperature was investigated using constant and alternating temperature treatments (60 conditions). In addition, gibberellic acid (GA3) treatment was performed to overcome physiological dormancy. We determined the germination (GP, %) and the number of days to reach 50% maximum germination (T50). The optimum temperature regime was 7°C / 23°C: GP was 95%, and T50was 15 days. The GA3treatment increased the GP ofP. chinenseseeds from 28 to 94% and decreased the T50value from 14.6 to 6.3 days at concentrations above 40 mg L–1. After the GA3treatment, the growth of radicles was delayed or inhibited. For the germination ofP. chinenseseeds, a diurnal temperature difference of ≥ 15°C is required.

Alcohol-related diseases and liver metastasis: Role of cell-free network communication.

Alcohol intake is a risk factor for cancer development and metastatic disease progression. Extracellular vesicle (EV)-mediated interorgan communication is assumed to be significant in boosting tumorigenic pathways and disease progression. Recent research indicates that exosomes have a variety of roles in the development of cancer during pathophysiological conditions. The involvement of EV signaling during cancer progression in the alcohol environment is unknown. Therefore, understanding communication networks and the role of EVs as biomarkers can contribute significantly to developing strategies to address the serious public health problems associated with alcohol consumption and cancer.

Alcohol solution strength preference predicts compulsive-like drinking behavior in rats.

Understanding compulsive drinking behavior is key to improving outcomes in the treatment of addiction. In the present study, we investigated compulsive-like drinking in alcohol-addicted rats using the alcohol deprivation effect (ADE) model of relapse behavior, which involves repeated deprivation and reintroduction phases; the latter approximate relapse. High-resolution longitudinal drinking and locomotor data were measured while rats (n= 30) underwent a four-bottle (water, 5%, 10%, 20% alcohol v/v) free-choice ADE paradigm. Alcohol bottles were adulterated with the bitter compound quinine during a reintroduction phase to test for compulsive behavior. We characterized how drinking and locomotor behavior during ADE + quinine differed from a regular ADE and how, at the individual level, behavioral parameters extracted from the regular ADE related to compulsive-like drinking. Associations of drinking with locomotor activity were also examined. In the ADE with quinine, we observed reduced consumption of alcohol and a shift to preference for stronger alcohol. Quinine acted by decreasing both the access size and frequency of drinking of 5% alcohol while increasing the frequency of consumption of 20% alcohol. Preference for higher alcohol concentrations prior to the quinine challenge was associated with greater compulsive-like drinking behavior; higher baseline consumption of 20% alcohol correlated with more drinking of quinine-adulterated solutions while high frequency and amount of 5% alcohol consumption at baseline were correlated with being more strongly affected by quinine. Associations between locomotor activity and drinking behavior were observed at the hourly level. These associations reflected changing preferences across experimental phases. Drinking patterns, and specifically solution preference, may offer insights into the presentation of compulsive-like drinking. The findings provide a preclinical basis for observations from epidemiological studies that link higher risk and burden of alcohol-related disease to stronger alcohol concentrations and encourage further translational studies to better understand the underlying mechanisms.

'I have a healthy relationship with alcohol': Australian midlife women, alcohol consumption and social class.

Alcohol consumption by Australian women during midlife has been increasing. Health promotion efforts to reduce alcohol consumption in order to reduce alcohol-related disease risk compete with the social contexts and value of alcohol in women's lives. This paper draws on 50 qualitative interviews with midlife women (45-64 years of age) from different social classes living in South Australia in order to gain an understanding of how and why women might justify their relationships with alcohol. Social class shaped and characterized the different types of relationships with alcohol available to women, structuring their logic for consuming alcohol and their ability to consider reducing (or 'breaking up with') alcohol. We identified more agentic relationships with alcohol in the narratives of affluent women. We identified a tendency for less control over alcohol-related decisions in the narratives of women with less privileged life chances, suggesting greater challenges in changing drinking patterns. If classed differences are not attended to in health promotion efforts, this might mitigate the effectiveness of alcohol risk messaging to women.

