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Sepsis is a prevalent life-threatening condition related to a systemic infection, and with unresolved issues including refractory septic shock and organ failures. Endogenously released catecholamines are often inefficient to maintain blood pressure, and low reactivity to exogenous catecholamines with risk of sympathetic overstimulation is well documented in septic shock. In this context, apelinergics are efficient and safe inotrope and vasoregulator in rodents. However, their utility in a larger animal model as well as the limitations with regards to the enzymatic breakdown during sepsis, need to be investigated. The therapeutic potential and degradation of apelinergics in sepsis were tested experimentally and in a cohort of patients. (1) 36 sheep with or without fecal peritonitis-induced septic shock (a large animal experimental design aimed to mimic the human septic shock paradigm) were evaluated for hemodynamic and renal responsiveness to incremental doses of two dominant apelinergics: apelin-13 (APLN-13) or Elabela (ELA), and (2) 52 subjects (33 patients with sepsis/septic shock and 19 healthy volunteers) were investigated for early levels of endogenous apelinergics in the blood, the related enzymatic degradation profile, and data regarding sepsis outcome. APLN-13 was the only one apelinergic which efficiently improved hemodynamics in both healthy and septic sheep. Endogenous apelinergic levels early rose, and specific enzymatic breakdown activities potentially threatened endogenous apelin system reactivity and negatively impacted the outcome in human sepsis. Short-term exogenous APLN-13 infusion is helpful in stabilizing cardiorenal functions in ovine septic shock; however, this ability might be impaired by specific enzymatic systems triggered during the early time course of human sepsis. Strategies to improve resistance of APLN-13 to degradation and/or to overcome sepsis-induced enzymatic breakdown environment should guide future works.

Background The French National Cancer Institute recommends the use of survivorship care plans (SCP) for all cancer survivors. Developing useful SCP's requires understanding of what survivors and their providers need and how SCP's can be implemented in practice. We conducted a study to assess the delivery of SCP comprehensive binders for breast cancer women (BCW) and their general practitioners (GP) in a Cancer center from January 2019. Methods SCP binders, containing a full range of information on topics related to post-cancer care to survivor-specific information and referrals, were given to BCW during a post-treatment dedicated consultation. Then a letter, containing the treatment summary and 5-year follow-up schedule, was sent to their GPs. Comprehensive binder delivery assessment was carried out using item checkbox, and anonymous open-answered, self-reported questionnaires were sent by email to BCW and their GPs. Results The questionnaire response rates were 81.3% for BCW (n = 109/134) and 48.6% for their GPs (n = 52/107). Most BCW (85%) reported that SCP binders provided useful and comprehensive information. However, some of them (18%) felt abandoned and anonymous during the post-treatment follow-up. Most GPs found SCP letters from our anti-cancer center physicians to be useful for their patients, 38% of them had used this information to assure transition of care with other care providers. In addition, GPs were unanimous to express their feeling that this SCP could improve the long-term surveillance of BCW. There was a high concordance between BCW survivors’ and PCP’ answers, especially regarding SCPs as a communication bridge between GPs and BCW survivors. Response results concerning use of the binders: to talk about them: 59% for BCW vs. 51% for GPs, and to show them: 35% for BCW vs. 31% for GPs. Conclusion The opinions of BCW survivors’ and PCP’ opinions about the use of SCP's by our Cancer Center seems to be favourable. It is essential to implement and develop SCP's as a key tool in long-term surveillance and support for cancer patient survivors and they are a useful instrument for care providers in communication and transition.

We assessed long-term associations of Granulocyte-Colony Stimulating Factors (G-CSF) use with patient-reported outcomes (PROs) and hematologic toxicity among chemotherapy-treated, early-stage breast cancer patients in CANTO (NCT01993498). Among 2920 patients longitudinally followed-up until year-4 after diagnosis, 49% used G-CSF. In multivariable-adjusted mixed-models, EORTC QLQ-C30 pain and summary score were not substantially different between groups (overall adjusted mean difference, use vs no-use [95%CI]: +1.27 [-0.33 to +2.87] and −1.01 [-1.98 to −0.04], respectively). PROs were slightly worse at year-4 among patients receiving G-CSF, although differences were of trivial clinical significance. No major differences were observed in leukocyte or platelet count over time., Highlights • Studies on long-term side effects of G-CSF, including on quality of life, are lacking. • We evaluated PROs and hematological values until year-4 after diagnosis among women with early breast cancer receiving G-CSF. • 49% women treated with adjuvant chemotherapy in CANTO (N = 2920) used G-CSF. • Long-term PROs and hematological values were not substantially different in women using G-CSF or not. • There were slightly worse outcomes at year-4 in patients using G-CSF, although of trivial clinical significance.

