Protective Effect In Patients Research Articles

Re-appraisal of the obesity paradox in heart failure: a meta-analysis of individual data

BackgroundHigher body mass index (BMI) is associated with better outcome compared with normal weight in patients with HF and other chronic diseases. It remains uncertain whether the apparent protective role of obesity relates to the absence of comorbidities. Therefore, we investigated the effect of BMI on outcome in younger patients without co-morbidities as compared to older patients with co-morbidities in a large heart failure (HF) population.MethodsIn an individual patient data analysis from pooled cohorts, 5,819 patients with chronic HF and data available on BMI, co-morbidities and outcome were analysed. Patients were divided into four groups based on BMI (i.e. ≤ 18.5 kg/m2, 18.5–25.0 kg/m2; 25.0–30.0 kg/m2; 30.0 kg/m2). Primary endpoints included all-cause mortality and HF hospitalization-free survival.ResultsMean age was 65 ± 12 years, with a majority of males (78%), ischaemic HF and HF with reduced ejection fraction. Frequency of all-cause mortality or HF hospitalization was significantly worse in the lowest two BMI groups as compared to the other two groups; however, this effect was only seen in patients older than 75 years or having at least one relevant co-morbidity, and not in younger patients with HF only. After including medications and N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin concentrations into the model, the prognostic impact of BMI was largely absent even in the elderly group with co-morbidity.ConclusionsThe present study suggests that obesity is a marker of less advanced disease, but does not have an independent protective effect in patients with chronic HF.Graphic abstractCategories of BMI are only predictive of poor outcome in patients aged > 75 years or with at least one co-morbidity (bottom), but not in those aged < 75 years without co-morbidities (top). The prognostic effect largely disappears in multivariable analyses even for the former group. These findings question the protective effect of obesity in chronic heart failure (HF).

The effect of Remote Ischemic Preconditioning (RIPC) on myocardial injury and inflammation in patients with severe aortic valve stenosis undergoing Transcatheter Aortic Valve Replacement (TAVΙ)

BackgroundRemote ischemic preconditioning (RIPC) is being evaluated as a strategy to reduce cardiac injury and inflammation in patients undergoing diverse cardiac invasive and surgical procedures. However, it is unclear whether RIPC has protective effects in patients undergoing the transfemoral- transcatheter aortic valve implantation (TF-TAVΙ) procedure. MethodsBetween September 2013 and September 2015, 55 random consecutive patients were prospectively assigned to receive SHAM preconditioning (SHAM, 22 patients) or Remote Ischemic Preconditioning (RIPC) (4 cycles of 5 min intermittent leg ischemia and 5 min reperfusion, 33 patients) prior to TF-TAVI. The primary endpoint was to determine the serum levels of: hs-cTn-I (necrosis), CK-18 (apoptosis), and IL-1b (inflammation). Quantification was performed using commercially available ELISA kits. Patients were sampled 1-day pre TF-TAVΙ and 24-hours post TF-TAVΙ. Secondary endpoints included: total mortality, incidence of periprocedural clinical acute myocardial infarction (AMI), acute kidney injury (AKI), and stroke. Results22 SHAM patients and 33 RIPC patients were finally analyzed. Our data revealed no significant difference in serum levels of hs-cTn-I and CK-18 among various groups. However, in the RIPC group, the increase in IL1b level was significantly lower for 24-h post TF-TAVΙ, (p < 0.01). There were no significant differences between groups in the secondary endpoints at the follow-up interval of one month. RIPC-related adverse events were not observed. ConclusionsOur data suggest that RIPC did not exhibit significant cardiac or kidney protective effects regarding necrosis and apoptosis in patients undergoing TF-TAVΙ. However, an important anti-inflammatory effect was detected in the RIPC group.

Anticoagulation and antiplatelet therapy post coronary artery bypass surgery.

Coronary artery bypass grafting (CABG) is the gold standard treatment for patients with multivessel coronary heart disease. Although its use has proven long-term survival benefits, there is a relative degree of graft failure which increases morbidity and mortality rates. This review discusses clinical outcomes following antiplatelet and anticoagulant therapy after CABG. There is wide variation of evidence about the use of clopidogrel or ticagrelor to aspirin postoperatively in relation to improving graft patency rates or clinical outcomes over the use of aspirin alone. These dual therapies may have significant protective effects in patients undergoing off-pump CABG. Recent studies suggest that superior outcomes may be attained by combining prasugrel with aspirin. Further research is needed to evaluate this, as well as compare the effectiveness of different dual antiplatelet regimens. There is weak evidence for post-CABG anticoagulation, with warfarin and rivaroxaban providing no protection against graft failure but decreasing long-term major adverse cardiac events. Anticoagulation seems to be indicated only in post-CABG patients at high risk of future ischemic events. The use of dual anti-platelet therapy post coronary artery bypass surgery needs further research. Potentially, selective patient groups will benefit more from the addition of thienopyridine antiplatelets or anticoagulants to aspirin after CABG.

