Hyperlipidemia Research Articles

Efek hipoglikemik dan hipolipidemik dendeng daging itik curing dengan ekstrak kurkumin kunyit pada Tikus Wistar

<p class="MDPI17abstract"><strong>Objective: </strong>This research aimed to determine hypoglycemic and hypolipidemic effects of cured duck meat jerky with curcumin using male Wistar rats as experimental animals.</p><p class="MDPI17abstract"><strong>Methods: </strong>This research involved a completely randomized design in oneway pattern with 4 treatments on diabetic (TD) and hyperlipidemic (HD) rats : zero jerky (standard feed, PS), low jerky 0.96 g/head/day (DR), high jerky 1.91g/head/day (DT) and vitamin E 28.80 mg/head/day as control antioxidants (equivalent to 400 IU tocopherol). There were 24 rats divided into 4 treatments for hypoglycemic and hypolipidemia each. The treatment spanned 4 weeks, with hypoglycemic parameters (body weight and blood glucose) observed every week, and hypolipidemic (total cholesterol, triglycerides, HDL, and LDL). Furthermore, an analysis of variance was conducted to determine body weight. When a significant difference was observed, it was continued with Duncan's New Multiples Range Test, while other parameters were analyzed descriptively.<strong></strong></p><p class="MDPI17abstract"><strong>Results: </strong>The hypoglycemic effect showed a significant difference in body weight where the PS treatment were relatively stable, while DT and vitamin E treatment experienced the highest weight loss. Blood glucose also decreased with the increasing addition of curcumin and vitamin E. Meanwhile, the hyperlipidemic showed a decrease in cholesterol, triglycerides, and LDL, while HDL increased as the concentration of curcumin from jerky increased, the amount of which was equivalent to antioxidant control of vitamin E.<strong></strong></p><strong>Conclusions: </strong>The diet of cured duck meat jerky as much as 1.91g/head/day (equivalent to 106.26 g/person/day or 400 IU tocopherol/vitamin E) can lower diabetic blood glucose and improve blood lipid profile.

Abstract 14448: National Adherence to Guideline-Directed Medical Management of Aortic Disease

Introduction: Guidelines for the medical management of aortic (AD) and coronary artery disease (CAD) recommend treatment for hypertension (HTN), hyperlipidemia (HLD), and tobacco use (TU) (Class 1). Hypothesis: Adherence to guidelines for the management of AD is low, and inferior to CAD. Methods: Adults in the Clinformatics Data Mart database diagnosed with AD or CAD and concomitant HTN, HLD, and/or TU between 2004 and 2019 were included. Those with less than six months of continuous enrollment or prior cardiovascular procedures were excluded. Adherence was calculated as the proportion of patients with a given comorbidity (or combination thereof) who received a prescription for the appropriate intervention. Any beta-blocker, ACEi, or ARB for HTN. Any statin for HLD. Bupropion, varenicline, or referral to counseling for TU. Composite adherence for patients with AD and CAD was compared using a Z-test. Temporal trends were analyzed using a Chi-square test for trend. Results: There were 354,851 patients with AD and 907,997 with CAD who met the inclusion criteria. Composite adherence was 50% for those with AD compared to 59% for CAD (p<0.01). No clinically-significant changes in composite adherence overtime occurred for either group (Figure 1A). Among those with AD, adherence was highest among those with HTN alone (73%), followed by combined HTN/HLD (58%) and HLD alone (45%). Diagnosis of TU was associated with lower adherence across all risk factor combinations. There has been a significant improvement in adherence for TU overtime (p<0.01) (Figure 1B). Conclusions: Adherence to guidelines for medical management of AD is low, and significantly lower than for CAD.

Abstract 9539: Treatment of Hyperlipidemia: Assessment of Providers’ Competency With Edocate® Virtual Patient Simulation Application

Management of hyperlipidemia (HL) in patients with Type 2 diabetes (T2DM) has been taught extensively but the real-life competency is difficult to evaluate. Edocate’s proprietary virtual patient simulation smartphone and web-based application (APP) allows an innovative way of learning and objective assessment of the provider’s proficiency in approach to and management of a given medical condition. We utilized this novel educational APP to analyze the real-life knowledge of 894 healthcare providers (HCP) in several projects within multiple geographies in the management of HL in patients with T2DM. The HCP managed 1-3 patients with T2DM and HL in their virtual clinic. HCP chose medications, made diagnostic adjustments, and ordered laboratory tests of their choice. Based on their selections, the APP simulated the course of diabetes and hyperlipidemia throughout multiple virtual visits, requiring diverse management decisions and addressing medications’ side effects, while adhering to guidelines and accepted standards of care. Results: Conclusions: 1. Innovative patient simulation-based learning APP revealed adequate but not perfect HL management skills. 2. NP - DM have the best guideline-recommended approach to therapy, followed by practicing MD/DO. 3. Intensive therapy achieving LDL levels below 50 or even 70 mg/dl remains elusive. 4. Edocate’s patient simulation-based learning application helps identify knowledge gaps, prescription patterns and HCP decision-making processes. 5. This APP accurately assesses the “real-life” knowledge and patterns of practice while offering cutting-edge ways of learning to dramatically improve competency levels.