P1225: SECONDARY PRIMARY MALIGNANCIES (SPM) AFTER HIGH-DOSE CHEMOTHERAPY (HDT) WITH AUTOLOGOUS STEM CELL TRANSPLANT (ASCT) FOR LYMPHOMA: A DANISH NATIONWIDE COHORT STUDY

Background: High-dose chemotherapy (HDT) with autologous stem cell transplant (ASCT) have resulted in more long-term lymphoma survivors. However, HDT-ASCT is potentially associated with an increased risk of secondary primary malignancies (SPM) leading to loss of lifetime for these patients. Aims: To investigate the risk and types of SPM in lymphoma patients treated with HDT-ASCT compared to the risk of malignancies in a matched background population and to explore risk factors for SPM in HDT-ASCT treated lymphoma patients. Methods: In a nationwide matched cohort study, The Danish Lymphoma Register was used to identify all adult patients treated with HDT-ASCT in Denmark between 2001-2017 for diffuse large B-cell lymphoma, Hodgkin lymphoma, peripheral T-cell lymphoma, or mantle cell lymphoma, excluding patients with other prior cancers. Patients were matched in a ratio of 1:5 to cancer-free comparators from the Danish background population. Malignancies were identified in the Danish National Patient Register using ICD-10 codes and compared between the two groups using the Aalen-Johansen estimator, Cox regression, and incidence rate ratios (IRRs). Results: A total of 856 HDT-ASCT treated lymphoma patients and 4,280 matched comparators were followed for a median of 8 years. The cumulative risk of SPM with death as competing risk was higher for patients compared to comparators with risks at 5, 10, and 15 years of 8.9% [95% confidence interval 6.9;11.0], 16.3% [13.3;19.3], and 20.1% [16.1;24.2] for patients compared to 4.8% [4.1;5.5], 10.5% [9.3;11.7], and 16.6% [14.6;18.5] for comparators (Fig. 1a). The crude hazard ratio (HR) of SPM among patients vs comparators was 2.26 [1.83;2.79]. After adjusting for sex, educational level (low/high), chronic obstructive pulmonary disease (COPD), and alcohol-related diseases (neurological, mental, cardiovascular, or chronic use), the HR was 2.50 [2.02;3.10]. Compared to comparators, patients had increased rates of non-melanoma skin cancer (IRR 3.47 [2.18;5.38]) and myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) (IRR 35.32 [15.73; 94.26]) (Table 1). Rates of other malignancies (oral, gastrointestinal, respiratory, breast, female- or male genital, urinary, soft tissue, and melanoma) were similar between the two groups. The 15-year cumulative risk of MDS/AML was 4.6% [2.8;6.3] for patients (Fig. 1c) and the median overall survival following secondary MDS/AML was only 7 months. In comparison, median overall survival was 40 months in a sex- and age matched background population with newly diagnosed MDS/AML (Fig. 1d). Risk factors for SPM in lymphoma patients were older age (HR 1.06 [1.04;1.08] per year) and COPD (HR 3.15 [1.16;8.57]). Prior therapy (number of lines, intensive chemotherapy, radiotherapy), time since diagnosis, Ann Arbor stage, performance status, alcohol-related disease, and education were not associated with SPM. Table 1. - Rates of SPM per 1,000 person-years in lymphoma patients and matched comparators Comparators Patients SPM type Rate Rate IRR IRR 95% CI Overall 11.35 24.77 2.18 1.76; 2.18 Hematological 0.45 7.74 17.05 9.5; 32.16 MDS/AML 0.18 6.41 35.32 15.73; 94.26 MDS 0.12 3.98 32.89 12.27; 113.84 AML 0.06 2.43 40.19 10.79; 259.78 Non-melanoma skin cancer 1.79 6.19 3.47 2.18; 5.38 Image:Summary/Conclusion: Lymphoma patients treated with HDT-ASCT have an increased risk of SPM compared to a matched background population, especially for non-melanoma skin cancer and MDS/AML. Risk factors for SPM in patients were older age and COPD. These findings are important in the light of new potential treatment alternatives, such as CAR-T.

