Near-infrared fluorescence imaging-guided surgery improves recurrence-free survival rate in novel orthotopic animal model of head and neck squamous cell carcinoma

International audienceBackground. Appropriate animal models are required to test novel therapeutics for head and neck squamous cell carcinoma (HNSCC) such as near-infrared (NIR) imaging-guided surgery. Methods. We developed an optimized animal model of orthotopic HNSCC (in female athymic NMRI (Naval Medical Research Institute) nude mice) with a prolonged survival time. Resection of the orthotopic tumors was performed 30 days after implantation with or without the aid of a minia-turized clinical grade NIR optical imaging device, after systemic administration of a fluorescent RGD-based probe that targets a v b 3 integrin. Results. NIR optical imaging-guided surgery increased the recurrence-free survival rate by 50% through the detection of fluorescent cancer residues as small as 185 mm; these fragments could remain unidentified if resection was performed exclusively under unaided visual guidance. Conclusion. NIR optical imaging-guided surgery showed an improved HNSCC tumor resection quality in our optimized orthotopic animal model

Ophthalmic complications of Lemierre syndrome

PURPOSE: Lemierre syndrome is a life-threatening condition characterized by head/neck bacterial infection, local suppurative thrombophlebitis and septic embolic complications in a range of sites of distant organs. No prior study focused on the course and characteristics of ophthalmic complications of Lemierre syndrome. METHODS: We analysed data of 27 patients with ophthalmic complications from a large cohort of 712 cases with Lemierre syndrome reported globally between 2000 and 2017. We focused on initial manifestations, early (in-hospital) course and long-term ophthalmic deficits at the time of hospital discharge or during postdischarge follow-up. The study protocol was registered in the International Prospective Register of Systematic Reviews PROSPERO (CRD42016052572). RESULTS: Nine (33%) patients were women; the median age was 20 (Q1-Q3: 15-33) years. Fusobacterium spp. was involved in 56% of cases. The most prevalent initial manifestations were decreased vision (35%) and periocular oedema (38%), followed by impaired eye movements/nerve palsy (28%) and proptosis (28%). Venous involvement, notably cerebral vein thrombosis (70%) and ophthalmic vein thrombosis (55%), explained the symptomatology in most cases. Septic embolism (7%), orbital abscesses (2%) and carotid stenosis (14%) were also present. Ophthalmic sequelae were reported in 9 (33%) patients, often consisting of blindness or reduced visual acuity, and nerve paralysis/paresis. CONCLUSION: Ophthalmic complications represent a severe manifestation of Lemierre syndrome, often reflecting an underlying cerebral vein thrombosis. Visual acuity loss and long-term severe complications are frequent. We call for an interdisciplinary approach to the management of patients with Lemierre syndrome and the routine involvement of ophthalmologists

Drug-related adverse events necessitating treatment discontinuation in pediatric inflammatory bowel disease patients.

BACKGROUND AND AIMS Inflammatory bowel disease (IBD) requires long-term drug therapy in most patients, posing a risk for adverse drug events with the need for discontinuation. In this study, we investigated adverse events (AE) necessitating drug discontinuation in pediatric and adolescent IBD patients. METHODS We used data prospectively collected from IBD patients below the age of 18 enrolled in the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), namely demographic variables, medical characteristics, drug treatments and related AE. We analysed the frequency, type, and risk factors for AE necessitating drug discontinuation. RESULTS A total of 509 pediatric IBD patients fulfilled the inclusion criteria of which 262 (51.5%) were diagnosed with Crohn's disease (CD), 206 (40.5%) with ulcerative colitis (UC), and 41 (8%) with IBD-unclassified (IBD-U). In total, 132 (25.9%) presented with at least one drug-related AE that required drug cessation. Immunomodulators (methotrexate 29/120 (24.2%), azathioprine 57/372 (15.3%)) followed by tumor necrosis factor (TNF)-alpha antagonists (adalimumab 8/72 (11.1%), infliximab 22/227 (9.7%)) accounted for the highest proportions of AE necessitating treatment discontinuation. Treatment schemes with at least 3 concomitant drugs significantly amplified the risk for development of drug-related AE (OR = 2.50, 95%CI [1.50-4.17]) in all pediatric IBD patients. CONCLUSIONS Drug-related AE necessitating discontinuation are common in pediatric and adolescent inflammatory bowel disease patients. Caution needs to be taken in the case of concomitant drug use

Brain activations in speech recovery process after intra-oral surgery: an fMRI study

International audienceThis study aims at describing cortical and subcortical activation patterns associated with functional recovery of speech production after reconstructive mouth surgery. Our ultimate goal is the understanding of how the brain deals with altered relationships between motor commands and auditory/orosensory feedback, and establishes new inter-articulatory coordination to preserve speech communication abilities. A longitudinal sparse-sampling fMRI study involving orofacial, vowel and syllable production tasks on 9 patients and in three different sessions (one week before, one month and three months after surgery) was conducted. Healthy subjects were recorded in parallel. Results show that for patients in the pre-surgery session, activation patterns are in good agreement with the classical speech production network. Crucially, lower activity in sensorimotor control brain areas during orofacial and speech production movements is observed for patients in all sessions. One month after surgery, the superior parietal lobule is more activated for simple vowel production suggesting a strong involvement of a multimodal integration process to compensate for loss of tongue motor control. Altogether, these results indicate both altered and adaptive sensorimotor control mechanisms in these patients. Index Terms: Neurophonetics, fMRI, speech recovery, motor control, glossectomy, whole-brain analysis, sparse-sampling

Evolution des activations cérébrales lors de la production de parole après exérèse au niveau de la cavité orale