Background: Nowadays, the assessment of health related quality of life (HRQOL) in women with breast cancer (BC) has become very important, with the improvement of their prognosis and the growing number of BC survivors. HRQOL is therefore a main endpoint in cancer therapeutic care and its improvement should be an important goal of BC treatment. The aim of this study was to assess HRQOL at the end of acute treatment in BC patients using data of the multicenter prospective French CANTO cohort. Methods: CANTO (NCT 01993498) is a multicenter prospective observational study (26 centers in France) whose main objective is to study the chronic toxicities of anticancer treatments in 12,000 women with localized stages I to III BC. HRQOL was assessed at baseline and at the end of acute treatments (surgery +/- radiotherapy +/- chemotherapy) using the EORTC-QLQ-C30 questionnaire and its BC specific module, the EORTC-QLQ-BR23 questionnaire. The EORTC-QLQ-C30 is composed of 30 items which allow generating 15 scales which are: 5 functional scales, 8 symptom scales, a global health status and a financial difficulties scale. The EORTC-QLQ-BR23 comprises 23 items and contains 4 functional scales and 4 symptoms scales. The minimal clinically important change score (MCID) was defined as a mean difference of at least 10 points in HRQOL scores between the baseline and the end of acute treatments (M0). Mixed linear model was used to assess the determinants of HRQOL For the dimensions with MCID. Results: from March 2012 to December 2014, 5801 BC patients were included in the CANTO cohort. The mean age at diagnostic was 57 years (SD=11.5) and 22.1 % of patients was single. Ninety percent of women had a good performance status and 79 % did not have comorbidities. Most of patients underwent surgery (99.7%), among which 77% by conservative surgery, and respectively 90.3 % were treated with radiotherapy, 80.2 % with hormone therapy and 53.3 with chemotherapy. Out of 23 dimensions, treatments for the disease did not impact the HRQOL of patients for global health status and 17 others dimensions of the QLQ-C30 and QLQ-BR23. However, with the means change score (MD) over 10 points, body image functional scale (MD= -14, p Conclusion: Results of this study did not show an impact of acute treatments for early stage BC on global health status of patients. The most affected dimensions, by the treatments, were body image, pain, breast symptoms, arm symptoms and upset by hair loss. Overweight, anxiety, depression, education level, hormonal status and chemotherapy were the main determinant of HRQOL. Citation Format: Oumar Billa, Olivia Dialla, Sarah Dauchy, Barbara Pistilli, Paul-Henri Cottu, Anne Lesur, Florence Lerebour, Olivier Tredan, Laurence Vanlemmens, Christelle Jouannaud, Christelle Levy, Charles Cecile, Anne Laure Martin, Sibille Everhard, Florence Joly, Charles Coutant, Fabrice Andre, Patrick Arveux, Sandrine Dabakuyo-Yonli. Health related quality of life at the end of acute treatments for early stage breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-04.

Adjuvant endocrine therapy is highly effective and appropriate for all breast cancer patients with hormone receptor positive tumors, pre and post menopausal women. It's an oral daily pill for many years, after primary treatment. Although this medication dramatically reduces reccurrence rates and risk of death, many breast cancer survivors either fail to take pills with prescribed frequency (adherence) or discontinue therapy (persistence) or even never begin to take it. It's difficult to know exactly the prevalence of adherence and persistence but women age younger than 40 years had the highest risk of discontinuation. Medical literature of the last 15 years in this area has been carefully reviewed considering initiation treatment background, specificity of premenopausal young women population, healthcare provider and patient communication and respective views. It's highlighted that dedicated care, at first and after in follow up, is an essential part for better adherence. Guidelines processing are more and more complicated, expert medical assesment is required, shared decision must be provide. Patients need enhanced knowledge about mode of action, benefits but also potential side effects, and optimized patient provider relationship for empathy and better comprehension. Providers must believe in treatment relevance and convey their convictions.

Resume Introduction : Objectifs : Evaluer la tolerance du Tamoxifene (TAM) en termes d’effets secondaires et statut hormonal, la persistance du traitement sur cinq ans et rapporter les donnees du suivi lointain. Methodes : La population etudiee a inclus 55 patientes entre janvier 2001 et novembre 2002 a l’Institut de cancerologie de Lorraine, de 50 ans ou moins, traitees par TAM a la dose quotidienne de 20 mg, pour une duree prevue de 5 ans, en situation adjuvante, pour un cancer du sein, non menopausees au diagnostic. Les donnees du suivi au-dela de 24 mois apres l’introduction du TAM ont ete recueillies retrospectivement entre janvier et mars 2019. Resultats : Les incidences cumulees de l’apparition de kystes ovariens et de bouffees de chaleur a 5 ans etaient respectivement de 68,5 et 77,6 %. Parmi les 33 patientes en amenorrhee chimio-induite, la moitie ont eu une reprise des cycles dans un delai median de 9 mois. Chez les 10 patientes sans amenorrhee chimio-induite, 4 ont eu un arret des cycles. Parmi elles, 3 patientes ont eu une reprise des cycles dans un delai de 1, 4 et 8 mois. Trente-quatre patientes (61,3 %) avaient pris du TAM au moins 5 ans. A 15 ans, les survies globale et sans progression etaient respectivement 90,7 et 67,4 %. Conclusion : L’observation de la tolerance du traitement pendant les 5 ans et au-dela contribue a la qualite des informations delivrees aux futures patientes debutant le traitement, permettant une meilleure comprehension et a terme une meilleure observance.