552. Could Anticoagulant Use Prior to Infection with COVID-19 Decrease Mortality?

BackgroundThe novel coronavirus (COVID-19) has resulted in substantial morbidity and mortality worldwide. Infection with COVID-19 has been associated with coagulopathy and inflammation. This prothrombotic state has been identified in the literature as an indicator of poor prognosis and those with COVID-19 who receive anticoagulation therapy may have better outcomes. Due to this prothrombotic state, patients who are currently receiving anticoagulation therapy for other indications prior to infection with COVID-19 may have better outcomes.MethodsThis was a retrospective case control study conducted at an inner city hospital. Patients were eligible if they were hospitalized between March 15, 2020 and May 15, 2020 and had confirmed infection due to COVID-19. Patients were matched by age, sex, body mass index (BMI), diabetes mellitus (DM), hypertension (HTN) and estimated glomerular filtration rate (eGFR) by chronic kidney disease (CKD) state. This study evaluated morality in patients who were receiving long term anticoagulation therapy prior to infection with COVID-19 compared to those who were not.ResultsOf the 436 patients hospitalized with confirmed infection due to COVID-19, 400 were eligible for analysis. Twenty-two were on anticoagulation therapy prior to admission. Among those patients, 68% were male and 32% were female. The majority of the patients were greater than 60 years of age (82%). Comorbidities were present in 21 patients and were as follows: HTN (95%), CKD (67%), DM (57%), obesity (36%). Of the 22 patients, five expired due to COVID-19 infection compared to 52 patients from the 149-patient matched cohort [z-score 1.13, p = 0.26; odds ratio (OR) 1.82; 95% confidence interval [CI], 0.69–4.71].ConclusionPrior long-term anticoagulation use does not appear to have a protective effect in patients with COVID-19 infection. Studies with larger sample size will be needed to answer this important question.Disclosures Jihad Slim, MD, Abbvie (Speaker’s Bureau)Gilead (Speaker’s Bureau)Jansen (Speaker’s Bureau)Merck (Speaker’s Bureau)ViiV (Speaker’s Bureau)

Long-Term Outcomes Stratified by Body Mass Index in Patients Undergoing Transcatheter Aortic Valve Implantation

Transcatheter aortic valve implantation (TAVI) is emerging as the default strategy for older patients with severe, symptomatic, and trileaflet aortic stenosis. Increased body-mass index (BMI) is associated with a protective effect in patients undergoing percutaneous coronary intervention. We assessed whether elevated BMI was associated with a similar association in TAVI. We evaluated prospectively collected data from 634 patients who underwent TAVI at 2 centers from August 2008 to April 2019. Patients were stratified as normal weight (BMI 18.5 to 24.9 kg/m2, n = 214), overweight (25 to 29.9 kg/m2, n = 234), and obese (>30 kg/m2, n = 185). Outcomes were reported according to VARC-2 criteria. Mortality was assessed using Cox proportional hazards regression analysis (median follow-up 2 years). Kaplan-Meier analysis was used to estimate cumulative mortality. Baseline differences were seen in age (85 vs 84 vs 82, p <0.001), STS-PROM score (4.3 vs 3.4 vs 3.6, p <0.001), sex (50% vs 36% vs 55% female, p <0.001), clinical frailty score (p = 0.02), diabetes (21% vs 29% vs 40%, p <0.001), and presence of chronic obstructive pulmonary disease (COPD) (13% vs 13% vs 23%, p = 0.009). On multivariable analysis there was no mortality difference between normal and obese patients (hazard ratio [HR] 0.70, confidence interval [CI] 0.46 to 1.1 p = 0.11), however overweight patients had significantly lower mortality (HR 0.56 CI 0.38 to 0.85, p = 0.006). Variables independently associated with increased mortality were increasing age, male sex, COPD, previous balloon valvuloplasty, and higher STS-PROM. In conclusion, overweight patients have lower long-term mortality when compared with normal weight and obese patients undergoing TAVI.

Liraglutide improves obesity-induced renal injury by alleviating uncoupling of the glomerular VEGF-NO axis in obese mice.

