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Introduction: The severity of SARS-CoV-2 virus infection is mainly related to its respiratory complications. However, it can also lead to numerous and varied thromboembolic events. Symptoms may include headache, fever, and neurological disorders. Since 2020, the clinical presentation of COVID-19 infection have become increasingly varied, leading in some cases to complex symptom associations, including numerous neurological symptoms. SARS-CoV-2 may lead to neurotropism which could reach the central nervous system and all cranial nerves. Cavernous sinus thrombosis is a rare condition, occurring as a complication of an ear, nose, and throat (ENT) or facial infection. Case presentation: A 73-year-old man without personal or family history of thrombosis, was referred to the emergency room for a sudden appearance of diplopia and ptosis, 3 days after testing positive for COVID-19 infection. An initial head CT-scan found no signs of stroke. He underwent a cerebral MRI 7 days later, which revealed a thrombosis of his right cavernous sinus. A brain CT scan follow-up 7 days later showed regression of the thrombosis with complete recanalization of the cavernous sinus. This was accompanied by a complete regression of diplopia and fever. He was discharged from the hospital 10 days after hospital admission. Conclusions In this case report, we describe a rare event of cavernous thrombophlebitis following a COVID-19 infection.

International audience; Background While the effect of anti-TNFs on postoperative outcomes in patients with Crohn's disease (CD) has been widely studied, the impact of vedolizumab and ustekinumab on the risk of postoperative complications remains poorly known. Methods All consecutive patients who underwent intestinal resection for CD between July 2014 and April 2022 within 22 French centers were included in a retrospective cohort. The risk of early post-operative complications (≤30days) in patients exposed to biologics was compared to patients not exposed by logistic regression and propensity score-matched analysis adjusted for age, previous intestinal resection, corticosteroids or immunosuppressants exposure, disease activity, presence of abscess, urgent surgery and initial stoma (preoperative contra-indication to anastomosis). Results Among the 1201 patients included, respectively 491 (41%), 76 (6.3%) and 57 (4.7%) were exposed to anti-TNFs, ustekinumab, or vedolizumab within six months before surgery. A total of 317 (26.4%) patients had at least one complication of which 123 (38%) were considered as severe (DINDO III/IV). New surgery was necessary in 69 (5.7%) patients and secondary stoma in 23 (1.9%). Three deaths were observed (0.25%). The rates of overall complications in patients not exposed to biologics, exposed to anti-TNFs, ustekinumab or vedolizumab were respectively 26.1%, 25.1%, 34.7% and 29.8%. The risks of intra-abdominal infectious complications in these four groups were respectively 13.5%, 11.1%, 13.3% and 8.8%. In multivariate analysis, age [OR, 1.02 (1.01-1.04); p=0.004], disease activity [OR, 8.36 (1.79 – 149); p=0.037], the presence of an abscess [OR, 2.01 (1.25-3.20); p=0.004] and initial stoma [OR, 1.70 (1.10 –2.61); p=0.016] were significantly associated with intra-abdominal infectious complications. Conversely, preoperative enteral nutrition [OR, 0.12 (0.01 -0.59); p=0.040] was associated with a reduction in this risk. Exposure to anti-TNFs [OR, 0.80 (0.51-1.24); p=0.31], ustekinumab [OR, 1.17 (0.39-3.51); p=0.78] and vedolizumab [OR, 1.28 (0.32-5.17); p=0.72] within the 3 months before surgery were not associated with the risk of intra-abdominal infectious complications. Similar results were observed in patients exposed to these treatments in the month before surgery. Conclusion In this large cohort, a quarter of patients operated on for CD presented an early postoperative complication and 10% a severe complication. Preoperative exposure to anti-TNFs, vedolizumab or ustekinumab was not associated with an increased risk of early postoperative complications. Preoperative enteral nutrition was associated with a reduced risk of intra-abdominal infectious complication.

Les lacunes des armements francais ont ete mises en evidence pendant le conflit et des programmes de rattrapage ont alors ete lances, meme si certains n’ont pas abouti faute de financement. Le retard technologique a ete en partie comble, mais la course ne s’arrete plus desormais dans un environnement concurrentiel.

