The ideal lifestyle intervention to battle both obesity and diabetes is currently unknown. The aim of this pilot uncontrolled intervention trial was to assess the effect of a modified Mediterranean diet (MedDiet) on weight loss and glucoregulation among overweight/obese adults. Eleven men and women with overweight/obesity, aged 37 ± 12 years, participated in a free-living intervention until 10% weight loss was achieved. Participants followed an individualized MedDiet high in monounsaturated fat and protein with decreased carbohydrate and saturated fat contents. Physical activity and dietary intake were monitored with pedometers and food records, respectively. Upon weight loss achievement, anthropometric measurements, blood metabolic profiles and individual responses to oral glucose and mixed-meal tests were evaluated pre- and post-intervention. The results showed significant ameliorations in body fat, waist circumference and leptin levels (p < 0.01), with concomitant increases in adiponectin–leptin ratios (p < 0.001). Glucoregulation was significantly improved according to glucose and insulin responses, homeostatic model assessment of insulin resistance indices and postprandial insulin sensitivity indices (p < 0.05). In conclusion, the modified Mediterranean diet may induce significant improvements in body composition, adipocytokine profile and glucose metabolism in overweight/obese individuals. Notably, ameliorated glycemia and increased insulin sensitivity may be retained even at postprandial level, irrespective of the meal consumed.

Abstract Background/Purpose Anatomically, hemodynamically relevant and validated animal models for aortic valve stenosis are of great need. Drolet rabbit model with tricuspid anatomy produced conflicting results for unclear reasons. We hypothesized that limitations concentrate in the regimen administration. We sought to evaluate multiple doses, ways of administration and time periods. Methods We included New Zealand rabbits in 4 groups: Group A (Drolet): was fed with normal chaw (nc)+0.5% cholesterol (chol)+3500 IUs Vitamin D2/kg (VD2, ergocalciferol, Sigma) in water daily for 12 weeks (wks), Group B: nc+0.5%chol+3500 IUs/kg VD2 in oil incorporated in a bisquit daily for 8 wks, Group C: nc+0.5%chol+8750 IUs/kg VD2 in oil-biscuit for 8 wks, Group D: nc+0.5%chol+17500 IUs VD2 in oil-biscuit for 8 wks vs controls (fed only with nc). After 12 and 8 wks the rabbits were sacrificed. Aortic valve area (AVA) and mean gradient (meanGr) were assessed with echocardiography (Vivid 7, M3S transducer, GE) and serum obtained, at baseline and before sacrifice. VD2 levels were evaluated through Chemiluminescent Microparticle Immuno Assay (CMIA, Abbott) and liquid chromatography – tandem mass spectrometry (LC-APCI-MS/MS). Animals received i.v. 18F-NaF one hour before sacrifice and valve was ex-vivo imaged with microPET/CT (Mediso nanoScan). Aortic cusps were analyzed with Fourier-Transformed Infrared Spectroscopy (FT-IR, Nicolet 6700 spectrometer, OMNIC 7.3 software). Valves from surgical patients with severe stenosis served for comparison purposes. Results In Group A at 12 wks AVA and meanGr remained unchanged but biomineralization was detected with FT-IR with vibrations in the region of 1800–800 cm–1 demonstrating the deposition of CaCO3 and non-hydroxyapatite Ca3(PO4)2 identical to human lesion. Calcification was detected on cusps with 18F-NaF. VD2 levels were out of upper detection range with CMIA due to cross reaction, whereas all samples measured through LC-MS/MS were below the detection limit of the method (<19,1 ng/mL). Significant Assessment heterogeneity (RSD=27%) was observed on VD2 water regimen. In Group B, AVA changed from 0.5 cm2 to 0.4 cm2 and meanGr increased from 1.1 to 2.1 mmHg, p<0.05 and in Group C AVA: 0.5 cm2 to 0.3 cm2 and meanGr: 1 to 2.95 mmHg, p<0.05, while VD2 serum concentration were 511 ng/mL. In Group D animals die unexpectedly at 2 weeks, with autopsy revealing massive myocardial hypertrophy of the left ventricle (LVH) without compromise of the aortic valve. Conclusions The modified diet produces aortic valve stenosis and biomineralization detectable with 18F-NaF, chemically identical to human lesion. Very high doses of Vitamin D2 directly produce LVH, possibly leading to arrythmiogenesis. The modified high-fat-vitamin D2 rabbit model proved suitable for translational research of aortic valve stenosis disease. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National and Kapodistrian University of Athens