Obesity-related kidney disease is associated with generalized endothelial dysfunction. Liraglutide, a glucagon-like peptide-1 agonist, has cardiovascular-renal protective effects in patients with diabetes. In this study, the ability of liraglutide to reduce urinary albumin excretion by alleviating glomerular vascular endothelial growth factor-nitric oxide (VEGF-NO) axis uncoupling was assessed in high fat diet-induced obese mice. C57BL/6J mice were divided into control and obesity groups, treated with or without liraglutide (200μg/kg/day). Blood biochemistry and urinary albumin excretion were measured. Glomerular VEGF and the AMPK-endothelial nitric oxide synthase (eNOS) pathway were assayed by western blotting. Glomerular NO, renal haeme oxygenase-1 activity, and malondialdehyde levels were also measured. Treatment of obese mice with liraglutide led to significant reductions in body weight gain (46±1g vs 55±1g, P<.0001), visceral fat (8.9±0.6g vs 14.5±0.6g, P<.0001), perirenal fat (2.9±0.2g vs 5.4±0.3g, P<.0001), and free fatty acid (1.71±0.12mmol/L vs 1.02±0.08mmol/L, P<.0001). Liraglutide significantly improved glucose homeostasis, which was impaired in obese mice. Liraglutide reduced urinary albumin excretion and glomerular hypertrophy in obese mice. Additionally, liraglutide significantly decreased VEGF and increased glomerular NO production in glomeruli, indicating restoration of the glomerular VEGF-NO axis. Furthermore, liraglutide activated the glomerular AMPK-eNOS pathway in obese mice, upregulated renal haeme oxygenase-1 activity, and reduced the renal malondialdehyde levels in obese mice. In conclusion, liraglutide reduced microalbuminuria and ameliorated renal injury by alleviating the uncoupling of the glomerular VEGF-NO axis.

Prognostic value of desmoplastic stroma in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinomas (iCCs) are primary tumors of the liver characterized by the presence of a desmoplastic stroma. While tumor stroma may have a protective or a pejorative value depending on the type of malignant disease, the precise role of the desmoplastic stroma in iCC remains poorly understood. The aim of the present study was to evaluate the prognostic value of stromal compartment in iCC through a multiparametric morphological analysis. Forty-nine surgically resected iCCs were included. For all cases, tumor paraffin blocks of iCCs were selected for stromal morphological characterization through quantitative and qualitative approaches using immunohistochemistry and second-harmonic generation imaging. Intratumor heterogeneity was also evaluated in regards with the different stromal features. High proportionated stromal area (PSA) (defined by stromal to tumor area ratio) was inversely correlated with vascular invasion (62.5% vs 95.7%, p = 0.006) and positively correlated with well-differentiated grade (60% vs 12.5%, p = 0.001). Patients with high PSA had a better disease-free survival (DFS) than patients with low stromal area (60% vs 10%, p = 0.077). Low activated stroma index (defined by cancer-associated fibroblasts number to stromal area ratio) was associated with a better DFS (60% vs 10%, p = 0.05). High collagen reticulation index (CRI), defined as the number of collagen fiber branches within the entire length of the collagen network, was associated with a poorer overall survival (42% vs NR, p = 0.026). Furthermore, we showed that CRI was also an homogeneous marker throughout the tumor. Based on morphological features, desmoplastic stroma seems to exert a protective effect in patients with iCC. Stromal collagen reticulation may provide additional clinically relevant information. In addition, these data support the potential value to evaluate CRI in biopsy specimen.

The obesity paradox in the stress echo lab: fat is better for hearts with ischemia or coronary microvascular dysfunction.

Obesity is an independent risk factor for coronary artery disease (CAD), but once CAD has developed it has been associated with improved survival ("obesity paradox"). To assess how obesity affects prognosis in patients with or without inducible ischemic regional wall motion abnormalities (RWMA) and/or abnormal coronary flow velocity reserve (CFVR) during stress echocardiography (SE). In an observational retrospective two- center study design, we analyzed 3249 consecutive patients (1907 men; age 66 ± 12 years; body mass index, BMI, 26.9 ± 4.1 kg/m2) with known (n = 1306) or suspected (n = 1943) CAD who underwent dipyridamole SE with simultaneous evaluation of RWMA and CFVR. All-cause death was the outcome end-point. 1075 patients were lean (BMI 18.5-24.9 kg/m2), 1523 overweight (BMI 25.0-29.9 kg/m2), and 651 obese (≥30.0 kg/m2). Ischemic test result for RWMA occurred in 28 (3%) lean, 69 (4%) overweight, and 28 (4%) obese patients (p = 0.03). An abnormal CFVR (≤2.0) was found in 281 (26%) lean, 402 (26%) overweight and 170 (26%) obese patients (p = 0.99). During 68 ± 44 months of follow-up, 496 (15%) patients died. At multivariable Cox analysis, BMI ≥ 30 was an independent predictor of reduced mortality in the 878 patients with stress-induced (≥2 segments) RWMA and/or CFVR abnormality (HR 0.58, 95% CI 0.40-0.84; p = 0.003), while showed no effect at univariate analysis in the 2371 patients with no RWMA and normal CFVR (HR 1.04, 95% CI 0.74-1.46; p = 0.84). Obesity exerts a "paradoxical" protective effect in patients with stress-induced ischemia and/ or coronary microvascular dysfunction, and shows a neutral effect in patients with normal CFVR and no stress-induced RWMA.

