Université de Rouen Normandie

Background Pancreatic enucleation is indicated for selected patients and tumours with very low oncological risk to preserve a maximum of healthy pancreatic parenchyma. Minimally invasive pancreatic enucleation (MIPE) is increasingly performed. This study aims to assess the impact of tumor location and center experience on textbook outcomes (TBO) in patients undergoing MIPE. Methods Retrospective nationwide multicentric cohort study including MIPE performed between 2010 and 2021. Tumor localization was classified as head/uncus, neck or body/tail (results are presented in this order). Centers were classified according to a mean volume of MI pancreatectomies performed per year: lower (< 5/year), intermediate (5 to 10/year) and higher volume (≥ 10/year). TBO was defined as meeting all 6 criteria: no postoperative pancreatic fistula (POPF), no post-pancreatectomy haemorrhage (PPH), no bile leak, no readmission, no mortality, and no severe morbidity. Results 27 participating centers performed 200 MIPE located in head/uncus (n = 65, 33%), neck (n = 26, 13%) and body/tail (n = 109, 55%), 8% of them performed by robotic approach. Mortality reached 1.5% (n = 3). Head/uncus lesions were larger (p = 0.03), frequently BD-IPMN (p = 0.04), with significant longer operative time (p = 0.002). TBO achievement was high across all tumor locations (52 vs. 73 vs. 67%, p = 0.09) with higher PPH (p = 0.03) or bile leaks (p = 0.03) for head/uncus lesions. In multivariate analysis, overweight (OR 0.49), preoperative biopsy (OR 0.41) and head/uncus lesion (OR 0.34) were independently associated with lower TBO. No independent risk factor was found for POPF or severe morbidity. While expertise level influenced indications, with more cystic lesions (p = 0.002), larger tumors (p = 0.003), 3D use (p = 0.001), and head/uncus lesions (p = 0.04) in high volume centers, TBO was not significantly different (p = 0.45). Conclusions MIPE is feasible with 1.5% mortality whatever its localization with higher morbidity for head/uncus lesions, justified by the will to avoid pancreaticoduodenectomy. High volume centers push the limits of MIPE without increasing morbidity.

Introduction Conductive disturbances requiring permanent pacemaker (PPM) implantation remain a major concern after transcatheter aortic valve implantation (TAVI). Aims To assess the impact of aortic valve calcium score (AVCS) on conductive disturbances requiring PPM after TAVI. Methods All patients who underwent TAVI with accessible AVCS from the preprocedural CT scan report were included in this retrospective single-centre study. The primary endpoint was the occurrence of a conductive disturbance requiring PPM at 30 days. The association between PPM and AVCS, with its incremental prognostic value, was analysed using multivariable logistic regression, receiver operating characteristic curve analysis and likelihood ratio (LR) test. Results We included 761 patients of which 125 (16%) required PPM at 30 days. AVCS score was significantly higher in patients requiring PPM (3788 (2487–5218) vs 3050 (2043–4367) AU, p<0.001). Using multivariable analysis, preprocedural right bundle branch block (RBBB) (OR 6.61, 95% CI 3.82 to 11.5, p<0.001), first atrioventricular block (OR 1.71, 95% CI 1.03 to 2.83, p=0.037), self-expanding valve (OR 3.25, 95% CI 1.17 to 9.09, p=0.025) and AVCS>4510 AU (OR 1.83, 95% CI 1.04 to 3.20, p=0.035) were independently associated with PPM. AVCS had an incremental discriminative value (C-index 0.79 vs 0.77, LR test p=0.036) over and above traditional PPM risk factors. An algorithm was proposed based on the initial presence of RBBB, AVCS and the type of implanted valve. Conclusion Even if RBBB remained the strongest predictor of PPM post-TAVI, this study suggests that a high AVCS may help identifying patients at increased risk of PPM after TAVI, especially among those without pre-existing RBBB.

We introduce mechanochemical deracemization (MCDR) as a novel strategy for obtaining enantiopure compounds. This study demonstrates the successful transposition of six archetypical deracemization reactions from a solvent‐based to a solvent‐minimized ball milling environment. The scope includes a ketone, isoindolinones, imines, an ester, and an inorganic compound, all of which deracemized successfully. Key parameters such as milling material, ball number and size, the use of a bulk material and liquid‐assisted grinding (LAG) were systematically investigated, revealing their crucial role. Quantitative enantiomeric excesses (ee) were achieved, while reaction times were reduced by up to 97 % and solvent consumption by as much as 100 %. This work establishes MCDR as a versatile, sustainable pathway to enantiopure compounds. By highlighting the generalizability of this approach and its huge potential for minimizing waste, this study provides the foundation for future advancements in mechanochemical deracemization.

