Postprandial hyperglycaemia: to treat or not to treat?

Accumulating evidence suggests that the postprandial or the post-75 g glucose load rise in plasma glucose are a contributing factor to the development of atherosclerosis. Many epidemiological studies have shown that post-load hyperglycaemia is a strong and independent risk factor for cardiovascular disease. The few interventional studies available also support a role for postprandial or post-load hyperglycaemia on cardiovascular disease or mortality or on validated surrogates of atherosclerosis. The mechanism through which acute hyperglycaemia could exert its deleterious effects on the vessel wall is very likely multifactorial, but the overproduction of free radicals is probably involved. There is growing evidence that treating postprandial hyperglycaemia should probably be part of the strategies for the prevention and management of cardiovascular diseases in pre-diabetes as well as in diabetes.     

Management of severe acute to fulminant hepatitis B: to treat or not to treat or when to treat?

Despite a decline in cases of acute hepatitis B and the low hepatitis B virus (HBV) chronicity rates in adults, still some patients progress to HBV-related fulminant liver failure. In this review, we discuss treatment options that may prevent the progression of severe acute hepatitis B to fulminant liver failure and death. In severe acute HBV with prolonged prothrombin time and increased bilirubin, interferon failed to be effective while antiviral treatment, particularly with lamivudine, appears to improve survival (mean survival almost 80%). Outcome without antiviral therapy has remained considerably poor, whereas there is no convincing evidence of amelioration of HBV-targeted immunity. Of note, most patients who died or required transplantation despite lamivudine therapy, were started on lamivudine at advanced stages compared with those survived. This suggests that prompt and timely antiviral therapy is crucial. Owing to the abovementioned results the design of randomized placebo-control trials in the setting of severe acute hepatitis B seems unethical. On the contrary, the design of multicentre double-blind randomized trials to compare the efficacy between lamivudine and entecavir or even tenofovir in acute severe HBV cases is ideally needed, but these studies appear to be very difficult to perform considering that these cases are not frequent and therefore, it is almost impossible to have two arms adequately numerous and homogenous for statistical evaluation. Thus, in the absence of solid evidence based data, the hepatologists could treat their patients with severe acute hepatitis B with lamivudine or the most potent antivirals entecavir or tenofovir.     

Primary HIV infection: to treat or not to treat?

PURPOSE OF REVIEW: The aim of this article is to review new data on the use of antiretroviral therapy in primary HIV infection. RECENT FINDINGS: The concept of 'hit HIV hard and early' supporting the use of antiretroviral therapy to treat the early stages of HIV infection has been revisited. Recent demonstration of massive, rapid and largely irreversible HIV-mediated destruction of memory CD4+ T cells predominantly occurring in the gut suggests that primary HIV infection may be the only time that intervention could confer lasting immunological benefit. There are no data, however, from randomized controlled trials supporting the use of antiretroviral therapy in primary HIV infection, although a number of observational studies have demonstrated limited, transient improvements in measured immunological outcomes. The first randomized controlled trials powered to address whether antiretroviral therapy of a limited duration in primary HIV infection can influence long-term CD4 decline (SPARTAC) is now fully recruited but will report in 2-3 years. In addition, given that individuals with primary HIV infection contribute disproportionately towards onward HIV transmission, there may be an additional public health impetus for earlier diagnosis and intervention in primary HIV infection. SUMMARY: In the absence of randomized controlled trials data demonstrating clinical benefit of antiretroviral therapy intervention in primary HIV infection, clinical guidelines remain unclear. Intervention seems a logical strategy to counter the high viraemia, enhanced onward transmissibility, and immunological destruction which occurs during primary HIV infection. The nature, duration and timing of that intervention after HIV acquisition remains unknown.     

Adjuvant treatment in biliary tract cancer: to treat or not to treat?

Biliary tract cancer is a rare malignant tumor. There is limited knowledge about biology and natural history of this disease and considerable uncertainty remains regarding its optimal diagnostic and therapeutic management. The role of adjuvant therapy is object of debate and controversy. Although resection is identified as the most effective and the only potentially curative treatment, there is no consensus on the impact of adjuvant chemotherapy and/or radiotherapy on the high incidence of disease recurrence and on survival. This is mainly due to the rarity of this disease and the consequent difficulty in performing randomized trials. The only two prospectively controlled trials concluded that adjuvant chemotherapy did not improve survival. Most of the retrospective trials, which had limited sample size and included heterogeneous patients population and non-standardized therapies, suggested a marginal benefit of chemoradiotherapy in reducing locoregional recurrence and an uncertain impact on survival. Well-designed multi-institutional randomized trials are necessary to clarify the role of adjuvant therapy. Two ongoing phase III trials may provide relevant information.     

The metabolic syndrome: what to treat, how to treat, what are the goals?

Metabolic syndrome is a cluster of risk factors for cardiovascular disease that include obesity, atherogenic dyslipidemia, raised blood pressure, and insulin resistance. The growing trend of obesity is associated with increased prevalence of metabolic syndrome. Optimizing diet and exercise are still the leading therapy for controlling the metabolic syndrome. Based on the current evidence, further emphasis should be placed on aggressive management of other metabolic risk factors such as high blood pressure and dyslipidemia.