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International audience; Objectives: To assess the contribution of whole-body magnetic resonance imaging (WBMRI) and bone scintigraphy (BS) in addition to skeletal survey (SS) in detecting traumatic bone lesions and soft-tissue injuries in suspected child abuse.Methods: In this prospective, multicentre, diagnostic accuracy study, children less than 3 years of age with suspected physical abuse were recruited. Each child underwent SS, BS and WBMRI. A blinded first review was performed in consensus by five paediatric radiologists and three nuclear medicine physicians. A second review investigated discrepancies reported between the modalities using a consensus result of all modalities as the reference standard. We calculated the sensitivity, specificity and corresponding 95% confidence interval for each imaging modality (SS, WBMRI and BS) and for the combinations [SS + WBMRI] and [SS + BS].Results: One hundred seventy children were included of which sixty-four had at least one lesion. In total, 146 lesions were included. The sensitivity and specificity of each examination were, respectively, as follows: 88.4% [95% CI, 82.0-93.1] and 99.7% [95% CI, 99.5-99.8] for the SS, 69.9% [95% CI, 61.7-77.2] and 99.5% [95% CI, 99.2-99.7] for WBMRI and 54.8% [95% CI, 46.4-63.0] and 99.7% [95% CI, 99.5-99.9] for BS. Sensitivity and specificity were, respectively, 95.9% [95% CI, 91.3-98.5] and 99.2% [95% CI, 98.9-99.4] for the combination SS + WBMRI and 95.2% [95% CI, 90.4-98.1] and 99.4% [95% CI, 99.2-99.6] for the combination SS + BS, with no statistically significant difference between them.Conclusion: SS was the most sensitive independent imaging modality; however, the additional combination of either WBMRI or BS examinations offered an increased accuracy.Key points: • SS in suspected infant abuse was the most sensitive independent imaging modality in this study, especially for detecting metaphyseal and rib lesions, and remains essential for evaluation. • The combination of either SS + BS or SS + WBMRI provides greater accuracy in diagnosing occult and equivocal bone injuries in the difficult setting of child abuse. • WBMRI is a free-radiation technique that allows additional diagnosis of soft-tissue and visceral injuries.

Background The COVID‐19 pandemic may induce post‐traumatic stress disorder (PTSD) symptoms among patients with cancer, who also face adaptations to their treatment. The authors assessed the occurrence of PTSD symptoms, investigated pandemic‐induced adjustments in medical oncology practice in patients with cancer, and explored risk factors for PTSD and the association between PTSD symptoms, insomnia, and quality of life (QoL). Methods This prospective French study was conducted in patients with solid/hematologic tumors who were receiving medical treatment in the day care departments of 2 cancer centers during the lockdown. Adjustments to medical oncology practice were collected from medical records. PTSD (measured using the Impact of Event Scale‐Revised), insomnia (measured using the Insomnia Severity Index), QoL (measured using the Functional Assessment of Cancer Therapy‐General instrument), and cognitive complaints (measured using the Functional Assessment of Cancer Therapy–Cognitive Function instrument) were collected through validated questionnaires. Results Clinical data and questionnaires were available for 734 and 576 patients, respectively. The median patient age was 64 years, and 69% of patients were women. Twenty‐one percent of patients had PTSD. Twenty‐seven percent (95% CI, 23%‐30%) had an adjustment in their medical oncology program, including adjournments (29%), treatment interruptions (16%), modified treatment plans (27%), or adapted monitoring (27%). Women and patients experiencing an adjustment in oncology practice had a higher odds of PTSD (odds ratio= 2.10 [95% CI, 1.07‐4.14] and 1.65 [95% CI, 1.03‐2.63]; P, Post‐traumatic stress disorder symptomatology occurred in 21% of patients with cancer during the first lockdown due to COVID‐19, was more frequent among women, and was associated with adjustment in medical oncology treatments. Caregivers should pay special attention to the psychological needs of patients with cancer to prevent or manage post‐traumatic stress disorder symptoms.

Summary Background Abnormal coronary pattern may complicate coronary transfer during arterial switch operation. Objective To evaluate the accuracy of echocardiography in assessing the anatomy of coronary arteries in neonates with transposition of the great arteries, and determine impact on outcomes. Methods We conducted a retrospective analysis of data in neonates with transposition of the great arteries. Preoperative echocardiographic coronary artery pattern and surgical intraoperative reports were compared. Mismatch between transthoracic echocardiography and surgical intraoperative reports and the impact on perioperative outcome were assessed. Coronary patterns were classified into four groups: type 1 (normal); type 2 (risk of coronary with intramural course); type 3 (coronary loop); and type 2 + 3. Results Overall, 108 neonates who underwent an arterial switch operation were included: 68 were classified as type 1; seven as type 2; 32 as type 3; and one as type 2 + 3. Overall, 10 adverse events occurred. Five patients died, three from coronary causes. Survival was 96% at 1 month. Transthoracic echocardiography and surgical intraoperative reports differed in 17.6% of cases. Mortality was 15.8% in case of inappropriate diagnosis and 2.2% for appropriate diagnosis (P = 0.01). Mortality in type 2 was 66.7% in case of discordance versus 0% when concordant. Multivariable analysis found that inappropriate preoperative transthoracic echocardiography diagnosis of coronary pattern was the only significant risk factor for mortality (P = 0.04). Conclusions Echocardiography can assess coronary artery anatomy in neonates with transposition of the great arteries. Intramural coronary course is often misdiagnosed. Preoperative misdiagnosis of coronary artery anomaly may impact perioperative mortality. However, this assessment will have to be confirmed by further larger studies.

Three posture asymmetries and their connections were assessed by a statistical study as rigorous as possible on the subjects of a sample from a population considered as normal after negative criteria. The comparison of probabilities observed with random probabilities shows that there is less than one chance in a thousand to make an error by rejecting the hypothesis that the asymmetries of the orthostatic posture are random. The definition of the limits of these asymmetries thus fits in the search for the conditions of a clinical examination of the posture.

Traumatic brain injury (TBI) is a chronic pathology, inducing long-term deficits that remain understudied in pre-clinical studies. In this context, exploration, anxiety-like behavior, cognitive flexibility, and motor coordination were assessed until 5 and 10 months after an experimental TBI in the adult mouse, using two cohorts. In order to differentiate age, surgery, and remote gray and white matter lesions, three groups (unoperated, sham-operated, and TBI) were studied. TBI induced delayed motor coordination deficits at the pole test, 4.5 months after injury, that could be explained by gray and white matter damages in ipsilateral nigrostriatal structures (striatum, internal capsule) that were spreading to new structures between cohorts, at 5 versus 10 months after the injury. Further, TBI induced an enhanced exploratory behavior during stressful situations (active phase during actimetry test, object exploration in an open field), risk-taking behaviors in the elevated plus maze 5 months after injury, and a cognitive inflexibility in the Barnes maze that persisted until 9 months after the injury. These behavioral modifications could be related to the white and gray matter lesions observed in ipsi- and contralateral limbic structures (amygdala, hilus/cornu ammonis 4, hypothalamus, external capsule, corpus callosum, and cingular cortex) that were spreading to new structures between cohorts, at 5 months versus 10 months after the injury. The present study corroborates clinical findings on TBI and provides a relevant rodent chronic model which could help in validating pharmacological strategies against the chronic consequences of TBI.