Despite proven survival benefits after breast cancer, long-trem compliance with adjuvant hormone therapy remains a major issue, partly due to the side effects of treatment. In young women treated for breast cancer, these treatments include tamoxifen, anti-aromatase and LH-RH analogues, with even more side effects when these treatments are combined, especially for younger patients with more aggressive disease. The management of the potential side effects requires first of all detailed and precise information at initiation of treatment, and preventive measures including patient education. Once the treatment has been initiated, clinicians should be able to propose to their patients appropriate measures to alleviate the potential of the side effects, which can be of various types: biological (dyslipidemia), physical (weight gain, hot flushes, vaginal dryness, sexual disorders with low libido, musculoskeletal symptoms…) or psychosocial (anxio-depressive disorders, poor body image, difficulties of professional reintegration). Management of these effects can combine various modalities: drugs (switching hormone therapy, anti-depressants, hormonal treatments of vaginal dryness in some cases, gabapentin), physical treatments (CO2 laser for vulvovaginal atrophy) or psycho-physical techniques (physical activity, mindfulness, acupuncture…). Eventually, the lenghth of these adjuvant hormonal treatments requires supportive measures to help young patients engage in new lifestyle measures, in particular in term of physical activity and diet. This will help them mitigate the symptoms related to these side-effects while reducing the long-term risks related to their disease and treatments.

Introduction/Background* Endometrial cancer (EC) is the most common gynecological cancer in developed countries. There are no screening tools for its early diagnosis, and the diagnostic process starts with the apparition of related symptoms, mainly, abnormal vaginal bleeding (AVB). It is estimated that ~7M women with AVB will undergo the diagnostic process every year in Europe, and from those, 9% will have EC. Importantly, the current diagnostic process relies on the pathological examination of an endometrial biopsy that is always obtained by minimally-invasive to invasive methods. This overdiagnosis creates a big burden to the healthcare systems, so the development of non-invasive tools for EC diagnosis would revolutionize this scenario. Our aim is to approach a non-invasive diagnosis by the identification of protein biomarkers to accurately diagnose EC in liquid cervical cytologies. Methodology The discovery phase consisted of a shotgun label-free proteomic approach. It included 60 patients (20 EC, 20 controls suffering AVB without endometrial or cervical pathology, and 20 controls without endometrial pathology but cervical pathology). The levels of a statistically significant set of 75 proteins (110 peptides) from the discovery phase were measured in a verification phase including 234 (107 non-EC; 127 EC) patients by LC-MSMS/PRM. Analysis was performed using MaxQuant, Skyline, SPSS and R software. Result(s)* The discovery study permitted to determine a total number of 2,888 proteins in our samples. Statistical analysis identified 75 potential proteins differently expressed between EC and non-EC patients to be further assessed and verified. Verification phase revealed the potential of 58 proteins measured in cervical cytologies to reach a non-invasive diagnosis of EC. Specifically, 16 proteins achieved an AUC > 0.75, and 3 proteins an AUC > 0.8. Additionally, an ELISA assay of the best performing protein was tested reproducing the results obtained by mass-spectrometry and reaching an AUC=0.927 in this dataset. Conclusion* We identified protein biomarkers in liquid cervical cytologies to diagnose EC patients with a diagnostic power up to 92%. These results are promising for a subsequent development of an early and non-invasive screening tool for EC. This tool is expected to change the standard of care in EC diagnosis.

The contribution talks about the application of AESA technology for telemetry ground antennas. The proposed AESA concept is a 1-axis electronically steerable antenna (elevation axis), while the azimuth axis remains mechanically driven. The design will lead to a 1m2 effective area antenna, dedicated to short - medium range telemetry, for target with high potential dynamics. The present paper describes the concept and the technology used during this development plan. The paper focuses on performances but also tries to compare this technology to the legacy antennas used in telemetry, to point the improvements test ranges could get with such innovative antenna. The contribution will cover the interests to develop an AESA antenna, the principle and technology chosen, the electromagnetic simulations, a comparison between a standard parabolic of flat panel antenna and this work, and a conclusion regarding the possible application of AESA technology for ground telemetry antennas.

During autoscopic phenomena, people perceive a double of themselves in extrapersonal space. Such clinical allocentric self-experiences sometimes co-occur with auditory hallucinations, yet experimental setups to induce similar illusions in healthy participants have generally neglected acoustic cues. We investigated whether feeling the presence of an auditory double could be provoked experimentally by recording healthy participants’ own versus another person’s voice and movements using binaural headphones from an egocentric (the participants' own) and an allocentric (a dummy head located elsewhere) perspective. When hearing themselves allocentrically, participants reported feeling a self-identified presence extracorporeally, an arguably distinct quality of autoscopy. Our results suggest that participants without hallucinatory experiences localized their own voice closer to themselves compared to that of another person. Explorative findings suggest that distinct patterns for hallucinators should be further investigated. This study suggests a successful induction of the feeling of an acoustic doppelganger, bridging clinical phenomena and experimental work.

Bodily self-identification has shown to be easily altered through spatiotemporally congruent multimodal signals. While such manipulations are mostly studied through visuo-tactile or visuo-motor stimulation, here we investigated whether congruent visuo-olfactory cues might enhance illusory self-identification with an arbitrary object. Using virtual reality, healthy individuals saw a grapefruit from its supposed first-person perspective that was touched in synchrony with their own body. The touch attempted to replicate what was seen as softly squeezing the grapefruit. Crucially, when we additionally presented the smell of a grapefruit in synchrony with the squeezing, they self-identified stronger with the fruit than when they smelled strawberry.

