Incident Cytopenia in a National Cohort Study: The Reasons for Geographic and Racial Differences in Stroke

INTRODUCTION: Cytopenia, defined as low counts in 2 or more blood cell lines is commonly associated with nutritional deficiencies, medications and chronic inflammation. In some individuals, cytopenia may reflect a pre-malignant condition or precursor of hematologic cancer. We recently demonstrated that cytopenia is associated with increased risk of mortality and was predictive of stroke risk in Black individuals (Blacks). In the current study, we sought to determine the sociodemographic and clinical characteristics associated with incident cytopenia in a large biracial prospective study, REasons for Geographic and Racial Differences in Stroke (REGARDS). METHODS: The REGARDS study recruited 30,239 Black and White individuals ≥45 years in the United States (US) between 2003 and 2007 (44% Black, ~50% females, 56% living in the southeast US). Socio-demographics and medical history were obtained by telephone interview and self-administered questionnaires, and laboratory studies (including complete blood count [CBC]) from an in-home visit at baseline and at a 10 year follow up visit. Cytopenia was defined as presence of 2 or more of the following: i) Hemoglobin in age-, sex-, and race-specific ≤5th percentile; ii) White cell count in race-specific ≤5th percentile; iii) Platelet count in ≤5th percentile, and iv) Macrocytosis (mean corpuscular volume [MCV] >98fL), due to known differences in CBC based on these demographic characteristics. We excluded participants without CBC at study enrollment and at the 2nd follow up visit, those who had cytopenia at baseline or died before the 10 year follow up visit, yielding an analytic sample of 8,081 participants. Baseline characteristics of those with or without incident cytopenia were tabulated and compared using Chi-Square tests or t-tests. Multivariable logistic regression using a purposeful selection algorithm was performed to identify factors independently associated with incident cytopenia. RESULTS: Incident cytopenia occurred in 213 of 8,081 (2.6%) participants, with the highest incidence in White men ≥65 years (4.6%) and the lowest incidence in Black women <65 years (1.0%). Baseline factors univariately associated with cytopenia are shown in Table 1. The purposeful selection algorithm yielded a multivariable model including the following factors associated with incident cytopenia: older age, male sex, White race, heavy alcohol intake, coronary heart disease, abnormal blood counts at baseline visit including lower white count, lower platelet count, lower hemoglobin and high MCV (all p<0.05) (Table 2). The area under the receiver operating characteristic curve for this model was 0.81. CONCLUSION: In this large biracial cohort, the incidence of cytopenia was 2.6% over 10 years. Adjusting for baseline blood counts, risk factors for cytopenia included older age, male sex, White race, heavy alcohol intake and coronary heart disease. Baseline blood counts were also important predictors. This study provides valuable insights into the pattern of abnormal blood counts and the sociodemographic and clinical characteristics associated with incident cytopenia. Research is ongoing to define the cause(s) of cytopenia including the role of clonal mutations in the peripheral blood of this population. Figure 1 Figure 1. Disclosures Gangaraju: Alexion: Consultancy; Sanofi Genzyme: Consultancy.

Brain-specific inhibition of mTORC1 eliminates side effects resulting from mTORC1 blockade in the periphery and reduces alcohol intake in mice

Alcohol Use Disorder (AUD) affects a large portion of the population. Unfortunately, efficacious medications to treat the disease are limited. Studies in rodents suggest that mTORC1 plays a crucial role in mechanisms underlying phenotypes such as heavy alcohol intake, habit, and relapse. Thus, mTORC1 inhibitors, which are used in the clinic, are promising therapeutic agents to treat AUD. However, chronic inhibition of mTORC1 in the periphery produces undesirable side effects, which limit their potential use for the treatment of AUD. To overcome these limitations, we designed a binary drug strategy in which male mice were treated with the mTORC1 inhibitor RapaLink-1 together with a small molecule (RapaBlock) to protect mTORC1 activity in the periphery. We show that whereas RapaLink-1 administration blocked mTORC1 activation in the liver, RapaBlock abolished the inhibitory action of Rapalink-1. RapaBlock also prevented the adverse side effects produced by chronic inhibition of mTORC1. Importantly, co-administration of RapaLink-1 and RapaBlock inhibited alcohol-dependent mTORC1 activation in the nucleus accumbens and attenuated alcohol seeking and drinking.