Sex-Specific Effects of Acute Ethanol Exposure on Locomotory Activity and Exploratory Behavior in Adult Zebrafish (Danio rerio).

The zebrafish (Danio rerio) is an established model organism in pharmacology and biomedicine, including in research on alcohol use disorders and alcohol-related disease. In the past 2 decades, zebrafish has been used to study the complex effects of ethanol on the vertebrate brain and behavior in both acute, chronic and developmental exposure paradigms. Sex differences in the neurobehavioral response to ethanol are well documented for humans and rodents, yet no consensus has been reached for zebrafish. Here, we show for the first time that male zebrafish of the AB strain display more severe behavioral impairments than females for equal exposure concentrations. Adult zebrafish were immersed in 0, 1 or 2% (v/v) ethanol for 30 min, after which behavior was individually assessed in the zebrafish Multivariate Concentric Square Field™ (zMCSF) arena. Males exposed to 2% ethanol showed clear signs of sedation, including reduced activity, increased shelter seeking and reduced exploration of shallow zones. The 1% male group displayed effects in the same direction but of smaller magnitude; this group also explored the shallow areas less, but did not show a general reduction in activity nor an increase in shelter seeking. By contrast, 1 and 2% exposed females showed no alterations in explorative behavior. Females exposed to 2% ethanol did not display a general reduction in activity, rather activity gradually increased from hypoactivity to hyperactivity over the course of the test. This mixed stimulatory/depressant effect was only quantifiable when locomotory variables were analyzed over time and was not apparent from averages of the whole 30-min test, which may explain why previous studies failed to detect sex-specific effects on locomotion. Our results emphasize the importance of explicitly including sex and time as factors in pharmacological studies of zebrafish behavior. We hypothesize that the lower sensitivity of female zebrafish to ethanol may be explained by their greater body weight and associated larger distribution volume for ethanol, which may render lower brain ethanol concentrations in females.

Tremelimumab (day 1 only) and durvalumab in combination with transarterial chemoemobilization (TACE) in patients with hepatocellular carcinoma (HCC).

e16175 Background: TACE induces a peripheral anti-tumor immune response, which may be amplified by immune checkpoint inhibitors (ICI). Combining TACE with dual ICI therapy has been shown to be safe and feasible. Recent data has suggested that Day-1 only anti-CTLA4 dosing, at a higher level of 300mg, could lead to a stronger immune response, and drive a greater expansion than lower dose regimens, whilst maintaining a tolerable safety profile. This novel schedule has not previously been combined with TACE. Methods: Patients with HCC (Childs Pugh A/B7, Barcelona clinic liver cancer stage B/C; ECOG 0/1; sorafenib-naive or experienced) were enrolled in a pilot study of tremelimumab at 2 dose levels (DL1: 75mg IV q4-weekly x 4 and DL2: 300mg IV D1 only) in combination with durvalumab (1500mg IV q-28d) and TACE (D36 +/- 96 hours) until progression of disease (per irRECIST) or off-study criteria. Peripheral immune monitoring was performed and tumor biopsies were obtained at time of TACE. Results: 13 patients enrolled on study; N = 3 at DL1 and N = 10 at DL2. M:F 10:3. Median age 70 (65-74). BCLC B/C 4/9. Extrahepatic disease 6/7. Aetiology: NASH (N = 3), alcohol-related disease (N = 1), HCV (N = 2), hemochromatosis (N = 1), unknown (N = 6). 1 pt discontinued due to G3 colitis. All patients evaluable for response with 2/10 pts on DL2 experiencing PR (at 8 weeks) and overall 7/13 SD and 1/13 PD as best response. Updated PFS and OS data to be presented. Conclusions: Tremelimumab (Day 1 only) and Durvalumab in combination with TACE is safe and feasible in patients with HCC. Follow-up is ongoing and full safety and efficacy data will be presented. Clinical trial information: 2019-002767-98.

