Beta Coef Research Articles

Odor Identification Moderates Relationship Between Cognitive Training and Cognitive Decline

AbstractBackgroundOlfactory deficits have been shown to predict cognitive decline. Recent findings suggest that computerized cognitive training may reduce the risk of cognitive decline and dementia. However, the impact of olfaction deficits on cognitive training outcomes is unclear. In this study, we investigate how lower odor identification may moderate the relationship between treatment assignment (cognitive games versus crossword puzzles) and cognitive outcomes in older adults diagnosed with mild cognitive impairment (MCI).MethodData were drawn from the Cognitive Training and Neuroplasticity in Mild Cognitive Impairment (COG‐IT) Trial (NCT03205709). In this two‐site, single‐blinded, 78‐week trial, participants with MCI — stratified by age, severity (early/late MCI), and site — were randomly assigned to 12 weeks of intensive, home‐based, Computerized Cognitive Training (CCT) or computerized Crossword Puzzle Training (CPT), followed by six booster sessions. 106 patients received neuropsychological and olfactory assessments through the 11‐item Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog) and the 40‐item University of Pennsylvania Smell Identification Test (UPSIT). In linear mixed‐model analyses, the effect of baseline UPSIT score on change in the ADAS‐Cog score from baseline over 78 weeks by treatment group, adjusted for age and baseline ADAS‐Cog, was assessed.ResultAmong 106 older adults (n = 50 [games]; n = 56 [crosswords]), higher baseline UPSIT scores predicted improved ADAS‐Cog performance at week 78 for all patients randomized to CPT (beta coefficient, 0.15, 95% confidence interval [CI], 0.02 to 0.27; P = 0.02). Greater baseline UPSIT score predicted improved ADAS‐Cog performance at weeks 12, 52, and 78 for early MCI patients randomized to CPT (Week 12: beta coef. 0.26, 95% CI 0.09 to 0.43; Week 52: beta coef. 0.23, 95% CI 0.05 to 0.40; Week 78: beta coef. 0.22, 95% CI 0.05 to 0.39). This was not shown in early MCI patients randomized to CCT. Higher baseline UPSIT predicted significant improvement in ADAS‐Cog for late MCI patients randomized to CCT at week 78 (beta coefficient, 0.24, 95% CI 0.05 to 0.42; P = 0.01).ConclusionOur results are consistent with literature, suggesting that impaired olfaction moderates memory decline. Our preliminary results show that individuals with less impaired olfaction may experience greater cognitive improvement following cognitive training.

Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus.

Interleukin-6 (IL-6) is a proinflammatory cytokine that mediates pleiotropic functions in immune responses and inflammatory diseases. The literature lacks studies, with a clinical perspective, on the relationship between IL-6 serum levels and the characteristics of the disease in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to analyze the association between circulating IL-6 and disease manifestations in a well-characterized series of patients with SLE. Serum IL-6 levels and disease activity (SLEDAI-2K), severity (Katz) and damage index (SLICC-DI), complete lipid profile, and subclinical carotid atherosclerosis were evaluated in 284 patients with SLE. In addition, a complete characterization of the complement system was performed in samples from patients with SLE. A multivariate linear regression analysis was carried out to study the relationship between clinical and laboratory characteristics of the disease and IL-6 levels. Age (beta coef. 0.07 [95%CI 0.01-0.1] pg/mL, p = 0.014), C-reactive protein (beta coef. 0.21 [95%CI 0.16-0.25] pg/mL, p < 0.01), and male gender (beta coef. 2 [95%CI 0.3-0.5] pg/mL, p = 0.024), were positively associated with higher IL-6 levels in SLE patients. Most disease characteristics and damage and activity indices did not show significant relationships with IL-6. However, after multivariate analysis, IL-6 was associated with lower serum levels of HDL cholesterol (beta coef. -0.04 [95%CI -0.08-(-0.1)] pg/mL, p = 0.011), and apolipoprotein A1 (beta coef. -0.02 [95%CI -0.04-(-0.001)] pg/mL, p = 0.035). In contrast, the alternative complement cascade, C1inh, and C3a were all positively and independently associated with higher serum levels of IL-6. Moreover, stratification of the Systematic Coronary Risk Assessment 2 (SCORE2) results according to different categories of cardiovascular risk was associated with higher circulating serum IL-6 levels (beta coef. 0.2 [95%CI 0.02-0.4], pg/mL, p = 0.028). In conclusion, in a large series of SLE patients, IL-6 was not associated with disease-related features of SLE, including damage, severity, or activity indices. However, an association was found between serum IL-6 levels and circulating C3a and cardiovascular risk. Our study emphasizes the importance that IL-6 could have in cardiovascular disease and complement system disruption of SLE patients. Therapies targeting IL-6 could have a role in these two clinical manifestations of patients with SLE.

