Antiplatelet therapy in very elderly and comorbid patients with acute coronary syndromes

With population ageing and rise of life expectancy,a progressively increasing proportion of patients presenting with an acute coronary syndrome(ACS)are older adults,including those at extreme chronological age.Increasing amounts of data,including randomized clinical trials,have shown that the benefits of an early revascularization are maintained also at very old age,resulting in improved outcome after an acute coronary event.On the contrary,the optimal antiplatelet therapy(APT)remains unclear in these patients,because of both safety and efficacy concerns.Indeed,age-related multiple organ dysfunction and high prevalence of comorbidities may on the one hand reduce the therapeutic effects of administered drugs;on the other hand,it leads to increased vulnerability to drug toxicity and side effects.Therefore,management of APT is particularly challenging in elderly patients because of higher risk of both ischemic and bleeding events.The aim of the present paper is to review the current evidence,gaps in knowledge and ongoing research regarding APT in the setting of an ACS in elderly and very elderly patients,and in those with significant comorbidities including chronic kidney disease,diabetes mellitus and frailty.

Role of nutritional ketosis in the improvement of metabolic parameters following bariatric surgery

BACKGROUND Ketone bodies(KB)might act as potential metabolic modulators besides serving as energy substrates.Bariatric metabolic surgery(BMS)offers a unique opportunity to study nutritional ketosis,as acute postoperative caloric restriction leads to increased lipolysis and circulating free fatty acids.AIM To characterize the relationship between KB production,weight loss(WL)and metabolic changes following BMS.METHODS For this retrospective study we enrolled male and female subjects aged 18-65 years who underwent BMS at a single Institution.Data on demographics,anthropometrics,body composition,laboratory values and urinary KB were collected.RESULTS Thirty-nine patients had data available for analyses[74.4%women,mean age 46.5±9.0 years,median body mass index 41.0(38.5;45.4)kg/m^(2),fat mass 45.2%±6.2%,23.1%had diabetes,43.6%arterial hypertension and 74.4%liver steatosis].At 46.0±13.6 d post-surgery,subjects had lost 12.0%±3.6%of pre-operative weight.Sixty-nine percent developed ketonuria.Those with nutritional ketosis were significantly younger[42.9(37.6;50.7)years vs 51.9(48.3;59.9)years,P=0.018],and had significantly lower fasting glucose[89.5(82.5;96.3)mg/dL vs 96.0(91.0;105.3)mg/dL,P=0.025]and triglyceride levels[108.0(84.5;152.5)mg/dL vs 152.0(124.0;186.0)mg/dL,P=0.045]vs those with ketosis.At 6 mo,percent WL was greater in those with postoperative ketosis(-27.5%±5.1%vs 23.8%±4.3%,P=0.035).Urinary KBs correlated with percent WL at 6 and 12 mo.Other metabolic changes were similar.CONCLUSION Our data support the hypothesis that subjects with worse metabolic status have reduced ketogenic capacity and,thereby,exhibit a lower WL following BMS.

Risk factors distribution and cardiovascular disease prevalence in the Italian population: The CHECK study

Objective: To evaluate the distribution of cardiovascular risk factors and the prevalence of cardiovascular disease in a sample of the Italian population. Methods: CHECK (Cholesterol and Health: Education, Control and Knowledge) is a cross-sectional observational study in a randomised sample of the Italian adult population aged 40 - 79 years, in the setting of general practice. Results: 5846 subjects (50.3% male) were included in the analysis. The mean age [±SD] of the observed cohort was 57.8 (±10.3) years. One out of five subjects smoked cigarettes and almost 80% didn’t engage in regular leisure-time physical activity. The mean blood pressure was 132.0 [±14.7]/81.2 [±7.9] mmHg. The total and LDL-cholesterol levels were respectively 205.3 [±35.9] mg/dL and 124.9 [±29.9] mg/dL. The mean glucose concentration was 98.3 [±28.2] mg/dL. The prevalence rate of hypertension, hypercholesterolemia, and type 2 diabetes were respectively 51.8%, 55.6%, and 13.0%. 8.9% of the observed subjects had a history of cardiovascular events, while in the primary prevention group the 10-year-risk of coronary heart disease (Framingham algorithm) was 10.1% [±8.3%] and of cardiovascular disease (CUORE algorithm) was 5.2% [±5.9%]. Conclusion: The CHECK study provides a detailed description of a randomised sample of the Italian population, contributing to evaluate the prevalence of cardiovascular risk factors and the main cardiovascular disease in Italy and to provide a baseline to set priorities and objectives for future intervention of health policy.

Reconstruction of tendon losses

This review discusses the latest literature-based evidence on reconstructive strategies following tendon losses,with a final focus on the innovative regenerative approach.Significant improvements in primary tendon repair techniques have radically reduced the failure rate and therefore decreased the use of reconstructive procedures.However,in specific conditions,such as crush injuries with loss of substance,avulsion injuries and inveterate injuries,the tendon gap cannot be repaired with a primary suture,making the procedure much more challenging for the surgeon.This article aims to guide the treatment of tendon losses,which is still a complex topic in hand surgery.

Intravenous immune globulin suppresses angiogenesis in mice and humans

Human intravenous immune globulin(IVIg),a purified IgG fraction composed of~60%IgG1 and obtained from the pooled plasma of thousands of donors,is clinically used for a wide range of diseases.The biological actions of IVIg are incompletely understood and have been attributed both to the polyclonal antibodies therein and also to their IgG(IgG)Fc regions.Recently,we demonstrated that multiple therapeutic human IgG1 antibodies suppress angiogenesis in a target-independent manner via FcγRI,a high-affinity receptor for IgG1.Here we show that IVIg possesses similar anti-angiogenic activity and inhibited blood vessel growth in five different mouse models of prevalent human diseases,namely,neovascular age-related macular degeneration,corneal neovascularization,colorectal cancer,fibrosarcoma and peripheral arterial ischemic disease.Angioinhibition was mediated by the Fc region of IVIg,required FcγRI and had similar potency in transgenic mice expressing human FcγRs.Finally,IVIg therapy administered to humans for the treatment of inflammatory or autoimmune diseases reduced kidney and muscle blood vessel densities.These data place IVIg,an agent approved by the US Food and Drug Administration,as a novel angioinhibitory drug in doses that are currently administered in the clinical setting.In addition,they raise the possibility of an unintended effect of IVIg on blood vessels.

Human IgG1 antibodies suppress angiogenesis in a target-independent manner

Aberrant angiogenesis is implicated in diseases affecting nearly 10%of the world’s population.The most widely used antiangiogenic drug is bevacizumab,a humanized IgG1 monoclonal antibody that targets human VEGFA.Although bevacizumab does not recognize mouse Vegfa,it inhibits angiogenesis in mice.Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI(CD64)and c-Cbl,impairing macrophage migration.Other approved humanized or human IgG1 antibodies without mouse targets(adalimumab,alemtuzumab,ofatumumab,omalizumab,palivizumab and tocilizumab),mouse IgG2a,and overexpression of human IgG1-Fc or mouse IgG2a-Fc,also inhibited angiogenesis in wild-type and FcγR humanized mice.This anti-angiogenic effect was abolished by Fcgr1 ablation or knockdown,Fc cleavage,IgG-Fc inhibition,disruption of Fc-FcγR interaction,or elimination of FcRγ-initated signaling.Furthermore,bevacizumab’s Fc region potentiated its anti-angiogenic activity in humanized VEGFA mice.Finally,mice deficient in FcγRI exhibited increased developmental and pathological angiogenesis.These findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies.