Lancing: Quo Vadis?

Today, lancing fingertips or alternative sites for obtaining a blood sample for self-monitoring of blood glucose (SMBG) is a standard procedure for most patients with diabetes. The need for frequent lancing and associated discomfort and pain can be seen as a key hurdle for patients to comply with SMBG regimens. This article provides an overview of the status quo and future of lancing, focusing on key areas for future developments driven by customer and market needs. We also review technical issues and provide a background for possible improvements. The act of puncturing the skin with a lancet to obtain a blood sample seems to remain the standard procedure for the foreseeable future, because alternate ways of providing a blood sample have not demonstrated overall superiority (e.g., with laser technology). Other methods, which avoid lancing entirely, have also not gained broad market acceptance (e.g., minimally invasive continuous glucose monitoring) or not shown technical viability (e.g., noninvasive glucose monitoring). In relation to blood glucose (BG) meters and test strips, lancing has been a "stepchild" with regards to commercial attention and development efforts. Nevertheless, significant technological improvements have been made in this field to address key customer needs, including better performance (regarding pain, wound healing, and long-term sensitivity), reduced cost, and higher integration with other components of BG monitoring (e.g., integration of the lancing device with the glucose monitor). From a technical perspective, it is apparent that highly comfortable lancing can be accomplished; however, this still requires fairly advanced and complex devices. New developments are necessary to achieve this level of sophistication and performance with less intricate and costly system designs. Manufacturers' motivation to pursue these developments is compromised by the fact that they might not recoup their development cost on commercial advanced lancing systems through direct profits, but only through its positive influence on adherence and increased more profitable sensor utilization. We believe that two main driving forces will continue to push the evolution of lancing and sampling technology: (1) the need for maximum lancing comfort and (2) the advent of fully integrated systems, realizing a device in which all steps for SMBG are incorporated, thus providing a "one-step" experience. Rendering lancing a "nonissue" will eliminate a key barrier to adherence with appropriate SMBG regimens. Providing sophisticated lancing devices that allow the highest level of comfort and/or seamless blood sampling is key to improving user acceptance. This may have a greater impact on metabolic control than many of the new and expensive antidiabetic drugs.     

Endothelial progenitor cells: more than an inflammatory response?

The formation of new capillaries (angiogenesis) may be of clinical importance in facilitating reperfusion and regeneration of hibernating cardiac tissue after myocardial infarction and in microvascular ischemia. Evidence is accumulating that as part of the response to hypoxia, bone marrow-derived circulating endothelial progenitor cells (CEPs) are mobilized and subsequently differentiate into proper endothelial cells. There are also indications that such CEPs can facilitate endothelial repair and angiogenesis in vivo. It is not clear yet, however, whether these CEPs are essential for these adaptive processes or what the relative contribution of CEP is compared with that of other mononuclear inflammatory cells that are mobilized to areas of ischemia. Moreover, there are still many uncertainties about how cardiovascular risk factors alter CEP function. Particularly when therapeutically mobilizing CEPs, a further understanding of this issue is essential to assess the risk of potentially harmful side effects of altered CEP function.     

Quo Vadis: Whither Homocysteine Research?

Four decades of research on the link between hyperhomocysteinemia and cardiovascular disease has led to a crossroads. Several negative studies on the role of homocysteine-lowering B-vitamin therapy in reducing the risk of atherothrombotic cardiovascular disease have dampened enthusiasm for this important field of research. In this review, we assess the present state of homocysteine research and suggest potential avenues that would help to clarify the purported link between the plasma homocysteine level and cardiovascular risk. We address several questions raised by the findings of various basic, epidemiological and clinical studies and attempt to construct a framework that we believe will allow us to address the fundamental unresolved issues in this controversial area, specifically focusing on the risk of coronary vascular disease and cardiac failure. This review should allow researchers to deconstruct this complex field into separate areas that, when addressed adequately, may lead to findings that elucidate the overall link between hyperhomocysteinemia and cardiovascular disease and allow the design of appropriate clinical trials.     

Biologics in Pediatric Rheumatology: Quo Vadis?

The past two decades have brought immense satisfaction to pediatric rheumatologists and families of children with rheumatologic diseases. We have been able to better classify, recognize, and diagnose rheumatologic diseases, but most importantly, the discovery of biologic therapies and their efficacy and relative safety in treating multiple rheumatologic conditions, improving quality of life for the patients we care for. We will review the advances of the past two decades and discuss potential areas for new discoveries.     

Endothelial progenitor cells for the treatment of diabetic vasculopathy: panacea or Pandora’s box?

The discovery of endothelial progenitor cell (EPC) a decade ago has refuted the previous belief that vasculogenesis only occurs during embryogenesis. The reduced circulating concentration of EPCs is a surrogate marker of endothelial function and has been implicated in the pathogenesis of many vascular diseases. To date, the therapeutic benefit of neovascularization in ischaemic conditions in a non-diabetic setting has been demonstrated. This article aims to review the biology of EPCs in the diabetic setting with special emphasis on the effects of cardiovascular risk factor modification on EPC phenotype and methods to reverse or augment EPC dysfunction. The potential of the use of EPCs in the treatment of the diabetic vascular dysfunction will also be discussed.     

FV-100 for the Treatment of Varicella-Virus (VZV) Infections: Quo Vadis?

The bicyclic nucleoside analogue (BCNA) Cf1743 and its orally bioavailable prodrug FV-100 have unique potential as varicella-zoster virus (VZV) inhibitors to treat herpes zoster (shingles) and the therewith associated pain, including post-herpetic neuralgia (PHN). The anti-VZV activity of Cf1743 depends on a specific phosphorylation by the VZV-encoded thymidine kinase (TK). The target of antiviral action is assumed to be the viral DNA polymerase (or DNA synthesis in the virus-infected cells).     

Drug- and Herb-Induced Liver Injury in Clinical and Translational Hepatology: Causality Assessment Methods,Quo Vadis?

Drug-induced liver injury (DILI) and herb-induced liver injury (HILI) are typical diseases of clinical and translational hepatology. Their diagnosis is complex and requires an experienced clinician to translate basic science into clinical judgment and identify a valid causality algorithm. To prospectively assess causality starting on the day DILI or HILI is suspected, the best approach for physicians is to use the Council for International Organizations of Medical Sciences (CIOMS) scale in its original or preferably its updated version. The CIOMS scale is validated, liver-specific, structured, and quantitative, providing final causality grades based on scores of specific items for individual patients. These items include latency period, decline in liver values after treatment cessation, risk factors, co-medication, alternative diagnoses, hepatotoxicity track record of the suspected product, and unintentional re-exposure. Provided causality is established as probable or highly probable, data of the CIOMS scale with all individual items, a short clinical report, and complete raw data should be transmitted to the regulatory agencies, manufacturers, expert panels, and possibly to the scientific community for further refinement of the causality evaluation in a setting of retrospective expert opinion. Good-quality case data combined with thorough CIOMS-based assessment as a standardized approach should avert subsequent necessity for other complex causality assessment methods that may have inter-rater problems because of poor-quality data. In the future, the CIOMS scale will continue to be the preferred tool to assess causality of DILI and HILI cases and should be used consistently, both prospectively by physicians, and retrospectively for subsequent expert opinion if needed. For comparability and international harmonization, all parties assessing causality in DILI and HILI cases should attempt this standardized approach using the updated CIOMS scale.