Apolipoprotein C-III is linked to the insulin resistance and beta-cell dysfunction that are present in rheumatoid arthritis

BackgroundInsulin resistance and beta-cell dysfunction are manifestations of rheumatoid arthritis (RA). Apolipoprotein C-III (ApoC3) has been associated with such insulin resistance and beta-cell dysfunction in the general population. Our purpose was to study whether ApoC3 is also related to the insulin resistance and beta-cell dysfunction that are present in patients with RA.MethodsThree hundred thirty-eight non-diabetic patients with RA who had a glycemia lower than 110 mg/dl were recruited. Insulin, C-peptide, and ApoC3 were assessed. Insulin resistance and beta-cell function were calculated using the Homeostasis Model Assessment (HOMA2) indices. A multivariable regression analysis was performed to study the relationship of ApoC3 with those molecules and indices adjusting for classic factors associated with insulin resistance that included glucocorticoids.ResultsApoC3 was related to significant higher levels of circulating insulin (beta coef. 0.37 [95%CI 0.01–0.73] µU/ml, p = 0.044) and C-peptide (beta coef. 0.13 [95%CI 0.05–0.22] ng/ml, p = 0.003), and higher insulin resistance —HOMA2-IR— (beta coef. 0.05 [95%CI 0.00–0.09], p = 0.041) and beta-cell dysfunction —HOMA2-%B— (beta coef. 2.94 [95%CI 0.07–5.80], p = 0.044) indices. This was found after a fully multivariable analysis that included, among others, prednisone intake and the classic factors associated with carbohydrate metabolism such as triglycerides, waist circumference, and obesity.ConclusionApoC3, insulin resistance, and beta-cell dysfunction are independently associated in patients RA.

Apolipoprotein C3 Is Downregulated in Patients With Inflammatory Bowel Disease.

INTRODUCTION:Inflammatory bowel disease (IBD) has been associated with an abnormal lipid profile. Apolipoprotein C-III (ApoC3) is a key molecule of triglyceride metabolism that is known to be related to inflammation and cardiovascular disease. In this study, we aim to study whether ApoC3 serum levels differ between patients with IBD and controls and whether the hypothetical disturbance of ApoC3 can be explained by IBD characteristics.METHODS:This is a cross-sectional study that included 405 individuals, 197 patients with IBD and 208 age-matched and sex-matched controls. ApoC3 and standard lipid profiles were assessed in patients and controls. A multivariable analysis was performed to analyze whether ApoC3 serum levels were altered in IBD and to study their relationship to IBD characteristics.RESULTS:After fully multivariable analysis including cardiovascular risk factors, use of statins, and changes in lipid profile caused by the disease itself, patients with IBD showed significant lower serum levels of ApoC3 (beta coef. −1.6 [95% confidence interval −2.5 to −0.7] mg/dL, P = 0.001). Despite this, inflammatory markers, disease phenotypes, or disease activity of IBD was not found to be responsible for this downregulation.DISCUSSION:Apolipoprotein C3 is downregulated in patients with IBD.

Apolipoprotein C-III in patients with systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) has been associated with atherosclerotic cardiovascular disease (CV) and an altered lipid profile. High levels of apolipoprotein C-III (ApoC3) are associated with elevated triglyceride levels and an increased risk of CV. In the present study, we aimed to study circulating ApoC3 in patients with SLE and describe its relationship with the manifestations of the disease.MethodsThis is a cross-sectional study that included 186 patients with SLE. Disease-related data, CV comorbidity, full lipid profile, and serum levels of ApoC3 were assessed. A multivariable regression analysis was performed to study how ApoC3 was related to SLE features.ResultsClassic CV risk factors were significantly and strongly associated with circulating ApoC3. After a fully multivariable analysis that included classic CV risk factors and lipid profile molecules, SLICC damage (beta coef. 0.10 [95% CI 0.02–0.19] mg/dl, 0.020) and Katz severity (beta coef. 0.11 [95% CI 0.03–0.19] mg/dl, p = 0.011) indices and SLEDAI activity score (beta coef. 0.05 [95% CI 0.05–0.08] mg/dl, p = 0.004) were all independently associated with higher levels of circulating ApoC3.ConclusionAmong SLE patients, disease activity, severity, and disease damage are independently associated with higher ApoC3 serum levels.

