Incretins: a new treatment option for type 2 diabetes?

This article describes how the discovery of a protein almost 100 years ago led to a clinical treatment for type 2 diabetes. Food intake, but also stimulation of the sympathetic nervous system (for example physical exercise), stimulates the secretion of glucagon-like-peptide-1 (GLP-1), derived from the glucagon precursor proglucagon in the small intestine. GLP-1 stimulates the production and secretion of insulin, the release of somatostatin, glucose utilisation by increasing insulin sensitivity and in animal studies also beta-cell function and expansion (proliferation). It inhibits glucagon release, gastric emptying, appetite and food intake via the central nervous system and in animal experiments also apoptosis of beta-cells. Since GLP-1 has to be administered parenterally and its half-life is short, a long-acting GLP-1 receptor agonist (exenatide) and a long-acting GLP-1 analogue (liraglutide) have been developed as well as an inhibitor of DPP-IV (the enzyme that breaks down endogenous GLP-1). Clinical studies with exenatide and liraglutide as monotherapy show a significant increase in the postprandial insulin concentration as well as a smaller increase in the postprandial glucose values. Adding these drugs to standard oral glucose-lowering medication shows improvement in glucose and insulin concentrations and HbA1c compared with adding placebo. The effect of exenatide on HbA1c is the same as adding a long-acting insulin analogue (glargine), but the increase in weight after adding insulin is not seen after exenatide, where even a small decrease in weight is found. This is an important advantage, because most type 2 patients are already obese. Whether less beta-cell apoptosis and maintenance of beta-cell function occurs, as has been shown in animal studies, has to be awaited. Clinical studies with the oral DPPIV inhibitors sitagliptin and vildagliptin show promising results, but are only published as abstracts at scientific meetings.     

Is heart transplantation for primary cardiac sarcoma a useful therapeutic option?

Primary cardiac sarcomas are rapidly progressive malignant tumors. No good therapeutic option is known. In recent years, heart transplantation has sometimes been performed in selected patients with cardiac sarcoma.We retrospectively analyzed 8 patients with primary cardiac sarcoma referred to our center to undergo assessment for heart transplantation. After an exhaustive study of the extension of the tumor, 6 patients were added to the waiting list for heart transplantation. Heart transplantation was not performed in 3 of these patients due to evidence of extracardiac extension, but the procedure was completed in the remaining 3 patients. The median survival in intention-to-treat analysis (transplantation or a frustrated transplantation attempt) was 8.5 months. Overall, the median survival of the 3 patients who underwent transplantation (12 months) was similar to that of the 5 patients who did not (11 months).     

Self-testing for HIV: a new option for HIV prevention?

Self-testing has the potential to be an innovative component to community-wide HIV-prevention strategies. This testing method could serve populations who do not have access to standard voluntary counselling and testing services or because of privacy concerns, stigma, transport costs, or other barriers do not use facility-based, standard HIV testing. This paper reviews recent research on the acceptability, feasibility, and cost of rapid testing and home-specimen collection for HIV, and suggests that self-testing may be another important strategy for diagnosing HIV infection. Several research questions are posed that should be answered before self-testing is realised.     

Bariatric embolization: a new and effective option for the obese patient?

Introduction: Obesity is a public health epidemic in the United States, which results in significant morbidity, mortality, and cost to the healthcare system. Despite advancements in traditional therapeutic options for the obese patients, there is a treatment gap for patients in whom lifestyle modifications alone have not been successful, but for whom bariatric surgery is not a suitable option.

Areas covered: This treatment gap needs to be addressed and thus, complimentary or alternative treatments to lifestyle changes and surgery are urgently needed. Recent evidence suggests that embolization of the gastric fundus (‘Bariatric Embolization’), which is predominantly supplied by the left gastric artery, may affect energy homeostasis by decreasing ghrelin production. The purpose of this special report is to discuss the background, rationale and latest data on this topic, as well as provide the latest data from the ongoing BEAT Obesity clinical trial.

Expert commentary: A multipronged approach is essential in the treatment of obesity. Bariatric embolization looks to treat the hormonal imbalances which contribute to obesity. If proven successful in the long-term, bariatric embolization represents a potential minimally invasive approach to treat obesity offered by interventional radiologists.     

Is amiodarone still a reasonable therapeutic option for rhythm control in atrial fibrillation?