Resume Introduction Le traitement dans le cancer de l’ovaire localement avance est une chirurgie optimale suivie d’une chimiotherapie. Les patientes avec une dissemination tumorale importante, un OMS superieur a deux et un âge superieur a 75 ans sont de mauvaises candidates pour une chirurgie premiere agressive. La chirurgie d’intervalle, apres une chimiotherapie neo adjuvante, a pour but d’obtenir davantage de chirurgies completes, d’augmenter la survie et de diminuer la morbidite liee a la chirurgie. Le critere principal de jugement etait la survie sans progression. Les criteres secondaires de jugement etaient la survie globale et la morbi-mortalite post-chirurgie. Methode Il s’agit d’une etude retrospective effectuee dans deux centres de reference francais entre janvier 2000 et decembre 2015. Les patientes qui ne pouvaient pas beneficier d’une chirurgie initiale complete etaient operees apres trois cures de chimiotherapie au centre Francois Baclesse et apres au moins cinq cures au centre Rene Gauducheau. Resultats La population analysee comportait 104 patientes, 43 (41,0 %) patientes traitees au centre Rene Gauducheau (groupe 1) et 61 (59,0 %) patientes traitees au centre Francois Baclesse (groupe 2). La survie sans progression et globale etait similaire entre les deux groupes. Elles etaient respectivement de 15,9 mois et 34 mois dans le groupe 1 vs 15,4 mois et 37,6 mois dans le groupe 2 (p = 0,72 ; p = 0,65). La duree d’hospitalisation moyenne et la morbidite postoperatoire etait similaire dans les deux groupes. Conclusion Pour des patientes fragiles, afin de limiter une chirurgie invasive, faire plus de cinq cures de chimiotherapie peut etre une option raisonnable.

BackgroundCervical cancer is the tenth diagnosed cancer in the world. Early-stage and locally recurrent disease may be cured with radical surgery or chemo-radiotherapy. However, if disease persists or recurs, options are limited and the prognosis is poor. In addition to chemotherapy, bevacizumab, an antiangiogenic agent, has recently demonstrated its efficacy in this setting. Cabozantinib is an oral small molecule tyrosine kinase inhibitor that exhibits potent inhibitory activity against several receptor tyrosine kinases that are known to influence tumor growth, metastasis, and angiogenesis. The main targets of Cabozantinib are VEGFR2, MET and AXL. It is currently approved for the treatment of metastatic renal cell carcinoma, hepatocellular carcinoma and medullary thyroid carcinoma. Given its angiogenic properties associated with growth factor receptors inhibition, Cabozantinib represents a potential active treatment in cervical carcinoma. In this context, we propose to assess the efficacy and safety of cabozantinib monotherapy in advanced/metastatic cervical carcinoma (CC) after failure to platinum-based regimen treatment.MethodsThis study is a single-arm two-stage multicenter phase II aiming to simultaneously assess efficacy and safety of Cabozantinib among advanced/metastatic cervical carcinoma (CC) after failure to platinum-based regimen treatment. The main criterion will be based on both safety and clinical efficacy by conducting a Bryant-and-Day design. Safety endpoint is the proportion of patients with clinical gastro-intestinal (GI) perforation/fistula, GI-vaginal fistula and genito-urinary (GU) fistula events grade ≥ 2 (NCI CTCAE V.5.0) occurring up to one month after the end of treatment. Efficacy endpoint is the proportion of patients with disease control rate 3 months after Cabozantinib initiation. A patients’ self-reported quality of life evaluation is also planned, as well as the investigation of nutritional outcomes. Cabozantinib will be administered at the daily dose of 60 mg given orally, without interruption until disease progression or discontinuation for any cause.DiscussionCabozantinib is a promising drug for patients with advanced/metastatic cervical cancer where few therapeutics options are available after failure to platinum-based regimen metastatic CC. It appears challenging to assess the interest of Cabozantinib in this indication, taking into account the potential toxicity of the drug.Trial registrationNCT04205799, registered “2019 12 19”.Protocol versionVersion 3.1 dated from 2020 08 31.

The adult Göttingen Minipig is an acknowledged model for safety assessment of antisense oligonucleotide (ASO) drugs developed for adult indications. To assess whether the juvenile Göttingen Minipig is also a suitable nonclinical model for pediatric safety assessment of ASOs, we performed an 8-week repeat-dose toxicity study in different age groups of minipigs ranging from 1 to 50 days of age. The animals received a weekly dose of a phosphorothioated locked-nucleic-acid-based ASO that was assessed previously for toxicity in adult minipigs. The endpoints included toxicokinetic parameters, in-life monitoring, clinical pathology, and histopathology. Additionally, the ontogeny of key nucleases involved in ASO metabolism and pharmacologic activity was investigated using quantitative polymerase chain reaction and nuclease activity assays. Similar clinical chemistry and toxicity findings were observed, however, differences in plasma and tissue exposures as well as pharmacologic activity were seen in the juvenile minipigs when compared with the adult data. The ontogeny study revealed a differential nuclease expression and activity, which could affect the metabolic pathway and pharmacologic effect of ASOs in different tissues and age groups. These data indicate that the juvenile Göttingen Minipig is a promising nonclinical model for safety assessment of ASOs intended to treat disease in the human pediatric population.

Evaluating the aerosolization of droplets from surgical instruments to assess the implications of surgery in SARS-CoV-2 transmission for both patients and providers. Cadaver study. Outpatient surgery center. Aerosolized particles between 0.3 and 25 microns were measured. Instruments tested included monopolar cautery with and without suction, bipolar cautery, a bipolar vessel sealing device, and tissue scissors. Each trial was compared to a background reading. Monopolar cautery without suction, Ligasure used continuously and Bipolar cautery produced the most aerosols. Monopolar cautery with simultaneous suction produced no detectable aerosols. Ligasure used for a single cycle produced notably fewer aerosols than during continuous use. Most aerosols produced were

General practitioners (GPs) are first-line clinicians in melanoma diagnosis. It is, therefore, important to ensure that they maintain their melanoma diagnostic accuracy over time. The objective of this study was to assess the short- and long-term competences of GPs after a training session in naked-eye melanoma diagnosis. An interventional prospective study was conducted whereby, over a 6-month period, GPs attended a 1-h melanoma diagnostic training session. To assess their acquired competences, GPs were asked to fill in a questionnaire on basic melanoma knowledge and to evaluate 10 clinical images of pigmented skin lesions prior to training, immediately after and 1 year later. In total, 89 GPs completed the questionnaire prior and immediately after training. As expected, the number of GPs who appropriately managed \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\ge$$\end{document}≥ 50% of the melanoma cases increased after training (P

International audience; BACKGROUND. High circulating levels of ceramides (Cer) and sphingomyelins (SM) have been associated with cardiometabolic diseases. The consumption of whole-fat dairy products, which naturally contain such polar lipids (PL), is associated with health benefits, but the impact on sphingolipidome remains unknown. We investigated how milk PL supplementation impacts circulating and intestinal SM and Cer composition in association with improvement of cardiovascular markers.METHODS. In a 4 week-randomized double-blind controlled study, 58 postmenopausal women consumed daily a cream cheese containing 0, 3 or 5 g of milk PL. Postprandial metabolic explorations were performed before and after the supplementation. SM and Cer species were analyzed in serum, intestine-derived chylomicrons and feces. The ileal content of 4 ileostomy patients was also explored after milk PL intake in a crossover double-blind study.RESULTS. Milk PL consumption decreased serum atherogenic C24:1 Cer (Pgroup = 0.033), C16:1 (Pgroup = 0.007) and C18:1 (Pgroup = 0.003) SM species. Changes in serum C16+18 SM species were positively correlated with the reduction of total cholesterol (r = 0.706, P < 0.001), LDL-C (r = 0.666, P < 0.001) and ApoB (r = 0.705, P < 0.001). Milk PL decreased the concentration in chylomicrons of total SM (Pgroup < 0.0001) and of C24:1 Cer (Pgroup = 0.001). Saturated SM and Cer species, which are also the major species found in milk PL-enriched cheeses, increased in ileal efflux and feces. There was a marked increase in total fecal Cer after milk PL supplementation (Pgroup = 0.0002). Milk PL also modulated the abundance of some specific SM and Cer species in ileal efflux and feces, suggesting differential absorption and metabolization processes in the gut.CONCLUSION. These data demonstrate that milk PL supplementation decreases atherogenic SM and Cer species associated with an improvement of cardiovascular risk markers. Our findings bring new insights on sphingolipid metabolism in the gastrointestinal tract, especially Cer as such signaling molecules potentially participating in the beneficial effect of milk PL. ClinicalTrials.gov, NCT02099032, NCT02146339.