Key Molecules of Triglycerides Pathway Metabolism Are Disturbed in Patients With Systemic Lupus Erythematosus.

BackgroundElevated triglycerides or triglyceride-rich lipoproteins are an additional cause of cardiovascular (CV) disease. Given that patients with systemic lupus erythematosus (SLE) have a high prevalence of premature CV disease and show an altered lipid profile, our objective was to study whether three molecules that play a central role in the triglyceride metabolism: apolipoprotein C-III (ApoC3), angiopoietin-like protein 4 (ANGPLT4), and lipoprotein lipase (LPL) differ between SLE patients and controls, and how they are related to disease characteristics, including disease damage.MethodsCross-sectional study that included 347 women, 185 of them diagnosed with SLE and 162 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in SLE patients and controls. A multivariable analysis was performed to assess whether ANGPTL4, ApoC3 and LPL molecules differ between patients and controls and to study their relationship with SLE disease damage.ResultsAfter fully multivariable analysis that included classic CV risk factors, and the modifications that the disease itself produces over the lipid profile, it was found that ApoC3 was significantly lower (beta coef. -1.2 [95%CI -1.6- -0.8) mg/dl, <0.001), and ANGPTL4 (beta coef. 63 [95%CI 35-90] ng/ml, <0.001) and LPL (beta coef. 79 [95%CI 30-128] ng/ml, p=0.002) significantly higher in patients with SLE compared to controls. Disease damage score was significantly and independently associated with higher serum levels of LPL (beta coef. 23 [95%CI 10-35] ng/ml, p=0.001). Mediation analysis suggested that the relationship between disease damage and LPL was direct and not mediated by ApoC3 or ANGPLT4.ConclusionThe ApoC3, ANGPLT4 and LPL axis is disrupted in patients with SLE. Disease damage explains this disturbance.

The angiopoietin-like protein 4, apolipoprotein C3, and lipoprotein lipase axis is disrupted in patients with rheumatoid arthritis

BackgroundModulators of triglyceride metabolism include lipoprotein lipase (LPL), angiopoietin-like protein 4 (ANGPTL4), and apolipoprotein C-3 (ApoC3). There is evidence on the influence of this triangle of molecules on an increased risk of atherosclerotic cardiovascular disease (CV) in the general population. Patients with rheumatoid arthritis (RA) present changes in lipid profiles and accelerated CV disease. In the present study, we set out to study whether the ANGPTL4, ApoC3, and LPL axis differs in subjects with RA compared to controls. In a further step, we investigated the relationship of this axis with subclinical atherosclerosis in patients with RA.MethodsCross-sectional study that included 569 individuals, 323 patients with RA and 246 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in RA patients. A multivariable analysis was performed to assess whether the ANGPTL4, ApoC3, and LPL axis was altered in RA and to study its relationship with RA dyslipidemia and subclinical carotid atherosclerosis.ResultsMost lipid profile molecules did not differ between patients and controls. Despite this, and after fully multivariable analysis including CV risk factors, use of statins, and changes in the lipid profile caused by the disease itself, patients with RA showed higher serum levels of ANGPTL4 (beta coef. 295 [95% CI 213–376] ng/ml, p<0.001) and ApoC3 (beta coef. 2.9 [95% CI 1.7–4.0] mg/dl, p<0.001), but lower circulating LPL (beta coef. −174 [95% CI −213 to −135] ng/ml, p<0.001). ANGPTL4 serum levels were positively and independently associated with a higher cIMT in patients with RA after fully multivariable adjustment.ConclusionThe axis consisting in ANGPTL4, ApoC3, and LPL is disrupted in patients with RA. ANGPTL4 serum levels are positively and independently associated with a higher cIMT in RA patients.