Abstract 10498: The Use of a Digital Telehealth Platform to Understand the Prevalence and Control of Cardiovascular Disease Risk and Risk Factors in the Indian Population - A Pilot Study

Introduction: Despite the enormous & growing burden of CVD in India, there is still lack of awareness about the importance of guideline based prevention and risk factor control. Objectives: To understand the feasibility & utilization pattern of an open-to-public digital health (mHealth) platform designed to assess CVD risk, risk factors (RF), RF control and adequacy of prevention, and provide appropriate education and guidance based on the assessment. Methods: Data was collected over 2 months through the mHealth platform that was open to all adults aged 25-80 years. It was accessible at no cost via all web browsers on smart phones, computers & tablets with internet connectivity and was available in 2 languages. Utilization of the platform was significantly higher in males - 93.7% (251/268) respondents. Therefore, the study population for this study comprised of 251 males (age 45.4 + 11.7 yrs). Females were not included due to the small sample size; hence the corresponding results will be published once adequate sample size is reached. 10 year CVD Risk was calculated using the Framingham Risk Score (FRS). RF, RF control and adequacy of prevention were assessed using national & international guidelines, as appropriate. Statin indicated conditions were atherosclerotic disease, diabetes mellitus, familial hyperlipidemia and FRS-CVD risk >=10%. Results: Results are summarized in Fig 1. Overall 186 subjects met the criteria of having statin indicated conditions; however, only 37.6% of them reported taking a Statin. The commonest RFs were hypertension (68.5%) & sedentary lifestyle (57%). Rates of undiagnosed RFs were high -diabetes 45.7%, hypertension 20%, high normal BP 28%, and pre-diabetes 24.9%. RF control was poor with only 23.2% of people with hypertension reporting BP <130/80, 38.9% of diabetics reporting HbA1c <7% and 26.2% of those taking Statins reporting LDL <70 mg/dL. Conclusion: The use of a digital health tool for CVD prevention is feasible and reveals a large unmet need.

Prevalence and Risk Factor for Hepatocellular Carcinoma in Individuals with Hemophilia in the Era of Direct-Acting Antiviral Agents: A National Inpatient Sample Study

▪Background: Hepatocellular carcinoma (HCC) is a major complication of chronic hepatitis C virus (HCV) infection. HCV is the leading cause of liver disease in hemophilia population and was acquired with their first transfusion. While direct-acting antiviral agents (DAAs) are effective in HCV eradication, its impact on preventing HCC remains unclear. Few data on HCC in hemophilia after DAA are available. We undertook an observational study to determine the prevalence of and risk factors for HCC in hemophilia since the introduction of DAAs.Methods: We conducted an observational study including adult male discharges in the National Inpatient Sample (NIS) database from 2016-2018. Status of hemophilia (H) and non-hemophilia (NH), HCV, HCC, and other relevant medical conditions were identified using ICD-10 codes. Analysis included NIS-provided discharge-level weights to reflect national estimates. Categorical and continuous variables were assessed by Rao-Scott Chi-Square and weighted simple linear regression, respectively. Weighted multivariable logistic regression was performed to determine HCC risk factors. Variables included were age, race, HCV, HIV, alcoholism, smoking, obesity, hyperlipidemia (HLD), non-alcoholic steatohepatitis (NASH), substance abuse, transfusion, and Charlson comorbidity index (CCI).Results: In total, 7,674,969 adult male discharges, including 3,370 with H (0.04%), were identified between 2016 and 2018. Between 2016 and 2018, the diagnosis rates of HCV were 10.06% (95%CI 8.97%-11.26%) in H vs. 1.22% (95%CI 1.19%-1.25%) in NH, and the rates of HCC were 1.07% (95%CI 0.76%-1.51%) in H vs. 0.27% (95%CI 0.26%-0.28%) in NH. The diagnosis rates of HCV and HCC were similar in 2016, 2017 and 2018, for both H and NH populations. Compared with H without HCC, H with HCC were older (58.6 vs. 50.9 years-old, p<0.001), had higher CCI (mean : 6.5 ± 0.6 vs. 2.0 ± 2.0, p<0.001), and higher prevalence of HCV (36.11% vs. 9.78%, p<0.001), HBV (11.11% vs. 0.45%, p<0.001), NASH (5.56% vs. 0.12%, p<0.001), end-stage liver disease (88.89% vs. 8.61%, p<0.001), portal hypertension (27.78% vs. 2.61%, p<0.001), and platelet transfusion (11.11% vs. 1.44%, p<0.001). The prevalence of HIV infection between H with and without HCC was similar (8.33% vs. 8.82%, p=0.919). Among these with HCC, H were more likely to be younger (58.6 vs. 64.1 years-old, p=0.001), HIV (+) (8.33% vs. 1.64%, p=0.002), and less likely to have alcoholism (11.1% vs. 33.2%, p=0.018) and HLD (2.78% vs. 20.8%, p=0.008), than NH. The rates of cirrhosis, NASH, autoimmune hepatitis, and biliary cirrhosis were similar between groups. Multivariable logistic regression analysis among H patients indicated that NASH (OR 21.6, 95%CI 4.63-100.6), HCV (OR 3.96, 95%CI 1.55-10.2), and CCI (OR 1.54, 95%CI 1.39-1.72) were significant risk factors for HCC, while HIV (OR 0.02, 95% CI 0.00-0.13) and HLD (H: OR 0.07, 95% CI 0.01-0.39) were protective.Conclusion: From 2016 to 2018, the rate of HCC did not significantly decrease in discharges with hemophilia in the NIS database. Chronic HCV infection remains a significant risk factor of HCC in hemophilia despite availability of DAA therapy. NASH and Charlson comorbidity contribute to HCC risk, while HIV and hyperlipidemia appear protective. DisclosuresRagni: Takeda Therapeutics: Membership on an entity's Board of Directors or advisory committees; BioMarin Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Bioverativ (Sanofi): Membership on an entity's Board of Directors or advisory committees; Spark Therapeutics: Membership on an entity's Board of Directors or advisory committees; Alnylam (Sanofi): Membership on an entity's Board of Directors or advisory committees; University of Pittsburgh: Research Funding.

