Thyroid nodules were assessed by ultrasound in 3 621 presumably healthy free-living French subjects participating in the SU.VI.MAX cohort (2 160 females aged 35-60 years and 1 461 males aged 45-60 years). Urinary iodine was measured in all participants in random morning urine samples. Nodular thyroid structures ranging from 3 mm to 57 mm in diameter were found in 14.5% of the population, without significant differences between regions in the different age and sex groups. Single nodules and multiple lesions were found in, respectively, 9.7% and 3.1% of the subjects. In females, nodules increased from 12.9% to 19.2% between 35-45 years and 45-60 years, respectively (p<0.001). Thyroid nodularity was more frequent among women aged 45-60 years than among men of those ages (19.2% vs. 11.0%, p=0.001). Descriptive data provided by ultrasound differentiated the nodules into solid (43.4%), cystic (38.4%), and mixed solid-cystic (18.2%). Most solid thyroid nodules, 76.1%, were hypoechoic, while 16.6% were iso-, and 7.3% were hyperechoic. The median of iodine concentrations (n=3 276) was 8.0 microgram/100 ml, with 19.4% of the samples being<5 microgram/100 ml. Median iodine concentrations displayed wide regional variations, with values significantly higher in residents of western regions than among those living in the eastern areas (p<0.001), independently of age and sex. No relationship was found between prevalence of nodular thyroid structure and the state of borderline iodine status observed in France.

info:eu-repo/semantics/nonPublished

Vieillissement cutane : evaluations cliniques et bio-instrumentales, a propos de la vitamine C en topique P. Humbert Service de dermatologie, Laboratoire d'ingenierie et de biologie cutanees, CHU Saint-Jacques, 25000 Besancon. Les methodes de biometrologie Depuis l'introduction de la bio-ingenierie dans le domaine medical, la recherche dermatologique fondamentale [...]

From the evaluation of losses and savings, the authors specify, according to the reserves before pregnancy and the true diet intake, the indications for therapeutic supplement during pregnancy.

Cutaneous melanoma (CM) is the most aggressive form of skin cancer, and its worldwide incidence is rapidly increasing. Early stages can be successfully treated by surgery, but once metastasis has occurred, the prognosis is poor. However, some 5-10% of thick (≥2 mm) melanomas do not follow this scenario and run an unpredictable course. Little is known about the factors that contribute to metastasis in some patient with thick melanomas and the lack thereof in thick melanoma patients who never develop metastatic disease. We were therefore interested to study differential gene expression and pathway analysis and compare non-metastatic and metastatic thick melanomas. We found that the TNF-like weak inducer of apoptosis (TWEAK) pathway was upregulated in thick non-metastasizing melanomas. MAP3K14 (NIK1), BIRC2 (cIAP1), RIPK1, CASP7, CASP8, and TNF play an important role in inhibiting proliferation and invasion of tumor cells via the activation of the non-canonical NF-κB signaling pathway. In particular, this pathway sensitizes melanoma cells to TNF-alpha and activates the apoptosis module of the TWEAK pathway in thick non-metastasizing melanomas. Hence, our study suggests a potential role of the TWEAK pathway in inhibiting thick melanoma from metastasis. Exploitation of these genes and the pathway they control may open future therapeutic avenues.

Abstract Primary and acquired resistance to anti-PD-1 and CTLA-4 immunotherapies remains a major obstacle to improving the outcomes of cancer patients. This study utilized a combination of scRNAseq, CITE-seq, a method for CODEX, 40+ protein marker tissue imaging to characterize the molecular and spatial features of cells within melanoma biopsies of patients receiving anti-PD-1 and CTLA-4 immunotherapies. Analysis was conducted on melanoma biopsies taken pre-treatment, early during treatment (7-14 days) and after disease progression. Five patients underwent all analyses; three were responding, two had primary resistance and one had acquired resistance. Tissue dissociates underwent ssRNAseq along with CITE-seq, which incorporated 153+ antibodies to extensively define tumor and immune cell phenotypes. A separate portion of the same lesion underwent formalin fixation and paraffin embedding and was then analyzed using the CODEX high-multiplex imaging system to spatially localize 40+ markers in the tumor. The CODEX imaging system and processor (Akoya Biosciences) were used to generate multiplex images. HALO AI (Indica Labs) was used to perform cell segmentation and quantify single-cell marker expression of the 40+ markers. Tumor areas were classified into vasculature (CD34+/CD31+), melanoma (SOX10+) and stroma regions using the DenseNet deep learning classifier within HALO AI. The subsequent output contained single-cell expression, tissue classification and x and y location data, which were used to map to the CITE-seq data using the CamaraLab STvEA (Govek et al, biorix 2019) to identify CITE-seq defined populations within tissue sections. CODEX analysis of 2.2M cells revealed distinct immune phenotypes of tumor infiltrated cells compared to their peritumor counterparts, with a gradient in the upregulation of immunosuppressive and exhaustive signaling upon entering the tumor region. Changes in cellular populations during treatment were significantly related to the spatial location of the cells within the tumor. Treatment with immunotherapies causes a dynamic change in these profiles which relates to the development of tumor resistance. Citation Format: Camelia Quek, Ines P. Silva, Ghamdan Al-Eryani, Aaron Mayer, Nenad Bartonicek, Kate Harvey, Chi Buckley, Oliver Braubach, John F. Thompson, Jonathan R. Stretch, Robyn P M Saw, Kerwin F. Shannon, Alexander M. Menzies, Richard A. Scolyer, Georgina V. Long, Alexander Swarbrick, James S. Wilmott. CODEX highly multiplex image mapping to CITEseq datasets reveal the spatial dynamics of the TME during the development of acquired resistant in immunotherapy treated melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2761.