Increased Risk for Substance Use-Related Problems in Mild Intellectual Disability: A Population-Based Cohort Study

IntroductionIntellectual disability (ID) has been linked to substance use-related problems (SUP). However, previous research is limited by the small sample sizes, lack of general population comparison and have not accounted for familial confoundings. The role of other psychiatric comorbidities also remains unknown.ObjectivesTo examine the risk of SUP in individuals with mild-ID and assess whether the associations depend on other psychiatric comorbidities, controlling for potential familial confounding.MethodsPopulation-based cohort study of individuals born in Sweden 1973-2003. We identified 19,078 individuals with mild-ID, 953,900 reference individuals from the general population, and 20,722 full-siblings of individuals with mild-ID. Conditional logistic regression models were used to compare individuals with mild-ID to the general population and their full-siblings regarding the risk of SUP, including alcohol and substance use disorders, alcohol and substance-related somatic diseases, substance-related crime, and substance-related death. Analyses were repeated stratified by the presence of psychiatric comorbidities.ResultsIndividuals with mild-ID had increased risks of any SUP (adjusted OR [95%CI]: 1.41 [1.35, 1.47]), compared to the general population, including alcohol-related somatic diseases (3.27 [1.92, 5.59]), alcohol (2.05 [1.91, 2.22]) and drug-use disorder (1.79 [1.69, 1.91]), and alcohol (1.36 [1.19, 1.49]) and drug-related crime (1.27 [1.19, 1.36]). The risk of SUP for individuals with mild ID was particularly elevated with comorbid mood (3.74 [3.47, 4.04]), anxiety (3.30 [3.09, 3.53]) and attention-deficit/hyperactivity disorders (2.61 [2.44, 2.80]). Increased risk of SUP remained significant when controlling for familial confounding.ConclusionsIndividuals with mild-ID, especially those with other psychiatric comorbidities, are at increased risks of SUP.DisclosureNo significant relationships.

Alcohol-Drinking Under Limited-Access Procedures During Mature Adulthood Accelerates the Onset of Cognitive Impairment in Mice.

A history of heavy drinking increases vulnerability to, and the severity of, Alzheimer’s disease (AD) and related dementias, with alcohol use disorder identified as the strongest modifiable risk factor for early-onset dementia. Heavy drinking has increased markedly in women over the past 10 years, particularly in mature adult women during the coronavirus (COVID-19) pandemic. This is concerning as women are more sensitive to many alcohol-related disease states, including AD and related dementias. Herein, we conducted two studies to determine if a 1-month period of binge drinking during mature adulthood (i.e., 5–9 months of age) impairs spatial and working memory to a greater extent in female vs. male C57BL/6J (B6J) mice. The anxiogenic and cognitive-impairing effects of binge drinking were also compared between mature adult and old B6J mice (18 months of age) in a third study. Throughout, females consumed more alcohol than males, indicating that a sex difference in binge drinking persists into old age. Despite the sex difference in intake, we detected no consistent sex difference in our measures of alcohol withdrawal-induced anxiety during a behavioral test battery. Although mature adult females exhibited more cognitive deficits than males, the precise outcome exhibiting a female-selective effect varied across studies. Old mice drank lower amounts of alcohol than mature adult mice, yet their blood ethanol concentrations (BECs) were within error of the 80 mg/dl criterion for binge drinking, indicative of an age-related slowing of alcohol metabolism. As expected, 18-month-old controls exhibited more signs of cognitive impairment than their 6-month-old counterparts, and binge drinking history impaired the Morris water maze performance of mice of both ages. In contrast, binge drinking history impaired the radial arm maze performance of 6-month-old mice only, and the extent of the impairment was comparable to the behavior exhibited by the older mice. We conclude from our studies that: (1) both biological sex and the age of drinking onset are subject factors that impact voluntary alcohol consumption by mice into old age; (2) binge drinking during later life elicits a negative affective state that is relatively sex-independent; (3) binge drinking during both mature adulthood and old age impairs spatial learning and memory; (4) binge drinking during mature adulthood accelerates deficits in working memory; and (5) mature adult females tend to exhibit more alcohol-induced cognitive impairments than males. If relevant to humans, these findings suggest that binge-like drinking by older adult men and women induces a negative affective state and cognitive decline, but that mature adult women, in particular, may be more sensitive to both the immediate and persistent cognitive-impairing effects of heavy drinking.