Tetrahydropalmatine Alleviates Hyperlipidemia by Regulating Lipid Peroxidation, Endoplasmic Reticulum Stress, and Inflammasome Activation by Inhibiting the TLR4-NF-κB Pathway.

Hyperlipidemia (HLP) is a lipid metabolism disorder that can induce a series of cardiovascular and cerebrovascular diseases, such as atherosclerosis, myocardial infarction, coronary heart disease, and stroke, which seriously threaten human health. Tetrahydropalmatine (THP) is a component of the plant Rhizoma corydalis and has been shown to exert hepatoprotective and anti-inflammatory effects in HLP. However, whether THP regulates lipid peroxidation in hyperlipidemia, endoplasmic reticulum (ER) stress and inflammasome activation and even the underlying protective mechanism against HLP remain unclear. An animal model of HLP was established by feeding a high-fat diet to golden hamsters. Our results showed that THP reduced the body weight and adipose index; decreased the serum content of ALT, AST, TC, TG, and LDL-C; decreased the free fatty acid hepatic lipid content (liver index, TC, TG, and free fatty acid); inhibited oxidative stress and lipid peroxidation; extenuated hepatic steatosis; and inhibited ER stress and inflammasome activation in high-fat diet-fed golden hamsters. In addition, for the first time, the potential mechanism by which THP protects against HLP through the TLR4-NF-κB signaling pathway was demonstrated. In conclusion, these data indicate that THP attenuates HLP through a variety of effects, including antioxidative stress, anti-ER stress, and anti-inflammatory effects. In addition, THP also inhibited the TLR4-NF-κB signaling pathway in golden hamsters.

Carotid Artery Temperature Reduction with Statin Therapy in Patients with Familial Hyperlipidemia Syndromes.

Background: Microwave radiometry (MWR) assesses non-invasive carotid artery temperatures reflecting inflammation. In the present study, we aimed to investigate the impact of hypolipidemic therapy either with simvastatin or with combination simvastatin plus ezetimibe on carotid artery temperatures of patients with familial hyperlipidemia syndromes (FHS). Methods: Consecutive patients with diagnosis of either familial heterozygous hypercholesterolemia (heFH) or familial combined hyperlipidemia (FCH) were included in the study. Patients were assigned to either simvastatin 40 mg or simvastatin 40 mg plus ezetimibe 10 mg, according to the discretion of the physician. FHS patients who refused statin therapy were used as a control group. Common carotid intima-media thickness (ccIMT) was measured and ΔΤ (maximum-minimum) temperature measurements were performed across each carotid during MWR evaluation. RESULTS: In total, 115 patients were included in the study. Of them, 40 patients received simvastatin (19 heFH and 21 FCH), 41 simvastatin + ezetimibe (31 heFH and 10 FCH), and 34 (21 heFH and 13 FCH) no statin. Carotid artery temperatures were significantly reduced at 6 months in FH patients who received hypolipidemic treatment (0.83 ± 0.34 versus 0.63 ± 0.24 °C, p = 0.004 for simvastatin, 1.00 ± 0.38 versus 0.69 ± 0.23 °C, p < 0.001 for simvastatin + ezetimibe), but no change was recorded in controls (0.72 ± 0.26 versus 0.70 ± 0.26 °C, p = 0.86). Conclusions: Hypolipidemic therapy reduced carotid temperatures in FHS patients.

Risk Factors for and Intraoperative Management of Intolerance to Flow Reversal in TCAR

BackgroundIn patients deemed high risk for carotid endarterectomy (CEA) who are indicated for treatment of carotid artery stenosis (CAS), transcarotid artery revascularization (TCAR) has been demonstrated as a safe and effective alternative to trans-femoral carotid artery stenting (TF-CAS). Compared to CEA, where approx. 12% of patients undergoing awake intervention do not tolerate internal carotid artery (ICA) clamping, only 1–2% of patients were observed to have intolerance to flow reversal during TCAR based on data from the ROADSTER1/2 trials. This study reviewed awake interventions from those trials to assess factors associated with intolerance to flow reversal and review how those cases were managed. MethodsThis is a retrospective review of prospectively collected data from Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) multicenter trial along with the subsequent post-approval (ROADSTER-2) trial. The subset of patients from both trials undergoing awake TCAR was analyzed to compare demographics, procedural details, and anatomic factors between patients who did and did not experience intolerance to reversal of flow to assess for predisposing factors. Patients were deemed intolerant to flow reversal at the discretion of the operator, often related to changes in completion of neurologic tasks, hemodynamic stability, or patient reported symptoms. ResultsA total of 103 patients from ROADSTER and 194 patients from ROADSTER-2 underwent TCAR under local/regional anesthesia. Of these, 8 patients had intolerance to flow reversal, though all cases were successfully completed. While intraoperative hemodynamic data was only available for 5 of the 8 intolerant patients, none experienced hypotension. 4 cases were completed under low flow reversal, 3 cases were successfully weaned from low to high flow over several minutes, and 1 case required general anesthesia. No significant association was found between intolerance to flow reversal and comorbidities including diabetes mellitus (DM), hypertension (HTN), hyperlipidemia (HLD), congestive heart failure (CHF), prior MI or angina, pre-op CAS-related symptoms, prior stroke, prior CAS or CEA, prior neck radiation, tandem stenosis, high cervical stenosis, or hostile neck. A trend towards significance was seen with chronic obstructive pulmonary disease (COPD) and contralateral carotid artery occlusion (P = 0.086 and 0.139, respectively). ConclusionsDespite intolerance to flow reversal, TCAR cases were successfully completed by adjusting reversal-of-flow rate and do not typically require conversion to GETA. While factors contributing to intolerance of flow reversal during TCAR remain poorly understood, this study identified a trend towards significance with an association of preexisting COPD and contralateral carotid artery occlusion. Given the low number of patients who experienced this issue, a larger sample size is required to better elucidate these trends.