Objectives: Arterial hypertension, when exacerbated by excessive dietary salt intake, worsens the morbidity and mortality rates associated with cardiovascular and renal diseases. Stimulation of the apelinergic system appears to protect against several circulatory system diseases, but it remains unknown if such beneficial effects are conserved in severe hypertension. Therefore, we aimed at determining whether continuous infusion of apelinergic ligands (i.e., Apelin-13 and Elabela) exerted cardiorenal protective effects in spontaneously hypertensive (SHR) rats receiving high-salt diet.Methods: A combination of echocardiography, binding assay, histology, and biochemical approaches were used to investigate the cardiovascular and renal effects of Apelin-13 or Elabela infusion over 6 weeks in SHR fed with normal-salt or high-salt chow.Results: High-salt intake upregulated the cardiac and renal expression of APJ receptor in SHR. Importantly, Elabela was more effective than Apelin-13 in reducing high blood pressure, cardiovascular and renal dysfunctions, fibrosis and hypertrophy in high-salt fed SHR. Unlike Apelin-13, the beneficial effects of Elabela were associated with a counter-regulatory role of the ACE/ACE2/neprilysin axis of the renin-angiotensin-aldosterone system (RAAS) in heart and kidneys of salt-loaded SHR. Interestingly, Elabela also displayed higher affinity for APJ in the presence of high salt concentration and better resistance to RAAS enzymes known to cleave Apelin-13.Conclusion: These findings highlight the protective action of the apelinergic system against salt-induced severe hypertension and cardiorenal failure. As compared with Apelin-13, Elabela displays superior pharmacodynamic and pharmacokinetic properties that warrant further investigation of its therapeutic use in cardiovascular and kidney diseases.

Standard adjuvant therapies for breast cancer such as chemotherapy or aromatase inhibitor and LH-RH agonist hormone therapy are associated with significant survival gains but also induce bone loss by aggravating the estrogen deprivation. The bone loss may be substantial, notably during early treatment, and occurs regardless of the baseline bone mineral density values. The objective of developing these recommendations was to achieve a practical consensus among various scientific societies, based on literature review, about osteoporosis prevention and treatment in these patients. The following scientific societies contributed to the work: Société Française de Rhumatologie (SFR), Groupe de Recherche et d'Information sur les Ostéoporoses (GRIO), Groupe Européen d'Etudes des Métastases Osseuses (GEMO), Association Francophone pour les Soins Oncologiques de Support (AFSOS), Société Française de Sénologie et de Pathologie Mammaire (SFSPM), Société Française de Radiothérapie Oncologique (SFRO). Drug prescription and reimbursement modalities in France were taken into account. These recommendations apply to postmenopausal women taking systemic chemotherapy and/or aromatase inhibitor therapy, non-postmenopausal women taking LH-RH agonist therapy, and non-postmenopausal women with persistent amenorrhea 1 year after chemotherapy completion. All women in these three categories should undergo an evaluation of bone health and receive interventions to combat risk factors for bone loss. Patients with a history of severe osteoporotic fracture and/or a T-score value-2.5 should receive osteoporosis drug therapy. The FRAX® score should be used to guide treatment decisions in patients whose T-score is between -1 and -2.5. General osteoporosis prevention measures should be applied in patients without criteria for osteoporosis drug therapy, who should undergo bone mineral density measurements 18-24 months later if the baseline T-score is-1 and 3-5 years later if the baseline T-score is-1. The anti-tumor effect of bisphosphonates and denosumab was not considered when establishing these recommendations.

Background: Randomized trials, although not all, suggest exercise therapy improves treatment completion rates / relative dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy (CT). In addition, preclinical studies show that exercise therapy adds to the antitumor activity of standard CT in murine models of breast cancer. We evaluated the association between exercise and pathologic complete response (pCR) rate (i.e., ypT0ypN0) in patients receiving neoadjuvant CT for operable breast cancer. Methods: Using a prospective design, patients with stage I-III breast cancer receiving anthracycline-taxane (± trastuzumab) neoadjuvant CT participating in a multicenter, national cohort study in France (CANTO, NCT01993498) completed questionnaire assessing self-reported exercise behavior (GPAQ 16). Multivariate logistic models were performed to determine the relationship between pre-CT exercise exposure (total MET-h/wk categorized into the proportion of patients meeting WHO exercise guidelines, the equivalent of ≥10 MET-h/wk), pCR rates, CT± trastuzumab dose reductions, delays, treatment completion or interruptions for the overall cohort and on the basis of clinical subtype. Results: Between March, 2012 to December, 2014, a total of 989 patients participating in CANTO received neoadjuvant CT and completed GPAQ 16. Here we present interim analyses on 608 patients. Fifty-four percent of patients engaged on of ≥10 MET-h/wk prior to CT administration. In multivariable analysis for the overall cohort, exercise exposure was not associated with higher pCR (p=0.69). The pCR rate was 27.7% for patients reporting Conclusion: On the basis of interim analyses, higher pretreatment exercise exposure is not associated with higher clinical response or treatment tolerability in breast cancer patients receiving uniform conventional neoadjuvant CT. Full results will be presented at the meeting. Citation Format: Baker JL, Di Meglio A, El Mouhebb M, Iyengar NM, Michiels S, Cottu P, Lerebours F, Coutant C, Lesur A, Tredan O, Soulie P, Vanlemmens L, Jouannaud C, Levy C, Everhard S, Martin A-L, Arveux P, Fabrice A, Vaz Luis I, Jones LW. Association between exercise, pathological complete response, and treatment tolerability in patients receiving neoadjuvant chemotherapy for operable breast cancer: Results from the CANTO study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-03.