Background Subcutaneous infliximab (IFX-SC) was launched in France for the treatment of patients with inflammatory bowel disease (IBD) in 2021. Real-life and pharmacokinetic (PK) data after switching from intravenous infliximab (IFX-IV) to IFX-SC are needed. The PEREM study is a French multicenter prospective cohort aiming to describe the persistence of IFX-SC after switch from IFX-IV. Methods IBD patients in steroid-free clinical remission [Harvey Bradshaw Index (HBI) ≤ 4 for Crohn's disease (CD) and partial Mayo score (PMS) ≤ 2 with each subscore ≤ 1 for UC] for at least 6 months on IFX-IV therapy were proposed to switch to IFX-SC as part of routine care. Patients were included in 40 centers between Oct 2021 and May 2022. Clinical scores (HBI, PMS), biological samples (CRP and fecal calprotectin - FC), PK and anti IFX antibodies (ATI) were evaluated 3, 6, 12 and 24 months after switch. In case of IFX-SC discontinuation, time and reason for withdrawal were documented. Safety and adverse events of interest were recorded. The primary endpoint was IFX-SC persistence at 12 months. As not all patients met this primary endpoint at the time of writing this abstract, we present here the results at 6 months (M6). Results Among the 444 patients included [44% female, median age: 37 years (Min, Max: 18-88), 72% Crohn's], 71% were receiving IFX-IV at a dose of 5 mg/kg every 8 weeks and 84% were treated on monotherapy. Among the 417 patients analyzed, five withdrew their consent before the M6 visit and 324 were assessed at M6; 25/324 (7.7%) discontinued IFX-SC before M6 (seven for relapse, twelve for intolerance, two for pregnancy, four for unknown reasons) including one (0.3%) switch back to IFX-IV. Rate of survival without IFX-SC discontinuation at M6 was 92.6% (95% CI 89.3-95.1). Among the patients evaluated at M6, median clinical scores did not vary between inclusion and M6: HBI from 0 (IQR: 0-1) to 0 (IQR: 0-1), PMS from 0 (IQR: 0-0) to 0 (IQR: 0-0), respectively. The median CF and CRP levels were respectively 52 μg/g (IQR: 19-142) at inclusion and 37 μg/g (IQR: 14-129) at M6, and 1 mg/L (IQR: 1-4) at inclusion and 1 mg/L (IQR 0-4) at 6 months. At baseline, median infliximab levels were 6.6 μg/mL (min, max: 0-29) and 20 μg/mL (min, max: 0.3- 79.2) at M6. No major safety signals were recorded. Conclusion In a national real-life multicenter cohort, rate of persistence of IFX-SC after 6 months was 92.6% in IBD patients switched in remission, without significant clinical or biological changes. Treatment switch was associated with an increase in IFX levels. These data are confirming the good efficacy and safety of IFX-SC after switch.

Analysis of cochlear structures and postoperative temporal bone (TB) imaging are gaining importance in the evaluation of cochlear implantation (CI°). Our aims were to explore the microarchitecture of human cochlea using micro-computed tomography (μCT), analyze electrode's placement inside cochlea after CI°, and compare pre-/post-implantation μCT scans with cone-beam CT (CBCT) scans of same TBs.Cadaveric TBs were scanned using μCT and CBCT then underwent CI° using straight electrodes. Thereafter, they underwent again μCT and CBCT-imaging.Ten TBs were studied. μCT allowed visualization of scala tympani, scala vestibuli, basilar membrane, osseous spiral lamina, crista fenestrae, and spiral ligament. CBCT showed same structures except spiral ligament and crista fenestrae. After CI°, μCT and CBCT displayed the scalar location and course of electrode array within the cochlea. There were 7 cases of atraumatic electrode insertion and 3 cases of insertion trauma: basilar membrane elevation, electrode foldover with limited migration into scala vestibuli, and electrode kinking with limited migration into scala vestibuli. Insertion trauma was not correlated with cochlea's size or crista's maximal height but with round window membrane diameter. Resolution of μCT was higher than CBCT but electrode artifacts were similar.μCT was accurate in visualizing cochlear structures, and course and scalar position of electrode array inside cochlea with any possible trauma to cochlea or array. CBCT offers a good alternative to μCT in clinical practice for cochlear imaging and evaluation of CI°, with lower radiation and higher resolution than multi-slice CT. Difficulties related to non-traumatic CI° are multifactorial.