Effect of Nigella sativa oil supplement on risk factors for cardiovascular diseases in patients with type 2 diabetes mellitus.

This study aimed to evaluate the effects of Nigella sativa oil on serum level of systemic inflammation, oxidative stress, fasting blood glucose (FBG), and lipid profile in patients with type 2 diabetes mellitus (T2DM). This double-blind randomized clinical trial study was based on 50 patients with T2DM. Patients were allocated randomly to either N. sativa oil or placebo groups. The intervention group received 1,000 mg N. sativa oil as two capsules, daily for 8 weeks, whereas the placebo group received a corresponding placebo. At baseline and the end of the study, 5 ml blood was collected from each patient after 14-hour fasting for measuring serum C-reactive protein (hs-CRP), malondialdehyde (MDA), FBS, and lipid profile. Analyses covariance was performed to compare investigated parameters between two groups, controlled for relevant covariates. Using N. sativa supplement was significantly associated with decrease in FBS (p < .001), triglyceride (p < .001), total cholesterol (p < .001), low-density lipoprotein cholesterol (p < .001), serum hs-CRP, MDA (p < .001) and increase in serum level of high-density lipoprotein cholesterol (p < .001) in intervention group compared with placebo group. Nigella sativa oil supplement has cardiovascular protective effects in patients with T2DM, by improving the lipid profile and glycemia, by reducing the C-reactive protein level and the lipid peroxidation.

Linagliptin affects IRS1/Akt signaling and prevents high glucose-induced apoptosis in podocytes

Diabetes-induced podocyte apoptosis is considered to play a critical role in the pathogenesis of diabetic kidney disease (DKD). We proposed that hyperglycaemia can induce podocyte apoptosis by inhibiting the action of podocyte survival factors, thus inactivating the cellular effects of insulin signalling. In this study, we aimed to determine the effects of linagliptin on high glucose-induced podocyte apoptosis. Linagliptin reduced the increase in DNA fragmentation as well as the increase in TUNEL-positive cells in podocytes induced by high-glucose condition. Furthermore, linagliptin improved insulin-induced phosphorylation of insulin receptor substrate 1 (IRS1) and Akt, which was inhibited in high-glucose conditions. Adenoviral vector-mediated IRS1 overexpression in podocytes partially normalised DNA fragmentation in high-glucose conditions, while downregulation of IRS1 expression using small interfering RNA increased DNA fragmentation even in low-glucose conditions. Because reactive oxygen species inhibit glomerular insulin signalling in diabetes and Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is one of the most important intrinsic antioxidative systems, we evaluated whether linagliptin increased Nrf2 in podocytes. High-glucose condition and linagliptin addition increased Nrf2 levels compared to low-glucose conditions. In summary, linagliptin offers protection against DKD by enhancing IRS1/Akt insulin signalling in podocytes and partially via the Keap1/Nrf2 pathway. Our findings suggest that linagliptin may induce protective effects in patients with DKD, and increasing IRS1 levels could be a potential therapeutic target in DKD.

Abstract P3-08-21: High CYP27A1 expression at protein and transcript level predicts favorable outcome in node negative, premenopausal breast cancer

