Efficacy and Safety of Semaglutide for the Management of Obese Patients With Type 2 Diabetes and Chronic Heart Failure in Real-World Clinical Practice.

Background: The impact of glucagon-like peptide-1 receptor agonists on patients with heart failure has not been fully described. Our main objective was to evaluate the safety and clinical and glycemic efficacy of once-weekly semaglutide in obese patients with type 2 diabetes and heart failure. Methods: In this observational, retrospective, real-world study, we enrolled outpatients with type 2 diabetes, obesity, and heart failure who started semaglutide and were followed-up on at 3, 6, and 12 months. Results: A total of 136 patients were included. From baseline to 12 months, there was a significant improvement on the Kansas City Cardiomyopathy Questionnaire total symptom score (59.0 ± 24.1 vs 79.9 ± 28.4 points, p<0.01), a reduction in the proportion of patients with New York Heart Association functional class III (40.4% to 16.2%, p<0.01), and a reduction in N-terminal pro-brain natriuretic peptide levels (969.5 ± 653.5 vs 577.4 ± 322.1 pg/mL, p<0.01). Emergency department visits due to heart failure, hospitalizations due to heart failure, and all-cause hospitalizations also declined. Additionally, significant reductions in glycated hemoglobin (-1.4%) and body weight (-12.7 kilograms) were observed as well as a de-intensification of antidiabetic therapy. Moreover, semaglutide was safe and well-tolerated. Conclusion: In obese patients with type 2 diabetes and heart failure, the use of once-weekly semaglutide was safe and clinically efficacious, improving health and functional status. Nevertheless, more strong evidence on glucagon-like peptide-1 receptor agonists in heart failure is required.

Polyphenol intake and cardiovascular risk in the PREDIMED-Plus trial. A comparison of different risk equations.

INTRODUCTION AND OBJECTIVES: Quantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results. Our aim was to assess the possible association between intake of the various polyphenol classes and established cardiovascular scores. METHODS: This cross-sectional analysis involved 6633 PREDIMED-Plus study participants. Food polyphenol content was estimated by a semiquantitative food frequency questionnaire, adjusted for total energy intake according to the residual method. The association between polyphenol intake and cardiovascular risk was tested using linear regression analyses. RESULTS: Total polyphenol and flavonoid intake were directly and significantly associated only with the LS7 scale. Intake of lignans was directly and significantly associated with SCORE and LS7 scales, stilbene intake with SCORE, and phenolic acid intake with Framingham and Framingham-REGICOR scores. Other polyphenol classes were associated in a protective and significant manner in Framingham, SCORE and LS7 scores. In women, intake of all the polyphenol classes, except phenolic acids, showed a protective trend in the results of the Framingham, Framingham-REGICOR scores and LS7 scale. CONCLUSIONS: An inverse association was found between consumption of the 'other polyphenols' class and, especially among women, with estimated cardiovascular risk. The results were similar to those of Framingham, Framingham-REGICOR and LS7 (after eliminating the diet component) and differed from those of SCORE, but the predictors included were limited in the latter case.

Statins and Peripheral Arterial Disease: A Narrative Review.

Peripheral arterial disease (PAD) is a highly prevalent atherosclerotic condition. In patients with PAD, the presence of intermittent claudication leads to a deterioration in quality of life. In addition, even in asymptomatic cases, patients with PAD are at high risk of cardiac or cerebrovascular events. Treatment of PAD is based on lifestyle modifications; regular exercise; smoking cessation; and control of cardiovascular risk factors, including hypercholesterolemia. A growing number of studies have shown that statins reduce cardiovascular risk and improve symptoms associated with PAD. Current guidelines recommend the use of statins in all patients with PAD in order to decrease cardiovascular events and mortality. However, the prescribing of statins in patients with PAD is lower than in those with coronary heart disease. This review provides relevant information from the literature that supports the use of statins in patients with PAD and shows their potential benefit in decreasing lower limb complications as well as cardiovascular morbidity and mortality.