International audience; Background A clinical decision support tool (CDST) has been validated for predicting treatment effectiveness of vedolizumab (VDZ) in Crohn's disease. Aim To assess the utility of this CDST for predicting exposure-efficacy and disease outcomes. Methods Using data from three independent datasets (GEMINI, GETAID and VICTORY), we assessed clinical remission rates and measured VDZ exposure, rapidity of onset of action, response to dose optimisation and progression to surgery by CDST-defined response groups (low, intermediate and high). Results A linear relationship existed between CDST-defined groups, measured VDZ exposure, rapidity of onset of action and efficacy in GEMINI through week 52 (P < 0.001 at all time points across three CDST-defined groups). In GETAID, CDST predicted differences in clinical remission at week 14 (AUC = 0.68) and rapidity of onset of action (P = 0.04) between probability groups. The high-probability patients did not benefit from shortening of infusion intervals, and differences in onset of action between the high-intermediate and low-probability groups within GETAID were no longer significant when including low-probability patients who received a week 10 infusion. CDST predicted a twofold increase in surgery risk over 12 months of VDZ therapy among low- to intermediate-probability vs high-probability patients (adjusted HR 2.06, 95% CI 1.33-3.21). Conclusions We further extended the clinical utility of a previously validated VDZ CDST, which accurately predicts at baseline exposure-efficacy relationships and rapidity of onset of action and could be used to help identify patients who would most benefit from interval shortening and those most likely to require surgery while on active therapy.

Longtemps, la géographie est apparue comme seulement soucieuse de la description des lieux et, en conséquence, n’a donné que tardivement des études introspectives et épistémologiques sur la construction et le développement de la discipline et sur le rôle de ses grandes figures fondatrices, au tournant du siècle dernier, P. Vidal de la Blache, É. Reclus, É. Levasseur. Si les deux premiers cités sont indiscutablement des géographes, le troisième, plus oublié, venant de l’histoire économique, jo...