Abstract Background: Experimental evidence suggests that pathogenicity caused by cholesterol in breast cancer is partly elicited by 27-hydroxycholesterol (27HC), a primary cholesterol metabolite produced by the sterol 27-hydroxylase cytochrome p450 27A1 (CYP27A1). Targeting CYP27A1 abrogated the adverse effects of cholesterol and 27HC in preclinical studies. The prognostic relevance of CYP27A1 expression in patients with breast cancer is however not clearly defined. Previous studies suggest that the intratumoral expression of CYP27A1 might have diverse effects on prognosis depending on menopausal status. The aim of this study was to comprehensively evaluate the impact of both CYP27A1 protein and mRNA expression on tumor pathobiology and prognosis in pre-menopausal, node-negative breast cancer. Materials and Methods: CYP27A1 expression at the protein and transcript level was evaluated in a prospective cohort of 237 premenopausal women with node-negative, primary invasive breast cancer. Protein and mRNA expression were assessed by immunohistochemistry (IHC) and in situ hybridization technique-RNAscope, respectively. Associations of CYP27A1 expression with tumor pathological features and prognosis were assessed with chi-square test and Cox regression models, respectively. Multivariable models were adjusted for age, hormone receptor status, Ki67, and histological grade. Results: CYP27A1 protein was overexpressed in 28% and CYP27A1 mRNA in 23% of the tumors. The concordance between CYP27A1 protein and mRNA expression was 77.8% (rs=0.430). Among the discordant cases, 13.9% were only positive by IHC. Elevated expression of both protein and mRNA was significantly associated with aggressive tumor pathological features like high histological grade and high Ki67 expression (P&amp;lt;0.001). In multivariable Cox regression analyses, overexpression of CYP27A1 protein was independently prognostic for more than a factor-two reduced risk of disease recurrence (Recurrence-Free Survival (RFS): HR=0.40, 95% CI=0.23-0.86; Distant Recurrence-Free Survival (DRFS): HR=0.40, 95% CI=0.16-0.95). High CYP27A1 expression conferred even stronger protective effect for patients with estrogen receptor (ER) positive tumors when the analyses were stratified by ER status (RFS: HR=0.18, 95% CI=0.06-0.55; DRFS: HR=0.20, 95% CI=0.06-0.81). Likewise, high CYP27A1 mRNA expression was also independently prognostic for a longer RFS (HR=0.40, 95% CI=0.2-0.8), DRFS (HR=0.28; 95%CI=0.1-0.7) and in addition better overall survival (OS) (HR=0.20, 95% CI=0.08-0.60) in the overall population and in the subgroup of patients with ER positive tumors (OS: HR=0.14; 95% CI=0.03-0.65; RFS: HR= 0.22; 95% CI= 0.07-0.68; DRFS: HR=0.16; 95% CI=0.03-0.73). Conclusion: These results indicate that high intratumoral expression of CYP27A1 is a strong indicator for an extensive recurrence-free interval and overall survival in premenopausal women with ER positive, lymph node-negative breast cancer. CYP27A1 transcript expression may serve as an even more sensitive prognostic biomarker. Citation Format: Maria Inasu, Pär Ola Bendahl, Mårten Fernö, Per Malmström, Signe Borgquist, Siker Kimbung. High CYP27A1 expression at protein and transcript level predicts favorable outcome in node negative, premenopausal breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-21.

Does a previous aortic endograft confer any protective effect during abdominal aortic aneurysm rupture? Systematic review and meta-analysis of comparative studies.

Whether prior endovascular aneurysm repair confers a protective effect in patients with ruptured abdominal aortic aneurysm (rAAA) is not known. We aimed to systematically review and compare the outcomes of rAAA in patients with and without prior endovascular aneurysm repair. We performed a systematic review that conformed to the Preferred Reporting Items for Systematic Reviews and Meta-analysis. We selected studies comparing the outcomes in patients with rAAA after prior endovascular aneurysm repair (group 1) and those with de novo rAAAs (group 2). We conducted a proportion meta-analysis of perioperative mortality and obtained summary estimates of odds ratios (ORs) and 95% confidence intervals (CIs) using random-effects models. We included four studies (retrospective observational studies) in quantitative synthesis reporting a total of 719 patients (group 1 (89) group 2 (630)). The perioperative mortality in groups 1 and 2 was 30.4% and 41%, respectively, and there was no statistical significant difference between the groups (OR 0.66, 95% CI 0.30-1.43, P = 0.29, I2=58%). However, patients presenting with rAAA following previous endovascular aneurysm repair were more hemodynamically stable (OR 0.33, 95% CI 0.12-0.90, P = 0.03, I2=74%). The choice between endovascular or open surgery treatment in group 1 did not affect the perioperative mortality (OR 1.12, 95% CI 0.41-3.04 P = 0.82, I2=0%). Endoleak types I and III were the main causes of rAAA in group 1. Perioperative mortality was similar for rAAA either de novo or after prior endovascular aneurysm repair. However, ruptures in patients with prior endovascular aneurysm repair presented hemodynamically more stable.

898 The Obesity Paradox Extends to TAVI – Medium-Term Outcomes According to BMI

Transcatheter aortic valve implantation is a frequently performed cardiac procedure in those at elevated operative risk. Increased body mass index (BMI) portends a protective effect in patients undergoing percutaneous coronary intervention. We assessed whether elevated BMI was associated with a similar beneficial effect in TAVI. We evaluated prospective data from 634 patients who underwent TAVI at the Alfred and Epworth Hospitals from August 2008 to April 2019. Patients were stratified as normal weight (BMI 18.5-24.9kg/m2, n=214), overweight (25-29.9kg/m2, n=234) and obese (>30kg/m2, n=185). Outcomes were reported according to VARC-2 criteria. Mortality was assessed using Cox proportional hazards regression analysis (median follow-up 2 years). Kaplan-Meier analysis was used to estimate cumulative mortality. Baseline differences were seen in age (85 vs 84 vs 82, p<0.001), STS-PROM score (4.3 vs 3.4 vs 3.6, p<0.001), sex (50% vs 36% vs 55% female, p<0. 001), clinical frailty score (p=0.02), diabetes (21% vs 29% vs 40%, p<0.001), and COPD (13% vs 13% vs 23%, p=0.009). On multivariable analysis overweight BMI was independently associated with a lower mortality compared to normal BMI (HR 0.56 CI 0.38-0.85, p=0.006) whilst obese BMI was not (HR 0.70 CI 0.46-1.1 p=0.108). Variables independently associated with increased mortality were increasing age, male sex, COPD, prior balloon valvuloplasty and higher STS-PROM. Overweight patients have improved medium-term mortality when compared to normal weight patients following TAVI. Given the age of TAVI populations these findings may relate to sarcopenia and frailty, and further long-term data are needed.