Clinical analysis of alcoholic pellagra: A single‐center retrospective study

Pellagra caused by niacin deficiency in alcoholics can be easily misdiagnosed because of similar symptoms to other alcohol-related diseases and the lack of the classical triad of signs. This study aimed to define the clinical presentation of alcoholic pellagra for early diagnosis and timely treatment. The clinical data of 16 alcohol-dependent patients who had pellagra and treated in our hospital from January 2002 to December 2019 were retrospectively analyzed. The local medical ethics committee approval (Medical Ethics Committee of Affiliated Hospital of XuZhou Medical University, XYFY2020-KL247-02) for this study has been obtained. The main complaints of the 16 patients were skin lesions (six cases), diarrhea (six cases), and mental disorders (four cases). Then, 13 cases had typical skin lesions, and 3 patients had a full spectrum of diarrhea, dementia, and dermatitis (3D). In terms of the main diagnosis, 2 patients had pellagra and Wernicke's encephalopathy, 3 patients had pellagra and alcohol-withdrawal syndrome, and the other patients had pellagra. After sufficient amounts of niacin and multivitamin B were given, clinical symptoms improved rapidly, and no sequelae were observed during follow-up. Pellagra is rarely manifested as a full 3D spectrum, with only one or two characteristics, which lack diagnostic specificity, especially in individuals with alcoholism. Physicians should maintain a high degree of suspicion of niacin deficiency in alcoholics. Alcohol-dependent patients with pellagra may be accompanied by complications of Wernicke's encephalopathy and alcohol-withdrawal syndrome. Prompt identification and timely treatment with a sufficient amount of niacin in combination with other vitamins and a certain amount of Zn can achieve a good prognosis of pellagra.

The Effects of Alcohol Drinking on Oral Microbiota in the Chinese Population.

The dysbiosis of oral microbiota is linked to numerous diseases and is associated with personal lifestyles, such as alcohol drinking. However, there is inadequate data to study the effect of alcohol drinking on oral microbiota from the Chinese population. Here, we profiled the oral microbiota of 150 healthy subjects in the Chinese population by 16S rRNA gene sequencing. The results showed that drinkers had significantly higher alpha diversity than non-drinkers. A significant difference in overall microbiota composition was observed between non-drinkers and drinkers. Additionally, using DESeq analysis, we found genus Prevotella and Moryella, and species Prevotella melaninogenica and Prevotella tannerae were significantly enriched in drinkers; meanwhile, the genus Lautropia, Haemophilus and Porphyromonas, and species Haemophilus parainfluenzae were significantly depleted in drinkers. PICRUSt analysis showed that significantly different genera were mainly related to metabolism pathways. The oxygen-independent pathways, including galactose, fructose and mannose metabolism pathways, were enriched in drinkers and positively associated with genera enriched in drinkers; while the pyruvate metabolism pathway, an aerobic metabolism pathway, was decreased in drinkers and negatively associated with genera enriched in drinkers. Our results suggested that alcohol drinking may affect health by altering oral microbial composition and potentially affecting microbial functional pathways. These findings may have implications for better understanding the potential role those oral bacteria play in alcohol-related diseases.

In-depth investigation of the mechanisms of Echinacea purpurea polysaccharide mitigating alcoholic liver injury in mice via gut microbiota informatics and liver metabolomics