Information extraction from handwritten documents involves traditionally three distinct steps: Document Layout Analysis, Handwritten Text Recognition, and Named Entity Recognition. Recent approaches have attempted to integrate these steps into a single process using fully end-to-end architectures. Despite this, these integrated approaches have not yet matched the performance of language models, when applied to information extraction in plain text. In this paper, we introduce DANIEL (Document Attention Network for Information Extraction and Labelling), a fully end-to-end architecture integrating a language model and designed for comprehensive handwritten document understanding. DANIEL performs layout recognition, handwriting recognition, and named entity recognition on full-page documents. Moreover, it can simultaneously learn across multiple languages, layouts, and tasks. For named entity recognition, the ontology to be applied can be specified via the input prompt. The architecture employs a convolutional encoder capable of processing images of any size without resizing, paired with an autoregressive decoder based on a transformer-based language model. DANIEL achieves competitive results on four datasets, including a new state-of-the-art performance on RIMES 2009 and M-POPP for Handwriting Text Recognition, and IAM NER for Named Entity Recognition. Furthermore, DANIEL is much faster than existing approaches. We provide the source code and the weights of the trained models at https://github.com/Shulk97/daniel.

Background Li-Fraumeni syndrome (LFS) predisposes individuals to a wide range of cancers from childhood onwards, underscoring the crucial need for accurate interpretation of germline TP53 variants for optimal clinical management of patients and families. Several unclassified variants, particularly those potentially affecting splicing, require specialised testing. One such example is the NM_000546.6:c.1101-2A>C (rs587781664) variant, located at the splice acceptor site of the last intron of TP53 , identified in a female patient with breast cancer diagnosed in her 20s. Methods To interpret this variant, which has been classified as a variant of uncertain significance (VUS), we developed specific assays including a p53 functional assay, RT-QMPSF, Splice and Expression Analyses by exon Ligation and High-Throughput Sequencing and long RT-droplet digital PCR. Results We demonstrated a loss of p53 transcriptional activity, and a half reduction in TP53 mRNA expression. Additionally, we detected the use of a novel alternative last exon downstream of exon 11, which we have named exon 12. This transcript, typically detectable at low levels in most individuals, was found to be more highly expressed in the c.1101-2A>C carrier, predominantly transcribed from the mutant allele due to the disruption of the splice acceptor site in intron 10. Conclusion By combining these approaches, we successfully reclassified this intronic VUS as ‘pathogenic’, enabling appropriate genetic counselling for the patient and her family. Additionally, we identified a novel TP53 alternative transcript that is expressed in both physiological and pathological contexts, with heightened expression in the patient with LFS. This discovery provides a basis for further investigation into the role of TP53 isoforms in LFS oncogenesis.

The use of multiagent FOLFIRINOX chemotherapy for pancreatic adenocarcinoma in a neoadjuvant setting has been associated with an increased rate of complete pathological response (CPR) after surgery. This study investigated the long-term outcomes of patients with CPR in a multicenter setting to identify prognostic factors for overall survival (OS) and recurrence-free survival (RFS). This retrospective cohort study examined biopsy-proven pancreatic adenocarcinomas with CPR after neoadjuvant chemotherapy or chemoradiotherapy and surgery, between January 2006 and December 2023 across 22 French and 2 Belgian centers. Cox analyses were used to identify prognostic factors of OS and RFS. There were 101 patients with CPR after chemotherapy (n = 58, 57.4%) and chemoradiotherapy (n = 43, 42.6%) followed by surgery. Neoadjuvant FOLFIRINOX was used in 90% of patients. The median OS after surgery was 177 months (95% confidence interval (CI) 58.9–177 months) with 1-, 3-, 5-, and 10-year OS rates of 93%, 75%, 63%, and 51%, respectively. The median RFS was 67.8 months (95% CI:34.4–NR) with 1-, 3-, 5-, and 10-year RFS rates of 83%, 58%, 54%, and 49%, respectively. The multivariate Cox analysis of OS and RFS showed that preoperative radiotherapy was an independent negative prognostic factor for OS (hazard ratio (HR) 2.51; 95% CI 1.00–6.30; p = 0.03) and RFS (HR 2.62; 95% CI 1.27–5.41; p = 0.009). Complete pathologic response after neoadjuvant treatment is associated with remarkable long-term survival that is usually not seen after the resection of pancreatic adenocarcinomas. One-third of the patients still experienced disease recurrence, which was more common in those receiving preoperative chemoradiotherapy.