P485 Apolipoprotein C3 is Downregulated in Patients with Inflammatory Bowel Disease

Abstract Background Inflammatory bowel disease (IBD) has been associated with an abnormal lipid profile. Apolipoprotein C3 (ApoC3) is a key molecule of triglycerides metabolism that is known to be related to inflammation and cardiovascular (CV) disease. In the present study, we aim to study if ApoC3 serum levels differ between patients with IBD and controls, and if the hypothetical disturbance of ApoC3 can be explained by IBD characteristics. Methods Cross-sectional study that included 405 individuals, 197 patients with IBD and 208 age- and sex-matched controls. ApoC3 and standard lipid profiles were assessed in patients and controls. A multivariable analysis was performed to analyze whether ApoC3 serum levels were altered in IBD and to study their relationship to IBD characteristics. Results After fully multivariable analysis including CV risk factors, use of statins, and changes in the lipid profile caused by the disease itself, patients with IBD showed significant lower serum levels of ApoC3 (beta coef. -1.6 [95%CI -2.5- -0.7] mg/dl, p=0.001). Despite this, inflammatory markers, disease phenotypes or disease activity of IBD were not found to be responsible for this downregulation. Conclusion Apolipoprotein C3 is downregulated in patients with IBD.

Apolipoprotein C3 and beta-cell dysfunction are linked in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) has been associated with insulin resistance and beta-cell dysfunction. Apolipoprotein C3 (ApoC3) is a component of very low-density lipoproteins. Since ApoC3 has been linked to beta-cell impairment in the general population, in this study we aimed to discover if this lipoprotein is related to glucose homeostasis disturbance in patients with SLE. One hundred and forty non diabetic patients with SLE who had a glycaemia lower than 110 mg/dl were recruited. Insulin, C-peptide, and ApoC3 were assessed. Insulin resistance and beta-cell function were calculated using the Homeostasis Model Assessment (HOMA2) indices. A multivariable regression analysis was performed to study the relationship of ApoC3 to those molecules and indices adjusting for classical factors associated with insulin resistance that included glucocorticoids. In the multivariable regression analysis that included prednisone intake, a significant relation of ApoC3 to C-peptide was found (beta coef. 0.27 [95%CI 0.03-0.51) ng/ml, p=0.030). Similarly, ApoCa3 was associated with higher degree of beta-cell dysfunction (HOMA2-%B) although in this case statistical significance was not achieved (beta coef. 8 [95%CI-1-18], p=0.086). This relationship was not found with serum insulin levels or IR indices. Furthermore, in the univariable analysis, but not after multivariable adjustment, the disease damage score was found to significantly mediate the effect of ApoC3 on circulating C-peptide. and HOMA2-%B. Beta-cell dysfunction and ApoC3 are linked in patients with SLE.

Insulin Resistance Is Not Increased in Inflammatory Bowel Disease Patients but Is Related to Non-Alcoholic Fatty Liver Disease.

Background. Insulin resistance (IR) has been linked to inflammatory states. The aim of this study was to determine whether IR is increased in a cohort of inflammatory bowel disease (IBD) patients with low disease activity. We additionally intended to establish which factors were the determinants of IR in this population, including the presence of nonalcoholic fatty liver disease (NAFLD). Methods. Cross-sectional study encompassing 151 IBD patients and 174 non-diabetic controls. Insulin and C-peptide serum levels and IR and beta cell function (%B) indices based on homoeostatic model assessment (HOMA2) were assessed in patients and controls. Liver stiffness as measured by transient elastography, and the presence of NAFLD detected via ultrasound were additionally assessed. A multivariable regression analysis was performed to evaluate the differences in IR indexes between patients and controls, and to determine which predictor factors were associated with IR in IBD patients. Results. Neither HOMA2-IR (beta coef. −0.26 {95%CI −0.64–0.13}, p = 0.19) nor HOMA2-%B (beta coef. 15 {95%CI −14–44}, p = 0.31) indexes differed between patients and controls after fully multivariable analysis. Among classic IR risk factors, obesity, abdominal circumference, and triglycerides significantly and positively correlated with IR indexes in IBD patients. However, most features related to IBD, such as disease patterns, disease activity, and inflammatory markers, were not associated with IR. The presence of NAFLD was independently and significantly associated with beta cell dysfunction in patients with IBD (HOMA2—B grade 4, 251 ± 40 vs. grade 1, 107 ± 37, p = <0.001). Conclusions. IR is not increased in IBD patients with low disease activity compared to controls. However, the presence of NAFLD favors the development of IR in patients with IBD.

Amylin serum levels are upregulated in patients with systemic lupus erythematosus.