MON-170 OUTCOMES OF SGLT2 INHIBITORS USE IN DIABETIC RENAL TRANSPLANT PATIENTS- SINGLE CENTER EXPERIENCE

New-onset diabetes after transplantation (NODAT) is common among renal transplant patients. The use of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-transplant diabetic patients with cardiovascular (CV) disease has well established efficacy and safety. It has long term renal protective effects in patients with impaired kidney function. Data regarding the safety and long term efficacy of SGLT2 inhibitors use in diabetic renal transplant patients is lacking. We report our experience with use of SGLT2 inhibitors in diabetic renal transplant patients. A retrospective chart review study was conducted at our institution over 2 years from 6 /2016 until 10/2018. We included all diabetic transplant patients who were started on SGLT2 inhibitors. Demographic, clinical and laboratory data were collected and analyzed using descriptive analysis. Complications related to use of SGLT2 inhibitors were monitored. a total of 8 renal transplant patients were included, two patients (25%), had long standing diabetes mellitus type 2 and six patients (75%) had post-transplant diabetes (NODAT). The majority were males (75%), with mean age of 56.8 years. The co-morbid conditions in our cohort were hypertension (7 [87.5 %]), dyslipidemia (7 [87.5%]), history of urinary tract infection (2 [25%]) and obesity ( body mass index ) BMI > 30 (4 [50%]). Median years from transplantation were 9.6 years and all patients had transplant from living unrelated donors, with stable allograft function (eGFR >60). The immunosuppressant medications used were tacrolimus (62.5%), cyclosporine (37.5%), prednisolone (100%), and mycophenolate (62.5%), mycophenolic acid (37.5%) and all patients were maintained on triple therapy regime. The median baseline HbA1c was 9.3 and hypoglycemic medications used including; metformin (37.5%), gliclazide modified release (62.5%), DPP4 inhibitors (37.5%), insulin (37.5%), and dulaglutide 1.5 mg q wk (37.5%). SGLT2 inhibitors (empagliflozin (6), dapagliflozin (2)) were added for diabetic transplant patients for better glycemic control that was noted with minor reduction of HbA1c at 3 and 6 months in some patients. The renal graft functions were stable with use of SGLT2 inhibitors without any acute kidney injury event and there was minor reduction of weight. Incidence of acute urinary tract infections were low (1) and no reported fungal infections. The two patients who had previous history of UTI did not experience recurrent episodes, except one patient developed one episode of UTI after 1 year of SGLT2 use. SGLT2 inhibitors were well tolerated. diabetic renal transplant patients with stable kidney function and CKD stage I or II (eGFR>60), had slightly better glycemic control with use of SGLT2 inhibitors. There was no deterioration of kidney function and risk of recurrent UTI was low. Further studies are needed to explore the long term safety and efficacy of SGLT2 inhibitors in diabetic renal transplant patients.

171-OR: Metformin Prevents Microvascular Insulin Resistance and Preserves Endothelial Function in High-Fat Diet-Fed Rats

Endothelial dysfunction and vascular insulin resistance coexist and both contribute to the development of type 2 diabetes mellitus (T2DM) and increased cardiovascular risks. Insulin relaxes precapillary arterioles to increase insulin delivery to and action in muscle via recruiting muscle microvasculature and this action is impaired in the insulin resistant states. Metformin is the first line therapy for T2DM and has been shown to improve endothelial function beyond its hypoglycemic effects. Here we aim to examine whether metformin could restore vascular insulin responses in the setting of insulin resistance induced by high fat diet (HFD) feeding via the modulation of endothelial function. Adult, male Sprague-Dawley rats were fed on HFD with or without metformin treatment for 2 weeks. A chow fed group served as control. After dietary intervention, rats were fasted overnight and received a euglycemic-hyperinsulinemic clamp for 120 min. Insulin-mediated muscle microvascular recruitment was assessed before and during insulin infusion using contrast-enhanced ultrasound. Distal saphenous artery was isolated and used for determination of endothelial function and vascular insulin responses. Compared with controls, HFD feeding abolished insulin-induced muscle microvascular recruitment in muscle, decreased insulin-mediated whole body glucose disposal and blunted the vasodilatory response to insulin in small resistance vessel. Metformin treatment significantly enhanced insulin’s microvascular action, effectively rescued small arteriole endothelial function, but did not improve insulin-stimulated whole body glucose disposal in HFD rats. We conclude that metformin could reverse microvascular insulin resistance and attenuate endothelial dysfunction induced by HFD feeding. There findings may provide a novel mechanistic insight into metformin’s cardiovascular protective effect in patients with diabetes. Disclosure J. Liu: None. W. Chai: None. L. Gong: None. K.W. Aylor: None. Z. Liu: None. Funding American Diabetes Association (1-17-ICTS-059 to Z.L.); National Institutes of Health (R01HL094722, R01DK102359)