Background: Spinal cord injury and stroke are neurological disorders that lead to aerobic deconditioning and increased likelihood of cardiovascular disease. Sessions of at least 20 minutes of moderate-to-vigorous intensity exercise is recommended but decreased mobility limits engagement in such exercise. The aim of the study was to assess whether individuals can achieve exercise recommendations with the assistance of an end-effector robot assisted gait trainer (E-RAGT). Methods: We conducted an observational study during which participants were required to complete one exercise session on an E-RAGT. Heart rate, dyspnea, lower limb fatigue and enjoyment were monitored. Based on current guidelines, participants were considered to have reached exercise recommendations if they reached prespecified intensity thresholds for at least 20 minutes. Results: Five people with spinal cord injury and ten people with stroke agreed to participate. Every participant was able to reach moderate-to-vigorous exercise intensity and 3 out of 5 participants with spinal cord injury and 4 out of 10 participants with stroke were able to maintain this intensity for at least 20 minutes. Overall, participants rated their session as very enjoyable with a median score of 4 out of 5 on a Likert Scale (IQR 3 to 4). Discussion: Individuals with spinal cord injury or stroke who use an E-RAGT can reach moderate-to-vigorous exercise intensity, but not all are able to maintain this intensity of exercise according to disease-specific recommendations. Future research should explore the effectiveness of a training program using an E-RAGT.

Résumé Dans l’utilitarisme benthamien, le calcul, en fournissant une commensurabilité entre les langues, n’assure-t-il pas une universalité qu’aucune langue ne paraît pouvoir assurer par elle-même en raison de son inévitable contingence dont on s’aperçoit quand on la confronte avec les autres langues ? Une difficulté apparaît lorsqu’on prend en compte que Bentham a autant insisté sur l’aspect « calcul » de sa doctrine que sur ses aspects d’« utilité » et de « plaisir ». Si l’on veut bien reconnaître que les affects soient radicalement dépendants des langues, faut-il dire que les calculs dépendent aussi des langues et que « deux plus deux égale quatre » est une affaire de langage ? Pour obtenir une concordance entre langue vernaculaire, langue savante, plaisir et calcul, le relativisme de Bentham n’a-t-il pas été contraint d’aller jusque-là ? Toutefois, Bentham n’en reste pas à cette antinomie ; le but de la présente recherche est de montrer comment elle se résout.

Background: The artificial urinary sphincter has been an effective treatment for stress urinary incontinence caused by intrinsic sphincter deficiency in women. However, the use of this device has been limited by the technical difficulties and risks associated with the open implantation procedure. Preliminary studies using robotic techniques have shown promising results, but only one small study has compared robotic to open procedures. This study aims to compare the outcomes of robotic and open artificial urinary sphincter implantation in women with stress urinary incontinence due to intrinsic sphincter deficiency in a large multicenter cohort. Methods: Data were collected retrospectively from female patients who underwent open or robot-assisted artificial urinary sphincter implantation from 2006 to 2020 at 12 urology departments. The primary outcome was the rate of complications within 30 days after surgery, graded using the Clavien-Dindo Classification. Perioperative and functional outcomes were compared between the two groups. Results: A total of 135 patients were included, with 71 in the robotic group and 64 in the open group. The open group had a higher rate of intraoperative complications (27.4% vs. 12.7%; p = 0.03) and postoperative complications (46.8% vs. 15.5%; p < 0.0001). More patients in the robotic group achieved full continence (83.3% vs. 62.3%; p = 0.01). The open group had higher explantation (27.4% vs. 1.4%; p < 0.0001) and revision rates (17.5% vs. 5.6%; p = 0.02). The estimated 1-year explantation-free survival rate was higher in the robotic group. (98.6% vs. 78.3%; p = 0.001). Conclusions: Robot-assisted implantation may reduce perioperative morbidity and improve functional outcomes compared to open implantation in women with stress urinary incontinence.

In a European context of continuous urban expansion, even where population is declining, it is important to visualize and understand urban forms for informed urban planning, in the face of environmental and sustainability challenges. This study focuses on intra- and inter-urban scales through a center-periphery analysis using scaling laws. We develop and describe a web application to visualize the spatial distribution of artificial land use as a function of the distance to the city center and of city size. Using urban scaling laws, we eliminate the size effect to allow meaningful comparisons between cities. Indeed, after rescaling distances from the town hall, European cities show very similar patterns of land use in 2018. Our interactive tool allows users to visualize the land use profiles of 785 European cities and to compare them, irrespective of their size. The application also provides a center-periphery outlook on urban fabric, industry and roads, and is intended as a practical input for European planners. This visualization of urban land use reveals for instance specific national differences. French cities are generally more artificialized than the European average, while Spanish cities are less so.