Pain represents an embodied experience, wherein inferences are not only drawn from external sensory inputs, but also from bodily states. Previous research has demonstrated that a placebo administered to an embodied rubber hand can effectively induce analgesia, providing first evidence that placebos can work even when applied to temporarily embodied, artificial body parts. Using a heat pain paradigm, the present study investigates placebo analgesia and pain perception during virtual embodiment. We examined whether a virtual placebo (a sham heat protective glove) can successfully induce analgesia, even when administered to a virtual body. The analgesic efficacy of the virtual placebo to the real hand (augmented reality setting) or virtual hand (virtual reality setting) was compared to a physical placebo administered to the own, physical body (physical reality setting). Furthermore, pain perception and subjective embodiment were compared between settings. In this mixed design experiment, healthy participants (n = 48) were assigned to either an analgesia-expectation or control-expectation group, where subjective and objective pain was measured at pre- and post-intervention time points. Results demonstrate that pre-intervention pain intensity was lower in the virtual reality setting, and that participants in the analgesia-expectation group, after the intervention, exhibited significantly higher pain thresholds, and lower pain intensity and unpleasantness ratings than control-expectation participants, independent of the setting. Our findings show that a virtual placebo can elicit placebo analgesia comparable to that of a physical placebo, and that administration of a placebo does not necessitate physical bodily interaction to produce analgesic responses. PERSPECTIVE: This study demonstrates that a virtual placebo treatment, even when administered to a virtual body, can produce placebo analgesia. These findings indicate that the efficacy of a virtual placebo is comparable to that of a physical placebo, which could pave the way for effective new non-pharmacological approaches for pain management.

Pain represents an embodied process, wherein inferences are not only drawn from sensory inputs, but also from bodily states. Previous research has demonstrated that a placebo administered to an embodied rubber hand can effectively induce analgesia, providing first evidence that placebos can work even when applied to temporarily embodied, artificial body parts. Using a heat pain paradigm, the present study investigates placebo analgesia and pain perception during virtual embodiment. We examined whether a virtual placebo (a sham heat protective glove) can successfully induce analgesia, even when administered to a virtual body. The analgesic efficacy of the virtual placebo to the real hand (augmented reality setting) or virtual hand (virtual reality setting) was compared to a physical placebo administered to the own, physical body (physical reality setting). Furthermore, pain perception and subjective embodiment were compared between settings. Healthy participants (n=48) were assigned to either an analgesia-expectation or control-expectation group, where subjective and objective pain was measured at pre- and post-intervention time points. Results evinced that pre-intervention pain intensity was lower in the virtual reality setting, and that participants in the analgesia-expectation condition, after the intervention, exhibited significantly higher pain thresholds, and lower pain intensity and unpleasantness ratings than control-expectation participants, independent of the setting. Our findings evince that a virtual placebo can elicit placebo analgesia comparable to that of a physical placebo, and that administration of a placebo does not necessitate physical bodily interaction to produce analgesic responses, which might pave the way for effective new non-pharmacological approach for pain management.

PURPOSE Nonadherence to long-term treatments is often under-recognized by physicians and there is no gold standard for its assessment. In breast cancer, nonadherence to tamoxifen therapy after surgery constitutes a major obstacle to optimal outcomes. We sought to evaluate the rate of biochemical nonadherence to adjuvant tamoxifen using serum assessment and to examine its effects on short-term, distant disease-free survival (DDFS). PATIENTS AND METHODS We studied 1,177 premenopausal women enrolled in a large prospective study (CANTO/NCT01993498). Definition of biochemical nonadherence was based on a tamoxifen serum level < 60 ng/mL, assessed 1 year after prescription. Self-reported nonadherence to tamoxifen therapy was collected at the same time through semistructured interviews. Survival analyses were conducted using an inverse probability weighted Cox proportional hazards model, using a propensity score based on age, staging, surgery, chemotherapy, and center size. RESULTS Serum assessment of tamoxifen identified 16.0% of patients (n = 188) below the set adherence threshold. Patient-reported rate of nonadherence was lower (12.3%). Of 188 patients who did not adhere to the tamoxifen prescription, 55% self-reported adherence to tamoxifen. After a median follow-up of 24.2 months since tamoxifen serum assessment, patients who were biochemically nonadherent had significantly shorter DDFS (for distant recurrence or death, adjusted hazard ratio, 2.31; 95% CI, 1.05 to 5.06; P = .036), with 89.5% of patients alive without distant recurrence at 3 years in the nonadherent cohort versus 95.4% in the adherent cohort. CONCLUSION Therapeutic drug monitoring may be a useful method to promptly identify patients who do not take adjuvant tamoxifen as prescribed and are at risk for poorer outcomes. Targeted interventions facilitating patient adherence are needed and have the potential to improve short-term breast cancer outcomes.