Association between alcohol intake and the risk of systemic lupus erythematosus: A systematic review and meta-analysis

Objectives Previous studies have reported inconsistent results on the relationship between alcohol intake and the risk of systemic lupus erythematosus (SLE). Therefore, we conducted a systematic review and meta-analysis to illustrate the potential role of alcohol intake on the progression of SLE. Methods An electronic search of the PubMed, EmBase, and the Cochrane library databases was conducted from their inception up to March 2020. Observational studies that investigated the role of alcohol intake on the risk of SLE were eligible for inclusion in this study. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated as an effect estimate using the random-effects model. Results Seven case-control studies (n = 3, 251) and three cohort studies (n = 322, 479) were selected for the final meta-analysis. Mild (OR: 0.85; 95% CI: 0.53–1.38; p = 0.515) or heavy (OR: 0.63; 95% CI: 0.37–1.09; p = 0.102) alcohol intake were not associated with the risk of SLE, while moderate alcohol intake could protect against the risk of SLE (OR: 0.71; 95% CI: 0.55–0.93; p = 0.012). Sensitivity analysis suggested that heavy alcohol intake was associated with a reduced risk of SLE (OR: 0.47; 95% CI: 0.32–0.67; p < 0.001). Conclusions This study found that moderate alcohol intake could protect against the risk of SLE, while mild or heavy alcohol intake did not significantly affect the risk of SLE.

Abstract P236: Association Between Alcohol and Ideal Cardiovascular Health: The Multi-Ethnic Study of Atherosclerosis

Introduction: Alcohol intake is associated with cardiovascular disease (CVD), with moderate drinkers having a decreased CVD risk compared to non- and heavy drinkers. However, this association is yet to be examined using the AHA Life’s Simple 7 (LS7) metrics as a proxy for cardiovascular health (CVH). We explored associations between alcohol intake and CVH in a multi-ethnic population. Methods: Our cross-sectional analyses included 6,506 MESA participants, free of CVD, aged 45 to 84 years. The LS7 metrics (smoking, physical activity, body mass index, diet, blood pressure, total cholesterol and blood glucose) were each scored 0-2, with 2 indicating “ideal”, 1 “intermediate” and 0 “poor”. Total LS7 score ranged from 0-14. Alcohol data was obtained from personal history and food frequency questionnaires. Participants were classified as never, former or current drinkers. Current drinkers were categorized as <1 (light), 1-2 (moderate) and >2 (heavy) drinks/day. Multinomial logistic regression models assessed associations between alcohol intake and CVH, adjusted for age, sex, race/ethnicity, education, income and health insurance. Results: Mean (SD) age was 62 (10) years, 53% were women; 20% were never, 24% former and 56% current drinkers. Among current drinkers, 44% had <1, 9% 1-2 and 3% >2 drinks/day. Additionally, 47% had inadequate LS7 scores, 33% average and 20% optimal. Compared to never drinkers, those who drank <1 drink/day were more likely to have average and optimal scores, although most of the associations were not significant. Women with 1-2 drinks/day were more likely than men to have optimal scores. Overall and in men, those who drank >2 drinks/day were less likely to have average or optimal scores. Whites and Hispanics with >2 drinks/day were less likely to have optimal and average scores, respectively (Table). Conclusion: Light alcohol intake tended to show favorable CVH, whereas heavy alcohol intake was unfavorable. For moderate alcohol intake, the associations with CVH varied by sex and race/ethnicity.