The sulfur‐containing chemical warfare agents sulfur mustard HD and nerve agent VX are highly toxic and persistent in the environment. Therefore, their neutralisation requires harsh oxidation conditions, but also precise selectivity. Here we report the safe and effective detoxification of surrogates CEES and PhX by selective oxidation of the sulfur atom by generating peracetic acid from AcOEt and aq. H2O2 assisted by the supported lipase CALB. Morever, it is possible to perform these neutralisations with safe ‘on demand’ generation of AcOOH in a flow system by using a packed bed reactor containing the supported biocatalyst.

Introduction Chronic nausea and vomiting are symptoms of a wide range of gastrointestinal and non‐gastrointestinal conditions. Diagnosis can be challenging and requires a systematic and well‐structured approach. If the initial investigation for structural, toxic and metabolic disorders is negative, digestive motility and gut‐brain interaction disorders should be assessed. United European Gastroenterology (UEG) and the European Society for Neurogastroenterology and Motility (ESNM) identified the need for an updated, evidence‐based clinical guideline for the management of chronic nausea and vomiting. Methods A multidisciplinary team of experts in the field, including European specialists and national societies, participated in the development of the guideline. Relevant questions were addressed through a literature review and statements were developed and voted on according to a Delphi process. Results Ninety‐eight statements were identified and voted following the Delphi process. Overall agreement was high, although the grade of scientific evidence was low in many areas. Disagreement was more evident for some pharmacological treatment options. A diagnostic algorithm was developed, focussing on the differentiating features between gastrointestinal motility and gut‐brain interaction disorders with predominant nausea and vomiting. Conclusion These guidelines provide an evidence‐based framework for the evaluation and treatment of patients with chronic nausea and vomiting.

Herein, we report a novel and practical strategy to access α‐chloroketones from esters bearing diverse (hetero)aromatic, aliphatic, alkynyl and alkenyl substituents with transient chloromethyllithium under continuous flow conditions. This highly chemoselective method enables a fast (on a time scale of <5 s), efficient and straightforward access to a broad substrate scope (up to 99% yield) with a remarkable throughput of ∼10.6 g/h.

In this study, we attempt to illustrate fossil vertebrate dental tissue geochemistry and, by inference, its extent of diagenetic alteration, using quantitative, semi-quantitative and optical tools to evaluate bioapatite preservation. We present visual comparisons of elemental compositions in fish and plesiosaur dental remains ranging in age from Silurian to Cretaceous, based on a combination of micro-scale optical cathodoluminescence (CL) observations (optical images and scanning electron microscope) with in-situ minor, trace and rare earth element (REE) compositions (EDS, maps and REE profiles), as a tool for assessing diagenetic processes and biomineral preservation during fossilization of vertebrate dental apatite. Tissue-selective REE values have been obtained using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), indicating areas of potential REE enrichment, combined with cathodoluminescence (CL) analysis. Energy dispersive X-ray spectroscopy (EDS) mapping was also used to identify major elemental components and identify areas of contamination or diagenetic replacement. We conclude that the relative abilities of different dental tissues to resist alteration and proximity to the exposure surface largely determine the REE composition and, accordingly, the inferred quality of preserved bioapatite.

Purpose The main objective of this study was to conduct a radioanatomical study of the osteo-myo-cutaneous scapulo-dorsal pedicled flap. Methods A radiological study was performed to study the anatomical variations of the dorsal scapular pedicle (origin, course of the deep branch of the dorsal scapular artery (DSA) in relation to the medial border of the scapula, perforators from the superficial branch of the DSA). Perforators from the superficial branch of the DSA were also identified on anatomical subjects, and their cutaneous vascular territory was determined. Results The DSA originated from the transverse cervical artery in 95% of cases. The deep branch of the DSA was in an anterolateral position relative to the medial border of the scapula in 70% of cases, and in an anteromedial position in 30%. In most cases, between 1 and 2 perforators arised from the superficial branch of the DSA. The mean size of the cutaneous vascular territory arising from the perforators of the superficial branch of the DSA was 7.8cmx8.5 cm. Conclusion When mandibular reconstruction with this flap is considered, a preoperative CT angiogram could ensure that the transverse cervical vessels have been preserved, and determine the position of the deep branch of the DSA relative to the medial edge of the scapula.