Ustekinumab Biotherapy and Real-Time Psoriasis Capacitance Mapping: A Pilot Study

In recent years, the treatment of moderate to severe psoriasis has benefited from the development of targeted biologicals. Assessing this new class of drugs calls for precise modalities of severity/improvement ratings of the disease. Bioengineering-driven dermometrology aims at improving objective and quantitative assessments of disease severity and treatment efficacy. Skin capacitance mapping/imaging is one of those emerging methods. Among its clinical applications, psoriasis capacitance mapping (PCM) was introduced in order to assess both skin scaliness and water trapping inside the stratum corneum (inflammatory serum deposits) on lesional skin. PCM was used for assessing the therapeutic effects of ustekinumab on target lesions of 5 psoriatic patients. The reduction in the inflammatory dampness of the stratum corneum was conveniently seen after a 1-month ustekinumab treatment. The present pilot study suggests that PCM could be used as a fast and convenient method for assessing the anti-inflammatory efficacy of ustekinumab and other biotherapies

The life expectancy gains from pharmaceutical drugs: a critical appraisal of the literature

Several studies suggest that, on the basis of life expectancy (LE) regressions, new pharmaceutical drugs are responsible for some of the marked gains in LE observed over the last 50 years. We critically appraise these studies. We point out several modeling issues, including disentangling the contribution of new drugs from advances in disease management, changes in the distribution of health care and other confounding factors. We suggest that the studies estimates of pharmaceutical productivity are implausibly high. Some of the models have very large forecast errors. Finally, the models that we replicated were found to be sensitive to seemingly innocuous changes in specification. We conclude that it is difficult to estimate the bio-medical determinants of LE using aggregate data. Analyses using individual level data or perhaps disease specific data will likely produce more compelling results.pharmaceuticals, life expectancy, health production, treatment effects

Politique des relations extérieures et identité politique : la stratégie des entités fédérées de Belgique

Cet article examine la « politique des relations extérieures » des composantes de l'État belge, qui se caractérise par un mélange de paradiplomatie et de diplomatie. Pour l'aborder, trois paramètres ont été sélectionnés : la politique étrangère, le pouvoir (capacité) régional et l'identité politique. Ce choix est justifié par l'affirmation, sur la scène internationale, d'une double identité politique (régionale et étatique) par les entités fédérées de Belgique. Cette étude, pour des raisons évidentes et propres au cas belge, met l'accent sur le prolongement international des facteurs internes. Elle montre combien la variable « identité politique » induit des stratégies internationales différenciées entre Régions et Communautés belges.This article examines the « external relations policy » of the components of the Belgian state, which is characterized by a mixture of para-diplomacy and diplomacy. To address this subject, three parameters have been selected: foreign policy, regional power (capacity), and political identity. This choice is justified by the assertion, on the international stage, of a double political identity (regional and state) by Belgium's federated entities. This study, for obvious reasons specific to Belgium's case, stresses the international extension of internal factors. It shows the extent to which the « political identity » variable induces international strategies that have become differentiated between Belgium's Regions and Communities

The Skin Ivory Spot. A Possible Indicator for Skinfield Photo-Carcinogenesis in Recreational Sunbed Addicts

Introduction: For a decade or so, artificial sources of restricted light wavelengths, particularly sunbeds, have progressively gained popularity among adolescents and young adults. Warnings were raised focusing on the risk of accelerated photoaging and photocarcinogenesis. The ULEV (ultraviolet light-enhanced visualization) method is a convenient noninvasive way identifying subtle pigmentary changes presenting as a mottled subclinical melanoderma (MSM). Of note, rare spotty amelanotic macules presenting as skin ivory spots (SIS) was reported on any part of the body. Subjects and method: This work is the first attempt at evaluating the changes in the MSM and SIS spots developed on the skin of 33 phototype III young women designated as avid users involved in frequent exposures to sunshine and sunbeds for lifestyle purposes for a duration of at least 120 months. Results: MSM was markedly heterogeneous and was distinctly obvious in the majority of adepts of frequent natural and artificial photoexposures. SIS was particularly developed in subjects presenting with severe MSM patterns. Discussion: MSM and SIS are more severe in subjects frequently exposed to sunbeds and sun exposures. These signs possibly represent a risk marker for field photocarcinogenesis

Thigmotropism of Malignant Melanoma Cells

During malignant melanoma (MM) progression including incipient metastasis, neoplastic cells follow some specific migration paths inside the skin. In particular, they progress along the dermoepidermal basement membrane, the hair follicles, the sweat gland apparatus, nerves, and the near perivascular space. These features evoke the thigmotropism phenomenon defined as a contact-sensing growth of cells. This process is likely connected to modulation in cell tensegrity (control of the cell shape). These specifically located paucicellular aggregates of MM cells do not appear to be involved in the tumorigenic growth phase, but rather they participate in the so-called “accretive” growth model. These MM cell collections are often part of the primary neoplasm, but they may, however, correspond to MM micrometastases and predict further local overt metastasis spread

Cell Proliferation in Cutaneous Malignant Melanoma: Relationship with Neoplastic Progression

The establishment of the diagnosis of cutaneous malignant melanoma (CMM) always calls for histopathological confirmation. Further to the recognition of the CMM aspects, immunohistochemistry is helpful, in particular, in determining the size of the replicative compartment and the activity in each of the cell cycle phases (G1, S, G2, M). The involvement of cancer stem cells and transient amplifier cells in CMM genesis is beyond doubt. The proliferation activity is indicative of the neoplastic progression and is often related to the clinical growth rate of the neoplasm. It allows to distinguish high-risk CMM commonly showing a high growth rate, from those CMMs of lower malignancy associated with a more limited growth rate. The recruitment and progression of CMM cells in the cell cycle of proliferation depend on mitogen-activated protein kinase (MAPK) pathway and result from a loss of control normally involving a series of key regulatory cyclins. In addition, the apoptotic pathways potentially counteracting any excess in proliferative activity are out of the dependency of specific regulatory molecular mechanisms. Key molecular components involved in the deregulation of the growth fraction, the cell cycle phases of proliferation, and apoptosis are presently described in CMM

Smouldering Malignant Melanoma and Metastatic Dormancy: An Update and Review

The fund of knowledge regarding the versatility of presentation of MM metastases is still quite incomplete. The recent literature pertaining to the current understanding of the mechanisms underlying two special features of MM metastasis is reviewed. On the one hand, a long disease-free interval (MM dormancy) may occur before the surge of overt metastases. On the other hand, the so-called MM smouldering phenomenon refers to the condition where regional metastases wax and wane for long periods of time on restricted skin regions. It is important to emphasize that local micrometastases often predict sentinel lymph node involvement but may not reflect progression of the primary MM to full-blown visceral metastatic competence. It is likely that a combination of factors impacts the versatile MM metastasic progression. Among the main factors, one has to mention the phenotypic heterogeneity and variability in the phenotype of MM cells, the presence of MM stem cells and MM cells engaged in an amplification proliferation pool, as well as the host immune response, and possibly the induction of a particular stromal structure and vascularity