OBJECTIVE To determine whether ileocaecal endometriosis (ICE) is a marker for low rectal endometriosis (LRE) severity. DESIGN Retrospective cohort study. SETTING France. POPULATION AND SAMPLE Analysis of 375 colorectal resections performed in women undergoing complete surgery for LRE from January 1995 to December 2015 in a university centre for endometriosis. METHODS Univariate and multivariate analysis of anatomical, postoperative clinical, and long-term outcomes according to presence of ICE. MAIN OUTCOMES AND MEASURES Mean number and type of deep infiltrating endometriosis (DIE) lesions, the existence of an associated endometrioma, and mean total American Society for Reproductive Medicine (ASRM) score. RESULTS The prevalence of ICE was 25.6%. Primary end-point data showed that women with ICE had a significantly higher adjusted number of DIE lesions (OR = 1.43, 95% CI 1.02-3.03; P = 0.048), higher prevalence of endometriomas (OR = 1.91, 95% CI 1.04-3.51; P = 0.044), more associated DIE sigmoid lesions (OR = 2.12, 95% CI 1.07-3.91; P = 0.025), and a higher mean total ASRM score (OR = 2.07, 95% CI 1.12-4.14; P = 0.025). Women with ICE resected during the surgical procedure for LRE did not have more adverse postoperative clinical outcomes than ICE-negative patients. CONCLUSION Ileocaecal endometriosis was significantly associated with greater LRE severity. In a complete surgical resection strategy, combining resection of ICE and LRE did not appear to increase postoperative rates of complications, morbidity or recurrence, nor did it seem to impair long-term clinical outcomes. TWEETABLE ABSTRACT In women with low rectal endometriosis, 25% have an associated ileocaecal location that is a marker for severity.

Ineffective esophageal motility is the most frequent esophageal motility disorder. It is currently defined by 50% or more ineffective esophageal contractions and a normal lower esophageal sphincter relaxation on high-resolution esophageal manometry. Although reported in patients without symptoms, it is typically associated with gastro-esophageal reflux disease, and might be a consequence of the reflux. Ineffective esophageal motility can account for a certain degree of dysphagia, and is associated with a more severe gastroesophageal reflux. Todate, no specific endoscopic or pharmacologic treatment is available, and proton pump inhibitor are advisable when gastro-esophageal reflux is associated.

Purpose: Patient education constitutes a relevant strategy to improve pain management. In the field of therapeutic patient education (TPE), we aimed 1) to assess pain impact in cancer patients, 2) to identify patients' educative needs in pain management, and 3) to refine research criteria for its future evaluation. Patients and methods: Pain intensity, relief and interference were assessed in 75 cancer patients with unbalanced background pain. Self-assessment questionnaire evaluated i) patients' pain management and ii) their knowledge and needs in TPE. Results: Most patients experienced pain for more than 6 months and 41.6% reported adequate pain relief. Understanding pain and pain management were major patients' preferences (>58%). Most patients declared they knew their pain treatments, but fewer than half of them were able to name them. However, education concerning pain treatment was considered as essential in

International audience; BACKGROUND:Despite multimodality treatments including neurosurgery, radiotherapy and chemotherapy, glioblastoma (GBM) prognosis remains poor. GBM is classically considered as a radioresistant tumor, because of its high local recurrence rate, inside the irradiation field. The development of new radiosensitizer is crucial to improve the patient outcomes. Pre-clinical data showed that Poly (ADP-ribose) polymerase inhibitors (PARPi) could be considered as a promising class of radiosensitizer. The aim of this study is to evaluate Olaparib, a PARPi, as radiosensitizing agent, combined with the Stupp protocol, namely temozolomide (TMZ) and intensity modulated radiotherapy (IMRT) in first line treatment of partially or non-resected GBM.METHODS:The OLA-TMZ-RTE-01 study is a multicenter non-randomized phase I/IIa trial including unresectable or partially resectable GBM patients, from 18 to 70 years old. A two-step dose-escalation phase I design will first determine the recommended phase 2 dose (RP2D) of olaparib, delivered concomitantly with TMZ plus conventional irradiation for 6 weeks and as single agent for 4 weeks (radiotherapy period), and second, the RP2D of olaparib combined with adjuvant TMZ (maintenance period). Phase IIa will assess the 18-month overall survival (OS) of this combination. In both phase I and IIa separately considered, the progression-free survival, the objective response rate, the neurocognitive functions of patients, emotional disorders among caregivers, the survival without toxicity, degradation nor progression, the complications onset and the morphologic and functional MRI (magnetic resonance imaging) parameters will be also assessed as secondary objectives. Ancillary objectives will explore alteration of the DNA repair pathways on biopsy tumor, proton magnetic resonance spectroscopy parameters to differentiate tumor relapse and radionecrosis, and an expanded cognition evaluation. Up to 79 patients will be enrolled: 30 patients in the phase I and 49 patients in the phase IIa.DISCUSSION:Combining PARP inhibitors, such as olaparib, with radiotherapy and chemotherapy in GBM may improve survival outcomes, while sparing healthy tissue and preserving neurocognitive function, given the replication-dependent efficacy of olaparib, and the increased PARP expression in GBM as compared to non-neoplastic brain tissue. Ancillary studies will help to identify genetic biomarkers predictive of PARPi efficacy as radiosensitizer.TRIAL REGISTRATION:NCT03212742 , registered June, 7, 2017. Protocol version: Version 2.2 dated from 2017/08/18.

Background Patients with schizophrenia (SZ) present a higher level of cardiovascular morbidity than the general population due to poor physical fitness and a sedentary lifestyle. Moreover, despite major therapeutic advances in the management of SZ, some clinical symptoms remain resistant to pharmacological approaches. A large number of studies support the effectiveness of physical activity (PA) for both physical and mental health in SZ. The main objective of the present study is to assess the effects of a remote, web-based adapted PA program (e-APA) compared to a health education program (e-HE) on brain plasticity in SZ and healthy volunteers (HV). The secondary objectives are to assess the effects of e-APA on other cerebral variables as well as clinical, neurocognitive, circadian, biological, and physiological variables. Methods: The study is an interventional, multicenter, randomized open-label controlled trial. Forty-two SZ will be randomized to either the active group (e-APA, N = 21) or non-active group (e-HE, N = 21), and 42 HV will be matched to SZ according to age, gender, and level of PA. Interventions will consist of 32 sessions (2x60 minutes/week, for 16 weeks) via supervised home-based videoconferencing. The active group will carry out an individualized PA program of moderate to vigorous intensity. Pre- and post-intervention cerebral magnetic resonance imaging (MRI) will be performed to evaluate changes in global hippocampal volume. Other cerebral assessments using diffusion tensor imaging, arterial spin labelling, spectroscopy and resting-state functional MRI will be performed. In addition, clinical, neurocognitive and circadian rhythms assessments as well as physical tests and biological analyses will be conducted. Discussion: To our knowledge, this is the first study aiming to evaluate the efficacy of APA delivered by supervised home-based videoconferencing in SZ. Moreover, using multimodal MRI, this study could clarify the pathophysiological mechanisms underlying the efficacy of APA. Finally, this innovative approach (remote, web-based APA) might also increase participation in long-term PA since PA-based programs are known to have low adherence and early dropout. The results of this study should promote the inclusion of PA interventions as a novel adjunctive therapy for SZ. Trial registration: ClinicalTrials.gov identifier: NCT03261817. Registered on 16 August 2017.