Familial dysbetalipoproteinemia: highly atherogenic and underdiagnosed disorder

Familial dysbetalipoproteinemia (FD) is a genetic, highly atherogenic disorder. The penetrance of FD depends on the patient’s lifestyle and concomitant diseases. Despite the fact that FD was described almost half a century ago, it is still insufficiently studied and is extremely rarely diagnosed. In actual clinical practice, physicians do not have clear understanding of clinical course and genetic basis of FD. The aim was to present the most complete, but at the same time a critical review with a modern view on FD. We analyzed Russian and foreign publications from following electronic databases: PubMed, eLIBRARY, Google Scholar. As a result, the phenotypic features and genetic variability of the disease were considered and the main issues of diagnosis and treatment of patients with FD were discussed. The data presented will help the clinician to timely suspect the FD, conduct a full range of investigations and prescribe evidence-based lipid-lowering therapy.

The association between diabetes and mortality in young adults presenting with myocardial infarction

Abstract Background The incidence of diabetes mellitus and coronary artery disease continue to rise and collectively comprise two of the most prevalent and costly diseases worldwide. The goal of this study is to report the prognosis of young patients with diabetes presented with acute myocardial infarction (AMI). Methods This is a retrospective observational cohort study that included consecutive patients aged 18–45 years who underwent cardiac catheterization for AMI between 2006 and 2016 in an integrated healthcare system in Southern California. The prognosis of patients with diabetes were compared to those without diabetes. Results A total of 1,560 patients (average age 40.2±5.3 years, 25.6% female) presenting with AMI were included. Of these 272 (17.4%) had diabetes. Diabetics were older (41.1±4.4 vs 40.0±5.4 years), more likely to be female (32.4% vs 24.1%, p=0.006), Hispanic (51.5% vs 40.5%, p&amp;lt;0.001), have a higher body mass index (BMI) (33.6±7.1 vs 31.2±6.8kg/m2, p&amp;lt;0.001), have hypertension (HTN) (67.6% vs 23.8%, p&amp;lt;0.001), hyperlipidemia (HLD) (78.3% vs 24.1%, p&amp;lt;0.001), peripheral vascular disease (9.9% vs 1.9%, p&amp;lt;0.001), chronic kidney disease (CKD) (23.2% vs 2.7%, p&amp;lt;0.001), hypothyroidism (7% vs 4%, p=0.034), and prior strokes (4.4% vs 2.2%, p=0.034). On multivariate analysis accounting for other cardiovascular risk factors, the association remained significant (OR 1.82, 95% CI 1.04–3.19, p=0.036). At a median follow-up of 5.8 years (interquartile range 3.7–8.7 years), diabetes was independently associated with increased all-cause mortality (Hazard ratio [HR] 3.10, 95% CI 1.68–5.69, p&amp;lt;0.001) when adjusting for age, sex, race, BMI, HTN, HLD, CKD, hypothyroidism, prior stroke, and ACS etiology. In a propensity score matched cohort, diabetes remained significantly associated with all-cause mortality (HR 5.29, 95% CI 2.34–12.02, p&amp;lt;0.001). Conclusion Diabetes is an independent predictor of increased mortality in young adults &amp;lt;45 years old presenting with AMI. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): KAISER PERMANENTE LOS ANGELES MEDICAL CENTER

Progression of carotid intima-media thickness in patients treated with lipoprotein apheresis: real-world evidence over 12 years