The association between lipoprotein (a) (Lp(a)) and 10-year first fatal/nonfatal cardiovascular disease (CVD) risk in apparently healthy men and women was evaluated. The ATTICA prospective study was conducted during 2001-2012 and included n = 1514 men and n = 1528 women (age >18 years) from the greater Athens area, Greece. Follow-up CVD assessment (2011-2012) was achieved in n = 2020 participants (n = 317 cases); baseline Lp(a) was measured in n = 1890 participants. The recommended threshold of 50 mg/dL was used to define abnormal Lp(a) status. Ten-year CVD-event rate was 14% and 24% in participants with Lp(a) <50 and Lp(a) ≥50 mg/dL, respectively. Multivariate analysis revealed that participants with Lp(a) ≥50 mg/dL versus Lp(a) <50 mg/dL had about 2 times higher CVD risk (hazard ratio (HR) = 2.18, 95% confidence interval (CI) 1.11, 4.28). The sex-based analysis revealed that the independent Lp(a) effect was retained only in men (HR = 2.00, 95% CI 1.19, 2.56); in women, significance was lost after adjusting for lipid markers. Sensitivity analyses revealed that Lp(a) increased CVD risk only in case of abnormal high-density lipoprotein cholesterol, apolipoprotein A1, and triglycerides as well as low adherence to Mediterranean diet. Certain patient characteristics may be relevant when considering Lp(a) as a therapeutic or risk-prediction target.

BACKGROUND:New antibiotics are urgently needed to treat multi-drug resistant infections; however, production of novel antibiotics is diminishing. Synergistic combination drug therapy to enhance the activity of available antibiotics may improve management of patients with resistant infections.METHODS:Colistin-resistant Klebsiella pneumoniae isolates were collected from inpatients in 10 Greek hospitals and used to study combination activity of colistin plus azidothymidine. Combination activity was evaluated with the sum of fractional inhibitory concentrations (ΣFIC) using the mini checkerboard broth microdilution method.RESULTS:A hundred individual strains were tested. Synergistic activity was noted in 79% (79/100) of isolates and additive activity in the remaining 21% (21/100). ΣFIC50 and ΣFIC90 were 0.28 and 0.56, respectively.CONCLUSION:Colistin with azidothymidine exhibited promising synergistic activity against colistin-resistant Klebsiella pneumoniae isolates warranting further investigation of the combination.

Objectives: To evaluate the association of predicted lean and fat mass on 10-year first and recurrent CVD incidence separately for men and women. Methods: Two prospective studies, ATTICA (2002-2012, n= 3042 subjects free-of-CVD, n= 1514 men (46 +/- 13 years) and n= 1528 women (45 +/- 14 years)) and GREECS (2004-2014, n= 2172 subjects with acute coronary syndrome (ACS), n= 1649 men (65 +/- 13 years) and n = 523 women (62 +/- 11 years)) were used. Lean mass index (LMI) and fat mass index (FMI) were created through total body lean and fat mass (indirectly calculated through population formulas based on body weight, height and waist circumference) divided by height squared. Follow-up was performed in n = 2020 of ATTICA (n = 317 first CVD events) and in n= 2172 patients of GREECS (n= 811 recurrent CVD events). Results: In ATTICA study, CVD rate from 1st to 3rd FMI tertile was 9.4%, 16.1% and 19.9% while in GREECS 36.2%, 37.0%, 38.3%. The LMI-related rates were 17.1%, 15.0% and 11.9% vs. 38.8%, 35.8% and 36.7%. Multiadjusted analysis revealed U-shape trend between LMI and CVD recurrence with 2nd LMI tertile having the best prognosis; this observation was more evident in women. In apparently healthy subjects, LMI-cardioprotective association was revealed only in 3rd tertile (HR = 0.91 95%CI (0.74, 0.95)); this was more evident in men. The FMI aggravating association (3rd tertile) was retained significant only in healthy women and ACS men. Conclusion: This work expands previous findings regarding body composition and cardiac health, implying that the association of lean and fat mass on long-term CVD incidence varies according to sex and prevention stage. (C) 2019 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Background/Objectives: Metabolically benign obesity remains a scientific field of considerable debate. The aim of the present work was to evaluate whether metabolically healthy obese (MHO) status is a transient condition which propagates 10-year cardiovascular disease (CVD) onset. Methods: A prospective longitudinal study was conducted during 2001-2012, the ATTICA study studying 1514 (49.8%) men and 1528 (50.2%) women (aged >18 years old) free of CVD and residing in the greater Athens area, Greece. Follow-up assessment of first combined CVD event (2011-2012) was achieved in n 2020 participants; of them, 317 (15.7%) incident cases were identified. Obesity was defined as body mass index >= 30 kg/m(2) and healthy metabolic status as absence of all NCEP ATP III (2005) metabolic syndrome components (excluding waist circumference). Results: The MHO prevalence was 4.8% (n = 146) with 28.2% of obese participants presenting metabolically healthy status at baseline. Within this group, 52% developed unhealthy metabolic status during the 10-year follow up. MHO vs. metabolically healthy non-obese participants had a higher likelihood of presenting with 10-year CVD events, yet only the subset of them who lost their baseline status reached the level of significance (Hazard Ratio (HR) 1.43, 95% Confidence Interval (95% CI) 1.02, 2.01). Sensitivity analyses revealed that MHO status was independently associated with elevated CVD risk in women and participants with low adherence to the Mediterranean diet, low grade inflammation, and insulin resistance. Conclusions: MHO status is a transient condition where weight management is demanded to prevent the establishment of unhealthy cardiometabolic features. The existence of obese persons who remain "longitudinally" resilient to metabolic abnormalities is an emerging area of future research. (C) 2019 Elsevier Inc. All rights reserved.