Amylin is a pancreatic hormone that participates in glucose homeostasis. We aimed to investigate how serum amylin levels are expressed in patients with systemic lupus erythematosus (SLE) compared to matched controls, and their possible relationship to disease-related characteristics, such as activity or damage. 144 SLE patients and 96 non-diabetic sex- (female 96% vs. 91%, p=0.43) and age-matched controls (49±11 vs. 51±8 years, p=0.09) were included. Amylin, insulin and C-peptide serum levels, as well as insulin resistance indexes were assessed in both groups. Multivariable regression analysis was performed to compare amylin between groups and to explore its interrelations with SLE features. The analyses were adjusted for glucocorticoids intake and for insulin resistance classic risk factors. Patients with SLE exhibited significant higher serum levels of amylin when compared to controls after multivariable analysis (beta coef. 1.56 [95%CI 1.01-2.11], p=0.000). Moreover, SLE patients not on prednisone (beat coef. 1.54 [95%CI 0.98-2.10] ng/ml, p=0.000) and those on prednisone (beta coef. 1.51 [95%CI 0.96-2.07] ng/ml, p=0.000) disclosed higher amylin serum levels compared to controls in the fully multivariable analysis. Hyperamylinaemia in SLE patients remained significant even adjusting for differences in the insulin resistance and beta cell production rates between patients and controls. The damage produced by the disease and its severity were independently and positively associated with amylin serum levels. Amylin is upregulated in SLE patients compared to controls, regardless of the insulin resistance that SLE may present. The damage produced by the disease and its severity independently explains this upregulation.

MO695THE ASSOCIATION OF CIRCULATING CD14++CD16+ MONOCYTES, NATURAL KILLER CELLS AND REGULATORY T CELLS SUBPOPULATIONS WITH CARDIOVASCULAR DISEASE IN A COHORT OF PERITONEAL DIALYSIS PATIENTS

Abstract Background and Aims Advanced chronic kidney disease (CKD) is characterized by elevated expression of the proinflammatory and pro-atherogenic CD14++CD16+ monocytes subset. The role of lymphocyte subpopulations including natural killer (NK) cells and CD4+CD25+ regulatory T cells (Tregs) in the modulation of inflammation and immunity and subsequent cardiovascular implications have received increasing attention. The role of immune cell subpopulations remains to be determined in peritoneal dialysis (PD) patients. The aim of this pilot study was to investigate potential correlations between blood levels of CD14++CD16+ monocytes, NK cells and Tregs with phenotypes of established cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF) in a cohort of PD patients. Method 29 stable PD patients (mean age 66.96 years ±14.5, 62% males) were enrolled. Exclusion criteria were a history of malignancy, autoimmune disease, active or chronic infections and a recent (&amp;lt; 3 months) cardiovascular event. Demographic, laboratory and bioimpedance measurements data (overhydration, extracellular and total body water and their ratios) were collected. The analysis of peripheral blood immune cell subsets was performed using flow cytometry (FC). Additionally, in 7 PD patients the distribution of the immune cells was evaluated by FC at two time points: T0 (before initiation of PD - CKD stage G5) and T1 (after PD start). Results The median dialysis vintage was 34.5 (range 3.2-141) months. Overall, PD patients had 527 ± 199 monocytes and 1731 ± 489 lymphocytes while mean percentage of CD14++CD16+ monocytes was 9.3 ±6.36% (normal range 2-8%), NK cells 16.6±10.3% (normal range 5-15%) and Tregs 2.1±1.76% (normal range 1-3%). There was no correlation of either of these cell subpopulations with age, PD vintage, inflammation markers (CRP, fibrinogen, albumin, hsTroponin-I), overhydration markers or comorbidities. Only increased NK cells were associated with the presence of HF in PD (24.87 vs 14.92%, p 0.047). In multiple regression analysis, NK cells levels were strongly associated with the presence of edema (beta coef=13.7, p&amp;lt;0.001) and CAD (beta coef=7.1, p=0.046). At T0 mean percentage of CD14++CD16+ monocytes, NK cells and Tregs were 9.7 ±4.5%, 17.1 ±3.84% and 2.38± 1.26% respectively whereas at T1 mean percentage of CD14++CD16+ monocytes was 13.3% ±8.4, NK cells 19.8±6.47% and Tregs 1.5±0.6%. Paired t-test of cell subpopulations (T0 vs T1) showed that only the Tregs were significantly decreased (p =0.018), while the other subpopulations did not differ and remained increased. Conclusion Our study is the first to evaluate the potential association between specific immune cell subsets and cardiovascular disease in long-term PD patients. Increased NK cells levels directly correlate both with the presence of HF and CAD in PD patients. Longitudinal results suggest that CD14++CD16+ and NK cells remain increased after PD start, while Tregs decrease further. The state of pro-inflammation and immune deregulation appear to persist after initiating PD. Future research is required to evaluate the role of immune cells subsets as potential tools to identify patients who are at the highest risk for complications and to guide interventions that may improve clinical outcomes.