Abstract Background The extent of intervention effects on carotid intima-media thickness (CIMT) can predict the degree of atherosclerotic cardiovascular disease (ASCVD) risk reduction. There is limited evidence of long-term effects of lipoprotein apheresis on the CIMT progression. Purpose We hypothesized that regular lipoprotein apheresis over the course of 10 years may slow down progression of CIMT in patients with severe hypercholesterolemia. Methods This case series describes ten Caucasian patients (mean age 60±9 years, 70% female, 80% statin intolerant) with familial hypercholesterolemia and/or hyperlipoproteinemia(a) treated with lipoprotein apheresis at a single academic center between 2005 and 2020. The mean and maximum diastolic CIMT of the distal 1 cm of the far wall of the right and left common carotid arteries was measured by the same, trained sonographer utilizing an automated border-detection algorithm. Results The median pre-treatment low-density lipoprotein cholesterol (LDL-C) level was 214 mg/dL (95% confidence interval, 145 to 248), lipoprotein(a), 26 mg/dL (15 to 109; 40% with lipoprotein(a) &amp;gt;60 mg/dL). Using the imputed trajectories, period-specific on-treatment time-weighted averages for LDL-C and lipoprotein(a) were 141 mg/dL (IQR, 89 to 152) and 24 mg/dL (IQR, 12 to 119), respectively. The baseline mean CIMT was 850±170μm and maximum CIMT was 1040±220μm across the age range of 46 to 70 years. Over a median duration of 12 years, regular treatment with lipoprotein apheresis resulted in an average reduction in the mean CIMT of −40μm (IQR, −50 to 20) and maximum CIMT −30μm (IQR, −60 to −10). Among tested lipid and lipoprotein fractions in this sample, the follow-up mean CIMT values strongly correlated only with the baseline lipoprotein(a) levels. Median CIMT progression rates were as follows: mean common carotid, −4μm/y (IQR, −9 to 1), mean common carotid, −12μm/3y (IQR, −26 to 4), maximal common carotid, −3μm/y (IQR, −8 to −1). This translated into 70% (7/10) of cases demonstrating composite mean CIMT below their expected chronologic age, gender and race-stratified vascular age. There was a strong direct correlation between the mean CIMT value at the end of the treatment period and the age of treatment initiation. In this cohort of primary and secondary prevention of patients with severe hypercholesterolemia, the overall rate of ASCVD was 37.5 per 1000 person-years while on lipoprotein apheresis. Conclusions Our observation performed in the clinical setting, demonstrated a real-world effectiveness of lipoprotein apheresis. This analysis supports implementation of aggressive lipid-modifying strategies across all ages. Surveillance with CIMT allows for continued monitoring of atherosclerosis progression and increases compliance with the lipid-modifying therapies in the high-risk patients with poor statin tolerance in the clinical setting. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): KUMC

Negative correlation between endoglin levels and coronary atherosclerosis

BackgroundCoronary artery disease (CAD) is a common cardiovascular disease, and abnormal blood lipid metabolism is an important risk factor. Transforming growth factor-ß (TGF-ß) and its receptor (TGF-ßR) can inhibit the release of inflammatory factors through the SMAD pathway-mediated immune response, thereby suppressing the progression of CAD. Endoglin (TGF-ßRIII), a TGF-ßR family homologous receptor protein, is directly involved in the immunoregulatory process, but the exact mechanism is unclear. This study aimed to clarify the pathophysiological effects of endoglin on the development of atherosclerosis and to explore the mechanism of the signalling pathway.MethodsWe downloaded the GEO dataset to perform a functional analysis of SMAD family activity and TGF-ß receptor protein expression in the monocyte expression profiles of patients with familial hyperlipidaemia (FH). The effect of endoglin on endothelial cell proliferation, migration, and apoptosis was examined by disrupting the endoglin gene in human umbilical vein endothelial cells (HUVECs) and validated by western blotting. The related genes and pathways regulated by endoglin were obtained by analysing the sequencing data.ResultsResearch has shown that interference with endoglin can promote the proliferation and migration and significantly inhibit the apoptosis of vascular endothelial cells. Interference with endoglin particularly encourages the expression of VEGFB in vascular endothelial cells.ConclusionThe endoglin gene in vascular endothelial cells regulates the PI3K-Akt, Wnt, TNF, and cellular metabolism pathways by activating the SMAD pathway. RAB26, MR1, CCL2, SLC29A4, IBTK, VEGFB, and GOLGA8B play critical roles. Endoglin interacts closely with 11 proteins such as CCL2 and SEPRINE1, which participate in the vital pathway of plaque formation. Interference with endoglin can alter the course of coronary atherosclerosis.

S1172 Presence of NAFLD in Patients Receiving Immune Checkpoint Inhibitors Significantly Increases the Prevalence of Immune Medicated Hepatotoxicity

Introduction: Immune checkpoint inhibitors (ICPIs) are monoclonal antibodies the interrupt co-inhibitory signaling pathways (e.g cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1 & its ligand PD-L1) and promote immune mediated elimination of cell tumors. The use of ICPI has emerged in recent years in the field of both solid & liquid tumor therapy. Immune medicated hepatotoxicity is well known adverse event associated with ICPI utilization. The aim of this study is to assess the prevalence of hepatotoxicity in patients with underlying non-alcoholic fatty liver disease (NAFLD) receiving ICPI. Methods: We reviewed data from a large commercial database (Explorys IBM) that aggregates electronic health records from 26 large nationwide healthcare systems. Using systemized nomenclature of clinical medical terms (SNOMED CT) we identified adults received ICPI (regardless of indication) from 2011 to 2021. We identified adults with diagnosed with NAFLD. We excluded patients diagnosed with alcoholism, viral hepatitis, other drug induced liver injury, & biliary disease. Of this cohort, we collected data on hepatocellular injury and cholestasis. Risk factors known to be associated with NAFLD like diabetes mellitus type 1 or 2 (DM), hyperlipidemia (HLD) & Obesity (defined BMI >30) were also collected. Univariable and multivariable logistic regression were performed, adjusting to demographics and risk factors, to investigate hepatotoxicity (in patients with and without NAFLD) receiving ICPI. We used R version 3.6.3 for statistical analysis. Results: Out of 63.7 million active adults in the database, 18150 (0.02%) received ICPI, of them 1090 (6.0%) has documented NAFLD. Patients with Age > 65 years received ICPI were majority (61.3%). Male were 58.2% of this cohort. Percentage of patients on ICPI (without NAFLD) who had DM, HLD and Obesity were 30.7, 61.5 and 23.3, respectively. These factors were higher in the cohort with underlying NAFLD (DM 79.8%, HLD 87%, Obesity 88%). Presence of NAFLD in Patients on ICPI is associated with higher prevalence of hepatocellular injury (OR 3.62 [2.60-3.64]) vs (OR 2.34 [2.48-2.41]). Compared to patients on ICPI without NAFLD, presence of NAFLD was associated with slightly higher odds of developing cholestasis (OR 2.54 [2.48-2.61]) vs (OR 2.13 [2.01-2.15]). Conclusion: Patients with NAFLD have significant higher risk of hepatotoxicity from Immune checkpoint inhibitors. Further studies need to be done to better predict drug induced liver injury in this patient population.Table 1.: Title Characteristics if patients in Cohort ICPI: Immune checkpoint inhibitors NAFLD: non-alcoholic fatty liver disease.