Simple Summary The gold standard method for the diagnosis of bladder cancer (BC) is the invasive and expensive cystoscopy. Telomerase reverse transcriptase (TERT) promoter mutations occur frequently (60–90%) in BC. In this study, we developed highly sensitive droplet digital PCR (ddPCR) assays for detecting low-allelic fraction TERT promoter mutations (C228T, C228A, CC242-243TT and C250T) in urinary cell-free and/or cell pellet DNA of BC patients and compared their performance with our previously established NGS-based assay (UroMuTERT) in two independent case-control studies: DIAGURO (n = 89 cases and n = 92 controls) and IPO-PORTO (n = 49 cases and n = 50 controls). The sensitivity and specificity of the ddPCR assays in detecting TERT promoter mutations in BC cases and controls were very high and comparable to the UroMuTERT assay. However, the technical and analytical simplicity of the ddPCR assays make them suitable candidates for clinical implementation. Abstract Somatic mutations in the telomerase reverse transcriptase (TERT) promoter regions are frequent events in urothelial cancer (UC) and their detection in urine (supernatant cell-free DNA or DNA from exfoliated cells) could serve as putative non-invasive biomarkers for UC detection and monitoring. However, detecting these tumor-borne mutations in urine requires highly sensitive methods, capable of measuring low-level mutations. In this study, we developed sensitive droplet digital PCR (ddPCR) assays for detecting TERT promoter mutations (C228T, C228A, CC242-243TT, and C250T). We tested the C228T and C250T ddPCR assays on all samples with sufficient quantity of urinary DNA (urine supernatant cell-free DNA (US cfDNA) or urine pellet cellular DNA (UP cellDNA)) from the DIAGURO (n = 89/93 cases and n = 92/94 controls) and from the IPO-PORTO (n = 49/50 cases and n = 50/50 controls) series that were previously screened with the UroMuTERT assay and compared the performance of the two approaches. In the DIAGURO series, the sensitivity and specificity of the ddPCR assays for detecting UC using either US cfDNA or UP cellDNA were 86.8% and 92.4%. The sensitivity was slightly higher than that of the UroMuTERT assay in the IPO-PORTO series (67.4% vs. 65.3%, respectively), but not in the DIAGURO series (86.8% vs. 90.7%). The specificity was 100% in the IPO-PORTO controls for both the UroMuTERT and ddPCR assays, whereas in the DIAGURO series, the specificity dropped for ddPCR (92.4% versus 95.6%). Overall, an almost perfect agreement between the two methods was observed for both US cfDNA (n = 164; kappa coefficient of 0.91) and UP cellDNA (n = 280; kappa coefficient of 0.94). In a large independent series of serial urine samples from DIAGURO follow-up BC cases (n = 394), the agreement between ddPCR and UroMuTERT was (i) strong (kappa coefficient of 0.87), regardless of urine DNA types (kappa coefficient 0.89 for US cfDNA and 0.85 for UP cellDNA), (ii) the highest for samples with mutant allelic fractions (MAFs) > 2% (kappa coefficient of 0.99) and (iii) only minimal for the samples with the lowest MAFs (< 0.5%; kappa coefficient 0.32). Altogether, our results indicate that the two methods (ddPCR and UroMuTERT) for detecting urinary TERT promoter mutations are comparable and that the discrepancies relate to the detection of low-allelic fraction mutations. The simplicity of the ddPCR assays makes them suitable for implementation in clinical settings.

International audience; Background & aims - Few data are available on the effects of tumor necrosis factor (TNF) antagonist therapy for patients with internal fistulizing Crohn's disease (CD) and there is debate regarding the risk of abscess. We aimed to assess the long-term efficacy and safety of anti-TNF therapy for patients with internal fistulas. Methods - We performed a retrospective study of data collected from the Groupe d'Etude Thérapeutique des Affections Inflammatoires Digestives trial, from January 1, 2000, through December 31, 2017. Our final analysis included 156 patients who began treatment with an anti-TNF agent for CD with internal fistula (83 men; median disease duration, 4.9 y). The primary end point was the onset of a major abdominal surgery. Secondary analysis included disappearance of the fistula tract during follow-up evaluation and safety. The Kaplan-Meier method was used for statistical analysis. Results - After a median follow-up period of 3.5 years, 68 patients (43.6%) underwent a major abdominal surgery. The cumulative probabilities for being surgery-free were 83%, 64%, and 51% at 1, 3, and 5 years, respectively. A concentration of C-reactive protein >18 mg/L, an albumin concentration

Background and study aims Capsule endoscopy (CE) is the preferred method for small bowel (SB) exploration. With a mean number of 50,000 SB frames per video, SBCE reading is time-consuming and tedious (30 to 60 minutes per video). We describe a large, multicenter database named CAD-CAP (Computer-Assisted Diagnosis for CAPsule Endoscopy, CAD-CAP). This database aims to serve the development of CAD tools for CE reading. Materials and methods Twelve French endoscopy centers were involved. All available third-generation SB-CE videos (Pillcam, Medtronic) were retrospectively selected from these centers and deidentified. Any pathological frame was extracted and included in the database. Manual segmentation of findings within these frames was performed by two pre-med students trained and supervised by an expert reader. All frames were then classified by type and clinical relevance by a panel of three expert readers. An automated extraction process was also developed to create a dataset of normal, proofread, control images from normal, complete, SB-CE videos. Results Four-thousand-one-hundred-and-seventy-four SB-CE were included. Of them, 1,480 videos (35 %) containing at least one pathological finding were selected. Findings from 5,184 frames (with their short video sequences) were extracted and delimited: 718 frames with fresh blood, 3,097 frames with vascular lesions, and 1,369 frames with inflammatory and ulcerative lesions. Twenty-thousand normal frames were extracted from 206 SB-CE normal videos. CAD-CAP has already been used for development of automated tools for angiectasia detection and also for two international challenges on medical computerized analysis.