Effects of allisartan isoproxil on blood pressure and target organ injury in patients with mild to moderate essential hypertension.

Evidence has shown that angiotensin II type 1 receptor antagonists have lower blood pressure and have target organ protective effects, but this is not the case for the drug allisartan isoproxil. The aim of this study was to evaluate the effects of allisartan isoproxil on blood pressure and target organ injury in patients with mild to moderate essential hypertension.In total, 80 essential hypertensive participants were randomly divided into an allisartan group and a nifedipine group (n = 40 per group), and their blood pressure was measured once per month for 6 months. A 2-dimensional echocardiogram was performed at baseline and at the end of the study. The serum levels of renal injury indexes, endothelial function markers, inflammatory factors, blood biochemical assays and urinary measurements were determined at baseline and at 6 months.At the end of the study, both systolic and diastolic blood pressure were significantly decreased in the allisartan group compared with baseline and showed the same antihypertensive effect as the nifedipine group. Meanwhile, the left ventricular remodeling, 24-hours levels of urinary microalbumin, endothelial dysfunction, and arterial stiffness were all significantly improved compared with that of the baseline and the nifedipine group (all P < .05).The present study showed that allisartan isoproxil had favorable blood pressure lowering and heart, renal, and endothelial protective effects in patients with mild to moderate essential hypertension.

Intensive Lipid-Lowering Therapy Ameliorates Asymptomatic Intracranial Atherosclerosis.

Statins have proven to exert protective effects in patients with symptomatic intracranial atherosclerotic stenosis (SICAS). It is unclear whether intensive lipid-lowering therapy (ILLT) can ameliorate atherosclerosis in asymptomatic ICAS (AICAS). A single-center, prospective cohort study was performed in 71 AICAS patients with lipid-lowering therapy. Vascular stenoses were evaluated with transcranial color-coded sonography (TCCS) before and after statin treatment. With target therapeutic level of low-density lipoprotein cholesterol (LDL-C) ≤ 1.8 mmol/L or ≥ 50% reduction from baseline after the two years of follow-up, patients were divided into intensive statin treatment (IST) group and standard statin treatment (SST) group. A total of 104 stenotic intracranial arteries were detected in 51 patients belonging to the IST group and 47 arteries in 20 patients of the SST group. In the first year, LDL-C levels were significantly decreased in the IST compared with SST groups (1.48 ± 0.26 vs. 2.20 ± 0.58, P=0.000). However, the ratio of regressed ICAS in IST was not significantly higher than that in SST (26.3% vs. 5.9%, P=0.052). Forty-nine branches in 25 patients of the IST group and 16 branches in 7 patients of the SST group were followed up for two years. The LDL-C level was decreased in the IST compared with SST groups (1.55 ± 0.29 vs. 2.36 ± 0.77, P=0.048). The ratio of regressed ICAS in the IST group was significantly higher than that in SST group (34.7% vs. 6.3%, P=0.017). We concluded that the degree of stenosis in AICAS can be ameliorated with intensive lipid-lowering therapy within two years; target LDL-C level can be reached by moderate-intensity statin treatment for Chinese AICAS patients.

Preoperative short-term fasting protects liver injury in patients undergoing hepatectomy.

Our previous study demonstrated that preoperative short-term fasting attenuates mice hepatic ischemia/reperfusion injury (IRI), which greatly piqued our interest in verifying if fasting produces similar protective effects in patients undergoing hepatectomy. Eighty patients with liver tumors were randomized into control (Ctrl, n=40, preoperative fasting for 6 h) or fasting group (Fasting, n=40, preoperative fasting for 24 h). Serum was collected at pre-operation (Pre-Op), post-operation 1 day (POD-1), post-operation 3 days (POD-3), and post-operation 7 days (POD-7). Liver tissue was removed from the resected specimen. Sixty-three patients were eventually enrolled, with 33 in Ctrl and 30 in Fasting group. Our data showed that 24 h fasting effectively attenuated elevated sALT and sAST levels after operation (P<0.05), but serum total bilirubin was significantly lower at only POD-3 (P<0.05); and serum albumin was not markedly different in either of the groups. Interestingly, 24 h fasting partially attenuates expression of pro-inflammatory cytokine (TNF-α) and improves oxidative stress (MDA and SOD). Our data further showed short-term fasting triggered Nrf2 signaling pathway. This study demonstrates preoperative short-term fasting effectively improves clinical outcomes and markedly attenuates inflammatory responses and oxidative stress in patients undergoing hepatectomy, and Nrf2 signaling pathway may play a key role in fasting against inflammatory responses and oxidant stress.

