Biologicals dramatic advances in the treatment of psoriasis

Innovations in biotechnology have made possible the development of several new systemic therapies for psoriasis - the "biologicals", a new group of compounds including monoclonal antibodies, fusion proteins and recombinant proteins. These novel biotechnological advances potentially offer designer drugs, which interfere with specific targets in the pathophysiological network of psoriasis and are thus much safer. The therapeutic strategy of biologicals is based on the knowledge derived from pathogenetic studies, which have focused on targeting disease relevant T-cell- or mediator-systems. Important targets include inactivation of soluble mediators such as tumor-necrosis-factor-alpha, the blockade of receptors for cytokines, adhesion molecules and the interference with T-cell activation by antigen-presenting cells. In addition, recombinant cytokines are able to modulate the immunological balance of this chronic inflammatory skin disease. Currently, up to forty agents are under investigation for the treatment of psoriasis. Four of these agents, alefacept, efalizumab, etanercept and infliximab have already impacted on routine clinical practice. Current developments in the treatment of psoriasis with biologicals are reviewed.     

Secondary prevention of stroke with antiplatelet agents in patients with diabetes mellitus

The prevalence of diabetes mellitus (DM) varies from 1.2 to 13.3% in the general population. The most frequent is type 2 (non-insulin-dependent) DM, which constitutes 90-95% of all cases. DM increases the risk of cardiac disease, stroke, retinopathy, nephropathy, neuropathy and gangrene, and the disease is associated with an increased prevalence of other cardiovascular risk factors such as hypertension, hypercholesterolaemia, asymptomatic carotid artery disease, and obesity. The risk of stroke may be directly and indirectly increased by the presence of DM. Epidemiological data show that DM independently amplifies the risk of ischaemic stroke from 1.8- up to 6-fold, so that prevention of cardiovascular risk in diabetics is of utmost importance. The main goal is to control glycaemia, although it has never been shown to be beneficial in stroke patients. Other preventive strategies include antiplatelet treatment. The open-label Primary Prevention Project trial tested the efficacy of low-dose acetylsalicylic acid (ASA) in prevention of ischaemic events in high-risk patients, but failed to demonstrate a significant benefit of ASA in diabetic patients. However, in the CAPRIE trial, the benefit of clopidogrel was amplified in patients with DM versus those without DM in preventing ischaemic events. This difference was even more striking when comparing patients treated with insulin versus non-diabetics. Another trial -- MATCH -- tested the benefit of adding ASA to clopidogrel versus clopidogrel alone in the prevention of ischaemic events in high-risk cerebrovascular patients, two-thirds of whom had DM. Further research is needed to clarify the effects of different antiplatelet regimens in stroke prevention in diabetic patients, who should be considered as high vascular-risk patients.     

Novel Sensitizing Agent Formulation for Bulk Emulsion Explosives with Improved Energetic Parameters

Bulk emulsion explosives, although they are very convenient and safe to use, also have disadvantages, with the main one being the relatively low power in relation to cartridged emulsion explosives or classic nitroesters (e.g., dynamites). Therefore, materials of this type currently have only limited use. In addition, these materials are characterized by the variability of blasting parameters over time from loading into the blasthole, which is closely dependent on the utilised mining method of the mine, which makes it difficult to precisely control the fragmentation. The industry is trying to respond to the demand for bulk emulsion explosives with increased energy and improved parameter stability, but so far it has not been possible to do so in a safe and effective way. Methods of improving blasting parameters mainly rely on additives to oxidant solutions during production, which creates additional risks at the production stage, as it involves handling hot and concentrated ammonium nitrate solutions, for which there are known cases of uncontrolled decomposition of such solutions, even leading to an explosion. This paper presents a method of improving the thermodynamic parameters and the stability of the sensitization reaction without the need for changes in the oxidant solution.     

Short-term ventricular assist device in post-cardiotomy cardiogenic shock: factors influencing survival

Post-cardiotomy cardiogenic shock (PCCS) results in substantial morbidity and mortality, whereas refractory cases require mechanical circulatory support. The aim of this study was to evaluate factors influencing survival during short-term ventricular assist support in PCCS. In total, 154 CentriMag^® (Thoratec; CA, USA) devices were implanted for cardiogenic shock between 2004 and 2011 out of which 31 were for PCCS. A retrospective review was performed in 31 PCCS patients who required the CentriMag short-term VAD as a bridge to decision. Survivors and non-survivors were compared with respect to pre- and intra-operative characteristics as well as duration of short-term VAD support. Mean duration of support was 11.7 ± 15.4 days (range 1–65 days). Seventeen (54.83 %) patients died on support, 14 (45.16 %) were weaned off or upgraded to long-term device, while 11 (35.5 %) were discharged home. The overall survival to myocardial recovery and device explantation, or upgrade to a long-term VAD, was 41.9 % (n = 13) at the study cutoff. EuroSCORE II was significantly higher in non-survivors as compared to survivors (p = 0.047). The duration of short-term VAD support was significantly longer in survivors (p < 0.001). The CentriMag is a versatile, safe and effective short-term circulatory support for patients with PCCS as a bridge to decision which enables longer support and better recovery of both heart and end-organ function and thus may improve the survival of PCCS patients. Lower EuroSCORE may be essential for myocardial recovery in PCCS.