Colopancreatic Fistula: An Uncommon Complication of Recurrent Acute Pancreatitis

Colonic complications, including colopancreatic fistulas (CPFs), are uncommon after acute and chronic pancreatitis. However, they have been reported and are serious. CPFs are less likely to close spontaneously and are associated with a higher risk of complications. Therefore, more definitive treatment is required that includes surgical and endoscopic options. We present a case of a 62-year-old male patient with a history of heavy alcohol intake and recurrent acute pancreatitis who presented with a 6-month history of watery diarrhea and abdominal pain. His abdominal imaging showed a possible connection between the colon and the pancreas. A further multidisciplinary workup by the gastroenterology and surgery teams, including endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, and colonoscopy, resulted in a diagnosis of CPF. A distal pancreatectomy and left hemicolectomy were performed, and the diagnosis of CPF was confirmed intraoperatively. The patient showed improvement afterward.

Abstract TP336: Characteristics and Outcome of Patients With Acute Intracerebral Hemorrhage Who Overuse Alcohol

Background: Alcohol overuse (AO) is considered a cause of spontaneous intracerebral hemorrhage (ICH), but the clinical and outcome characteristics of these patients (AO+ICH) are not well known. Methods: All patients with ICH admitted from January 2005 to June 2015 to a single university tertiary stroke center were prospectively studied and followed up during 5 years. Demographic features, radiological characteristics, and clinical outcome of patients with acute ICH and previous heavy alcohol intake (>40 gr/day or >300 gr/week) were analyzed. Results: During the study period, 609 patients with ICH were admitted. Nineteen patients were excluded because data on alcohol intake was not available. At admission, 83 patients (13.6%) were identified with AO (22.7% of men vs 2.9% of women; p< 0.0001) and was more frequent in younger patients (mean age, 63.11 years, compared to 72.7 years overall; p< 0.0001). Smoking was associated with AO (63,9% vs 13,8% non-AO; p< 0.0001) but not significant differences were found according with cardiovascular risk factors (dyslipidemia, diabetes and hypertension). ICH score was lower in the AO group (1.3 vs 1.8, p= 0.009) and deep ICH were more frequent (p= 0.036), compared to non-AO. Adjusted by sex, age, and high blood pressure, a trend in favor of increased deep ICH in AO patients remained (HR: 1.68 [95% CI: 0.92-3.05], p= 0.086). Adjusted mortality at 3-month, 12-month, and 5-year follow-up was similar in both groups. Conclusions: AO was present in 13.6% of ICH patients. These patients were an average of 11.5 years younger, predominantly men, and smokers, compared to the non-AO group. Adjusted short-term and long-term mortality was similar in AO and non-AO groups.

Clinical profile of hepatocellular carcinoma and experience with sorafenib from a tertiary cancer centre in Southern India

Background: Hepatocellular carcinoma is a major health problem and a major cause of cancer mortality in India. There are no reports published on experience with sorafenib in advanced HCC from India. We analyzed the clinical presentation, possible etiological factors, tumor characteristics, outcomes and tolerability of sorafenib in the patients presenting to present cancer center.Methods: Retrospective chart review of 53 patients was done. 53 patients (male 37, female 16; median age 52 years, range 7-80 years) fulfilling the diagnostic criteria were analyzed for clinical characteristics, hematological and biochemical investigations, tumor characteristics, treatment taken and outcome.Results: 53 patients were diagnosed to have HCC between 2012-2015. Hepatitis B virus infection was the most common underlying etiologic factor (22.6%). Heavy alcohol intake was seen in 5 patients. PS ≥2 was noted in 66% of patients. 68% of the patients had BCLC stage C. Sorafenib was well tolerated with median OS of 3 months in patients taking sorafenib.Conclusions: Most of the patients had advanced inoperable HCC. Majority of the patients presented with BCLC Stage C and D. Hepatitis B infection was the most common underlying etiology. Sorafenib was well tolerated. More prospective studies are required for getting a clearer and correct picture of HCC and experience with sorafenib in Indian scenario.