Different Weight Loss Intervention Approaches Reveal a Lack of a Common Pattern of Gut Microbiota Changes.

Options for treatment of obesity include dietary approaches and bariatric surgery. Previous studies have shown that weight loss interventions have an impact on gut microbiota. However, a pattern of gut microbiota changes associated with weight loss independently of the type of intervention has not been described yet. This study includes 61 individuals who followed different weight loss strategies in three different trials: 21 followed a hypocaloric Mediterranean diet (MedDiet), 18 followed a very-low-calorie ketogenic diet (VLCKD) and 22 patients underwent sleeve gastrectomy bariatric surgery (BS). Gut microbiota profile was assessed by next-generation sequencing. A common taxon that had significantly changed within the three weight loss interventions could not be find. At the family level, Clostiridiaceae significantly increased its abundance with MedDiet and VLCKD, whilst Porphyromonadacean and Rikenellaceae significantly increased with VLCKD and BS. At genus level, in VLCKD and BS, Parabacteroides and Alistipes significantly increased their abundance whilst Lactobacillus decreased. At the species level, BS and VLCKD produced an increase in Parabacteroidesdistasonis and a decrease in Eubactieriumventriosum and Lactobacillusrogosae, whilst Orodibactersplanchnicus increased its abundance after the BS and MedDiet. Predicted metagenome analysis suggested that most of the changes after VLCKD were focused on pathways related to biosynthesis and degradation/utilization/assimilation, while BS seems to decrease most of the biosynthesis pathways. MedDiet was enriched in several pathways related to fermentation to short-chain fatty acids. Our results show that weight loss is not associated with a specific pattern of gut microbiota changes independently of the strategy used. Indeed, gut microbiota changes according to type of weight loss intervention.

Association between coffee consumption and total dietary caffeine intake with cognitive functioning: cross-sectional assessment in an elderly Mediterranean population.

PURPOSE: Coffee is rich in compounds such as polyphenols, caffeine, diterpenes, melanoidins and trigonelline, which can stimulate brain activity. Therefore, the possible association of coffee consumption with cognition is of considerable research interest. In this paper, we assess the association of coffee consumption and total dietary caffeine intake with the risk of poor cognitive functioning in a population of elderly overweight/obese adults with metabolic syndrome (MetS). METHODS: PREDIMED-plus study participants who completed the Mini-Mental State Examination test (MMSE) (n = 6427; mean age = 65 ± 5 years) or a battery of neuropsychological tests were included in this cross-sectional analysis. Coffee consumption and total dietary caffeine intake were assessed at baseline using a food frequency questionnaire. Logistic regression models were fitted to evaluate the association between total, caffeinated and decaffeinated coffee consumption or total dietary caffeine intake and cognitive impairment. RESULTS: Total coffee consumers and caffeinated coffee consumers had better cognitive functioning than non-consumers when measured by the MMSE and after adjusting for potential confounders (OR 0.63; 95% CI 0.44-0.90 and OR 0.56; 95% CI 0.38-0.83, respectively). Results were similar when cognitive performance was measured using the Clock Drawing Test (CDT) and Trail Making Test B (TMT-B). These associations were not observed for decaffeinated coffee consumption. Participants in the highest tertile of total dietary caffeine intake had lower odds of poor cognitive functioning than those in the reference tertile when screened by the MMSE (OR 0.64; 95% CI 0.47-0.87) or other neurophysiological tests evaluating a variety of cognitive domains (i.e., CDT and TMT-A). CONCLUSIONS: Coffee consumption and total dietary caffeine intake were associated with better cognitive functioning as measured by various neuropsychological tests in a Mediterranean cohort of elderly individuals with MetS. TRIAL REGISTRATION: ISRCTN89898870. Registration date: July 24, 2014.