Amiodarone is the most potent antiarrhythmic drug available and is commonly prescribed to treat and prevent not only life-threatening ventricular arrhythmias but also atrial fibrillation (AF). The latest European Society of Cardiology AF guidelines state that amiodarone is recommended for long-term rhythm control in all AF patients but that other antiarrhythmic drugs should be considered first whenever possible, due to its extracardiac toxicity. In patients without significant or with only minimal structural heart disease, amiodarone is not listed as a possibility in their therapeutic scheme. Still, amiodarone is widely and liberally used, and is the most prescribed antiarrhythmic drug for patients with AF despite its high toxicity profile. Non-cardiovascular death was more frequent with amiodarone treatment than with a rate control strategy in AFFIRM, while meta-analyses suggest an association between amiodarone use in patients without structural heart disease and increased non-cardiovascular mortality. Severe or even fatal outcomes due to amiodarone may occur years after treatment initiation and are often not acknowledged by the prescribing physician, who may no longer be following the patient. The lack of widely accepted diagnostic criteria and symptom definitions may lead to underestimation of the incidence of severe side effects and of its toxicity. Unlike the underestimated risk of toxicity with amiodarone, severe complications associated with catheter ablation are usually directly ascribed to the treatment even by non-medical personnel, possibly resulting in overestimation of risks. This brief review will address the issue of amiodarone overuse and the frequent underestimation of its toxicity, while suggesting scenarios in which its use is entirely reasonable, and compare it with catheter ablation.     

Is mizoribine a new therapeutic agent for Sjögren's syndrome?

In a multicenter, open-label study conducted in Japan between July 2004 and May 2005, Nakayamada et al. tested the safety and efficacy of mizoribine for the treatment of primary Sj?gren's syndrome (pSS). Mizoribine 50 mg was administered three times a day for 16 weeks to 59 patients with pSS, 7 of whom withdrew because of adverse drug reactions; however, no serious adverse events were noted. In the 48 patients who completed the study, an increase from baseline in median salivary secretion volume, evaluated using the Saxon test, was apparent at week 8 and was significant at week 16 (P <0.05). At 16 weeks, significant improvements from baseline were also seen in patients' assessments of dry mouth and dry eyes, physicians' assessment of oral sicca symptoms, labioangular sicca symptoms and physicians' overall assessment, all measured using a 10 cm visual analog scale. The findings suggest that mizoribine could be an effective treatment for pSS.     

Hypertrophy of the heart: a new therapeutic target?

Recent studies call into question the necessity of hypertrophic growth of the heart as a "compensatory" response to hemodynamic stress. These findings, coupled with recent progress in dissecting the molecular bases of hypertrophy, raise the prospect of suppressing hypertrophy without provoking circulatory insufficiency. In this article, we focus on signaling pathways that hold promise as potential targets for therapeutic intervention. We also summarize observations from animal models and clinical trials that suggest benefit from an antihypertrophic strategy.     

Role of recombinant human TSH in the management of large euthyroid multinodular goitre: a new therapeutic option? Pros and cons

Conventional 131I treatment has been used in the last 20 years for large nodular goitres when patients present high surgical risk or simply refuse surgery. 131I therapy causes a mean goitre volume reduction of about 40% after one year. However, the individual response is variable and for low radioiodine uptake and very large goitres, high 131I activities are needed in order to have a adequate 131I accumulation in the thyroid. rhTSH is approved for thyroid cancer management and has been tested off label in large goitres, in whom increases 131I uptake, thus reducing the 131I amount to be administered. The use of lower 131I activities allows to reduce the radiation burden to body and the time of social life restriction. Moreover, depending on the radiation regulations of the different countries, the 131I therapy could be carried out either as outpatients or in a shorter hospitalization period, implying a decrease of costs. The effects of rhTSH on goitre may be due not only to the 131I uptake increase, but also to a more homogeneous distribution of 131I in the gland, and to the thyroid cell activation that makes them more radiosensitive. Acute adverse effects are due to the surge of thyroid hormone in blood and to the goitre volume increase, that cause cardiac symptoms and tracheal compression, respectively. These effects are probably dose dependent and are negligible for rhTSH lower doses.     

Transvaginal rectal repair: a new treatment option for symptomatic rectocele?

Purpose  

Widely differing surgical methods have been propagated to correct symptomatic rectocele. With transvaginal rectal repair (TVRR), we evaluate a method to reestablish the continuity of the rectal muscle wall, strengthen the weakened tunica muscularis, and restore normal rectal capacity and function.     

Is sitaxsentan a good therapeutic option for pulmonary arterial hypertension associated with connective tissue disease?

Agents that indiscriminately block endothelin receptors have been shown to cause moderate improvements in the outcomes of patients who have pulmonary arterial hypertension (PAH) as a complication of connective tissue disease (CTD). Girgis et al. investigated the effects of sitaxsentan, a selective endothelin receptor type A antagonist, in patients with CTD and comcomitant PAH. After 12 weeks of treatment, patients who received sitaxsentan showed more improvement from baseline compared with those receiving placebo in terms of exercise capacity, hemodynamics and physical-health-related quality of life. At the end of the extension study (median total follow-up 26 weeks), 16 of the 41 patients with CTD had an improvement of at least one New York Heart Association functional class compared with at the start of sitaxsentan therapy. The effects of sitaxsentan observed in the CTD group were comparable to those seen in the idiopathic PAH group. The authors concluded that treatment with sitaxsentan might be beneficial in patients with PAH associated with CTD.