During autoscopic phenomena, people perceive a double of themselves in extrapersonal space. Such clinical allocentric self-experiences often co-occur with auditory hallucinations, yet experimental setups to induce similar illusions in healthy participants have been limited to visual doubles. We investigated whether feeling the presence of an auditory double could be provoked in healthy participants and how it might affect spatial aspects of bodily self-consciousness. We recorded the own versus another person’s voice while walking around in the room using binaural headphones from an egocentric and an allocentric perspective. In comparison to listening to their own moving voice egocentrically, when listening to themselves allocentrically, participants reported a strong feeling of a presence with a similarly high degree of self-identification, suggesting a successful induction of the feeling of an acoustic doppelganger. When pointing to the source of the own voice participants localized it closer to themselves than when listening to another person’s voice, suggesting a change in spatial perception. Interestingly, the opposite pattern was found in participants that had previous hallucinatory experiences. These findings show that listening to one’s own voice allocentrically can manipulate bodily self-consciousness and self-related spatial perception. This paradigm enables the experimental study of the relationship between auditory vocal hallucinations and bodily self-consciousness, bridging important clinical phenomena and experimental knowledge.

Background Hypertonic sodium lactate (HSL) may be of interest during inflammation. We aimed to evaluate its effects during experimental sepsis in rats (cecal ligation and puncture (CLP)). Methods Three groups were analyzed (n = 10/group): sham, CLP-NaCl 0.9%, and CLP-HSL (2.5 mL/kg/h of fluids for 18 h after CLP). Mesenteric microcirculation, echocardiography, cytokines, and biochemical parameters were evaluated. Two additional experiments were performed for capillary leakage (Evans blue, n = 5/group) and cardiac hemodynamics (n = 7/group). Results HSL improved mesenteric microcirculation (CLP-HSL 736 [407–879] vs. CLP-NaCl 241 [209–391] UI/pixel, p = 0.0006), cardiac output (0.34 [0.28–0.43] vs. 0.14 [0.10–0.18] mL/min/g, p p = 0.009). HSL also raised dP/dtmax slope (6.3 [3.3–12.1] vs. 2.7 [2.0–3.9] 103 mmHg/s, p = 0.04), lowered left ventricular end-diastolic pressure-volume relation (1.9 [1.1–2.3] vs. 3.0 [2.2–3.7] RVU/mmHg, p = 0.005), and reduced Evans blue diffusion in the gut (37 [31–43] vs. 113 [63–142], p = 0.03), the lung (108 [82–174] vs. 273 [222–445], p = 0.006), and the liver (24 [14–37] vs. 70 [50–89] ng EB/mg, p = 0.04). Lactate and 3-hydroxybutyrate were higher in CLP-HSL (6.03 [3.08–10.30] vs. 3.19 [2.42–5.11] mmol/L, p = 0.04; 400 [174–626] vs. 189 [130–301] μmol/L, p = 0.03). Plasma cytokines were reduced in HSL (IL-1β, 172 [119–446] vs. 928 [245–1470] pg/mL, p = 0.004; TNFα, 17.9 [12.5–50.3] vs. 53.9 [30.8–85.6] pg/mL, p = 0.005; IL-10, 352 [267–912] vs. 905 [723–1243] pg/mL) as well as plasma VEGF-A (198 [185–250] vs. 261 [250–269] pg/mL, p = 0.009). Conclusions Hypertonic sodium lactate fluid protects against cardiac dysfunction, mesenteric microcirculation alteration, and capillary leakage during sepsis and simultaneously reduces inflammation and enhances ketone bodies.

PURPOSE Adverse effects of breast cancer treatment can negatively affect survivors’ work ability. Previous reports lacked detailed clinical data or health-related patient-reported outcomes (PROs) and did not prospectively assess the combined impact of treatment and related sequelae on employment. METHODS We used a French prospective clinical cohort of patients with stage I-III breast cancer including 1,874 women who were working and ≥ 5 years younger than legal retirement age (≤ 57 years) at breast cancer diagnosis. Our outcome was nonreturn to work (non-RTW) 2 years after diagnosis. Independent variables included treatment characteristics as well as toxicities (Common Toxicity Criteria Adverse Events [CTCAE] v4) and PROs (European Organization for Research and Treatment of Cancer [EORTC] Quality of life Questionnaires, Breast cancer module [QLQ-BR23] and Fatigue module [QLQ-FA12], Hospital Anxiety and Depression Scale) collected 1 year after diagnosis. Logistic regression models assessed correlates of non-RTW, adjusting for age, stage, comorbidities, and socioeconomic covariates. RESULTS Two years after diagnosis, 21% of patients had not returned to work. Odds of non-RTW were significantly increased among patients treated with combinations of chemotherapy and trastuzumab (odds ratio [OR] v chemotherapy-hormonotherapy: for chemotherapy-trastuzumab, 2.01; 95% CI, 1.18 to 3.44; for chemotherapy-trastuzumab-hormonotherapy, 1.62; 95% CI, 1.10 to 2.41). Other significant associations with non-RTW included grade ≥ 3 CTCAE toxicities (OR v no, 1.59; 95% CI, 1.15 to 2.18), arm morbidity (OR v no, 1.59; 95% CI, 1.19 to 2.13), anxiety (OR v no, 1.47; 95% CI, 1.02 to 2.11), and depression (OR v no, 2.29; 95% CI, 1.34 to 3.91). CONCLUSION Receipt of systemic therapy combinations including trastuzumab was associated with increased odds of non-RTW. Likelihood of unemployment was also higher among patients who reported severe physical and psychological symptoms. This comprehensive study identifies potentially vulnerable patients and warrants supportive interventional strategies to facilitate their RTW.