Background/Objectives Physical activity (PA) has significant benefits for older adults. However, the recommended PA is rarely achieved in nursing homes. In this proof of concept study, we assessed whether virtual reality (VR) could help to increase spontaneous PA during a stationary cycling session. Design Prospective crossover proof of concept study. Setting Nursinghome. Participants Twelve participants (10 men) aged 63–88, able-bodied but with moderate cognitive impairment. Intervention TWO stationary cycling sessions with and withoutVR. Measurements Cycling distance, pedalling duration, average speed, mean pedalling cadence and the modified Borg rating of perceived exertion scale. Results Cycling distance and duration were significantly higher in the VR condition. Most participants would rather repeat cycling sessions with VR than without. Conclusion The use of VR seems feasible to help achieve PA recommendations for able-bodied people living in nursing homes, even with moderate cognitive impairments.

Aims Treatment decisions in patients with scimitar syndrome (SS) are often challenging, especially in patients with isolated SS who are often asymptomatic and who might be diagnosed accidentally. We queried a large multi-institutional registry of SS patients to evaluate the natural history of this condition and to determine the efficacy of surgical treatment in terms of survival and clinical status. Methods and results We collected data on 485 SS patients from 51 institutions; 279 (57%) patients were treated surgically (STPs) and 206 (43%) were clinically monitored (CMPs). Median age at last follow-up was 11.6 years (interquartile range 4-22 years). Overall survival probability at 30 years of age was 88% [85-92% confidence intervals (CI)] and was lower in patients with associated congenital heart disease (CHD) (P

Background: Endoscopic resection of extensive esophageal neoplastic lesions is associated with a high rate of esophageal stricture. Most studies have focused on the risk factors for post-endoscopic esophageal stricture, but data on the therapeutic management of these strictures are scarce. Our aim is to describe the management of esophageal strictures following endoscopic resection for early esophageal neoplasia. Methods: We included all patients with an endoscopic resection for early esophageal neoplasia followed by endoscopic dilatation at a tertiary referral center. We recorded the demographic, endoscopic, and histological characteristics, and the outcomes of the treatment of the strictures. Results: Between January 2010 and December 2019, we performed 166 endoscopic mucosal resections and 261 endoscopic submucosal dissections for early esophageal neoplasia, and 34 (8.0%) patients developed an esophageal stricture requiring endoscopic treatment. The indication for endoscopic resection was Barrett’s neoplasia in 15/34 (44.1%) cases and squamous cell neoplasia (SCN) in 19/34 (55.9%) cases. The median [(interquartile range) (IQR)] number of endoscopic dilatations was 2.5 (2.0–4.0). Nine of 34 (26.5%) patients required only one dilatation, and 22/34 (65%) had complete dysphagia relief following three endoscopic treatment sessions. The median number of dilatations was significantly higher for SCN [3.0 (2–7); range 1–17; p = 0.02], and in the case of circumferential resection [4.0 (3.0–7.0); p = 0.03]. Endoscopic dilatation allowed a sustained dysphagia relief in 33/34 (97.0%) patients after a mean follow-up of 25.3 ± 22 months. Conclusion: Refractory post-endoscopic esophageal stricture is a rare event. After a median of 2.5 endoscopic dilatations, 97.0% of patients were permanently relieved of dysphagia. Circumferential endoscopic esophageal resections should be considered when indicated.

Background: Treated cancer patients (pts) are at high risk to develop severe COVID-19 evolution and guidelines proposed some preventive medical oncologic treatments (tt) adjustments Pts had to face with this unprecedented situation, as caregivers forced to suddenly adjust their practices We assessed the pandemic-induced therapeutic modifications of pts cancer tt and the psychological impact on pts and caregivers Methods: This prospective French study was initiated among pts with solid/hematologic malignancy receiving a medical tt during the lockdown in outpatient departments of 2 cancer centers Tt modifications were collected from medical records Perceived and post-traumatic stress (PSS, IES-R), sleep (ISI), quality of life QoL (Fact-G) and cognitive complaint (Fact-Cog) were reported at baseline (during the lockdown) and will be collected at 3 and 6 months PSS and professional burnout/self-efficacy (MBI, GSES) were also reported by caregivers Results: Baseline clinical data are available for 621 pts and questionnaires for 575 pts (93%) and 73 caregivers Pts and caregivers median ages were 64 [24-89] and 40 [22-63], 69% and 81% women Caregivers were mainly nurses (48%) and oncologists (30%) 98% of pts had solid tumors, 59% with metastatic disease and 47% de novo treated Main tts included chemotherapy (72%), immunotherapy (31%) and targeted therapy (13%), 37% starting during the lockdown 27% of pts had tt modifications including 30% adapted monitoring (mainly phone-consultation), 15% tt interruptions, 32% postponed tt, 19% administration rhythm modifications, more frequently among lung cancer, tt initiated before lockdown, immunotherapy and targeted therapy Severe perceived stress, post-traumatic stress and insomnia were observed in 6%, 21% and 24% of pts More pts with tt modifications presented severe post-traumatic stress (27% vs 19%, p=0 05) Tt modifications did not impact on QoL/cognition Perceived stress score was higher among caregivers than pts (p=0 035) but 2/3 reported professional accomplishment and self efficacy Conclusions: Lockdown due to COVID-19 induced tt modification in 1/4 of pts with a majored post-traumatic stress Despite a high level of stress, caregivers coped with the situation Clinical trial identification: NCT04366154, registered on 2020, April, 16th Legal entity responsible for the study: Comprehensive Cancer Centre Francois Baclesse, Caen France Funding: French Fondation ARC (Cancer Research Association) Disclosure: All authors have declared no conflicts of interest

Purpose The aim of this prospective study (ClinicalTrials.gov: NCT01880203) was to evaluate the diagnostic and prognostic value of a 7-panel mutation testing in the aspirates of thyroid nodules with indeterminate cytology (IC). Methods Eligible patients had a thyroid nodule ≥15 mm with IC (Bethesda III–V) for which surgery had been recommended. Detection of BRAF and RAS mutations was performed using pyrosequencing and RET/PTC and PAX8/PPARγ rearrangements using Real-Time quantitative reverse transcription‐polymerase chain reaction (RT-PCR). Results Among 131 nodules with IC, 21 (16%) were malignant including 20 differentiated cancers and one thyroid lymphoma. Molecular abnormalities were identified in 15 nodules with IC corresponding to 10 malignant and 5 benign tumours. BRAF mutation was detected in 4 nodules all corresponding to classic PTC, and PAX8/PPARγ rearrangement in 2 HCC. In contrast, RAS mutation was identified in eight nodules, of which four were malignant, and one RET/PTC3 rearrangement in a follicular adenoma. This data resulted in an accuracy of 88%, sensitivity of 48%, specificity of 95%, positive-predictive value of 67%, and negative-predictive value of 91%. After a 56 month’s follow-up, the proportion of excellent response was similar in patients with molecular alterations (67%) and those without (60%). Conclusions By increasing the overall risk of cancer from 16 to 67% in mutated nodules and by diminishing it to 9% in wild-type, this study confirms the relevance of the 7-panel mutation testing in the diagnostic of nodules with IC. Genetic testing, however, did not predict outcome in the cancer patient subgroup.

