Vitamin E as a Treatment for Nonalcoholic Fatty Liver Disease: Reality or Myth?

Obesity is one of the major epidemics of this millennium, and its incidence is growing worldwide. Following the epidemics of obesity, nonalcoholic fatty liver disease (NAFLD) has become a disease of increasing prevalence and a leading cause of morbidity and mortality closely related to cardiovascular disease, malignancies, and cirrhosis. It is believed that oxidative stress is a main player in the development and progression of NAFLD. Currently, a pharmacological approach has become necessary in NAFLD because of a failure to modify lifestyle and dietary habits in most patients. Vitamin E is a potent antioxidant that has been shown to reduce oxidative stress in NAFLD. This review summarizes the biological activities of vitamin E, with a primary focus on its therapeutic efficacy in NAFLD

SGLT2 Inhibitors and the Diabetic Kidney

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether SGLT2 inhibitors, in addition to their glycemic and blood pressure benefits, may provide nephroprotective effects

Obesity management: at the forefront against disease stigma and therapeutic inertia

Obesity is a complex chronic relapsing disease, resulting from the interaction between multiple environmental, genetic and epigenetic causes, and supported by changes in the neuroendocrine mechanisms regulating energy balance and body weight. Adipose tissue dysfunction contributes to obesity-related complications. However, the prevalent narrative about the causes and mechanisms of obesity remains a much more simplistic one, based on the false assumption that individuals can fully control their body weight through appropriate behavioural choices. According to this narrative, obesity is simply reversible "persuading" the patient to follow healthier and more virtuous individual behaviours (moral judgement). This persistent narrative forms the deep root of the stigmatisation of people with obesity at the individual level and creates a clear discrepancy on how obesity prevention and cure are designed in comparison with the case of other non-communicable chronic diseases (clinical stigma). The promotion of systemic preventive measures against obesity is not supported at a political and social level by the persistence of a narrative of obesity as the simple consequence of individual failures and lack of willpower. The simplistic narrative of obesity as a self-imposed condition with an easy way-out ("eat less and move more") creates a clear discrepancy on how obesity is managed by health care systems in comparison with other NCDs. The over-estimation of the efficacy of therapeutic intervention solely based on patients education and lifestyle modification is responsible of therapeutic inertia in health care professionals and in clinical guidelines, limiting or delaying the adoption of more effective therapeutic strategies, like anti-obesity medications and bariatric surgery. In conclusion, the persistence of a narrative describing obesity as a self-induced easily reversible condition has profound consequences on how obesity prevention and management are build, including the design and implementation of obesity management guidelines and a tendency to therapeutic inertia.Level of evidence: No level of evidence

Effect of Sibutramine on Weight Management and Metabolic Control in Type 2 Diabetes

OBJECTIVE—The aim of this study was to provide a comprehensive meta-analysis of randomized controlled clinical studies on the effects of sibutramine on weight loss and glycemic control in obese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS—Controlled clinical trials assessing the effect sizes of sibutramine on weight loss effects on glycemia in obese subjects with type 2 diabetes were identified and reviewed using the Cochrane Library, Medline, EMBASE, and a manual search. RESULTS—Eight placebo-controlled, double-blind, randomized trials of sibutramine were included. After sibutramine treatment, the decrease in body weight and waist circumference was significantly greater than in the placebo group. Fasting blood glucose and HbA1c significantly decreased after sibutramine treatment. Treatment benefits were seen in plasma triglycerides and HDL, without significant variations in serum total and LDL cholesterol. No differences in systolic blood pressure between the sibutramine and the placebo groups were seen, while recording of diastolic blood pressure and heart rate showed that sibutramine produced a small increase relative to placebo. CONCLUSIONS—A pharmacological approach in a weight management program for patients with type 2 diabetes may be helpful in glycemic control and in the management of other risk factors. Sibutramine may help improve glucose control because it is conducive to weight loss. The reviewed data on the effect of sibutramine further enforce the recommendations that weight management may be the most important therapeutic task for most obese subjects with type 2 diabetes

Management of hypercholesterolemia, appropriateness of therapeutic approaches and new drugs in patients with high cardiovascular risk

Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Lowering low-density lipoproteins-cholesterol (LDL-C) has been shown to decrease the risk of CVD and of all-cause mortality. For appropriate management, estimation of each individual’s total cardiovascular risk is critical, as patients should receive treatment according to their cardiovascular risk category as well as their LDL-C level. However, available data indicate that a large proportion of patients fail to achieve lipid goals despite treatment, and a significant percentage of patients are not able to tolerate statin treatment. Researchers have therefore focused considerable attention on the development of novel LDL-C-lowering agents that act via different mechanisms. Among the most recent advances in clinical development are the proprotein convertase subtilisin/kexin 9 antibody inhibitors, including alirocumab and evolocumab, which appear particularly promising, with clinical trial data indicating these agents to be both well tolerated and highly efficacious in lowering LDL-C

Effect of Hypertension on Outcomes of High-Risk Patients After BCG-Treated Bladder Cancer

