Development of an enhanced burr accumulation model during orthogonal cutting of nickel-based super alloy

Burr size is a real issue in aeronautic for machining highly critical parts, such as broaching of turbine disks, it may affect the mechanical resistance of the part. However, the analysis and modelling of the burr formation and its accumulation is challenging due to the small concerned root area and the change of its shape after multiple cuts. In the state of the art, there is not much contribution on the burr mechanism during accumulation. To investigate this subject on nickel-based super alloy parts, an experiment with an in situ camera and LASER profilometer has been developed to follow the burr growth after multiple passes. Then, a phenomenological model of burr accumulation is formulated based on the description of a plastic hinge appearance during burr formations. It enables the modelling of burr height, root thickness and added material to the burr after each pass. Burr fracture occurrence is also discussed. This work proposes a new outlook on the burr formation mechanism and complete the models previously developed in the known literature

A simplified table using validated diagnostic criteria is effective to improve characterization of colorectal polyps: the CONECCT teaching program

International audienceIntroduction and study aims Accurate real-time endoscopic characterization of colorectal polyps is key to choosing the most appropriate treatment. Mastering the currently available classifications is challenging. We used validated criteria for these classifications to create a single table, named CONECCT, and evaluated the impact of a teaching program based on this tool.Methods A prospective multicenter study involving GI fellows and attending physicians was conducted. During the first session, each trainee completed a pretest consisting in histological prediction and choice of treatment of 20 colorectal polyps still frames. This was followed by a 30-minute course on the CONECCT table, before taking a post-test using the same still frames reshuffled. During a second session at 3 – 6 months, a last test (T3 M) was performed, including these same still frames and 20 new ones.Results A total 419 participants followed the teaching program between April 2017 and April 2018. The mean proportion of correctly predicted/treated lesions improved significantly from pretest to post-test and to T3 M, from 51.0 % to 74.0 % and to 66.6 % respectively (P < 0.001). Between pretest and post-test, 343 (86.6 %) trainees improved, and 153 (75.4 %) at T3 M. Significant improvement occurred for each subtype of polyp for fellows and attending physicians. Between the two sessions, trainees continued to progress in the histology prediction and treatment choice of polyps CONECCT IIA. Over-treatment decreased significantly from 30.1 % to 15.5 % at post-test and to 18.5 % at T3 M (P < 0.001).Conclusion The CONECCT teaching program is effective to improve the histology prediction and the treatment choice by gastroenterologists, for each subtype of colorectal polyp

Characteristics and treatment options of glucagonomas: a national study from the French Group of Endocrine Tumors and ENDOCAN-RENATEN network

International audienceOBJECTIVE: Glucagonoma is a very rare functional pancreatic neuroendocrine tumor (PanNET). We aimed to provide data on the diagnosis, prognosis, and management of patients with glucagonoma. DESIGN AND METHODS: In this retrospective national cohort, we included all patients with glucagonoma, defined by at least one major criterion (necrolytic migratory erythema (NME) and/or recent-onset diabetes and/or weight loss ≥ 5 kg) associated with either glucagonemia &gt;2xULN or positive glucagon immunostaining. Antisecretory efficacy was defined as partial/complete resolution of glucagonoma symptoms. Antitumor efficacy was assessed according to the time to next treatment (TTNT). RESULTS: Thirty-eight patients were included with median age 58.7 yo, primary PanNET located in the tail (68.4%), synchronous metastases (63.2%). Median Ki-67 index was 3%. Most frequent glucagonomas symptoms at diagnosis were NME (86.8%), weight loss (68.4%) and diabetes (50%). Surgery of the primary PanNET was performed in 76.3% of cases, mainly with curative intent (61.5%). After surgery, complete resolution of NME was seen in 93.8% (n = 15/16). The secretory response rates were 85.7%, 85.7%, 75% and 60% with surgery of metastases (n = 6/7), chemotherapy (n = 6/7), liver-directed therapy (n = 6/8) and somatostatin analogues (n = 6/10), respectively. All lines combined, longer TTNT was reported with chemotherapy (20.2 months). Median overall survival was 17.3 years. The Ki-67 index &gt;3% was associated with shorter OS (HR 5.27, 95%CI [1.11-24.96], p = 0.036). CONCLUSION: Patients with glucagonoma had prolonged survival, even in the presence of metastases at diagnosis. Curative-intent surgery should always be considered. Chemotherapy, PRRT or liver-directed therapy seem to provide both substantial antitumor and antisecretory efficacy