PURPOSE MINDACT demonstrated that 46% of patients with early breast cancer at high clinical but low genomic risk on the basis of MammaPrint may safely avoid adjuvant chemotherapy. A second random assignment (R-C) compared docetaxel-capecitabine with an anthracycline-based regimen. PATIENTS AND METHODS R-C randomly assigned patients 1:1 between standard anthracycline-based regimens, with or without taxanes (control) and experimental docetaxel 75 mg/m2 intravenously plus oral capecitabine 825 mg/m2 two times per day for 14 days (DC) every 3 weeks for 6 cycles. The primary end point was disease-free survival (DFS). Secondary end points included overall survival and safety. RESULTS Of 2,832 patients, 1,301 (45%) were randomly assigned, and 97% complied with R-C assignment. In the control arm, 29.6% only received taxanes (0.5% of N0 patients). DFS events (n = 148) were much less than required (n = 422) as a result of a lower-than-expected accrual and event rate. At 5 years of median follow-up, DFS was not different between DC (n = 652) and control (n = 649; 90.7% [95% CI, 88% to 92.8%] v 88.8% [95% CI, 85.9% to 91.1%]; hazard ratio [HR], 0.83 [95% CI, 0.60 to 1.15]; P = .26). Overall survival (HR, 0.91 [95% CI, 0.54 to 1.53]) and DFS in the clinical high and genomic high-risk subgroup (86.1% v 88.1%; HR, 0.83 [95% CI, 0.58 to 1.21]) were similar in both arms. DC led to more grade 1 neuropathy (27.1% v 11.2%) and more grade 2 hand/foot syndrome (28.5% v 3.3%) and diarrhea (13.7% v 5.8%). Serious cardiac events occurred in 9 patients (control, n = 4; DC, n = 5). Fifty-three patients developed second cancers (control, n = 32; DC, n = 21; leukemia: 2 v 1). Five treatment-related deaths occurred (control, 2 [0.3%]; DC, 3 [0.5%]). CONCLUSION Although underpowered, this second randomization in MINDACT did not show any improvement in outcome or safety with the use of DC compared with anthracycline-based chemotherapy.

This paper demonstrates a system capable of combining a sparse, indirect, monocular visual SLAM, with both offline and real-time Multi-View Stereo (MVS) reconstruction algorithms. This combination overcomes many obstacles encountered by autonomous vehicles or robots employed in agricultural environments, such as overly repetitive patterns, need for very detailed reconstructions, and abrupt movements caused by uneven roads. Furthermore, the use of a monocular SLAM makes our system much easier to integrate with an existing device, as we do not rely on a LiDAR (which is expensive and power consuming), or stereo camera (whose calibration is sensitive to external perturbation e.g. camera being displaced). To the best of our knowledge, this paper presents the first evaluation results for monocular SLAM, and our work further explores unsupervised depth estimation on this specific application scenario by simulating RGB-D SLAM to tackle the scale ambiguity, and shows our approach produces reconstructions that are helpful to various agricultural tasks. Moreover, we highlight that our experiments provide meaningful insight to improve monocular SLAM systems under agricultural settings., Comment: accepted to WACV 2021, acknowledgment added

International audience; Background: Splenic artery aneurysm (SAA) is a rare but potentially fatal condition. Rupture results in 25% mortality up to 75% in pregnant women with 95% fetal mortality. Brief reports suggest an increased risk of developing SAA in patients with HHT.Methods: We analyzed enhanced multidetector CT data in 186 HHT patients matched (gender and ± 5 year old) with 186 controls. We screened for SAA and recorded diameter of splenic and hepatic arteries and hepatic, pancreatic and splenic parenchymal involvements. We determined by univariate and multivariate analysis, the relationship with age, sex, genetic status, cardiovascular risk factors (CVRF) and visceral involvement.Results: SAA concerned 24.7% of HHT patients and 5.4% of controls, p

Lung cancer is the deadliest cancer worldwide, mainly due to its advanced stage at the time of diagnosis. A non-invasive method for its early detection remains mandatory to improve patients&rsquo, survival. Plasma levels of 351 proteins were quantified by Liquid Chromatography-Parallel Reaction Monitoring (LC-PRM)-based mass spectrometry in 128 lung cancer patients and 93 healthy donors. Bootstrap sampling and least absolute shrinkage and selection operator (LASSO) penalization were used to find the best protein combination for outcome prediction. The PanelomiX platform was used to select the optimal biomarker thresholds. The panel was validated in 48 patients and 49 healthy volunteers. A 6-protein panel clearly distinguished lung cancer from healthy individuals. The panel displayed excellent performance: area under the receiver operating characteristic curve (AUC) = 0.999, positive predictive value (PPV) = 0.992, negative predictive value (NPV) = 0.989, specificity = 0.989 and sensitivity = 0.992. The panel detected lung cancer independently of the disease stage. The 6-protein panel and other sub-combinations displayed excellent results in the validation dataset. In conclusion, we identified a blood-based 6-protein panel as a diagnostic tool in lung cancer. Used as a routine test for high- and average-risk individuals, it may complement currently adopted techniques in lung cancer screening.