P247 Carotid Plaque Assessment reclassifies patients with Inflammatory Bowel Disease into Very-High Cardiovascular Risk

Abstract Background The addition of carotid ultrasound into cardiovascular (CV) risk scores has been found to be effective in identifying patients with chronic inflammatory diseases at high-CV risk. We aimed to determine if its use would facilitate the reclassification of patients with inflammatory bowel disease (IBD) into the very high-CV-risk category and whether this may be related to disease features. Methods Multicenter cross-sectional study encompassing 186 IBD patients and 175 controls. Systematic Coronary Risk Evaluation (SCORE), disease activity measurements, and the presence of carotid plaques by ultrasonography were assessed. Reclassification was compared between patients and controls. A multivariable regression analysis was performed to evaluate if the risk of reclassification could be explained by disease-related features and to assess the influence of traditional CV risk factors on this reclassification. Results After evaluation of carotid ultrasound, a significantly higher frequency of reclassification was found in patients with IBD compared to controls (35% vs. 24%, p=0.030). When this analysis was performed only on subjects included in the SCORE low-CV-risk category, 21% IBD patients compared to 11% controls (p = 0.034) were reclassified into the very high-CV-risk category. Disease related data, including disease activity, were not associated with reclassification after fully multivariable regression analysis. Traditional CV risk factors showed a similar influence over reclassification in patients and controls. However, LDL-cholesterol disclosed a higher effect in controls compared to patients (beta coef. 1.03[95%CI 1.02–1.04] vs. 1.01[95%CI 1.00–1.02], interaction p=0.035) after adjustment for confounders. Conclusion Carotid plaque assessment is useful to identify high-CV risk IBD patients.

Carotid Plaque Assessment Reclassifies Patients with Inflammatory Bowel Disease into Very-High Cardiovascular Risk.

The addition of carotid ultrasound into cardiovascular (CV) risk scores has been found to be effective in identifying patients with chronic inflammatory diseases at high-CV risk. We aimed to determine if its use would facilitate the reclassification of patients with inflammatory bowel disease (IBD) into the very high-CV-risk category and whether this may be related to disease features. In this cross-sectional study encompassing 186 IBD patients and 175 controls, Systematic Coronary Risk Evaluation (SCORE), disease activity measurements, and the presence of carotid plaques by ultrasonography were assessed. Reclassification was compared between patients and controls. A multivariable regression analysis was performed to evaluate if the risk of reclassification could be explained by disease-related features and to assess the influence of traditional CV risk factors on this reclassification. After evaluation of carotid ultrasound, a significantly higher frequency of reclassification was found in patients with IBD compared to controls (35% vs. 24%, p = 0.030). When this analysis was performed only on subjects included in the SCORE low-CV-risk category, 21% IBD patients compared to 11% controls (p = 0.034) were reclassified into the very high-CV-risk category. Disease-related data, including disease activity, were not associated with reclassification after fully multivariable regression analysis. Traditional CV risk factors showed a similar influence over reclassification in patients and controls. However, LDL-cholesterol disclosed a higher effect in controls compared to patients (beta coef. 1.03 (95%CI 1.02–1.04) vs. 1.01 (95%CI 1.00–1.02), interaction p = 0.035) after adjustment for confounders. In conclusion, carotid plaque assessment is useful to identify high-CV risk IBD patients.

Beta-cell function is disrupted in patients with systemic lupus erythematosus.

