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TP53 aberrations are a major predictive factor of resistance to chemoimmunotherapy in chronic lymphocytic leukemia (CLL), and an assessment of them before each line of treatment is required for theranostic stratification. Acquisition of subclonal TP53 abnormalities underlies the evolution of CLL. To better characterize the distribution, combination, and impact of TP53 variants in CLL, 1,056 TP53 variants collected from 683 patients included in a multicenter collaborative study in France were analyzed and compared to UMD_CLL, a dataset built from published articles collectively providing 5,173 TP53 variants detected in 3,808 patients. Our analysis confirmed the presence of several CLL-specific hotspot mutations, including a two-base pair deletion in codon 209 and a missense variant at codon 234, the latter being associated with alkylating treatment. Our analysis also identified a novel CLL-specific variant in the splice acceptor signal of intron 6 leading to the use of a cryptic splice site, similarly utilized by TP53 to generate p53psi, a naturally truncated p53 isoform localized in the mitochondria. Examination of both UMD_CLL and several recently released large-scale genomic analyses of CLL patients confirmed that this splice variant is highly enriched in this disease when compared to other cancer types. Using a TP53-specific single-nucleotide polymorphism, we also confirmed that copy-neutral loss of heterozygosity is frequent in CLL. This event can lead to misinterpretation of TP53 status. Unlike other cancers, CLL displayed a high proportion of patients harboring multiple TP53 variants. Using both in silico analysis and single molecule smart sequencing, we demonstrated the coexistence of distinct subclones harboring mutations on distinct alleles. In summary, our study provides a detailed TP53 mutational architecture in CLL and gives insights into how treatments may shape the genetic landscape of CLL patients.

2015 a été une année importante en dermatologie, principalement dans le domaine thérapeutique. De nouveaux traitements sont disponibles dans l'urticaire chronique, le psoriasis et les angiofibromes du visage dans le cadre de la sclérose tubéreuse de Bourneville. En dermato-oncologie, le traitement du carcinome basocellaire non opérable et celui du mélanome métastatique ont connu des avancées significatives. Enfin, la méthylisothiazolinone reste un allergène majeur responsable d'épidémies d'allergie de contact et pour lequel il est urgent d'instaurer une limitation de son usage au niveau européen., [Innovations] 2015 was an important year in dermatology, especially in the therapeutic area. New treatments are available for chronic urticaria, psoriasis and angiofibromas of the face in the tubrous sclerosis complex context. In dermato-oncology, treatments of advanced cases of basal cell carcinomas and metastatic melanomas have significally improved. Finally, methylisothiazolinone remains a major allergen, responsible for contact allergy epidemic and for which it is urgent to establish a limitation of its use at European level.

info:eu-repo/semantics/published

Antiseptics have broader spectrums of antimicrobial activity than antibiotics and a much lower risk of bacterial resistance selection. Antiseptics are therefore appropriate alternatives to antibiotics for the management of localized superficial skin infections. Povidone iodine has the broadest spectrum of antimicrobial activity of the available antiseptics, and has a rapid and persistent microbicidal effect. It is active against Gram-positive and -negative bacteria, bacterial spores, fungi, protozoa and several viruses, including H1N1 influenza virus (swine flu). It also has good skin tolerance, and is only a weak allergen: it is rarely associated with immediate allergic reactions, which are more prevalent with chlorhexidine. It has also been shown to promote wound healing. Although additional data are needed from well-designed clinical trials, povidone iodine 10% can be considered as a first-choice antiseptic for the prevention and treatment of superficial skin infections.