BACKGROUND: General practitioners (GPs) are among the main actors involved in early melanoma diagnosis. However, melanoma diagnostic accuracy and management are reported to be insufficient among GPs in Europe. OBJECTIVES: The primary aim of this observational prospective study was to shed light on melanoma diagnostic practices among French-speaking Belgian GPs. The second aim was to specifically analyse these GPs’ pigmented skin lesion diagnostic accuracy and management. METHODS: GPs from the five French-speaking districts of Belgium were asked to complete a questionnaire, before taking part in a melanoma diagnostic training session. First, we assessed the GPs’ current melanoma diagnostic practices. Then, their pigmented skin lesion diagnostic accuracy and management were evaluated, through basic theoretical questions and clinical images. These results were subsequently analysed, according to the GPs’ socio-demographic characteristics and medical practice type. RESULTS: In total, 89 GPs completed the questionnaire. Almost half of the GPs (43%; CI=33;54) were confronted with a suspicious skin lesion as the main reason for consultation once every three months, while 33% (CI=24;43) were consulted for a suspicious lesion as a secondary reason once a month. Prior to training, one-third of the GPs exhibited suboptimal diagnostic accuracy in at least one of six “life-threatening” clinical cases among two sets of 10 clinical images of pigmented skin lesions, which can lead to inadequate patient management (i.e., incorrect treatment and/or inappropriate reinsurance). Conclusion: This study underlines the need to train GPs in melanoma diagnosis. GPs’ pigmented skin lesion diagnostic accuracy and management should be improved to increase early melanoma detection.

Background Brain metastases often occur in cancer evolution. They are not only responsible for death but also for disorders affecting the quality of life and the cognitive functions. Management of brain metastases usually consists in multi-modality treatments, including neurosurgery, whole brain radiotherapy (WBRT), and more recently radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT), systemic treatment (chemotherapy or targeted therapy), combined or not with corticosteroids. Almost 20% of brain metastases can present recent (within 15 days) bleeding signs on neuro-imagery. In these conditions, WBRT is the usual treatment. Yet, patients may benefit from a more aggressive strategy with SRT or FSRT. However, these options were suspected to possibly major the risk of brain haemorrhage, although no scientifically proven. Radiation oncologists therefore usually remain reluctant to deliver SRS/FSRT for bleeding brain metastases. It is therefore challenging to establish a standard of care for the treatment of bleeding brain metastases. We propose a phase II trial to simultaneously assess safety and efficacy of FSRT to manage brain metastases with hemorrhagic signal. Methods The STEREO-HBM study is a multicenter two-step non-randomised phase II trial addressing patients with at least one bleeding brain metastasis out of a maximum of 3 brain metastases. Each brain metastasis will be treated with 30 Gy in 3 fractions for 1 week. The main endpoint is based on both safety and efficacy endpoints as proposed by Bryant and Day’s design. Safety endpoint is defined as the rate of bleeding complications 4 months post-FSRT while efficacy endpoint is defined as the 6-month local control rate. Multi-modal MRI will be used to assess intra-tumoral hemorrhagic events before and after treatment. Patients’ quality of life will also be assessed. Discussion Management of bleeding brain metastases is still debated and poorly explored in clinical trials. There is sparse and weak data on the signification of pretreatment intra-tumour haemorrhagic signs or on the risk of brain bleeding complications after FSRT. We expect this first prospective phase 2 trial in this particular setting will allow to clarify the place of FSRT to optimally manage bleeding brain metastases. Trial registration NCT 03696680, registered October, 4, 2018. Protocol version Version 2.1 dated from 2018/11/09.

Background: Current guidelines recommend performing esophagectomy after endoscopic resection for early esophageal cancer when the risk of lymph node metastasis or residual cancer is found to be significant and endoscopic treatment is therefore noncurative. Our aim was to assess the safety and oncological outcomes of esophagogastric resection in this specific clinical setting. Patients and methods: A retrospective review from 2012 to 2018 was performed at four tertiary referral centers. All patients had a noncurative endoscopic resection of a clinical T1 esophageal cancer, followed by esophagectomy. Outcome measures were the rates of T0N0 specimens, overall survival, disease-free and cancer-specific survival, postoperative morbidity and mortality. Results: A total of 30 patients (13 with squamous cell carcinoma and 17 with adenocarcinoma) were included. The reasons for noncurative endoscopic resection were: positive vertical margins ( n = 12), squamous cell carcinoma with muscularis mucosae or submucosal layer invasion ( n = 3 and 9), adenocarcinoma with deep submucosal invasion ( n = 11), poorly differentiated tumor ( n = 6) and lymphovascular invasion ( n = 6). Overall, 63% of the esophagi were T0N0: most residual lesions were T1a metachronous lesions, and four (13%) patients had advanced pT status ( n = 3) or lymph node metastases ( n = 2). Overall survival, disease-free survival and cancer-specific survival were 83%, 75%, and 90% respectively. A total of 43% of patients had severe postoperative complications, and postoperative mortality was 7%. Conclusion: In this cohort, esophagectomy allowed the resection of residual advanced cancer or lymph node metastases in 13% of cases, at the cost of 43% severe morbidity and 7% mortality. Therefore, the possibility of close follow up needs to be balanced with a highly morbid surgical management in these patients.

The objective of this study was to assess long-term outcome and factors associated wih mortality in children after arterial switch operation (ASO) for transposition of the great arteries (TGA). Material and methods Retrospective analysis of all ASO performed from 2000 to 2016 in patients with TGA. Demographics, clinical and biological data, surgical techniques, echocardiographic measurements, and outcomes were collected. Pronostic factors for mortality were assessed. Results 364 patients were included (263 males). Antenatal diagnosis was made in 60,4%. Birth weight was 3207,5±511.2g, gestational age was 39.1±1.6weeks. Intramural coronary artery was present in 24 cases (6.6%). Long term follow-up was 9.2±4.8 years. Rashkind procedure was performed in 88.7% of the cases. Ventilatory support was needed in 56% and prostaglandins in 85% preoperatively. ASO occurred at the age of 7.44±6.26 days (1 to 56) and 5.6±4.6 days after admission. Bypass duration was 123.1±33.3mn. Overall and postoperative hospital stay were respectively 19.9±8.6 and 14.4±7.3 days. Survival rates were 95.3% at 1 month, 94.8% at 3, 6 and 12 months and 94.5% at 2.5 years and up to 18 years after surgery. Twenty patients died (5.5%): 17 early postoperatively (4.7%). Time from surgery to death was 64.2±207.9 days (0 to 919). Long-term events occurred in 49.6% of the patients: pulmonary stenosis, aortic or mitral regurgitation, residual shunt, coronary lesions (1.7%), arrhythmias (5.5%), cardiac failure. Freedom from late reintervention was 99.7%, 97.4%, 96.2% at 1, 3 and 6 months, 95.9%, 95%, 92.3% and 90.3% at respectively 1, 2, 5 and beyond 8 years after ASO. No Rashkind, postoperative ECMO support, delayed chest closure, bypass duration, troponine level and small birth weight were significant predictive factors of mortality (respectively p=0.006, p Conclusion This study showed that Rashkind procedure may have a favourable impact on prognosis of neonates with TGA. Postoperative ECMO support and troponine level, and small birth weight were associated with worse outcome.

Acute severe colitis is a potentially life-threatening medical and surgical emergency requiring hospitalization and intensive monitoring. The diagnosis of severe acute colitis is based on clinical and biological criteria. Colectomy should be discussed at each stage of management and is indicated immediately in case of complications. Thromboembolic prevention with low molecular weight heparin is essential in any patient with severe acute colitis. The first-line medical treatment is intravenous corticosteroid at a dose of 0.8mg/kg/day of prednisone equivalent. In case of failure, a second line of medical treatment can be attempted in the absence of complications. The two possible treatments are infliximab and ciclosporin.