Accumulating evidence suggests that the pathogenesis of alcoholic liver disease (ALD) is strongly correlated with abnormalities of the gut-liver axis. Echinacea purpurea polysaccharide (EPP) is a homogeneous polysaccharide, which has been shown to mitigate ALD. However, the effects of EPP on gut microbiome and consequently on hepatic metabolism have yet to be explored. In this study, the microbiome and metabolomics were combined to explore the effects of EPP on gut microbiota and hepatic metabolism, and the relationship between both was further revealed by Spearman correlation analysis. Results exhibited EPP reversed alcohol-induced disturbances in gut microbiota, evidenced by increased abundance of Muribaculaceae, Lactobacillus, and Bacteroides and decreased abundance of Escherichia_Shigella and Enterococcus. Besides, EPP promoted the production of n-butyric acid, a short-chain fatty acid that maintains the integrity of the intestinal barrier. Moreover, EPP improved alterations in hepatic metabolites, and characteristic metabolites such as Berberine and Ponasterone as well as key metabolic pathways, particularly Nitrogen metabolism, were identified. Furthermore, correlation analysis suggested significant associations between gut microbes and hepatic metabolites, which in turn confirmed EPP alleviated ALD via the gut-liver axis. Therefore, these findings elucidated in-depth mechanisms of EPP against ALD and provided a new target for intervention in alcohol-related diseases.

Familial Risks for Liver, Gallbladder and Bile Duct Cancers and for Their Risk Factors in Sweden, a Low-Incidence Country.

Simple SummaryFamilial risk of cancer implies that two or more family members are diagnosed with the same cancer. This may be due to the genes or environmental factors that family members share. Familial risk for liver and gallbladder cancer is about 2.7 which means that when one family member is diagnosed with these cancers other family members have 2.7 times higher risk of being diagnosed with the same cancers compared to families were no member is yet diagnosed with these cancers. Risk between spouses is entirely due to shared environmental factors and for liver cancer there is a small risk. The most important way to prevent these cancers is to avoid their risk factors, alcohol, smoking and overweight, and to seek medical care for diabetes and liver infections.We used the Swedish Cancer Registry data to address familial risks for concordant (same) and discordant (different) hepatobiliary cancers, including their associations with any other cancers and with known risk factors. Risks were also assessed between spouses. The analysis covered Swedish families and their cancers between years 1958 and 2018. Adjusted familial risks were expressed as standardized incidence ratios (SIRs). Familial SIRs for concordant hepatocellular carcinoma (HCC) were 2.60, and for gallbladder cancer they were at the same level (2.76). Familial risk was also found for intrahepatic bile duct cancer and for female extrahepatic bile duct cancer. HCC was associated with lung and cervical cancers; extrahepatic bile duct and ampullary cancers were associated with colon and pancreatic cancers, suggesting Lynch syndrome. Among spouses, hepatobiliary cancer was associated with HCC, stomach, pancreatic, cervical and upper aerodigestive tract cancers. Among risk factors, family members diagnosed with alcohol-related disease showed association with HCC. The observed familial risks for hepatobiliary cancers were relatively high, and considering the poor prognosis of these cancers, prevention is of the utmost importance and should focus on moderation of alcohol consumption, vaccination/treatment of hepatitis viral infections and avoidance of overweight and other risk factors of type 2 diabetes.

MEK1/2 inhibitors induce class I alcohol dehydrogenase (ADH1) expression by regulating farnesoid X receptor in hepatic cell lines and C57BL/6J mouse.

Alcohol is mainly catabolized by class I alcohol dehydrogenase (ADH1) in liver. ADH deficiency can aggravate ethanol-induced tissue injury. Extracellular signal-regulated kinases 1/2 (ERK1/2) is involved in alcohol metabolism. However, the relationship between ERK1/2 and ADH1 remains unclear. To inhibit ERK1/2, HepG2 and BNL cells were treated with mitogen-activated protein kinases 1/2 (MEK1/2) inhibitors (U0126 and PD98059), and C57BL/6J mice were fed U0126. After treatment, the protein and mRNA expression of ADH1 were determined by Western blot and quantitative real time-PCR. The activity of ADH1 promoter was detected using luciferase assay. The results showed MEK1/2 inhibitors significantly increased ADH1 protein expression by inducing its transcription activity. Then we demonstrated a farnesoid X receptor (FXR) response element (FXRE) in ADH1 promoter by ChIP assay. To test whether FXR mediates the induction of MEK1/2 inhibitors on ADH1, HepG2 cells were transfected with FXR siRNA or ADH1 promoters with FXRE mutation. We found both FXR siRNA and FXRE mutation in ADH1 promoter abolished MEK1/2 inhibitors-induced ADH1 expression, indicating the activation of MEK1/2 inhibitors on ADH1 depends on FXR. Our findings revealed inhibition of ERK1/2 can significantly increase ADH1 expression, indicating MEK1/2 inhibitors may possess potential application in alcohol-related diseases.

