👤 Thierry Lecomte

Despite awareness of polysubstance use-the co-use of multiple drugs-and its associated risks, there is a lack of research consensus on how to identify and classify individuals engaging in polysubstance use. Latent class analysis (LCA) and latent profile analysis (LPA) are data-driven approaches that may improve the identification and classification of polysubstance use. By clustering data using different indicators, LCA/LPA can extract subgroups of common drug use patterns within a sample. Variability in how LCA/LPA are conducted, however, can substantially impact how subgroups are extracted and have not been thoroughly reviewed. The present review was one of a two-part series preregistered on PROSPERO entitled, "A systematic review of studies using latent class analysis to examine patterns of polysubstance use in adults (Part 1) and adolescents (Part 2)" (CRD42022352293). The present review sourced relevant studies using LCA/LPA in the context of characterizing adult polysubstance use and identified factors influencing the number of latent classes extracted. Across several articles using LCA/LPA ( Show less

Small bowel adenocarcinoma is a rare disease. The genomic profiling tumours according to clinical characteristics and its impact on the prognosis remains unclear. A pooled analysis of clinical data, genomic profiling and MisMatch Repair (MMR) status from three databases was performed. A total of 188 tumour samples were analysed. A predisposing disease was reported in 22.3%, mainly Lynch syndrome and Crohn's disease. The tumours were localized in 80.2% and metastatic in 18.8%. The most frequent mutations were KRAS (42.0%) among them 7/79 are G12C, TP53 (40.4%), APC (19.1%), PIK3CA (18.6%), SMAD4 (12.8%) and ERBB2 (9.6%). Mutation distribution differed according to predisposing disease for TP53, ERBB2, IDH1, FGFR3, FGFR1 and KDR. KRAS and SMAD4 mutations were more frequent in metastatic tumour, whereas ERBB2 mutations were absent in metastatic tumour. For localized tumour, APC mutation was independently associated with a poor overall survival (OS) (p = 0.0254). 31.8% of localized tumours and 11.3% of metastatic tumours were dMMR (29.8% of the entire cohort). A dMMR status was associated with a better OS (HR = 0.61 [0.39-0.96], p = 0.0316). There is a different genomic profile according to the stage and predisposing disease. dMMR and APC mutation in localized tumour predict a better prognosis. Show less

Prostate cancer is the most common cancer among men and the development of new therapeutic agents is needed for its treatment and/or diagnosis. 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is involved in the production of androgens, which stimulates the proliferation of prostate cancer cells. Piperazinomethyl-androsterone sulfonamide derivatives were developed as 17β-HSD3 inhibitors and the concentration of a representative sulfonamide derivative (compound 1) was found to accumulate in prostate tumor tissues relatively to plasma in a mouse xenograft experiment. This finding gives us the opportunity to specifically target the prostate cancer tumors through the development of a radiolabelled version of compound 1 toward targeted molecular radiotherapy or radioimaging diagnosis. The chemical synthesis of fluorinated and iodinated analogs of compound 1 was achieved, leading to a series of compounds with similar levels of inhibition as the initial candidate. From 17β-HSD3 inhibition activity, molecular modeling and mouse plasma-concentration studies, the most promising compound of this series was selected, its Show less