Points essentiels La physiopathologie de l’achalasie est mal connue et repose sur la destruction des cellules ganglionnaires du plexus myenterique œsophagien. La manometrie haute resolution est l’examen diagnostique de reference. L’efficacite de la dilatation pneumatique et de la myotomie de Heller sont identiques, autour de 90 % a 1 an. La principale complication de la dilatation est la perforation œsophagienne, survenant dans environ 1 % des cas. La myotomie per-orale endoscopique est une option therapeutique prometteuse mais presentant des taux de reflux gastro-œsophagien majeurs.

As illustrated in the setting of immune checkpoint inhibitors (ICI), a crucial goal in the development of new therapeutics is to propose a companion diagnostic test. This challenge is particularly complex with a continuous marker for which a threshold is needed. We analyzed data that have demonstrated that blood-based tumor mutational burden (bTMB) may identify patients who may benefit from atezolizumab in second-line and higher NSCLC (Gandara, Nat Med 2018). Three approaches to determine a threshold for bTMB were used in the POPLAR dataset: 1) ROC curve to discriminate best overall response in the ICI arm (Youden index), 2) treatment effect on PFS among subgroups of high bTMB patients according to several thresholds, 3) marker-by-treatment predictiveness curves for PFS taking into consideration both arms. Effectiveness of predictive models was assessed on the OAK dataset using several utility measures (treatment effects, proportion of patients affected by the classification). Table 1 presents the threshold and the rate of patients in each bTMB subgroup for each approach. Treatment effects in bTMB groups were similar for the three methods, but the p-value for interaction between treatment and bTMB was the most significant for the predictive approach. Predictiveness analysis reclassified 72 patients (11.2%) as bTMB high compared to ROC analysis . In this reclassified subgroup, 6-month PFS rates were 6.65% [2.23; 19.8] (Control) and 23.40% [13.95; 39.3] (ICI). Marker-by-treatment predictiveness curves should be favoured over analyses on the experimental arm only. Prognostic approaches may not be useful for treatment selection. A prognostic value doesn't ensure that treatment effects will differ depending on marker value. Moreover, treatment interaction modelling at different timepoints is particulary relevant when proportional hazards assumption is violated. Pros and cons of each approach will be presented. Treatment effects within bTMB groups and interaction between treatment and bTMB in the OAK cohortDichotomization approachThresholdN (%)Treatment armHR for treatmentpinteractionROCbTMB Citation Format: Julia Gilhodes, Frédérique Penault-Llorca, Julien Mazières, Maurice Pérol, Christos Chouaid, Eve Leconte, Jean-Pierre Delord, Thomas Filleron. Development of companion tests based on continuous markers: Illustration with blood-based tumor mutational burden in NSCLC cancer patients treated with atezolizumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 264.

12123 Background: Sudden COVID-19 pandemic has enforced social restrictions across the globe, including social distancing, curfews and total lockdowns, which persist in many parts of the world. Beyond these measures, cancer patients have faced up to the threat of the risk of severe COVID-19 infections and the adaptations of medical oncology practices, with potential impact on their psychological well-being. We aimed to follow Post-Traumatic Stress Disorder (PTSD) symptoms and other Patient-Reported Outcomes (PROs) over this period among cancer patients from the French COVIPACT study. Methods: The COVIPACT study (NCT04366154) included patients with solid/hematologic malignancy receiving medical treatment during the first lockdown in outpatient departments of two cancer centers. Patients were asked to fulfill validated questionnaires on PTSD symptoms (IES-R), insomnia (ISI), quality of life (FACT-G) and cognition (FACT-Cog) at baseline (M0, first lockdown, Apr/May 2020), 3 months (M3, post-lockdown, Jul/Aug 2020) and 6 months (M6, second lockdown, Oct/Nov 2020). PTSD was defined as an IES-R score ≥33 and moderate/severe insomnia as an ISI score ≥15. Higher values on the FACT-G (range 0-108) and FACT-Cog (PCI subscale range 0-72) indicated better quality of life and cognition, respectively. Changes in PROs over time were assessed using mixed models for repeated measures. Results: Among the 734 patients included in COVIPACT, 579, 347 and 328 completed the questionnaires at M0, M3 and M6, respectively: median age, 64 years, 72% women, 59% metastatic status. Patients were mostly treated for breast (44%), lung, head and neck (20%), digestive (16%) and gynecologic cancers (11%). We observed a J-shaped evolution of PTSD over time, affecting 21.2% of patients during the first lockdown, 13.6% the post-lockdown and 23.6% during the second lockdown (p for time < 0.001). Moreover, patients reported linear deterioration of cognitive function over follow-up (p < 0.001). No change was observed in any dimension of quality of life (p for time = 0.06). 24.3%, 27.1% and 28.1% of the patients reported insomnia at M0,M3 and M6 (p for time = 0.35). At each time, PTSD was associated with more insomnia, worst quality of life and cognitive complain. At all the times, ≥50% of patients with PTSD reported insomnia compared to ≤23% in non-PTSD patients (p < 0.001). In addition, there was a clinically significant difference of ≥16 points on the FACT-G and ≥8 points on the FACT-Cog PCI between PTSD and non-PTSD patients (p < 0.001) at the all times. Conclusions: More than 20% of patients have developed PTSD during the different periods of lockdown, with strong association with poor quality of life, cognitive complain and insomnia. Psychosocial support promoting emotional resilience should be largely offered to cancer patients to prevent and/or reduce PTSD. Clinical trial information: NCT04366154.

Background:The clinical approach to a prolonged cough,i.e. a cough lasting more than three weeks, is challenging for general practitioners as well for primary care pediatricians. What the recommended clinical approach in primary care is, how cough duration or cough characteristics impact the diagnosis, and what the efficiency and safety of antibiotics or symptomatic treatments are remain in question for primary care physicians.Objective:The last Belgian guidelines were published in 2006 and needed to be reviewed. Those background questions were used to conduct our guideline updating procedure.Methods:We systematically performed a pyramidal literature search between the periods 2006-2014 in order to write evidence based guidelines. The data of the literature was summarized, discussed by the authors, experts and the Belgian primary care guidelines committee. Recommendations were formulated and scored following the GRADE classification.Results:The consultation history as well as the physical examination should be directed towards searching for warning signs (GRADE 1B) and towards the common etiologies depending on cough duration (GRADE 2C). If the cough lasts for more than eight weeks, chest radiography and spirometry should be considered (GRADE 2C). An antibiotic is recommended for a prolonged wet cough (over eight weeks) if prolonged bacterial bronchitis is suspected (GRADE 1B). In the absence of clinical signs of a specific etiology of a cough, no drug can be recommended (GRADE 1B). For all cases, it is initially suggested to avoid irritants (GRADE 1C) as well as to take into account the concerns of parents and inform them about the natural development of a cough.Conclusions:More research is needed to provide evidence on the clinical pathway on prolonged cough for primary care. Cough duration of more than eight weeks and prolonged wet cough are the most useful cough characteristics. Regarding a specific cough treatment, no medication has proved any effect greater than placebo. Attention to environmental triggers and patient-centered care remain the keystones of interventions

Background New generation hormone-therapies (NGHT) targeting the androgen signalling pathway are nowadays proposed to elderly patients with metastatic castration-resistant prostate cancer (CRPCa). The impact of these treatments on cognitive function has never been evaluated whereas cognitive impairment may have an impact on the autonomy and the treatment adherence. The aim of this study is to prospectively assess the incidence of cognitive impairment in elderly men after treatment by NGHT for a metastatic CRPCa. Methods/design The Cog-Pro study is a multicentre longitudinal study including CRPCa patients ≥70 years old treated with NGHT (n = 134), control metastatic prostate cancer patients without castration resistance treated with first generation androgen deprivation therapy (n = 55), and healthy participants (n = 33), matched on age and education. Cognitive, geriatric and quality of life assessment and biological tests will be performed at baseline, 3, 6 and 12 months after start of the treatment (inclusion time). The primary endpoint is the proportion of elderly patients receiving a NGHT who will experience a decline in cognitive performances within 3 months after study enrollment. Secondary endpoints concern: autonomy, quality of life, anxiety, depression, cognitive reserve, adherence to hormone-therapy, comparison of the cognitive impact of 2 different NGHT (abiraterone acetate and enzalutamide), impact of co-morbidities and biological assessments. Discussion Evaluating, understanding and analyzing the incidence, severity of cognitive impairments and their impact on quality of life, autonomy and adherence in this group of patients with advanced disease is a challenge. This study should help to improve cancer care of elderly patients and secure the use of oral treatments as the risk of non-observance does exist. Our results will provide up-to date information for patients and caregivers on impact of these treatments on cognitive function in order to help the physicians in the choice of the treatment. Trial registration NCT02907372, registered: July 26, 2016.