Adherence to the Mediterranean Lifestyle and Desired Body Weight Loss in a Mediterranean Adult Population with Overweight: A PREDIMED-Plus Study.

BACKGROUND: Body weight dissatisfaction is a hindrance to following a healthy lifestyle and it has been associated with weight concerns. OBJECTIVES: The aim of this study was to assess the association between the adherence to the Mediterranean lifestyle (diet and exercise) and the desired body weight loss in an adult Mediterranean population with overweight. METHODS: Cross-sectional analysis in 6355 participants (3268 men; 3087 women) with metabolic syndrome and BMI (Body mass index) between 27.0 and 40.0 kg/m2 (55-75 years old) from the PREDIMED-Plus trial. Desired weight loss was the percentage of weight that participants wished to lose. It was categorized into four cut-offs of this percentage (Q1: <10%, n = 1495; Q2: 10-15%, n = 1804; Q3: <15-20%, n = 1470; Q4: ≥20%, n = 1589). Diet was assessed using a validated food frequency questionnaire and a 17-item Mediterranean diet questionnaire. Physical activity was assessed by the validated Minnesota-REGICOR and the validated Spanish version of the Nurses' Health Study questionnaire. RESULTS: Participants reporting higher percentages of desired weight loss (Q3 and Q4) were younger, had higher real and perceived BMI and were more likely to have abdominal obesity. Desired weight loss correlated inversely to physical activity (Q1: 2106 MET min/week; Q4: 1585 MET min/week. p < 0.001) and adherence to Mediterranean diet (Q1: 8.7; Q4: 8.3. p < 0.001). CONCLUSIONS: In older Mediterranean individuals with weight excess, desired weight loss was inversely associated with Mediterranean lifestyle adherence. Deeply rooted aspects of the MedDiet remained similar across groups. Longitudinal research is advised to be able to establish causality.

Incidental Prophylactic Appendectomy Is Associated with a Profound Microbial Dysbiosis in the Long-Term.

Incidental prophylactic surgeries are performed in certain situations. Incidental prophylactic appendectomies were common practice within opened bariatric surgeries. The gut microbiota has emerged as an important actor within the homeostasis of the host. A new hypothesis has been formulated about the appendix function in relation to gut microbiota. Our objective was to study the gut microbiota profiles of patients that had suffered from an incidental prophylactic appendectomy during their bariatric surgeries, while comparing them to patients whose appendixes had remained intact. A case-control observational prospective study of 40 patients who underwent bariatric surgery, with or without an incidental prophylactic appendectomy, during 2004-2008 with an evaluation of their gut microbiota populations at the end of 2016 was conducted by sequencing the 16 S rRNA gene by Next Generation Sequencing of patients' stools and appendix tissues. Patients with their appendix removed showed lower levels of richness and diversity of their gut microbiota populations. Odoribacter, Bilophila, Butyricimonas, and Faecalibacterium levels were increased in the Intact group, while Lachnobacterium suffered an expansion in the group without the appendix. Moreover, a linear regression model introduced the concept that Butyricimonas and Odoribacter may be implicated in insulin regulation. Thus, gut microbiota should be considered in the decisions of practical surgery, regarding the appendix as a mediator of homeostasis in the host. Butyricimonas and Odoribacter require further investigation as key bacteria implicated in insulin regulation.

Effects of a long-term lifestyle intervention on metabolically healthy women with obesity: Metabolite profiles according to weight loss response.