Background: Basal cell carcinoma (BCC) is the most common form of skin cancer worldwide. Different treatment options exist. The efficacy of photodynamic therapy with methyl aminolevulinate (MAL-PDT) has been established in several randomized controlled trials RCTs). Real life data can differ greatly from data derived from randomized controlled trials (RCTs). Objectives: To describe the results of a Belgian observational study concerning superficial BCC (sBCC) vis-a-vis clinical and health economic outcomes in order to evaluate the real-life practice of MAL-PDT. Methods: This study was a prospective, single-arm, open study conducted at eight dermatological institutions during six months after the first MAL-PDT treatment. Eligible patients had to present with lesions, suitable for MAL-PDT according to Belgian reimbursement criteria. Resource use was collected during the study period. Clinical Response (CR) and Cosmetic Outcome (CO), as well as cost of care were evaluated. A subset analysis of patients with sBCC only was conducted. Results: Ninety patients were identified for the analysis (mean age 65 years; 61% female). The mean number of lesions per patient was 1.6, mostly located on the face, the back and the chest. For the entire period, the mean number of visits to a dermatologist was 4 per patient including two MAL-PDT sessions. The average, cumulative amount of MAL used per treatment was 1,256 mg. Two patients experienced adverse events at the application site, none of them serious; all resolved completely. The CR rate was 89% at the end of the study. The CO was "excellent" or "good" in 96% of the patients. Total cost of care was (sic)289 ($414 U.S.) per patient. Cost per lesion was (sic)195 ($280 U.S.). Conclusion: The results from the real-life practice study confirm the efficacy found in prior, prospective randomized trials. About four visits and less than one tube of MAL are needed for the full treatment of sBCC in one patient.

Clinical trials have shown that photodynamic therapy using methyl aminolevulinate (MAL-PDT) is an effective treatment for actinic keratosis (AK), and nodular and superficial basal cell carcinoma (nBCC and sBCC) unsuitable for other available therapies. Economic evaluation models have shown that it is a cost effective intervention as well. The objectives of this prospective, observational, one arm study were (i) to verify in a real-life practice study the results obtained in previous clinical trials with MAL-PDT in the treatment of AK, nBCC and sBCC; (ii) to calculate the real-life cost of treatment and validate predictions from an economic evaluation model. Patients with AK and/or BCC were selected according to Belgian reimbursement criteria for treatment with MAL-PDT. Clinical response, cosmetic outcome and tolerability were assessed. MAL-PDT cost was calculated and compared to published model cost data. Data were collected from 247 patients (117 AK, 130 BCQ. A complete clinical response was obtained for 83% of AK (85/102) and BCC (97/116) patients. A good or excellent cosmetic outcome was obtained for 95% of AK patients and 93% of BCC patients. Tolerability was good: only 2 patients withdrew for adverse events. Clinical results were similar to previous studies. Total cost of care per patient was (sic)381 forAK, (sic)318 for nBCC, and (sic)298 for sBCC. Total cost per lesion was (sic)58 for AK (identical to model prediction), (sic)316 for nBCC and (sic)178 for sBCC (both within 20% of model prediction). The clinical results of MAL-PDT in this real-life practice study confirm those demonstrated in previous clinical trials. Costs calculated from this study confirm predicted cost-effectiveness in the original model for MAL-PDT in the management of AK and BCC.

Synthetically useful unsymmetrical bis-silyl or silylstannyl isobutene derivatives are conveniently prepared from selenoisobutene 5, a versatile equivalent of the isobutene dianion. Sequential treatment of this selenated compound with n-butyl-lithium and the required chlorosilanes or chlorostannanes leads efficiently to the corresponding functionalized isobutenes.

Lewis-acid catalysed ring-opening of functionalised (cyclopropyl)methylstannane 10, in the presence of aldehydes or ketones, was found to afford the corresponding aldol adducts in high yields. Subsequent lactonisation under acid catalysis led quantitatively to substituted exo-methylene-delta-valerolactones, some of them possessing a unique spirocyclic structure. (c) 2005 Elsevier Ltd. All rights reserved.

(Cyclopropyl)methylstannanes, substituted with an electron-withdrawing group, have been found to be effective homo-allylating reagents of aldehydes and ketones. The reaction proceeds by Lewis-acid catalyzed ring opening, followed by an aldol condensation of the resulting enolate, providing homoallylation products in excellent yields. The diastercoselectivity of the process was found to be highly dependent upon the temperature and the solvent, the reaction giving mainly anti adducts at -78 degrees C and syn compounds at 0 'C. (c) 2005 Elsevier Ltd. All rights reserved.

Enantiomerically pure syn-anti and syn-syn configured triol units are efficiently synthesized by the SnCl4 mediated allylation of chiral alpha-benzyloxyaldehydes with the uniquely functionalised allylstannane 9. Remarkably, the stereochemistry of the adducts is solely governed by the amount of Lewis acid employed. (C) 2004 Elsevier Ltd. All rights reserved.