Sibutramine in cardiovascular disease: is SCOUT the new STORM on the horizon?

Imagine your favourite pizza, and, after half of it is gone,your desire to eat the rest is gone as well. Sibutramine seemsto have just this effect—at least for some. Doesn't thisappear like the ideal scenario for losing weight? We and otherauthors are not so sure about that.¹ Sibutramine, a centrallyacting monoamino (noradrenaline and serotonin) reuptake inhibitor,was originally developed as an antidepressant. Due to its ‘sideeffect’ of moderate weight loss mainly achieved via increasedsatiety, the drug was approved and introduced into the US marketin 1997, and is today licensed worldwide for the treatment ofobesity. The World Health Organization (WHO) estimates that currentlythere are >1 billion overweight adults worldwide, and     

Dermatomyositis and polymyositis: new treatment targets on the horizon

Polymyositis (PM) and dermatomyositis (DM) are rare idiopathic inflammatory myopathies (IIM) with a presumed autoimmune pathogenesis. Typical features are subacute onset, proximal, symmetric muscle weakness, elevated serum creatine kinase, and mononuclear cell infiltrates in the muscle biopsy. Strong support for an autoimmune pathogenesis comes from histopathological findings in biopsies of affected muscles. Furthermore, the association with autoantibodies supports the notion that immune-mediated inflammation is involved. PM and DM may occur in isolation or in connection with a connective tissue disease or cancer. The current treatment for IIM consists of first-line high-dose steroids and various conventional second-line treatments. Improvements in treatment for IIM are hampered by difficulties in the design of trials and the low incidence and prevalence of the disease. Cytokines and chemokines are factors involved in the inflammatory process in IIM, and are candidates for future therapeutic targets. Preliminary data with anti-tumour necrosis factor therapy are not very promising, but results of blockers of the lymphotoxin signalling pathway are to be awaited. Anti-B cell therapy may be a valuable therapeutic option for treatment of refractory IIM. The effects of anti-interferon-alpha in IIM are to be awaited, as are results of other anti-cytokine therapies and anti-chemokine therapy. Outcome measures to be used in clinical trials in II M include at present the core sets of outcome proposed by the International Myositis Assessment Clinical Study Group (IMACS).     

Percutaneous treatment of tricuspid regurgitation: A new therapeutic horizon

Functional tricuspid regurgitation is a prevalent disease, especially among patients with other valve disorders, and is associated with significant morbidity and mortality. Its management is challenging, and many patients deemed at high surgical risk are managed conservatively. Despite optimization of pharmacological treatment, many patients continue to be symptomatic, thus leading to interest in percutaneous interventional techniques. The Mitralign system has recently been used for the treatment of functional tricuspid regurgitation, with favorable clinical and imaging results.We report the first case in Portugal to our knowledge of percutaneous tricuspid regurgitation treatment with the Mitralign system.     

Immunosuppression on the horizon

Many novel immunosuppressive agents are under active clinical investigation. In addition, creative approaches are being developed for the use of established immunosuppressive agents, with the goal of minimizing immunosuppression as early as possible posttransplantation. The hope is that these approaches will minimize the toxicity of these agents without sacrificing efficacy. Evidence suggests that the nephrotoxicity of calcineurin inhibitors can be reduced using these approaches. The introduction of newer immunosuppressive agents, including the proliferation signal inhibitors, raises the possibility that some of the long-term scourges of cardiac transplantation, including cardiac allograft vasculopathy and malignancy, can be ameliorated. Finally, costimulatory pathway inhibitors and other new immunosuppressive agents offer hope that all these goals can be accomplished with very low long-term maintenance immunosuppression.     

The new horizon of biomarker in melanoma patients: A study based on autophagy-related long non-coding RNA

Autophagy-related long non-coding RNAs (arlncRNAs) play a crucial role in the pathogenesis and development of the tumor. However, there is a lack of systematic analysis of arlncRNAs in melanoma patients.Melanoma data for analysis were obtained from The Cancer Genome Atlas (TCGA) database. By establishing a co-expression network of autophagy-related mRNAs-lncRNAs, we identified arlncRNAs in melanoma patients. We evaluated the prognostic value of arlncRNAs by univariate and multivariate Cox analysis and constructed an arlncRNAs risk model. Patients were divided into high- and low-risk groups based on the arlncRNAs risk score. This model was evaluated by Kaplan–Meier (K–M) analysis, univariate-multivariate Cox regression analysis, and receiver operating characteristic (ROC) curve analysis. Characteristics of autophagy genes and co-expressive tendency were analyzed by principal component analysis and Gene Set Enrichment Analysis (GSEA) functional annotation.Nine arlncRNAs (USP30-AS1, LINC00665, PCED1B-AS1, LINC00324, LINC01871, ZEB1-AS1, LINC01527, AC018553.1, and HLA-DQB1-AS1) were identified to be related to the prognosis of melanoma patients. Otherwise, the 9 arlncRNAs constituted an arlncRNAs prognostic risk model. K–M analysis and ROC curve analysis showed that the arlncRNAs risk model has good discrimination. Univariate and multivariate Cox regression analysis showed that arlncRNAs risk model was an independent prognostic factor in melanoma patients. Principal component analysis and GSEA functional annotation showed different autophagy and carcinogenic status in the high- and low-risk groups.This novel arlncRNAs risk model plays an essential role in predicting of the prognosis of melanoma patients. The model reveals new prognosis-related biomarkers for autophagy, promotes precision medicine, and provides a lurking target for melanoma''s autophagy-related treatment.     

Hepatitis C in non-hepatic solid organ transplant candidates and recipients:A new horizon

Hepatitis C virus(HCV) infection is estimated to affect 130-150 million people globally which corresponds to2%-3% of the total world population. It remains the leading indication for liver transplant worldwide and has been demonstrated to negatively impact both patient and graft survival following non-hepatic organ transplantation. In the era of interferon-based therapy, although treatment and cure of HCV prior to nonhepatic transplant improved survival, tolerability and low cure rates substantially limited therapy. Interferon(IFN)-based therapy following non-hepatic solid organ transplant, due to the risk of allograft rejection, is generally contraindicated. Rapid advances in IFN-free therapy with direct acting antivirals(DAAs) in the last few years have completely changed the paradigm of hepatitis C therapy. Compared to IFN-based regimens, DAAs have less frequent and less severe adverse effects, shorter durations of therapy, and higher cure rates that are minimally impacted by historically negative predictors of response such as cirrhosis, ethnicity, and post-transplant state. Recent studies have shown that liver transplant(LT) recipients can be safely and effectively treated with DAA combination therapies; although data are limited, many of the principles of therapy in LT may be extrapolated to non-hepatic solid organ transplant recipients. Here we review the data on DAA combination therapies in transplantation, discuss the advantages and disadvantages of pre- vs post-transplant HCV therapy and future directions.     

A new proof of the interior gradient bound for the minimal surface equation in N dimensions

An interior gradient bound for classical solutions of the minimal surface equation in n variables was established by Bombieri, De Giorgi, and Miranda in 1968. We provide a new and simpler derivation of this estimate and partly develop in the process some new techniques applicable to the study of hypersurfaces in general.