Endoscopic mucosal resection: how, when, why?

Le traitement des cancers intramuqueux et de la dysplasie de haut grade dans l’oesophage de Barrett est, de nos jours, l’apanage de l’endoscopie. Le traitement endoscopique doit veiller à appliquer les mêmes standards que ceux de la chirurgie, à savoir une exérèse en bloc à visée curative R0. Les méthodes de mucosectomie classiques peuvent être utilisées dans la majorité des lésions néoplasiques ou dysplasiques. La dissection sousmuqueuse trouve ses indications dans les lésions de plus de 15-20 mm ou celles ne se soulevant pas après injection sousmuqueuse du fait d’antécédents d’ulcères, de résections muqueuses incomplètes ou de récidive tumorale. Par rapport aux techniques d’ablation thermique, de thérapie photodynamique ou de radiofréquence, les mucosectomies apportent la possibilité d’une analyse histopathologique des pièces réséquées pour déterminer la profondeur de l’envahissement tumoral et le caractère radical de l’exérèse. De plus, cette procédure permet le recours à la chirurgie pour les patients aptes à supporter l’intervention, dans le cas de résection incomplète ou de lésion envahissant la sous-muqueuse profonde. Des études seront encore nécessaires pour préciser la place résiduelle de la chirurgie et des indications respectives de la résection partielle ou totale du Barrett par endoscopie. Le rôle probablement complémentaire des techniques ablatives (plus superficielles mais grevées de moins de complications) et des mucosectomies (plus profondes, avec moindre risque de récidives, mais avec plus de risque de complications) commence à être défendu par les centres experts.The treatment of intramucosal cancers and of high-grade dyplasia in Barrett’s esophagus is nowadays the prerogative of endoscopy. Endoscopic treatment should be submitted to the same standards as those of surgery, i.e. curative R0 “en bloc” resection. Classical methods of mucosectomy can be applied to most neoplastic or dysplastic lesions. Submucosal dissection is indicated for lesions larger than 15-20 mm or to those, which cannot be lifted by submucosal injection due to a past history of ulcers, incomplete mucosal resections or tumour recurrence. Compared to thermal ablation, photodynamic therapy or radiofrequency, mucosectomy allows for a histopathological analysis of the resected samples thus enabling to determine the depth of the tumour invasion and the radical character of the exeresis. Moreover, in the case of incomplete resection or of a lesion infiltrating the deep submucosa, this procedure makes surgery available for patients eligible to it. Further studies will be necessary to precise the remaining role of surgery, the respective indications of partial or radical resection of Barrett oesophagus by endoscopy. Expert centres now start to advocate the role of complementary ablation techniques (more superficial but leading to less complications) and mucosectomy (deeper but with a lesser risk of recurrence but a higher risk of complications)

An outbreak of the peracute form of malignant catarrhal fever in Belgian cattle

A large outbreak of the peracute form of malignant catarrhal fever in cattle in Belgium is described. The main symptoms were nervous signs and high fever. Over a four-month period, 13 Belgian Blue yearlings and one cow died. Mortality was 16.3% of the herd. The diagnosis was confirmed by identifying ovine herpesvirus-2 DNA by PCR, both in the affected cattle and in the sheep on the farm. This case report illustrates the increasing importance of malignant catarrhal fever as a herd problem and the occurrence of the peracute form, as also reported in other European countries. It also illustrates the importance of malignant catarrhal fever as a differential diagnosis for nervous disorders in cattle

Brussels, a sustainable city

Observations As a reminder: Sustainable defines that which meets the current generations’ needs without jeopardising the possibilities for future generations to meet their own needs (that is to say, without exceeding resource renewal rates). More simply put, that which is capable of continuing is sustainable. A layout inherited from the modernist era The zoning of the city’s territory Brussels has been marked by monofunctionalism over the past few decades. This applies to both its central nei..

Brussel, duurzame stad

Vaststellingen Duurzame ontwikkeling is een ontwikkeling waarbij de huidige wereldbevolking in haar behoeften voorziet zonder de komende generaties te beperken om in hun behoeften te voorzien (namelijk zonder het vermogen om de rijkdommen te vernieuwen aan te tasten). Eenvoudiger gesteld: duurzaam is wat kan blijven bestaan… Stedenbouwkunde: een erfenis uit het modernistische tijdperk De indeling van het Brussels grondgebied De laatste decennia werd Brussel gekenmerkt door monofunctionalisme,..