Abstract Purpose: The site of metastasis in advanced melanoma patients (pts) influences pt response to immunotherapy and overall prognosis. Liver mets are particularly resistant to immunotherapy and their presence often confers shorter survival and reduced response rates. This study characterised and compared the tumor immune microenvironment of melanoma mets at different anatomical sites. Methods: T-cell and myeloid cell markers were stained using multiplex IHC on FFPE samples from 136 untreated metastatic melanoma pts, from 5 anatomical sites (liver, lung, brain, subcutaneous, and lymph node (LN)). Cell densities, subpopulations and the spatial distribution of cells were compared between sites. Results: CD3+ T cell infiltration was less dense in the liver (med = 154.3 cells/mm2) and brain mets (med = 180.7 cells/mm2) v's lung (med = 434.7 cells/mm2) and LN mets (med = 504.8 cells/mm2) (p&amp;lt;0.05), and T-cells were further away from melanoma cells in liver v's lung mets (med distance = 83µm v's 57µm respectively; P&amp;lt;0.05). The liver displayed a unique T-cell profile, with a significantly lower proportion of CD3+ T cells expressing PD-1 (med = 0.7%) compared to all other sites (P&amp;lt;0.05) while brain mets expressed the highest proportion of PD-1+ T cells (med = 8.9%). There were higher proportions of Tim3+ T cells in liver (10.7%) and lung mets (12.9%) v's brain, subcut and LN mets (P&amp;lt;0.05). Specifically, in liver mets CD3+ T cells within 20um of a melanoma cell had a significantly higher expression of Tim3 (med = 18.57%) v's PD-1 (med = 2%). Brain mets had the lowest density of CD68+ macrophages (med = 33 cells/mm2) v's lung (med = 372 cells/mm2), liver (med = 290 cells/mm2) and Subcut mets (med = 154 cells/mm2). Lung mets also had the highest proportion of PD-L1+ macrophages (med = 18.73%) compared to liver (med = 5.2%) and brain mets (med = 0.65%). While the most highly expressed T cell population varied between sites, CD16+ macrophages were consistently the highest expressed macrophage subpopulation regardless of metastatic site. Conclusion: These data suggest that liver mets are less immunogenic, with fewer T cells and greater distances between CD3+ T cells and melanoma cells, and may account for the poor prognosis of melanoma patients with liver metastases and their reduced response rate to immunotherapy compared to other mets. While liver mets have reduced PD-1 expression, higher Tim3 expression in the liver may provide a therapeutic opportunity to improve outcomes for pts with liver mets by using anti-TIM3 immunotherapy. Overall, these data provide novel insights into the site-specific biology of melanoma mets, heterogeneity in the tumor immune microenvironment, and the need for site specific biomarkers to be considered when selecting treatment targets. Citation Format: Jordan W. Conway, Robert V. Rawson, James S. Wilmott, Georgina V. Long, Richard A. Scolyer, Inês Pires Da Silva. Spatial distribution and immune cell infiltration at different sites of melanoma metastases (mets) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2762.

The state of borderline iodine deficiency observed in France, in association with a slightly goitrogenic environment, may result in sustained stimulation of the thyroid, independently of TSH level, and is of paramount importance in the formation of goitre. Smoking may affect the thyroid, inducing marked long-lasting thyroid enlargement.