To investigate how markers of beta-cell secretion (proinsulin-processing metabolites) are expressed in SLE patients and their potential relation to features associated with the disease such as activity or damage. One hundred and forty-four SLE patients and 69 nondiabetic sex- and age-matched controls were assessed. Beta-cell secretion molecules, as measured by insulin, split and intact proinsulins, and C-peptide levels were analysed in both groups. Multiple regression analysis was performed to compare proinsulin propeptides between groups and to explore the interrelations with SLE features. Analyses were adjusted for glucocorticoid intake and for insulin resistance classic risk factors. Fully multivariable analysis demonstrated that regardless of glucocorticoid use, SLE patients exhibited higher levels of split proinsulin. Likewise, the split proinsulin-to-insulin ratio was upregulated in patients with SLE undergoing glucocorticoid therapy [beta coeficient 0.19 (95% Confidence Interval 0.07, 0.30), P = 0.002] or not [beta coef. 0.09 (95% CI: 0.01, 0.17), P = 0.025]. Similar results were found for the intact proinsulin-to-insulin ratio, although differences were only statistically significant for patients taking glucocorticoids [beta coef. 0.08 (95% CI: 0.03, 0.12), P = 0.001]. SLE damage score was associated with higher serum levels of intact [beta coef. 0.51 (95% CI 0.17, 0.86) pmol/l, P = 0.004] and split proinsulins [beta coef. 1.65 (95% CI 0.24, 3.06) pmol/l, P = 0.022] after multivariable analysis, including disease duration and prednisone use. Among patients with SLE, proinsulin-processing metabolites, a marker of beta-cell disruption, are upregulated compared with matched controls. This disproportionate hyperproinsulinemia can be explained by the damage produced by the disease and occurs independently of prednisone use.

Cardioprotection in patients with cancer undergoing chemotherapy: A network meta-analysis.

e12008 Background: Introduction of anthracycline or trastuzumab based regimen for various types of cancer during the past two decades led to substantial improvement in life expectancy, yet resulting in increased prevalence of unintended side effects. Left ventricular systolic dysfunction is a known complication of the currently employed chemotherapy regimens with anthracycline or trastuzumab which not only affects patient’s cardiac outcome but also limits their therapeutic opportunities, especially continuation or reintroduction of chemotherapy treatment. We aimed to perform comprehensive network meta analysis to synthesize data from randomized clinical trials (RCT) comparing all modern regimens to prevent cardiotoxicity in such patients. Methods: We performed a comprehensive search of pubmed, embase, google scholar and TRIP database for all RCT comparing cardioprotective effects of medication in patients with various types of cancer on chemotherapy with either an anthracycline or trastuzumab based regimen from 1997 to 2019. Left ventricular ejection fraction (LVEF) was measured by transthoracic echocardiogram or cardiac magnetic resonance imaging. Patients treated with either Angiotensin Converting Enzyme-Inhibitor(ACE) or Angiotensin receptor blocker(ARB) were combined into one group. Primary outcome was change in LVEF between start and end of the chemotherapy. Network meta-analyses were conducted using consistency and inconsistency models. Results: A total of 16 studies with 1459 patients were included in the analysis where either an Anthracycline or Trastuzumab based chemotherapy regimen was administered. 369 patients received beta blockers(BB), 351 received either an ACE or ARB, 61 received a combination of BB and either an ACE or ARB, 20 received a statin and 657 were given a placebo. The primary cancer was breast cancer in 8 studies, one each of lymphoma, blood cancers and remaining 6 being mixed. Mean age was 48.81 years. Compared to patients on placebo there was a significant cardioprotective effect (smaller reduction in LVEF) noted with ACE/ARB (beta coef 5.2 (1.5-8.9), p&lt;0.01), BB(beta coef 4.62 (0.8-7.8), p&lt;0.02), and spironolactone beta coef 12.9 (1.9-23.4), p&lt;0.03) There was an evidence of inconsistency with all p&gt;0.3, other than in spironolactone arm as there were suggestion of inconsistency with p&lt;0.01 likely due to the presence of single study. Conclusions: BB and ACE/ARB are associated with reduction in cardiotoxicity in patients with cancer undergoing cancer chemotherapy with an anthracycline or trastuzumab based regimen.

THU0056 Impaired beta cell signaling is present in non diabetic rheumatoid arthritis patients

ObjectivesIt has been suggested that resistance to insulin action is a feature that accompanies rheumatoid arthritis (RA), a disease where chronic inflammation predominates and classical triggers for insulin resistance (IR)...