Cardiovascular disease is the prevalent cause of morbidity and mortality in the world, affecting many millions of individuals every year. Atherosclerosis, a chronic inflammatory condition that involves different cell types, several cytokines and adhesion molecules, is the underlying cause of cardiovascular disease. Vitamin D is known to control skeletal patho/physiology, regulating calcium and phosphorus and bone remodeling along with other calcium-regulating hormones. However, several active metabolites of vitamin D can exert both direct action, mainly via vitamin D3 receptor trans-activation and indirect actions on several other tissues by an endocrine, autocrine and paracrine manners. With regard to cardiovascular disease, vitamin D deficiency has been associated with activation of the pro-inflammatory mechanism, promoting atherogenesis. There are several large-scale clinical studies, as well as meta-analyses that support this finding. However, it is still unclear whether the plasma 25-hydroxyvitamin D level can be used as a biomarker for future cardiovascular disease. Herein we review the studies reporting a causative role for vitamin D in cardiovascular disease.

Background and aim A multicentre nationwide surveillance study was conducted in Greek hospitals to evaluate epidemiology of carbapenemase-producing Klebsiella pneumoniae clinical isolates, and their susceptibilities to last-line antibiotics. Methods: Minimum inhibitory concentrations (MICs) were evaluated by Etest, colistin MICs were also evaluated by broth microdilution SensiTest (now known as ComASP) Colistin. Carbapenemase genes were detected by PCR. Clonal relatedness was assessed by PFGE. Isolates were prospectively collected between November 2014 and April 2016, from 15 hospitals. Results : Among 394 isolates, K. pneumoniae carbepenemase (KPC) remained the most prevalent carbapenemase (66.5%). NDM was the second most prevalent (13.7%), identified in 12 hospitals, followed by VIM (8.6%). OXA-48- and double carbapenemase-producers remained rare (3.6%, 6.3%, respectively). Carbapenemase-producing K. pneumoniae isolates showed high resistance to last-line antibiotics. Gentamicin and colistin were the most active in vitro with 61.9% and 59.6% of the isolates to be inhibited at ≤ 2mg/L, followed by fosfomycin (susceptibility (S): 58.4%) and tigecycline (S: 51.5%). Ceftazidime/avibactam inhibited 99.6% of KPC and 100% of OXA-48-like-producing isolates, while temocillin was active against 58% of KPC isolates at urinary breakpoint of ≤ 32mg/L* and only 2.7% at systemic breakpoint of ≤ 8mg/L. NDM-producing isolates belonged mainly to one clone, whereas KPC, VIM, OXA-48 and double carbapenemase-producers were mainly polyclonal. Conclusions : KPC remains the predominant carbapenemase among K. pneumoniae in Greece, followed by NDM, whereas changing trends of resistance rates to last-line antimicrobials against carbapenemase-producing K. pneumoniae with the exception of ceftazidime/avibactam mandates continuing surveillance to support clinical practice.