Unconventional surface plasmon resonance signals reveal quantitative inhibition of transcriptional repressor EthR by synthetic ligands

International audienceEthR is a mycobacterial repressor that limits the bioactivation of ethionamide, a commonly used anti-tuberculosis second-line drug. Several efforts have been deployed to identify EthR inhibitors abolishing the DNA-binding activity of the repressor. This led to the demonstration that stimulating the bioactivation of ETH through EthR inhibition could be an alternative way to fight Mycobacterium tuberculosis. We propose a new SPR methodology to study the affinity between inhibitors and EthR. Interestingly, the binding between inhibitors and immobilized EthR produced a dose dependent negative SPR signal. We demonstrated that this signal reveals the affinity of the small molecules for the repressor. The affinity constants (KD) correlated with their capacity to inhibit the binding of EthR to DNA. We hypothesize that conformational changes of EthR during ligand interaction could be responsible for this SPR signal. Practically, this unconventional result open perspectives to the development of SPR assay that would at the same time tough on the structural changes of the target upon binding with an inhibitor and on the binding constant of this interaction

Sustainability limits needed for CO2 removal

International audienceMany governments and industries are relying on future large-scale, land-based carbon dioxide (CO2) removal (CDR) to avoid making necessary steep greenhouse gas (GHG) emission cuts today (1, 2). Not only does this risk locking us into a high overshoot above 1.5°C (3), but it will also increase biodiversity loss, imperiling the Kunming-Montreal Global Biodiversity Framework (KMGBF) goals (4). Such CDR deployments also pose major economic, technological, and social feasibility challenges; threaten food security and human rights; and risk overstepping multiple planetary boundaries, with potentially irreversible consequences (1, 5, 6). We propose three ways to build on the Intergovernmental Panel on Climate Change (IPCC) analyses of CDR mitigation potential by assessing sustainability risks associated with land-use change and biodiversity loss: estimate the sustainable CDR budget based on socioecological thresholds; identify viable mitigation pathways that do not overstep these thresholds; and reframe governance around allocating limited CDR supply to the most legitimate uses

Efficient and Specific Internal Cleavage of a Retroviral Palindromic DNA Sequence by Tetrameric HIV-1 Integrase

BACKGROUND: HIV-1 integrase (IN) catalyses the retroviral integration process, removing two nucleotides from each long terminal repeat and inserting the processed viral DNA into the target DNA. It is widely assumed that the strand transfer step has no sequence specificity. However, recently, it has been reported by several groups that integration sites display a preference for palindromic sequences, suggesting that a symmetry in the target DNA may stabilise the tetrameric organisation of IN in the synaptic complex. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the ability of several palindrome-containing sequences to organise tetrameric IN and investigated the ability of IN to catalyse DNA cleavage at internal positions. Only one palindromic sequence was successfully cleaved by IN. Interestingly, this symmetrical sequence corresponded to the 2-LTR junction of retroviral DNA circles-a palindrome similar but not identical to the consensus sequence found at integration sites. This reaction depended strictly on the cognate retroviral sequence of IN and required a full-length wild-type IN. Furthermore, the oligomeric state of IN responsible for this cleavage differed from that involved in the 3'-processing reaction. Palindromic cleavage strictly required the tetrameric form, whereas 3'-processing was efficiently catalysed by a dimer. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the restriction-like cleavage of palindromic sequences may be a general physiological activity of retroviral INs and that IN tetramerisation is strongly favoured by DNA symmetry, either at the target site for the concerted integration or when the DNA contains the 2-LTR junction in the case of the palindromic internal cleavage

Primary temporal bone angiosarcoma: a case report.