Economic Recession and the Long Term Risk of Psychiatric Disorders and Alcohol Related Diseases-A Cohort Study From Eastern Finland.

BackgroundLong-term development of psychiatric disorders and alcohol-related diseases after economic recessions is insufficiently studied. We investigated the overall impact of the economic recession between 1991 and 1994 in Finland on the long-term incidence of psychiatric and alcohol-related diseases.MethodsA population-based sample of 1,774 women and men aged 53–73 years were examined between 1998 and 2001 from the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD). Participants completed comprehensive questionnaires on the possible impact of the 1990s recession in Finland on their lives. They were followed-up until 2018. Cox proportional hazards regression was used to estimate hazard ratios (HR) of new incident psychiatric and alcohol-related disorders during the 20-years follow-up after linkage to the National Hospital Registry. Logistic regression was used to estimate odds ratios (OR) of psychiatric disorders at baseline.ResultsAt baseline, 93 participants had psychiatric disorders. During 20-years follow-up, 138 new psychiatric disorders and 45 alcohol-related diseases were developed. The covariate-adjusted risk of psychiatric disorders was over twice higher among men who experienced recession-induced hardships compared to those who did not (HR = 2.20, 95%CI = 1.04–4.70, p = 0.04). The risk of alcohol-related diseases was more than four times higher among men with hardships (HR = 4.44, 95%CI = 1.04–18.90, p = 0.04). No such associations were observed among women. No association was observed between recession-induced hardships and having psychiatric disorders at baseline in both genders (multivariate-adjusted p = 0.63 for women, multivariate-adjusted p = 0.36 for men).ConclusionLong-term risk of psychiatric disorders and alcohol-related diseases was increased after the 1990s economic recession in Finland, but only among middle-age and older men.

Cancer and other alcohol–related diseases in women and men

Cancer and other alcohol–related diseases in women and men

Tremelimumab (day 1 only) and durvalumab in combination with transarterial chemoemobilization (TACE) in patients with hepatocellular carcinoma (HCC).

451 Background: TACE induces a peripheral anti-tumor immune response, which may be amplified by immune checkpoint inhibitors (ICI). Combining TACE with dual ICI therapy has been shown to be safe and feasible. Recent data has suggested that Day 1-only anti-CTLA4 dosing could potentially lead to a stronger immune response with a tolerable safety profile though this novel schedule has not previously been combined with TACE. Methods: Patients with HCC (Childs Pugh A/B7, Barcelona clinic liver cancer stage B/C; ECOG 0/1; sorafenib-naive or experienced) were enrolled in a pilot study of tremelimumab at 2 dose levels (DL1: 75mg IV q4-weekly x 4 and DL2: 300mg IV D1 only) in combination with durvalumab (1500mg IV q-28d) and TACE (D36 +/- 96 hours) until progression of disease (per irRECIST) or off-study criteria. Peripheral immune monitoring was performed and tumor biopsies were obtained at time of TACE. Results: 13 patients enrolled on study; N = 3 at DL1 and N = 10 at DL2. M:F 10:3. Median age 70 (65-74). BCLC B/C 4/9. Extrahepatic disease 6/7. Aetiology: NASH (N = 3), alcohol-related disease (N = 1), HCV (N = 2), hemochromatosis (N = 1), unknown (N = 6). 1 patient discontinued due to G3 colitis. All patients evaluable for response with 2/10 patients on DL2 experiencing PR (at 8 weeks) and overall 8/13 SD and 3/13 PD as best response. Updated PFS and OS data to be presented. Conclusions: Tremelimumab (Day 1 only) and Durvalumab in combination with TACE is safe and feasible in patients with HCC. Follow-up is ongoing and full safety and efficacy data will be presented. Clinical trial information: 2019-002767-98.