The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors

IF 12.589International audienceBackgroundImmune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore.MethodsThe expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI). Their associations with patient survival were analyzed by Cox models, taking into account the microsatellite instability (MSI) status and affiliation with various Consensus Molecular Subgroups (CMS). PD-L1 and CD8 expression were examined on a subset of tumors with immunohistochemistry. All statistical tests were two-sided.ResultsThe expression of Immunoscore-like metagenes was statistically significantly associated with improved outcome in non-MSI tumors displaying low levels of both CTLs and immune checkpoints (ICKs; CMS2 and CMS3; hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.43 to 0.92, P = .02; and HR = 0.55, 95% CI = 0.34 to 0.90, P = .02, respectively), but clearly had no prognostic relevance in CRCs displaying higher levels of CTLs and ICKs (CMS1 and CMS4; HR = 0.46, 95% CI = 0.10 to 2.10, P = .32; and HR = 1.13, 95% CI = 0.79 to 1.63, P = .50, respectively), including MSI tumors. ICK metagene expression was statistically significantly associated with worse prognosis independent of tumor staging in MSI tumors (HR = 3.46, 95% CI = 1.41 to 8.49, P = .007). ICK expression had a negative impact on the proliferation of infiltrating CD8 T cells in MSI neoplasms (median = 0.56 in ICK low vs median = 0.34 in ICK high, P = .004).ConclusionsICK expression cancels the prognostic relevance of CTLs in highly immunogenic colon tumors and predicts a poor outcome in MSI CRC patients

Development of primary early-onset colorectal cancers due to biallelic mutations of the FANCD1/BRCA2 gene

International audienceFanconi anaemia (FA) is characterized by progressive bone marrow failure, congenital anomalies, and predisposition to malignancy. In a minority of cases, FA results from biallelic FANCD1/BRCA2 mutations that are associated with early-onset leukaemia and solid tumours. Here, we describe the clinical and molecular features of a remarkable family presenting with multiple primary colorectal cancers (CRCs) without detectable mutations in genes involved in the Mendelian predisposition to CRCs. We unexpectedly identified, despite the absence of clinical cardinal features of FA, a biallelic mutation of the FANCD1/BRCA2 corresponding to a frameshift alteration (c.1845_1846delCT, p.Asn615Lysfs*6) and a missense mutation (c.7802A>G, p.Tyr2601Cys). The diagnosis of FA was confirmed by the chromosomal analysis of lymphocytes. Reverse transcriptase (RT)-PCR analysis revealed that the c.7802A>G BRCA2 variation was in fact a splicing mutation that creates an aberrant splicing donor site and results partly into an aberrant transcript encoding a truncated protein (p.Tyr2601Trpfs*46). The atypical FA phenotype observed within this family was probably explained by the residual amount of BRCA2 with the point mutation c.7802A>G in the patients harbouring the biallelic FANCD1/BRCA2 mutations. Although this report is based in a single family, it suggests that CRCs may be part of the tumour spectrum associated with FANCD1/BRCA2 biallelic mutations and that the presence of such mutations should be considered in families with CRCs, even in the absence of cardinal features of FA

High-Dose Dexamethasone and Oxygen Support Strategies in Intensive Care Unit Patients With Severe COVID-19 Acute Hypoxemic Respiratory Failure

International audienc