BACKGROUND & AIMS: The benefits of weight loss in subjects with metabolically healthy obesity (MHO) are still a matter of controversy. We aimed to identify metabolic fingerprints and their associated pathways that discriminate women with MHO with high or low weight loss response after a lifestyle intervention, based on a hypocaloric Mediterranean diet (MedDiet) and physical activity. METHODS: A UPLC-Q-Exactive-MS/MS metabolomics workflow was applied to plasma samples from 27 women with MHO before and after 12 months of a hypocaloric weight loss intervention with a MedDiet and increased physical activity. The subjects were stratified into two age-matched groups according to weight loss: <10% (low weight loss group, LWL) and >10% (high weight loss group, HWL). Random forest analysis was performed to identify metabolites discriminating between the LWL and the HWL as well as within-status effects. Modulated pathways and associations between metabolites and anthropometric and biochemical variables were also investigated. RESULTS: Thirteen metabolites discriminated between the LWL and the HWL, including 1,5-anhydroglucitol, carotenediol, 3-(4-hydroxyphenyl)lactic acid, N-acetylaspartate and several lipid species (steroids, a plasmalogen, sphingomyelins, a bile acid and long-chain acylcarnitines). 1,5-anhydroglucitol, 3-(4-hydroxyphenyl)lactic acid and sphingomyelins were positively associated with weight variables whereas N-acetylaspartate and the plasmalogen correlated negatively with them. Changes in very long-chain acylcarnitines and hydroxyphenyllactic levels were observed in the HWL and positively correlated with fasting glucose, and changes in levels of the plasmalogen negatively correlated with insulin resistance. Additionally, the cholesterol profile was positively associated with changes in acid hydroxyphenyllactic, sphingolipids and 1,5-AG. CONCLUSIONS: Higher weight loss after a hypocaloric MedDiet and increased physical activity for 12 months is associated with changes in the plasma metabolome in women with MHO. These findings are associated with changes in biochemical variables and may suggest an improvement of the cardiometabolic risk profile in those patients that lose greater weight. Further studies are needed to investigate whether the response of those subjects with MHO to this intervention differs from those with unhealthy obesity.

Screening Versus Brief Domain-specific Tests to Assess Long-term Postoperative Cognitive Dysfunction After Concomitant Aortic Valve Replacement and Coronary Artery Bypass Grafting.

BACKGROUND: Although postoperative cognitive dysfunction is a relevant complication after surgery, assessment for the condition is not routine in clinical practice. OBJECTIVE: The aim of this study was to compare the use of screening versus brief domain-specific cognitive tests in assessing long-term cognitive dysfunction after concomitant aortic valve replacement and coronary artery bypass grafting. METHODS: In this observational prospective study, we evaluated 70 patients preoperatively and after 1, 6, and 12 months using 2 screening tests (Mini-Mental State Examination and Clock Drawing Test) and 2 brief domain-specific cognitive tests (Trail Making Test to evaluate attention and executive function, and Semantic and Phonological Tests to evaluate verbal fluency). RESULTS: The brief domain-specific cognitive tests detected significant postoperative worsening in performances (up to 19% on the Trail Making Test and 15.4% on verbal fluency tests at 6 months). Postoperative mild attention/executive dysfunction or inferior normal performance was detected with the maximums being seen at 6 months (44.6%, P < .001). Performances on screening tests did not significantly change during the study period. CONCLUSIONS: A brief domain-specific cognitive evaluation could be routinely implemented in perioperative care practice to detect postoperative cognitive dysfunction.

Glycaemic efficacy and safety of linagliptin for the management of non-cardiac surgery patients with type 2 diabetes in a real-world setting: Lina-Surg study.