S1456 Effect of Clostridium difficile Infection on Hospital-Based Outcomes in Patients With Gastric Ulcer

Introduction: Gastric Ulcer (GU) is a prevalent cause of gastrointestinal disease with a significant healthcare-associated burden. Patients hospitalized with GU have many risk factors for developing Clostridium Difficile infection (CDI). CDI is associated with poor outcomes in many diseases, but limited data is available in the GU population. We utilized the National Inpatient Sample (NIS) to understand the effect of CDI on inpatient mortality in GU patients. Methods: We used NIS 2017 to generate ICD-10 codes for GU and CDI. The primary outcome was inpatient mortality. Secondary outcomes were hospital length of stay and cost utilization. We then ran multivariate logistic regression analysis in STATA MP 16.1. Various comorbidities were accounted for by adding them into the analysis. These included the previous history of coronary artery disease (CAD), congestive heart failure (CHF), cerebrovascular disease (CVA), smoking, hyperlipidemia (HLD), myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG). Results: The gastric ulcer patients under investigation were all adults more than 18 years of age and numbered 13,776 patients. The mean age was 65.75 years. Among these, 54% were females. While examining inpatient mortality, we see that for patients that had CDI, the odds of inpatient mortality are higher (Odds Ratio (OR) 8.0, P = 0.0005, 95% Confidence Interval (CI) 1.87 – 34.6). History of CHF and increasing age also appear to contribute towards higher odds of mortality. Mean LOS was 4.5 days. Patients with Clostridium difficile infection stayed in the hospital longer by ∼5.0 days (Coef. 4.91, 95% CI 1.99 – 7.83). LOS was higher in patients with CHF. The total charge for hospitalizations from CDI is higher by $63722 (95% CI 23600 – 103845). Other factors incurring higher costs include the history of CHF, increasing age, Hispanic race, and teaching hospitals (Table 1). Conclusion: Among patients that present with a principal diagnosis of GU, having CDI, adversely affects patient outcomes that include mortality, hospital length of stay, and total hospitalization cost. Previous studies have reported adverse outcomes in patients with CDI who are on proton pump inhibitors (PPI). Although we cannot prove directly, we can presume that most of these patients with GU were on PPI. Therefore, this can serve as indirect evidence that PPI use could be the factor contributing to adverse outcomes in patients with GU and CDI.Table 1.: Mortality, LOS, and Total Charge.

DMD/BMD – OUTCOME MEASURES: EP.132 Double the trouble: familial hyperlipidemia and Becker muscular dystrophy with a hemizygous nonsense mutation in the dystrophin (DMD) gene

Becker muscular dystrophy (BMD) is an X-linked recessive disorder caused by the absence of dystrophin. It is characterized by progressive skeletal and cardiac muscle weakness that usually becomes apparent between the ages of 5 and 15. Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipid metabolism present from birth. It is characterized by remarkably high low-density lipoprotein cholesterol (LDL-C) levels causing premature coronary heart disease. We report a 9-year-old boy with familial hyperlipidemia who presented with creatinine kinase elevation. He was born after uneventful pregnancy and delivery with consanguineous marriage of his parents. The motor developmental milestones were normal. On physical and neurological examination at the age of 9, he had only mild pseudohypertrophy in the gastrocnemius muscles. Gowers’ sign was negative. He had no myotonia or muscle weakness. The cardiological evaluation was unremarkable. Serum creatine kinase (CK) level was elevated (2889 UI/L). Moreover, serum triglyceride (183 mg/dl), VLDL cholesterol (37 mg/dl), LDL cholesterol (212 mg/dl), and total cholesterol (289 mg/dl) were elevated. We identified a heterozygous mutation of c.1246 C>T (p.R416W) (paternal) in the LDLR gene and a hemizygous nonsense mutation of c.71G>A (p.W24) in the DMD gene. Based on the clinical manifestations, examination, and laboratory findings, we diagnosed BMD and familial hyperlipidemia. We described a case with familial hyperlipidemia presented with serum creatinine kinase (CK) elevation and identified hemizygous nonsense mutation of c.71G>A p.W24 in the dystrophin gene.