International audienceUsing functional MRI, acoustic data and motor oral assessment, brain correlates of speech recovery after dramatic structural changes in the vocal tract have been investigated during three tasks: orofacial movements and speech production (vowels and syllables). Eleven patients were recorded during three sessions, preoperatively and postoperatively, 1 month and 3 months after surgery (for seven of them also 9 months after surgery). Eleven healthy subjects were recorded in parallel. A "whole brain" group analysis (patients/healthy subjects) reveals a specific activation pattern for patients, in particular during vowel task, which is session-dependent. Moreover, global lower brain activation compared to healthy subjects was found for all tasks in primary, secondary and integrative sensorimotor regions. Differences are interpreted in relation with the emergence of new speech motor goals and changes in the internal models.A partir de données d'IRM fonctionnelle, acoustiques et praxiques, nous avons étudié les corrélats cérébraux de l'adaptation de la parole après une modification structurelle importante du conduit vocal lors de trois tâches : mouvements oro-faciaux silencieux, voyelles et syllabes. Onze patients ont été enregistrés lors de trois sessions, pré-opératoire et post-opératoire à 1 mois et 3 mois (pour sept d'entre eux aussi à 9 mois). Onze sujets contrôles ont été enregistrés en parallèle. Une analyse de groupe (patients/contrôles) " cerveau entier " révèle des patrons d'activation spécifiques aux patients au cours des différentes sessions en particulier pour la tâche de production de voyelles. De plus, une moindre activation cérébrale par rapport aux sujets sains a été observée pour toutes les tâches dans des régions motrices, sensorielles et d'intégration sensori-motrice. Nous interprétons ces résultats en relation avec la redéfinition des buts de parole et l'adaptation de modèles internes du système moteur périphérique

Drug development in oncology assisted by noninvasive optical imaging.

International audienceEarly and accurate detection of tumors, like the development of targeted treatments, is a major field of research in oncology. The generation of specific vectors, capable of transporting a drug or a contrast agent to the primary tumor site as well as to the remote (micro-) metastasis would be an asset for early diagnosis and cancer therapy. Our goal was to develop new treatments based on the use of tumor-targeted delivery of large biomolecules (DNA, siRNA, peptides, or nanoparticles), able to induce apoptosis while dodging the specific mechanisms developed by tumor cells to resist this programmed cell death. Nonetheless, the insufficient effectiveness of the vectorization systems is still a crucial issue. In this context, we generated new targeting vectors for drug and biomolecules delivery and developed several optical imaging systems for the follow-up and evaluation of these vectorization systems in live mice. Based on our recent work, we present a brief overview of how noninvasive optical imaging in small animals can accelerate the development of targeted therapeutics in oncology

ESVM Guideline on peripheral arterial disease

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Cooperative coupling of ultracold atoms and surface plasmons

Cooperative coupling between optical emitters and light fields is one of the outstanding goals in quantum technology. It is both fundamentally interesting for the extraordinary radiation properties of the participating emitters and has many potential applications in photonics. While this goal has been achieved using high-finesse optical cavities, cavity-free approaches that are broadband and easy to build have attracted much attention recently. Here we demonstrate cooperative coupling of ultracold atoms with surface plasmons propagating on a plane gold surface. While the atoms are moving towards the surface they are excited by an external laser pulse. Excited surface plasmons are detected via leakage radiation into the substrate of the gold layer. A maximum Purcell factor of $\eta_\mathrm{P}=4.9$ is reached at an optimum distance of $z=250~\mathrm{nm}$ from the surface. The coupling leads to the observation of a Fano-like resonance in the spectrum.Comment: 9 pages, 4 figure

Thrombin Generation Is Associated with Venous Thromboembolism Recurrence, but Not with Major Bleeding and Death in the Elderly: A Prospective Multicenter Cohort Study

It is currently unknown whether thrombin generation is associated with venous thromboembolism (VTE) recurrence, major bleeding, or mortality in the elderly. Therefore, our aim was to prospectively study the association between thrombin generation and VTE recurrence, major bleeding, and mortality in elderly patients with acute VTE. Consecutive patients aged ≥65 years with acute VTE were followed for 2 years, starting from 1 year after the index VTE. Primary outcomes were VTE recurrence, major bleeding, and mortality. Thrombin generation was assessed in 551 patients 1 year after the index VTE. At this time, 59% of the patients were still anticoagulated. Thrombin generation was discriminatory for VTE recurrence, but not for major bleeding and mortality in non-anticoagulated patients. Moreover, peak ratio (adjusted subhazard ratio 4.09, 95% CI, 1.12-14.92) and normalized peak ratio (adjusted subhazard ratio 2.18, 95% CI, 1.28-3.73) in the presence/absence of thrombomodulin were associated with VTE recurrence, but not with major bleeding and mortality after adjustment for potential confounding factors. In elderly patients, thrombin generation was associated with VTE recurrence, but not with major bleeding and/or mortality. Therefore, our study suggests the potential usefulness of thrombin generation measurement after anticoagulation completion for VTE to help identify among elderly patients those at higher risk of VTE recurrence

Joule-heating Effects In the Amorphous Fe40ni40b20 Alloy

The effects of Joule heating on the amorphous Fe40Ni40B20 alloy are investigated by measuring the time behavior of the electrical resistance of ribbon strips during such a treatment. The structural transformations occurring in subsequent stages of the process are studied by means of x-ray-diffraction, differential-scanning-calorimetry, and magnetic-permeability measurements. A continuous evolution from a fully amorphous to a fully crystalline structure may be followed. The crystallization mechanisms observed in Joule-heated samples differ from the ones occurring under conventional heating conditions. The electrical resistance displays a bump in the course of Joule heating. A quantitative model relating such a bump to the extra heat released to the sample by fast crystallization is proposed and discussed