In mammals, ejaculated spermatozoa must migrate into the female reproductive tract in order to reach and fertilize the oocyte (Figure 1). The number of spermatozoa that reach the oviductal isthmus (where they attach to oviductal cells and form the sperm reservoir) is small (1,2) and only ~10% of these spermatozoa in humans become capacitated (3) and acquire a state of readiness for fertilizing the oocyte. In addition, the sperm cells have a torturous and long way between the reservoir and the oocyte at the fertilization site (3–5 cm in humans) (2). These facts, together with the tiny dimensions of the gametes in comparison to the tube length make improbable the sperm arrival to the fertilization site and make evident the need for sperm guidance (4). Different guidance mechanisms appear essential for successful sperm arrival to the fertilization site: the short range mechanism such as chemotaxis (swimming up a chemoattractant gradient) (5) and the long range mechanisms such as rheotaxis (swimming against a fluid flow) and thermotaxis (the temperature-oriented cell motility). Fil: Lottero Leconte, Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Alonso, Carlos Agustín Isidro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Castellano, Luciana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Perez Martinez, Silvina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina

International audience; Background and AimsDifferent types of histologic lesions at the ileal margin, detected by histology, have been associated with increased rates of recurrence after ileocaecal surgery in patients with Crohn’s disease (CD). We aimed to characterize histologic features of the ileal margin and to evaluate their association with disease recurrence.MethodsWe collected histologic data from 211 patients with ileal or ileocolonic CD who underwent ileocolonic resections at hospitals in France from September 2010 through December 2016. Ileal margins were analyzed. Early endoscopic recurrence was defined by a Rutgeerts score of i2 or more, 6 months after surgery. We also collected data from 10 adults with healthy ileum who underwent ileocecal resection for colonic tumors (controls). Clinical relapse was defined by CD-related symptoms confirmed by imaging, endoscopy, therapy intensification, CD-related complication, or subsequent surgery.ResultsSix months after surgery, 49% of patients had endoscopic recurrence; 5 years after surgery, 57% of patients had clinical relapse. Ileal margins were macroscopically affected in 20.9% of patients. CD transmural lesions at the margin (defined by mucosal ulceration or cryptitis, submucosal fibrosis and lymphoplasmacytic infiltrate of the subserosa) were observed in 13.6% of patients. Endoscopic recurrence was observed in 75% of patients with CD transmural lesions vs 46% of patients without (P =.005). In multivariate analysis, CD transmural lesions at the margin were independently associated with early endoscopic recurrence (OR, 3.83; 95% CI, 1.47-11.05; P =.008) and clinical recurrence (OR 2.04; 95% CI, 1.09-3.99; P =.026).ConclusionIn patients with CD, transmural lesions at the ileal margin were associated with an increased risk of post-operative recurrence. Histologic features of the ileal margin should be included in making decisions about post-operative therapy.

International audience; Ambulatory surgery has grown to be the most common procedure in developed countries. Efficient quality of care and safety often require calling patient at day one after outpatient surgery to check patient's recovery and search for complications. This increasing flow in same day surgery centres motivates the use of automatic systems to contact patients. The overall objective of this study was to evaluate automated software sending text messages (TM) to patients at day 1 after ambulatory surgery compared to classical phone calls. This prospective study took place in Rennes Teaching Hospital, France, from June 1st, 2015 to December 15th, 2016. All patients owning a mobile phone were included, adults and children by means of their parents. The primary end point was the rate of successfully contacted patients, compared to usual phone calls in 2014. In cases of no response or an abnormal response, an automatic alert was sent to the ambulatory unit. Within the 7246 patients included, response rate to TM was significantly higher than response to phone calls in 2014 (87% vs 57%, respectively p

Background Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. Patients and Methods Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status. Results The sample consisted of women newly diagnosed with EBC (n = 118) and healthy controls (n = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant (p = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline. Conclusion This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC. Implications for Practice After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced accelerated cognitive decline. Initial cognitive functioning should be included in the balance of benefits and harms of systemic therapy for patients who are likely to be at highest risk for cognitive decline after cancer treatments. Regular cognitive follow-up of patients who had cognitive impairment before cancer treatment should monitor symptoms suggestive of neurodegenerative disease and avert the effect of cognitive disorders on patients’ autonomy.

International audience; Elhers-Danlos syndrome (EDS) is the clinical manifestation of connective tissue disorders, and comprises several clinical forms with no specific symptoms and selective medical examinations which result in a delay in diagnosis of about 10 years. The EDS hypermobility type (hEDS) is characterized by generalized joint hypermobility, variable skin hyperextensibility and impaired proprioception. Since somatosensory processing and multisensory integration are crucial for both perception and action, we put forth the hypothesis that somatosensory deficits in hEDS patients may lead, among other clinical symptoms, to misperception of verticality and postural instability. Therefore, the purpose of this study was twofold: (i) to assess the impact of somatosensory deficit on subjective visual vertical (SVV) and postural stability; and (ii) to quantify the effect of wearing somatosensory orthoses (i.e., compressive garments and insoles) on postural stability. Six hEDS patients and six age- and gender-matched controls underwent a SVV (sitting, standing, lying on the right side) evaluation and a postural control evaluation on a force platform (Synapsys), with or without visual information (eyes open (EO)/eyes closed (EC)). These two latter conditions performed either without orthoses, or with compression garments (CG), or insoles, or both. Results showed that patients did not exhibit a substantial perceived tilt of the visual vertical in the direction of the body tilt (Aubert effect) as did the control subjects. Interestingly, such differential effects were only apparent when the rod was initially positioned to the left of the vertical axis (opposite the longitudinal body axis). In addition, patients showed greater postural instability (sway area) than the controls. The removal of vision exacerbated this instability, especially in the mediolateral (ML) direction. The wearing of orthoses improved postural stability, especially in the eyes-closed condition, with a particularly marked effect in the anteroposterior (AP) direction. Hence, this study suggests that hEDS is associated with changes in the relative contributions of somatosensory and vestibular inputs to verticality perception. Moreover, postural control impairment was offset, at least partially, by wearing somatosensory orthoses.

Post-therapeutic surveillance is one important component of cancer care. However, there still is no evidence-based strategies to schedule patients’ follow-up examinations. Our approach is based on the modeling of the probability of the onset of relapse at an early asymptotic or preclinical stage and its transition to a clinical stage. For that we consider a multistate homogeneous Markov model, which includes the natural history of relapse. The model also handles separately the different types of possible relapses. The optimal schedule is provided by the calendar visit that maximizes a utility function. The methodology has been applied to laryngeal cancer. The different follow-up strategies revealed to be more efficient than those proposed by different scientific societies.