S102. CANNABIS MAY PROTECT AGAINST CERTAIN DISORDERS OF THE DIGESTIVE ORGANS IN PATIENTS WITH SCHIZOPHRENIA BUT NOT IN HEALTHY CONTROLS

BackgroundCannabis use disorder increases both overall mortality and several cause-specific mortalities. However, an unexpected finding has been that, in patients with schizophrenia, cannabis use disorders were associated with a decreased risk of death from causes related to the digestive organs. Further indications of potentially beneficial effects of cannabis were supported by a 2016 systematic review showing protective effects of cannabis in patients with established gastrointestinal disorders. Further, schizophrenia, either in itself or through the use of antipsychotics, may interact with cannabis in various organs, potentially leading to different associations. For these reasons, we aimed to investigate the associations between cannabis and later development of disorders of the digestive organs, both in patients with schizophrenia and in healthy controls.MethodsWe used the nationwide Danish registers in a prospective cohort study. All individuals born since 1955 in Denmark and diagnosed with schizophrenia were included, and matched to approximately ten controls on age and sex to healthy controls. Cannabis use disorders and alcohol and other substance use disorders (SUD) were identified through combinations of several health registers, as were the outcomes. We investigated the following outcomes: Any disorder of the digestive organs, cancers of the digestive organs, non-cancer disorders of the digestive organs, inflammatory bowel disease, disorders of the gut-brain axis, non-cancer disorders of the pancreas, non-cancer disorders of the liver, and a category of disorders of the digestive organs considered to be severe. For each analysis, people with a corresponding digestive-organ diagnosis before either the date of schizophrenia or the controls’ corresponding match-date were excluded.ResultsThe number of patients with schizophrenia varied between 17,718 and 22,636 in different analyses. After adjusting for other SUDs, cannabis use disorders showed protective effects in patients with schizophrenia against disorders of the gut-brain axis (HR=0.78, 95% CI 0.68–0.91, p=0.001), and serious disorders of the digestive organs (HR=0.81, 95% CI 0.69–0.96, p=0.02). Non-significant protective effects were also apparent for non-cancer disorders of the digestive organs (HR=0.93, 95% CI 0.85–1.02, p=0.11), inflammatory bowel disease (HR=0.67, 95% CI 0.42–1.08, p=0.10), and non-cancer disorders of the liver (HR=0.80, 95% CI 0.61–1.05, p=0.12). These protective effects were never shown in healthy controls, where cannabis use disorders generally were not associated in any direction with digestive-organ disorders in the fully adjusted analyses.DiscussionCannabis use disorders may show protective effects against certain disorders of the digestive organs in patients with schizophrenia. The explanations may be causal, which would however require further explanations as to why the same effects are not seen in healthy controls. This may be due to use of antipsychotic medication interacting with cannabis, or due to higher levels of cannabis consumption in cases with schizophrenia than in controls. The effect may also be in part explained by comorbid use of tobacco, as nicotine is also known to interact with the gastrointestinal system.

Impact of brain atrophy on 90-day functional outcome after moderate-volume basal ganglia hemorrhage

This study aimed to evaluate the effect of brain atrophy on the functional outcome of patients with moderate-volume basal ganglia hemorrhage. Of 1003 patients with spontaneous intracerebral hemorrhage, 124 with moderate-volume basal ganglia hemorrhage (hematoma volume of 20–50 mL) were enrolled. The intercaudate distance (ICD) and sylvian fissure ratio (SFR) were used as linear brain atrophy parameters. The patients were divided into groups with favorable and unfavorable outcomes, according to the Glasgow Outcome Scale score, 90 days after symptom onset. Demographic and radiographic features, including the ICD and SFR, were compared between the two groups. Among the 124 patients, 74 (59.7%) exhibited a favorable outcome. The ICD and SFR values were significantly greater for the favorable group than for the unfavorable group. Multivariate analysis indicated that young age, high Glasgow Coma Scale score at admission, small hematoma volume, and increased ICD (odds ratio [OR], 1.207; 95% confidence interval [CI], 1.004–1.451) and SFR (OR, 1.046; 95% CI, 1.007–1.086, per 0.001) values had a beneficial effect on functional outcome. In conclusion, brain atrophy exhibits protective effects in patients with moderate-volume basal ganglia hemorrhage, and is an important factor for predicting functional outcome.