How health warning labels on wine and vodka bottles influence perceived risk, rejection, and acceptance

BackgroundWine consumption has a particular place in the culture of many European countries, and beliefs that wine offers health benefits are widespread. High consumption of wine and other alcoholic beverages among many Europeans correlates with alcohol-related accidents and disease burdens. Health warning labels (HWLs) on alcohol containers have been increasingly recommended to deter consumers from drinking. However, findings on the impact of HWLs on consumers’ behavior have been mixed. Moreover, many European consumers have been found to reject the use of warning labels as a policy intervention, especially for wine, perhaps due to its cultural and economic importance.MethodsAn online study with a between-subjects design was conducted in Switzerland (N = 506) to assess whether HWLs can influence the perceived risk associated with drinking wine and vodka, a beverage insignificant to Swiss culture. Participants were presented an image of either a wine or vodka bottle with or without an HWL presenting a liver cancer warning statement. They were then asked to indicate their perceived risk of regularly consuming the depicted beverage. Acceptance and rejection of HWLs were also assessed.ResultsThe perceived risk of vodka consumption exceeded the corresponding risk for wine but was unaffected by an HWL. Perceived health benefits were the main, negative predictor of perceived consumption risk. Participants mainly rejected HWLs due to their perceived effectiveness, perceived positive health effects, social norms, and individualistic values.ConclusionsPerceived risk is an important determinant of drinking behavior, and our results suggest that HWLs may be unable to alter risk perceptions. Furthermore, a strong belief in the health benefits of alcohol consumption, particularly wine consumption, reduce risk perceptions and may be unaffected by HWLs.

Abstract IA-09: Liver cancer and differences across Hispanic groups: Importance of disaggregation in understanding cancer disparities

Abstract 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. All HCC cases diagnosed in Florida during 2005-2018 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 non-Hispanic White, non-Hispanic Black and Hispanic groups: Mexican, Cuban, Puerto Rican, Dominican, South, Central American. Of 19,956 HCC cases including 3,660 Hispanics, 87% matched with discharge data. For 2012-2018, HCV was the leading cause of HCC White, Black and Hispanic men (45.4%, 54.7% and 41.0% respectively) followed by NAFLD-related metabolic disorders and ALD. The leading cause of HCC among White and Black women was also HCV (38.3% and 50.2%) while for Hispanic women NAFLD-HCC (46.7%) was the most common form. Puerto Rican men had the highest HCV-HCC rates, 10.2 per 100 000. Metabolic-HCC rates were highest among populations above age 70 and among all Hispanics except Cubans. Mexican men had high rates of ALD-HCC. 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. Multifaceted approaches for HCC control and prevention are needed. Citation Format: Paulo S. Pinheiro. Liver cancer and differences across Hispanic groups: Importance of disaggregation in understanding cancer disparities [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA-09.

Free Papers Compiled

Background:Chronic and persistent alcohol use is known to induce sexual dysfunction, which leads to marked distress and interpersonal difficulty, which worsens the alcohol abuse. It may be due to the depressant effect of alcohol itself, alcohol-related disease or due to a multitude of psychological forces related to the alcohol use. There was a need to look at sexual dysfunction as per the severity of alcohol dependence.Aim:To study the sexual dysfunction in male patients of Alcohol Dependence Syndrome in age group 18-50 years.Methods:After institution of ethical approval and due consent, a cross sectional study was conducted among 85 Male inpatients of Alcohol Dependence Syndrome from Oct 2019 to Apr 2021 after meeting the inclusion and exclusion criteria. A specially designed data collection proforma and rating scales (SADQ, BFSI, IISF, IPE) were administered. Data thus generated was statistically analysed and compared with relevant literature in this direction.Results:Our study found that the sexual drive and sexual desire function domains had the strongest association with severity of alcohol dependence (p-value < 0.05). In addition, the erection function and overall intercourse satisfaction function also were associated with severity of alcohol dependence.Conclusions:Alcohol Consumption has a detrimental effect on sexual functioning with severity of alcohol dependence. The domains of sexual drive, sexual desire, erection and intercourse satisfaction are negatively affected to significant levels.