Background Intraoperative photography is used extensively for communication, research, or teaching. The objective of the present work was to define, using a standardized methodology and literature review, the best technical conditions for intraoperative photography. Materials and methods Using either a smartphone camera, a bridge camera, or a single-lens reflex (SLR) camera, photographs were taken under various standard conditions by a professional photographer. All images were independently assessed blinded to technical conditions to define the best shooting conditions and methods. Results For better photographs, an SLR camera with manual settings should be used. Photographs should be centered and taken vertically and orthogonal to the surgical field with a linear scale to avoid error in perspective. The shooting distance should be about 75 cm using an 80–100-mm focal lens. Flash should be avoided and scialytic low-powered light should be used without focus. The operative field should be clean, wet surfaces should be avoided, and metal instruments should be hidden to avoid reflections. For SLR camera, International Organization for Standardization speed should be as low as possible, autofocus area selection mode should be on single point AF, shutter speed should be above 1/100 second, and aperture should be as narrow as possible, above f/8. For smartphone, use high dynamic range setting if available, use of flash, digital filter, effect apps, and digital zoom is not recommended. Conclusions If a few basic technical rules are known and applied, high-quality photographs can be taken by amateur photographers and fit the standards accepted in clinical practice, academic communication, and publications.

Purpose Prevention of multidrug resistant (MDR) bacterial contamination remains a major challenge in ICUs. Many hospital outbreaks involving MDR transmitted through environmental contamination have been reported. Bedside high-density EEG allow for dynamic cognitive evaluation in brain-injured patients and is used more and more frequently in clinical practice to evaluate brain function and predict outcome in severely neurologically impaired patients. Unfortunately, the material used for this procedure is not entirely disposable. Method We performed a systematic analysis of MDR bacterial contamination in patients contaminated in our ICU using specific bacteriological methods. Results We report a proven case of cross-contamination of an extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae strain, and a possible case of cross-contamination of a carbapenem-resistant Acinetobacter baumannii strain. Conclusion Cross-contamination of MDR bacteria is possible through high-density EEG material. However, appropriate procedures can decrease this risk.

Background: Breast oncologic surgery and especially nodal surgery has become ever more minimally invasive. However, some aggressive breast cancers exhibit at their primary or recurrent presentation extensive nodal invasion at the axillary, retropectoralis and sometimes supraclavicular and cervical levels. Surgical treatment of these tumors is not standardized. Material and methods: Between January 2012 and April 2015, 7 primary breast cancer patients (group I) and 7 recurrent breast cancer patients (group II) were included in a prospective, non randomized study approved by our local ethics committee. All the patients had cytologically proven retropectoralis and infraclavicular lymph node invasion and 7 of them had cytologically proven cervical lymph node invasion (5 in the group of primary tumors and 2 in the group of recurrences). Four of the 7 primary tumors were triple negative and 3 were HER2 positive tumors, while 4 out of the 7 recurrent tumors were triple negative and 3were HER2 positive. All the patients underwent PET/CT and breast MRI at baseline. Visceral metastases were absent in all cases. In the group of primary tumors, all the patients were treated with neoadjuvant chemotherapy (plus trastuzumab for the 3 HER2 positive tumors); in the group of recurrent tumors, neoadjuvant chemotherapy associated with trastuzumab was administered in 3 patients, while the 4 other patients underwent complementary mastectomy plus extensive nodal surgery followed by chemotherapy. Radiotherapy was administered in all primary breast cancer patients and cervical radiotherapy was administered in 3 of the 7 recurrent diseases. The following parameters were assessed: disease-free survival, overall survival and adverse events of surgical treatment. Results: All the patients are still alive after a relatively short mean duration of follow-up [24 months in group I (6 to 40 months) and 29 months in group II (3 to 39 months)]. Six of the 7 patients in group I have no signs of recurrence, one has metastatic evolution (bilateral cervical and mediastinal node evolution) and is currently receiving chemotherapy in combination with a PARP inhibitor. In group II, 6 of the 7 patients have no signs of recurrence and one has metastatic evolution (inguinal nodes and bone metastases), treated with chemotherapy and HER2-targeted therapy. The major adverse event is arm lymphedema, affecting 4 out of 14 patients (28%). No persistent pain nor motor troubles are noted. Discussion: Patients with nodal metastases outside the axilla seem to benefit from extensive surgery integrated in a multidisciplinary therapeutic approach. Some studies have demonstrated survival benefits for patients undergoing surgical resection of these nodes. Conclusion: In aggressive breast tumors (HER2 positive or triple negative tumors) presenting with extensive nodal invasion, surgical excision of these nodal metastases must be integrated in the multidisciplinary treatment and patients need to be followed prospectively for a long time to confirm survival benefits. Citation Format: Berliere M, Duhoux F, Nardai P, Schmitz S, Taburiaux L, Galant C, Leconte I, Piette P, Lengele B. Is there any benefit to perform extensive nodal dissection in primary or recurrent aggressive form of breast cancer?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-12-04.

Abdominal emergencies during pregnancy (excluding obstetrical emergencies) occur in one out of 500-700 pregnancies and may involve gastrointestinal, gynecologic, urologic, vascular and traumatic etiologies; surgery is necessary in 0.2-2% of cases. Since these emergencies are relatively rare, patients should be referred to specialized centers where surgical, obstetrical and neonatal cares are available, particularly because surgical intervention increases the risk of premature labor. Clinical presentations may be atypical and misleading because of pregnancy-associated anatomical and physiologic alterations, which often result in diagnostic uncertainty and therapeutic delay with increased risks of maternal and infant morbidity. The most common abdominal emergencies are acute appendicitis (best treated by laparoscopic appendectomy), acute calculous cholecystitis (best treated by laparoscopic cholecystectomy from the first trimester through the early part of the third trimester) and intestinal obstruction (where medical treatment is the first-line approach, just as in the non-pregnant patient). Acute pancreatitis is rare, usually resulting from trans-ampullary passage of gallstones; it usually resolves with medical treatment but an elevated risk of recurrent episodes justifies laparoscopic cholecystectomy in the 2nd trimester and endoscopic sphincterotomy in the 3rd trimester. The aim of the present work is to review pregnancy-induced anatomical and physiological modifications, to describe the main abdominal emergencies during pregnancy, their specific features and their diagnostic and therapeutic management.

Resume Objectif Le syndrome de Beckwith-Wiedemann (SBW) est le syndrome d’exces de croissance congenitale le plus frequent avec une incidence de 1/13 700 naissances. Son diagnostic est le plus souvent realise apres la naissance. Il predispose a un risque eleve d’hypoglycemie en postnatal immediat et de tumeurs embryonnaires. Le but de ce travail est d’identifier les signes d’appel echographique en antenatal devant alerter tout echographiste afin de permettre une meilleure prise en charge perinatale. Methodes Il s’agit d’une etude retrospective concernant une serie de 14 cas de SBW de diagnostic perinatal dont 4 diagnostics evoques en antenatal. Les signes echographiques decrits en antenatal ont ete analyses et compares aux signes cliniques de la periode postnatale. Resultats Les signes majeurs le plus souvent rapportes etaient representes par la macrosomie pour 71,4 % des enfants avec une augmentation du perimetre abdominal et la macroglossie pour 78,6 %. Les signes mineurs etaient divers mais avec 64 % de visceromegalie (nephromegalie et/ou hepatomegalie), 50 % d’hydramnios et pour 80 % d’enfants de sexe masculin une anomalie genitale (cryptorchidie et/ou hypospade). Conclusion Cette etude a permis d’identifier certains signes echographiques antenataux devant alerter le clinicien vers un diagnostic de SBW. Un conseil genetique, apres confirmation par biologie moleculaire, pourrait etre propose dans un avenir plus au moins proche en prenatal, et cela afin d’ameliorer la prise en charge de ces enfants a risque neonatal.