The Effect of Low Glucose Degradation Product Dialysis Solution on Epithelial-To-Mesenchymal Transition in Continuous Ambulatory Peritoneal Dialysis Patients

Human peritoneal mesothelial cells (HPMCs) undergo a transition from an epithelial phenotype to a mesenchymal phenotype (EMT) during peritoneal dialysis (PD). That transition may be directly related to failure of peritoneal membrane function. In a randomized prospective controlled study, we investigated the effect of low glucose degradation product (GDP) dialysis solution on the transition of HPMCs. Among new continuous ambulatory PD patients, 60 patients completed a 12-month protocol (low-GDP solution group, n = 32; high-GDP solution group, n = 28). At the 1st, 6th, and 12th months, HPMCs drained from overnight effluent were cultured on T25. When they had nearly reached confluence, cell scores were measured blindly by the same person (score 1 = cobblestone-shaped HPMCs, score 2 = mixed, score 3 = fibroblast dominant). Cell scores and clinical indices, including peritoneal markers, were compared between the low-GDP and high-GDP groups at the 1st, 6th, and 12th months. The factors associated with EMT were analyzed with generalized estimating equations using STATA 7.0 (STATA Corp., College Station, Texas, USA). In addition, vimentin and cytokeratin 8/18 stains were used to verify EMT in cultured cells and peritoneal specimens in some patients. (1) The low-GOP group showed higher dialysate cancer antigen 125 levels from the 1st to 12th months (55.4 +/- 24.8 vs 8.8 +/- 1.7, 56.7 +/- 28.1 vs 22.1 +/- 11.3, and 54.2 +/- 28.2 vs 24.6 +/- 16.5 U/mL, at the 1st, 6th, and 12th months, respectively; all p = 0.000). (2) The low-GOP group showed lower cell scores at the 1st, 6th, and 12th months (1.22, 1.22, and 1.56 vs 1.61, 1.75, and 2.14; p < 0.05, p < 0.01, and p < 0.01, respectively). (3) At the 12th month, the number of fibroblast-dominant cultures (score 3) was significantly lower in the low-GOP group [4/32 (12.5%) patients vs 14/28 (50%), p < 0.05]. (4) Both cobblestone-shaped HPMCs and fibroblastoid cells were positively stained with cytokeratin and vimentin. (5) There were many cytokeratin- and vimentin-positive cells in the submesothelial area in the peritoneal biopsy specimens. (6) The consistent factor associated with EMT was only high-GOP solution (60 patients, n = 178, beta coefficient 0.312, p = 0.000; 46 patients, n = 137, beta coef: 0.228, p = 0.000) and not numbers of peritonitis episodes, duration of angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker medication, or diabetes. Low-GDP solution showed beneficial effects such as rapid remesothelialization and less EMT in the peritoneum with time on PD.

Osteoporosis and skeletal fractures in chronic liver disease.

In order to determine the prevalence and severity of hepatic osteodystrophy by non-invasive means we compared 115 consecutive ambulant patients with histologically proven chronic liver disease to 113 age and sex matched control subjects. Methods used included the assessment of fracture prevalence rates, spinal radiography, and measurements of bone mineral density in the spine and the forearm. Spinal and peripheral fractures were more prevalent in the patients than in the control subjects (p less than 0.03 and p less than 0.01 respectively). The type of the underlying liver disease did not significantly affect the fracture prevalence rates, but alcoholic patients sustained more peripheral fractures than patients with other hepatic disorders (p less than 0.05). The bone mineral densities of the spines and the forearms were significantly reduced in male patients of all age groups and in female patients aged 60 years or more (p less than 0.001 for men and p less than 0.01 for women for both measurements). The prevalence rates of spinal and forearm osteoporosis were twice as high among patients with liver disease than in control subjects regardless of the definitions used. The presence of cirrhosis and hypogonadism were major risk factors for development of both spinal (Beta coef = 0.190 and 0.176; SE = 0.079 and 0.086 respectively) and forearm osteoporosis (Beta coef = 0.20 and 0.29; SE = 0.073 and 0.80 respectively). Spinal bone density was the predominant determinant of spinal fractures (Beta coef = -0.007; SE = 0.001), while hypogonadism (Beta coef = 0.363; SE = 0.075) and cirrhosis (Beta coef = 0.185; SE = 0.068) were the major predictors of peripheral fractures. The concentrations of serum calcium and serum vitamin D metabolites and the use of corticosteroids were apparently without effect on the prevalence of skeletal fractures or bone density.