Introduction: The use of dipeptidyl peptidase-4 inhibitors in hospitalized patients is an area of active research. We aimed to compare the efficacy and the safety of the basal-bolus insulin regimen versus linagliptin-basal insulin in non-critically ill non-cardiac surgery patients in a real-world setting. Methods: We enrolled patients with type 2 diabetes hospitalized in non-cardiac surgery departments with admission glycated haemoglobin level < 8%, admission blood glucose concentration < 240 mg/dL, and no at-home injectable treatments who were treated with basal-bolus (n = 347) or linagliptin-basal (n = 190) regimens between January 2016 and December 2017. To match patients on the two regimens, a propensity matching analysis was performed. Results: After matching, 120 patients were included in each group. No differences were noted in mean blood glucose concentration after admission (p = .162), number of patients with a mean blood glucose 100-140 mg/dL (p = .163) and > 200 mg/dL (p = .199), and treatment failures (p = .395). Total daily insulin and number of daily insulin injections were lower in the linagliptin-basal group (both p < .001). Patients on linagliptin-basal insulin had fewer hypoglycaemic events (blood glucose < 70 mg/dL) (p < .001). Conclusion: For type 2 diabetes surgery patients with mild to moderate hyperglycaemia without pre-hospitalization injectable therapies, linagliptin-basal insulin was an effective, safe alternative with fewer hypoglycaemic events in real-world practice. Key messages Treatment with basal-bolus insulin regimens is the standard of care for non-critically ill hospitalized patients with type 2 diabetes. A differentiated treatment protocol that takes into account glycaemic control and clinical factors should be implemented in the hospital setting. Linagliptin-basal insulin is an effective, safe alternative with fewer hypoglycaemic events during the hospitalization of non-critically ill non-cardiac surgery patients with T2D in real-world practice.

Familial aortic coarctation: a rare cause of refractory hypertension in the elderly: a case report.

We report the first case of late presentation of familial aortic coarctation, a rare cause of hypertension. Diagnosis of familial aortic coarctation in the elderly is exceptional, given that in the absence of endovascular or surgical repair patients do not usually survive beyond 50 years of age. Our case concerns a 72-year-old woman with hypertension of long evolution, control of which improved markedly after endovascular repair of the coarctation. Her son had undergone surgery for repair of aortic coarctation at the age of 23 years.

Antioxidized LDL antibodies are associated with different metabolic pathways in patients with atherosclerotic plaque and type 2 diabetes.

OBJECTIVE: Oxidized lipoproteins and antioxidized LDL antibodies (antioxLDL abs) have been detected in human plasma and atherosclerotic lesions. The principle aim of this study was to analyze the possible relationship between IgG and IgM antioxLDL abs and factors involved in different metabolic pathways (inflammation, lipid metabolism, apoptosis, and cell cycle arrest profile) in the occluded popliteal artery (OPA) compared with the femoral vein (FV). RESEARCH DESIGN AND METHODS: Fifteen patients with advanced atherosclerosis and type 2 diabetes undergoing lower limb amputation participated in this study. Each patient had OPA and FV biopsy specimens and peripheral arterial occlusive disease. By real-time PCR, gene expression was analyzed from the OPA and FV specimens, and antioxLDL ab levels were measured by specific enzyme-linked immunosorbent assay. RESULTS: The OPA and FV showed a positive correlation between only IgM antioxLDL ab levels and the expression of genes involved in different metabolic pathways, including inflammation (TFPI), apoptosis (BAX, caspase 3, AKT1), plaque disruption (MMP2 and MMP10), lipid metabolism (SCARB1, PPARg), and cell turnover (CDKN1A), and genes for transcription and growth factors (NFkB and VEGFA, respectively). CONCLUSIONS: The results show that gene expression in the metabolic pathways (apoptosis, lipid metabolism, and inflammation) in the OPA and FV are directly related to the levels of IgM antioxLDL abs.

Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) after laparoscopic Roux-en-Y gastric bypass for morbid obesity: a case report.

INTRODUCTION: Kikuchi-Fujimoto disease, or histiocytic necrotizing lymphadenitis, is a rare, benign, autoimmune condition characterized by lymphadenopathy, fever and neutropenia. It is a self-limited condition of unknown etiology. CASE PRESENTATION: We report the case of a 45-year-old Caucasian man with the first known case of Kikuchi disease associated with dramatic weight loss after bariatric surgery. CONCLUSION: Although the association between Kikuchi disease and bariatric surgery may be entirely coincidental, we speculate whether the immune dysfunction associated with weight loss may have played an etiologic role in this process.