Plant-predominant eating patterns – how effective are they for treating obesity and related cardiometabolic health outcomes? – a systematic review

The obesity epidemic is a main driver of the chronic disease epidemic; however, present treatment approaches have suboptimal efficacy. To assess the efficacy of plant-predominant (vegan, vegetarian, plant-based whole foods [PBWFs]) diets in treating obesity and its main cardiometabolic sequelae: hyperlipidemia (HLD); indices of insulin resistance, glycemic control, and diabetes mellitus type 2 (DM2); and cardiovascular disease (CVD), including hypertension (HTN). A systematic search of multiple databases was conducted for articles published between November 2019 and February 2020; databases searched included: PubMed, Medline (Ovid), Cochrane, CENTRAL, and CINAHL. All interventional trials (randomized controlled trials [RCTs] and trials of non-randomized experimental design) that met the inclusion criteria (English language, duration of at least 4 weeks, primary end point congruent with above objectives, no major flaws in research design that would prevent interpretation) were included in the review. A total of 3135 articles were scanned and 84 were selected. The articles were collated and summarized in 2 evidence tables. Risk of bias for RCTs was assessed using the Cochrane Risk-of-Bias tool 2 as a guide. For non-randomized trials, higher risk of bias was assumed, and the JBI Critical Appraisal tool was used as a guide to determine inclusion. Plant-based diets, in general, demonstrated improved weight control and cardiometabolic outcomes related to lipids, cardiovascular end points, blood pressure, insulin sensitivity, A1C, and fasting glucose, and a lower risk of diabetes compared with usual diets and in some cases standard health-oriented diets such as the American Heart Association (AHA), American Diabetic Association (ADA), and Mediterranean diets. Preliminary studies suggest plant-predominant diets practiced as part of healthy lifestyle interventions may stabilize or even reverse DM 2 and CVD. The acceptability and sustainability of plant-predominant diets where measured were generally similar to other health-oriented diets. Plant-predominant diets can play a major role in reversing the obesity and chronic disease epidemics. In the setting of sustained lifestyle intervention programs, they may arrest or even reverse DM2 and CVD. Further higher-level RCTs are needed to confirm and expand on these findings.

Anti-hyperlipidemic, Anti-inflammatory, and Ameliorative Effects of DRP1 Inhibition in Rats with Experimentally Induced Myocardial Infarction.

This study aims to investigate the biological role of DRP1 in myocardial infarction (MI) in concert with hyperlipidemia (HL). Based on the available literatures, 10 genes related to MI with HL (HL-MI) were screened and detected in clinical samples. High-fat diet (HFD) was used to establish HL rat models, after which the rats were subcutaneously injected with PBS or isoproterenol hydrochloride to induce acute MI. Then, rats with HL-MI were injected with pcDNA3.1, pcDNA3.1-DRP1, sh-NC, or sh-DRP1. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) were measured. Cardiac function was evaluated by detecting left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF). Infarct size and histopathological changes were assessed as well as myocardial apoptosis and collagen deposition. The concentration of IL-6, IL-1β, and TNF-α in rat serum and cardiac tissues was also measured by ELISA. Mitochondrial function was shown by measuring the morphology, mitochondrial membrane potential (MMP), and intracellular reactive oxygen species (ROS) level. Pro-apoptotic proteins (Bax, caspase-1, and cleaved caspase-1) and NLRP3 inflammasome activation were also assessed. The expressions of the 10 genes were measured in clinical samples and DRP1 was selected for further experiments with significantly upregulated expression in MI patients. HFD-induced rats showed increased body weight, concurrent with higher levels of TG, TC, and LDL-C and lower HDL-C level. Compared with the BD-PBS group, the HFD-PBS group presented higher mRNA and protein expression levels of DRP1, exacerbated cardiac functions, enlarged infarct size, loss of cardiomyocytes, and disordered island cardiomyocytes. In the HL-MI rat model, injection of pcDNA3.1-DRP1 enhanced the levels of serum lipids and inflammation cytokines, induced loss of a number of cardiomyocytes and collagen deposition, and decreased LVFS and LVEF, while injection of sh-DRP1 ameliorated myocardial injuries, inflammation, and cardiomyocyte apoptosis and fibrosis. In coronary artery endothelial cells from the rats, loss of MMP was observed in the HFD-MI, LV-NC, LV-DRP1, and sh-NC groups and concomitantly, the sh-DRP1group showed increased MMP and decreased levels of mitochondrial ROS, cytochrome C, pro-apoptotic proteins, and NLRP3. Inhibition of DRP1 markedly suppressed HL, systematic inflammation, and myocardial injuries induced by HL-MI through partly restoring mitochondrial function and reducing NLRP3 expression.

MP52-20 THE IMPACT OF LOWER URINARY TRACT SYMPTOMS (LUTS) ON DEPRESSION AND DEPRESSIVE SYMPTOMS AMONG WOMEN 20-69 YEARS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II (MP52)1 Sep 2021MP52-20 THE IMPACT OF LOWER URINARY TRACT SYMPTOMS (LUTS) ON DEPRESSION AND DEPRESSIVE SYMPTOMS AMONG WOMEN 20-69 YEARS Stephanie Gleicher, Timothy Byler, and Natasha Ginzburg Stephanie GleicherStephanie Gleicher More articles by this author , Timothy BylerTimothy Byler More articles by this author , and Natasha GinzburgNatasha Ginzburg More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002082.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Studies have shown that women with LUTS have higher rates of depression, anxiety, and overall worse health perception. Correlations have been shown between symptom severity and worsened mental health status. The aim of this study was to compare the impact of varying urinary symptoms, such as SUI, UUI, and nocturia, on depression and depressive symptoms among women aged 20-69 years. METHODS: We queried NHANES between 2013-2018 for women aged 20-69 years. We defined SUI as “leakage during physical activity”, UUI as “leakage during non-physical activity” and nocturia as “≥ 2 voids/night”. Depression was defined by DSM criteria with cases reporting ≥5 symptoms from the patient health questionnaire (PHQ9) depression screening tool. We assessed various demographic and clinical variables such as age, race, education, insurance status, smoking status, hypertension (HTN), hyperlipidemia (HLD), body mass index (BMI), hemoglobin A1c (HbA1c), perceived heath status, and visits to mental health providers. We performed univariate analysis and multivariable logistic regression. RESULTS: Of the 6284 participants, 27% reported nocturia, 42% had SUI, and 9% had UUI. Depression was found in 5% of the cohort. Women with depression were significantly less educated, had less health insurance, more commonly smoked, had HTN and HLD, had higher BMI, and had higher HbA1c. Depressed women were twice as likely to have nocturia (51% vs 26%, p<0.001). 64% of depressed women had SUI and 21% had UUI (p<0.001). Depressed women were three times more likely to have negative health perception (36% vs 9%, p<0.001). Multivariate regression revealed increased risk of depression among women with SUI (OR 1.79, p=0.004) and nocturia (OR 1.65, p=0.007), but not UUI. While evaluating the impact of specific PHQ9 elements and SUI, multivariate analysis revealed significant correlations with “feeling tired” (OR 1.26) and suicidal ideation (OR 1.77). Nocturia and depression were significantly correlated with decreased interest (OR 1.39), poor sleep (OR 1.71), “feeling tired” (OR 1.26) and changes in appetite (OR 1.37). CONCLUSIONS: SUI and nocturia appear to be significantly associated with depression and depressive symptoms. These findings reinforce that LUTS cannot be considered an isolated symptom, but a factor impacting overall mental-health wellbeing. Source of Funding: N/A © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e938-e938 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stephanie Gleicher More articles by this author Timothy Byler More articles by this author Natasha Ginzburg More articles by this author Expand All Advertisement Loading ...

Impact of switching to tenofovir alafenamide on weight gain as compared to maintaining a non-tenofovir alafenamide containing regimen.

Evaluate the impact of switching to an anti-retroviral regimen containing tenofovir alafenamide (TAF) on weight and the development of metabolic complications compared to remaining on a non-TAF containing regimen.Single-center retrospective case-control study.We evaluated people living with human immunodeficiency virus (PLWH) who were on an anti-retroviral regimen not containing TAF and were switched to a regimen containing TAF between January 1, 2016 and September 30, 2018. The control group included PLWH on a TAF free regimen throughout the study period. The primary outcome was change in weight from baseline to 12 months postswitch. Secondary outcomes included percent change in weight, change in body mass index (BMI), change in BMI class, and new diagnoses of diabetes, hypertension, and hyperlipidemia (HLD) during the study period.PLWH switched to TAF (n = 446) demonstrated significantly greater mean increase in weight compared to the control group (n = 162) (1.97 vs 0.88 kg, P = .01), however the effect was only seen in those switched from tenofovir disoproxil fumarate. Those that switched to TAF also had a significantly higher percent increase in weight, increase in BMI, and BMI class. We observed a higher rate of new diagnosis of HLD in the control group compared to the TAF switch group during the study period.PLWH switched to TAF had greater increases in weight after 1 year as compared to those continuing on a TAF free regimen. However, this did not translate to higher rates of obesity related illnesses such as diabetes, hypertension, and HLD during the follow up period.

Role of Advanced Glycation End Products in Assessment of Diabetes Mellitus as a Risk Factor for Retinal Vein Occlusion

Aim: In this study, we aimed to assess the correlation between diabetes mellitus (DM) and the retinal vein occlusion (RVO) based on skin autofluorescence (SAF) measurement, which reflects the accumulation of advanced glycation end products (AGE) in patients who have undergone an episode of central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). Material and methods: In total, 23 patients (16 males, 7 females) with RVO were included in this study. Among these 23 participants, 12 (52%) had been diagnosed with CRVO and 11 (48%) with BRVO. The control group consisted of 14 healthy volunteers (11 females, 3 males). To calculate the risk of cardiovascular diseases (CVD) and DM, we conducted SAF examinations. We compared the SAF levels in three groups of patients: (1) with CRVO, (2) with BRVO, and (3) the control group. Basic demographic and clinical information and detailed history of the concurrent diagnoses of systemic diseases, such as systemic hypertension (HTN), DM, hyperlipidemia (HL), and heart diseases, were obtained. Results: In total, 10 (43.5%) patients were diagnosed with DM, 6 (55%) in the BRVO group and 4 (33%) in the CRVO group. The mean SAF value was significantly higher in the BRVO group than in the control group (2.64 a.u. and 2.35 a.u., respectively) (p = 0.023). More patients with risk of DM were identified in the CRVO group than in the BRVO group (p = 0.024). Conclusions: The advanced glycation end products (AGE) in the skin autofluorescence (SAF) is a viable method of evaluating the risk of DM in patients with RVO. We confirmed a correlation between RVO and DM, which was significantly pronounced in the CRVO form, although further carefully devised studies on the relationship between RVO and DM with a larger number of responders should be conducted in the future.