Immunotherapy with Bacillus Calmette Guerin (BCG) is the most efficacious treatment for high-risk bladder cancer (BC) (Ta/T1 or carcinoma in situ) to reduce the risk of recurrence. Our aim was to evaluate whether hypertension and diabetes influence the outcome of patients with noninvasive BC treated with BCG instillations. In order to collect homogeneous data, we considered as "hypertensive" only those patients who had previous diagnosed hypertension and a history of taking medical therapy with antihypertensive drugs (AHT), and as "diabetic" only those prescribed oral antidiabetics or insulin (ADT). We analyzed 343 high-risk BC patients undergoing BCG 1995 2010) with a median follow-up of 116 months (range 48-238). The distribution of various kinds of AHT and antidiabetic drugs was homogeneous, with no significant differences (p > 0.05). In both univariate and multivariate analyses, the only statistically significant parameter propostic for recurrence after BCG treatment was AHT. Recurrence-liee survival curves showed a significant correlation with AHT (p = 0.0168, hazards ratio [HR] 1.45, 95% confidence interval [CI] 1.0692-1.9619); there was no correlation ( p = 0.9040) with ADT (HR 0.9750, 95% CI 0.6457-1.4721). After stratification of AHT and A.DT according to drug(s) prescribed, there were no significant differences in the BC recurrence rate (p > 0.05). In this study with a very long-term follow-up, hypertension alone (evaluated by AHT) revealed the increased risk of BC recurrence after BCG treatment. Several hypotheses have been formulated to support these findings, but further prospective studies are needed to both evaluate the real influence of hypertension and identify a possible prognostic factor to be used in selecting poor-prognosis BC patients as early candidates for surgical treatment

Obesity, Male Reproductive Function and Bariatric Surgery

Overweight and obesity are associated with several chronic complications, such as type 2 diabetes, arterial hypertension and atherosclerotic cardiovascular diseases, with relevant consequences for patients and public health systems. Reproductive function abnormalities, such as obesity-related secondary hypogonadism, erectile dysfunction and infertility, represent other abnormalities negatively affecting the quality of life of men suffering from obesity but, despite their high prevalence, these are often understated because of a general lack of awareness in clinical practice. Obesity and gonadal function are closely related, with obesity being associated with hypogonadism that is reversed by body weight reduction thus ameliorating reproductive and sexual health. Clinical studies specifically evaluating the impact of non-surgical weight loss on testosterone levels sometimes showed conflicting results, whereas extensive literature has demonstrated that weight loss after bariatric surgery is correlated with an increase in testosterone levels greater than that obtained with only lifestyle interventions, suggesting the role of surgery also for the treatment of hypogonadism in obese male. However, studies concerning the consequences of bariatric surgery on overall reproductive function in the male, including also sexual activity and fertility, are limited and data regarding long-term effects are lacking. Here we present a brief review summarizing the evidence regarding the interplay between obesity and reproductive abnormalities in the obese male, together with the role of bariatric surgery for the treatment of these complications, describing both the positive effects and the limitations of this procedure

Relationship between Heart Disease and Liver Disease: A Two-Way Street

In clinical practice, combined heart and liver dysfunctions coexist in the setting of the main heart and liver diseases because of complex cardiohepatic interactions. It is becoming increasingly crucial to identify these interactions between heart and liver in order to ensure an effective management of patients with heart or liver disease to provide an improvement in overall prognosis and therapy. In this review, we aim to summarize the cross-talk between heart and liver in the setting of the main pathologic conditions affecting these organs. Accordingly, we present the clinical manifestation, biochemical profiles, and histological findings of cardiogenic ischemic hepatitis and congestive hepatopathy due to acute and chronic heart failure, respectively. In addition, we discuss the main features of cardiac dysfunction in the setting of liver cirrhosis, nonalcoholic fatty liver disease, and those following liver transplantation

IM -ORIGINAL Rational error in internal medicine

Abstract Epistemologists have selected two basic categories: that of errors committed in scientific research, when a researcher devises or accepts an unfounded hypothesis, and that of mistakes committed in the application of scientific knowledge whereby doctors rely on knowledge held to be true at the time in order to understand an individual patient's signs and symptoms. The paper will deal exclusively with the latter, that is to say the mistakes which physicians make while carrying out their day-to-day medical duties. The paper will deal with the mistakes committed in medicine trying also to offer a classification. It will take into account also examples of mistakes in Bayesian reasoning and mistakes of reasoning committed by clinicians regard inductive reasoning. Moreover, many other mistakes are due to fallacies of deductive logic, logic which they use on a day-to-day basis while examining patients in order to envisage the consequences of the various diagnostic or physiopathologic hypotheses. The existence of a different type of mistakes that are part of the psychology of thought will be also pointed out. We conclude that internists often make mistakes because, unknowingly, they fail to reason correctly. These mistakes can occur in two ways: either because he does not observe the laws of formal logic, or because his practical rationality does not match theoretical rationality and so his reasoning becomes influenced by the circumstances in which he finds himself

Review and prospects for autonomous observing systems in vessels of opportunity

This paper focuses on the state of the art on Autonomous Observing Systems (AOS) used in Vessels of Opportunity (VOO) for collecting in situ atmospheric, oceanic and biogeochemical data. The designation Vessels of Opportunity includes all kinds of ships, even if not having scientific goals, which may carry proper devices that autonomously measure environmental variables. These vessels can be merchant, military, research, cruise liners, fishing, ferries, or even private yachts or sailing boats. The use of AOS can provide the opportunity for highly refined oceanographic data and improved derived data estimation, for local, regional or global scales studies. However, making the collected information accessible, both for scientific and technical purposes, provides a challenge in data management and analysis, which must, above all, ensure trusted useful data to the stakeholders. An overall review of the systems implemented is presented. This includes the definition of objectives, the recruitment of vessels and a review on the installation of proper acquisition devices; the selection and collection of Essential Oceanic Variables (EOV); the mechanisms for transmitting the information, and the quality control analysis and dissemination of data. The present and future capabilities of VOO for measuring EOV, within the Portuguese context are referred.PTDC/CTA-AMB/31141/2017 - MAR-01.04.02-FEAMP-0002 - UIDB/UIDP/00134/2020 - UIDB/04326/2020info:eu-repo/semantics/publishedVersio