BACKGROUND & AIMS:Polyunsaturated fatty acids (PUFAs) may affect the cardiovascular system with a multiplicity of mechanisms. We assessed the effects of omega-3 PUFAs supplements on inflammation, fibrosis, left ventricle performance and endothelial function of ischemic heart failure (HF) patients. METHODS:In this double-blind, placebo controlled, cross-over trial we enrolled 31 patients with ischemic HF, followed by a 6-week wash-out period. Omega-3 PUFAs (2 g daily, 8 weeks) were administered PO in the intervention arm. Left ventricle ejection fraction (EF), global longitudinal strain and the ratio E/e' (early ventricular filling to early mitral annulus velocities)were measured. Endothelial function was evaluated by flow mediated dilation and myocardial fibrosis by soluble ST2. High sensitive C Reactive protein (hsCRP) levels were measured as an inflammatory marker. RESULTS:Treatment with omega-3 PUFA, compared to placebo, improved: left ventricle EF (percent increased by 4.7% vs 1.7%); global longitudinal strain (decreased by -10.6% vs -2.3%); the E/e' ratio (decreased by -9.47% vs -2.1%); ST2 levels (decreased by -4.53% vs -2.37%); flow mediated dilation (percent increased by 44% vs. 11% and hsCRP levels (decreased by -6.13% vs 4.35%) (p < 0.05 for all). CONCLUSION:Short term treatment with omega-3 PUFAs in subjects with stable ischemic HF improved inflammatory and fibrotic status as well as endothelial function in parallel with systolic and diastolic performance of left ventricle. These findings provide further insights regarding the impact of omega-3 PUFAs administration on left ventricle performance indices, systemic inflammation and fibrosis biomarkers in patients with ischemic HF.

AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis.METHODS: We prospectively collected clinical, laboratory characteristics, type of administered antibiotic, susceptibility and resistance of bacteria to antibiotics in one hundred thirty cases (68.5% males) with positive ascitic fluid and/or blood cultures during the period from January 1, 2012 to May 30, 2014. All patients with SBP had polymorphonuclear cell count in ascitic fluid > 250/mm(3). In patients with SB a thorough study did not reveal any other cause of bacteremia. The patients were followed-up for a 30-d period following diagnosis of the infection. The final outcome of the patients was recorded in the end of follow-up and comparison among 3 groups of patients according to the pattern of drug resistance was performed.RESULTS: Gram-positive-cocci (GPC) were found in half of the cases. The most prevalent organisms in a descending order were Escherichia coli (33), Entero-coccus spp (30), Streptococcus spp (25), Klebsiella pneumonia (16), S. aureus (8), Pseudomanas aeru-ginosa (5), other Gram-negative-bacteria (GNB) (11) and anaerobes (2). Overall, 20.8% of isolates were multidrug-resistant (MDR) and 10% extensively drug-resistant (XDR). Health-care-associated (HCA) and/or nosocomial infections were present in 100% of MDR/XDR and in 65.5% of non-DR cases. Meropenem was the empirically prescribed antibiotic in HCA/nosocomial infections showing a drug-resistance rate of 30.7% while third generation cephalosporins of 43.8%. Meropenem was ineffective on both XDR bacteria and Enterococcus faecium (E. faecium). All but one XDR were susceptible to colistin while all GPC (including E. faecium) and the 86% of GNB to tigecycline. Overall 30-d mortality was 37.7% (69.2% for XDR and 34.2% for the rest of the patients) (log rank, P = 0.015). In multivariate analysis, factors adversely affecting outcome included XDR infection (HR = 2.263, 95% CI: 1.005-5.095, P = 0.049), creatinine (HR = 1.125, 95% CI: 1.024-1.236, P = 0.015) and INR (HR = 1.553, 95% CI: 1.106-2.180, P = 0.011).CONCLUSION: XDR bacteria are an independent life-threatening factor in SBP/SB. Strategies aiming at restricting antibiotic overuse and rapid identification of the responsible bacteria could help improve survival.

Purpose To evaluate the in vitro efficacy of several anti-staphylococcal agents against a nationwide collection of contemporary Staphylococcus aureus clinical isolates from several healthcare centres in Greece. Methods Thirty hospitals throughout Greece (18 in Attica) provided all clinical isolates of S.aureus from April 2012 to May 2013 to a central lab to be re-submitted to susceptibility testing. The MICs were evaluated by Vitek® 2 with the exception of ceftaroline (OXOID M.I.C. Evaluator™). Vancomycin and daptomycin MICs were also evaluated by Etest®. Heterogeneously vancomycin-intermediate strains (hVISA) were detected by the Etest® GRD. VISA phenotype was confirmed by PAP-AUC. Results A total of 1005 isolates (39% MRSA) were studied. Susceptibility rates were: erythromycin 66.5%, clindamycin 79.2%, SXT 98.9%, rifampicin 97.3%, fusidic acid 67%, moxifloxacin 78.8%, vancomycin 99.9%, ceftaroline 92.9% and linezolid, tigecycline and daptomycin 100%. For mupirocin, high level resistance could be excluded for 98.9% of isolates. Vancomycin Etest® MIC50/90 were 1.5/1.5 mg/L, 58.5% of isolates exhibited a MIC > 1 and 8.7% a MIC of 2 mg/L, while Vitek® MIC50/90 were 1/1 and 3.1% showed MIC > 1 mg/L. One VISA strain was detected. Among the selected 175 isolates that were screened for hVISA phenotype, six (3.4%) were positive. In 315 bloodstream isolates, 64.1% had a vancomycin Etest® MIC > 1 mg/L. Conclusions This multi-centre surveillance study revealed that a significant percentage of contemporary S.aureus isolates from Greek patients have a vancomycin MIC (> 1 mg/L) that may compromise the clinical efficacy of the drug for the treatment of serious infections. The in vitro activity of SXT, rifampicin, mupirocin, linezolid, tigecycline, daptomycin and ceftaroline remains excellent.