We present a rare case of temporal bone angiosarcoma diagnosed in a 26-year-old female patient at 36 week of pregnancy. The patient was referred with a 2 months history of left otalgia and tinnitus with a tender swelling above the mastoid. Cranial imaging studies showed a 7 x 5 x 4 cm hypervascularized mass located in the left middle fossa with lysis of the temporal bone and extension to the subcutis. After the baby was delivered by caesarean section, the patient entered the oncology protocol. Selective embolization of the feeding vessels was followed by gross total surgical resection using a combined supra- and infra-tentorial approach. Pathological findings were those of a poorly differentiated, highly malignant sarcoma with a large epitheloid component and immunohistochemical evidence of endothelial differentiation (CD31, Factor VIII related antigen, CD34), consistent with an angiosarcoma with epitheloid features. No extra-cranial tumor was found after extensive staging. The patient received adjuvant radiotherapy followed by a course of chemotherapy consisting of 6 cycles of paclitaxel. At 15 months follow-up, she developed multiple distant metastasis to a left postauricular lymph node and to the lungs and ribs. The patient was given a second line chemotherapy using doxorubicine and ifosfamide. Despite an initial good response, she died with metastatic disease 26 months after diagnosis. We present a rare case of primary temporal bone angiosarcoma and report our experience with a multimode therapeutic approach combining surgery, radiotherapy and chemotherapy.Peer reviewe

An externally validated fully automated deep learning algorithm to classify COVID-19 and other pneumonias on chest computed tomography.

peer reviewedPurpose: In this study, we propose an artificial intelligence (AI) framework based on three-dimensional convolutional neural networks to classify computed tomography (CT) scans of patients with coronavirus disease 2019 (COVID-19), influenza/community-acquired pneumonia (CAP), and no infection, after automatic segmentation of the lungs and lung abnormalities. Methods: The AI classification model is based on inflated three-dimensional Inception architecture and was trained and validated on retrospective data of CT images of 667 adult patients (no infection n=188, COVID-19 n=230, influenza/CAP n=249) and 210 adult patients (no infection n=70, COVID-19 n=70, influenza/CAP n=70), respectively. The model's performance was independently evaluated on an internal test set of 273 adult patients (no infection n=55, COVID-19 n= 94, influenza/CAP n=124) and an external validation set from a different centre (305 adult patients: COVID-19 n=169, no infection n=76, influenza/CAP n=60). Results: The model showed excellent performance in the external validation set with area under the curve of 0.90, 0.92 and 0.92 for COVID-19, influenza/CAP and no infection, respectively. The selection of the input slices based on automatic segmentation of the abnormalities in the lung reduces analysis time (56 s per scan) and computational burden of the model. The Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) score of the proposed model is 47% (15 out of 32 TRIPOD items). Conclusion: This AI solution provides rapid and accurate diagnosis in patients suspected of COVID-19 infection and influenza

Pathogenesis of vestibular schwannoma in ring chromosome 22

<p>Abstract</p> <p>Background</p> <p>Ring chromosome 22 is a rare human constitutional cytogenetic abnormality. Clinical features of neurofibromatosis type 1 and 2 as well as different tumour types have been reported in patients with ring chromosome 22. The pathogenesis of these tumours is not always clear yet.</p> <p>Methods</p> <p>We report on a female patient with a ring chromosome 22 presenting with severe mental retardation, autistic behaviour, café-au-lait macules and facial dysmorphism. Peripheral blood lymphocytes were karyotyped and array CGH was performed on extracted DNA. At the age of 20 years she was diagnosed with a unilateral vestibular schwannoma. Tumour cells were analyzed by karyotyping, array CGH and <it>NF2 </it>mutation analysis.</p> <p>Results</p> <p>Karyotype on peripheral blood lymphocytes revealed a ring chromosome 22 in all analyzed cells. A 1 Mb array CGH experiment on peripheral blood DNA showed a deletion of 5 terminal clones on the long arm of chromosome 22. Genetic analysis of vestibular schwannoma tissue revealed loss of the ring chromosome 22 and a somatic second hit in the <it>NF2 </it>gene on the remaining chromosome 22.</p> <p>Conclusion</p> <p>We conclude that tumours can arise by the combination of loss of the ring chromosome and a pathogenic <it>NF2 </it>mutation on the remaining chromosome 22 in patients with ring chromosome 22. Our findings indicate that patients with a ring 22 should be monitored for NF2-related tumours starting in adolescence.</p