Detection of molecular alterations in lung cancer bone metastasis (LCBM) is particularly difficult when decalcification procedure is needed. The Idylla™ real-time (RT)-PCR is compared to the routine method used in our laboratory, which combines next generation and Sanger sequencing, for the detection of EGFR mutations in LCBM.LCBM subjected to EDTA or formic acid decalcification were analysed for EGFR mutational status using two methods: first, the Ion Torrent Ampliseq next generation sequencing (NGS) assay +/- Sanger sequencing was used prospectively; then, the fully-automated, RT-PCR based molecular testing system Idylla™ EGFR Mutation Test was applied retrospectively.Out of the 34 LCBM assayed, 14 (41.2%) were unsuitable for NGS analysis and five remained unsuitable after additional Sanger EGFR sequencing (5/34, 14.7%). Using Idylla™, valid results were observed for 33/34 samples (97.1%). The concordance between the NGS +/- Sanger sequencing method and the RT-PCR method was 89.7% (26/29), one false positive EGFR S768I mutation and two false negative results were observed using Idylla™; one of these false negative cases was diagnosed by Sanger sequencing with a rare exon 19 EGFR mutation not covered by the Idylla™ EGFR Mutation Test design.Detection of EGFR mutations in decalcified LCBM is challenging using NGS, more than half of samples showing invalid results. Alternative methods should thus be preferred to spare clinical samples and decrease delay. The Idylla™ EGFR Mutation Test shows a good performance on decalcified bone samples and could be used as a first step. In case of negative results, a sequencing approach is mandatory to check the presence of rare EGFR mutations sensitive to EGFR tyrosine kinase inhibitors. Keywords: Lung carcinoma, EGFR mutation, Bone metastases, Decalcification, Tyrosine kinase inhibitor

Highlights • Molecular status determination following decalcification procedures is challenging. • The Idylla™ EGFR assay demonstrates good performance on decalcified bone samples. • The choice of EGFR assay should be adapted to patient and sample specificities., Detection of molecular alterations in lung cancer bone metastasis (LCBM) is particularly difficult when decalcification procedure is needed. The Idylla™ real-time (RT)-PCR is compared to the routine method used in our laboratory, which combines next generation and Sanger sequencing, for the detection of EGFR mutations in LCBM. LCBM subjected to EDTA or formic acid decalcification were analysed for EGFR mutational status using two methods: first, the Ion Torrent Ampliseq next generation sequencing (NGS) assay +/- Sanger sequencing was used prospectively; then, the fully-automated, RT-PCR based molecular testing system Idylla™ EGFR Mutation Test was applied retrospectively. Out of the 34 LCBM assayed, 14 (41.2%) were unsuitable for NGS analysis and five remained unsuitable after additional Sanger EGFR sequencing (5/34, 14.7%). Using Idylla™, valid results were observed for 33/34 samples (97.1%). The concordance between the NGS +/- Sanger sequencing method and the RT-PCR method was 89.7% (26/29), one false positive EGFR S768I mutation and two false negative results were observed using Idylla™; one of these false negative cases was diagnosed by Sanger sequencing with a rare exon 19 EGFR mutation not covered by the Idylla™ EGFR Mutation Test design. Detection of EGFR mutations in decalcified LCBM is challenging using NGS, more than half of samples showing invalid results. Alternative methods should thus be preferred to spare clinical samples and decrease delay. The Idylla™ EGFR Mutation Test shows a good performance on decalcified bone samples and could be used as a first step. In case of negative results, a sequencing approach is mandatory to check the presence of rare EGFR mutations sensitive to EGFR tyrosine kinase inhibitors.