BACKGROUND:Spontaneous bacterial peritonitis (SBP) is historically caused by Gram-negative bacteria (GNB) almost exclusively Enterobacteriaceae. Recently, an increasing rate of infections with Gram-positive cocci (GPC) and multidrug-resistant (MDR) microorganisms was demonstrated.AIMS:To assess possible recent changes of the bacteria causing SBP in cirrhotic patients.METHODS:We retrospectively recorded 47 cases (66% males) during a 4-year-period (2008-2011).RESULTS:Twenty-eight (60%) patients had healthcare-associated infections while 15 (32%) received prophylactic quinolone treatment. GPC were found to be the most frequent cause (55%). The most prevalent organisms in a descending order were Streptococcus spp (n = 10), Enterococcus spp (n = 9), Escherichia coli (n = 8), Klebsiella pneumonia (n = 5), methicillin-sensitive Staphylococcus aureus (n = 4) and coagulase-negative Staphylococcus spp (n = 3). Nine of the isolated bacteria (19%) were MDR, including carbapenemase-producing K. pneumonia (n = 4), followed by extended-spectrum beta-lactamase-producing E. coli (n = 3) and Pseudomonas aeruginosa (n = 2). MDR bacteria were more frequently isolated in healthcare-associated than in community-acquired infections (100% vs 50%, P = 0.006), in patients receiving long-term quinolone prophylaxis (67% vs 24%, P = 0.013) and in those with advanced liver disease as suggested by higher MELD score (28 vs 19, P = 0.012). More infections with GNB than GPC were healthcare-associated (81% vs 42%, P = 0.007). Third-generation cephalosporin resistance was observed in 49% and quinolone resistance in 47%.CONCLUSIONS:GPC were the most frequent bacteria in culture-positive SBP and a variety of drug-resistant microorganisms have emerged. As a result of high rates of resistance in currently recommended therapy and prophylaxis, the choice of optimal antibiotic therapy is vital in the individual patient.

Arterial hypertension is an established risk factor for acute coronary syndromes, and physical exertion may trigger the onset of such an event. The mechanisms involved include the rupture of a small, inflamed, coronary plaque and the activation of thrombogenic factors. Blood pressure (BP)–lowering treatment has been associated with beneficial effects on subclinical inflammation and thrombosis at rest and during exercise. This prospective study sought to compare the effect of different antihypertensive drugs on the inflammatory and thrombotic response during exercise. A total of 60 never-treated hypertensive patients were randomized to an angiotensin receptor blocker (ARB)- or non-dihydropyridine calcium channel blocker (CCB)-based regimen. Patients with inflammatory or coronary artery disease were excluded. Six months after pharmaceutical BP normalization, the patients underwent a maximal treadmill exercise testing. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cells (WBC), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), total fibrinogen (TF) and von Willebrand factor (vWF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity were measured in blood samples taken while the patients were at rest and during peak exercise. All of these biomarkers increased with exercise, except PAI-1, which decreased ( P <0.05 for the difference between resting and peak exercise for all biomarkers). The ARB group had less marked ( P <0.05) exercise-induced changes than the CCB group in hsCRP (5.8% vs. 7.7%), SAA (4.2% vs. 7.2%), WBC (46.8% vs. 52.6%), TNF-α (16.3% vs. 24.3%), TF (9.5% vs. 16.9%) and PAI-1 (−9.5% vs. −12.3%) but a similar ( P =NS) change in IL-6 (39.4% vs. 38.6%) and vWF (29.2% vs. 28.6%). In conclusion, ARBs are most likely more effective than CCBs at suppressing the exercise-induced acute phase response. Potential protection against exercise-related coronary events remains to be elucidated.