Background There is no large prospective trial assessing mid-term adverse effects of adjuvant chemotherapy. In order to address this question, we developed CANTO (CANcer TOxicities - NCT01993498 - http://etudecanto.org/), a prospective trial dedicated to the quantification of side effects after treatment for patients with early breast cancer and to develop predictors of such toxicities. The aim of this presentation is to assess chemotherapy (CT) practice and to report toxicities that persist 3-6 months after CT. Methods CANTO is a prospective study enrolling newly diagnosed invasive cT0-cT3, cN0-3, M0 breast cancer patients (pts) of 26 French comprehensive cancer centers. The study has included 10 500 patients at the time of submission. Pts are assessed at diagnosis, 3-6, 12, 36, 48 and 60 months after treatment completion. CANTO collects >100 items related to toxicities. In the current study, we focus on the first set of data available from the trial (1st database lock, n=6090). We here assess CT practice and toxicities at 3 months. Results Information about (neo)adjuvant CT (NACT/ACT) is available in 5805 pts (96%). Median age at diagnosis was 57y (22-93). Pts had HR+/HER2-, HER2+ or triple negative (TN) tumors in 74%, 15% and 11% of cases. Ki67 was assessed in 70%, and genomic tests in 1% of pts, respectively. Overall, 3074 pts (53%) received CT, either adjuvant (ACT: 76%) or neoadjuvant (NACT: 24%). ACT/NACT pts (84%) received a sequential anthracyclines–taxanes based 6 courses CT schedule. CT was administered in 44.7%, 87.2% and 92.3% of HR+/HER2+/TN tumors, respectively. ACT was administered in 73.2% of pT2+ pts (vs 36.0% in pT0-1 – p We focus here on clinically most relevant patient reported symptoms at 3 m (any grade). side effects at 3m no CT (%)CT (%)p valuePain76.682.1 Pain complaint was recorded in 3596 pts (97.2% of pts with available data), with a median value of 4 on the VAS (range 1-10). In ACT/NACT pts, muscle and joint pain were predominant. Neurological symptoms were seen in 3024 pts (59%), the most frequent pertaining to cognitive disorder (attention trouble, CT: 61.2% vs noCT: 56% - p=.06) and peripheral neuropathy (overall 31%). Paresthesias and sensory neuropathy were much more frequent in CT vs noCT pts: respectively 37.3% vs 20.3% and 25.7% vs 12.8% (both p Conclusions In this real life, prospective cohort, CT is frequently prescribed and appears in good compliance with current guidelines. Overall, symptoms burden at treatment completion is strikingly high, and much higher in pts receiving CT. A special attention should be given to pain and neurological symptoms. Dedicated questionnaires and sub-studies will explore in depth these side effects. Extended analyses of CT practice and toxicities will be presented. Citation Format: Cottu PH, Amar Y, Pistilli B, Bonsang-Kitzis H, Lesur A, Lerebours F, Vanlemmens L, Tredan O, Levy C, Jouannaud C, Fournier M, Soulie P, Rigal O, Giacchetti S, Arnaud A, Arsene O, Savignoni A, Mesleard C, Andre F, Arveux P. CANTOCHEM: Analysis of chemotherapy practice and early side effects in the 6090 first patients from the prospective CANTO cohort [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-18.

Across the European continent, the integration of increasing numbers of renewable energy sources within the electricity grids has become a strategic objective, requiring the modernization and expansion of the grids. In particular, recent studies have emphasized the major role of bulk power lines with lengths of several hundred kilometers. These pan-European transmission corridors with capacities of 5 to 20 GW were shown to be necessary, no matter which energy scenario is explored [1], [2].

Catecholamines, in concert with fluid resuscitation, have long been recommended in the management of septic shock. However, not all patients respond positively and controversy surrounding the efficacy-to-safety profile of catecholamines has emerged, trending toward decatecholaminization. Contextually, it is time to re-examine the “maintaining blood pressure” paradigm by identifying safer and life-saving alternatives. We put in perspective the emerging and growing knowledge on a promising alternative avenue: the apelinergic system. This target exhibits invaluable pleiotropic properties, including inodilator activity, cardio-renal protection, and control of fluid homeostasis. Taken together, its effects are expected to be greatly beneficial for patients in septic shock.

Activating ESR1 mutations have recently been reported as a key mechanism leading to Aromatase Inhibitor (AI) resistance. ESR1 mutations occur rarely in primary breast cancers. However, in large retrospective studies, ESR1 mutations occurred in up to 39% of Estrogen-Receptor(ER)-positive metastatic breast cancer resistant to AI. Numerous hotspot mutations have been identified, most of them affecting the ligand-binding domain (LBD) and leading to ligand-independent activation of the ER and to resistance to AI. Phosphatidylinositol 3-kinase (PI3K)/AKT pathway is involved in key Cellular Mechanisms and mutations in PIK3CA and AKT1 are frequently reported in breast cancer. In this study, we propose to use a capture-based Next Generation Sequencing (NGS) assay and to use the barcoding and polishing features in our analysis pipeline. This assay will be able to detect all mutations on AKT1, PIK3CA, ESR1 and other genes on circulating tumor DNA (ctDNA) extracted from blood samples of patients with breast cancer. We consider that this exon-screening strategy is relevant according to the recent knowledge. We plan to prospectively include women with advanced breast cancer about to begin standard-of-care first line endocrine therapy (ET). Patients will be required to have histologically confirmed ER-positive, HER2-negative breast cancer and documented loco-regionally advanced or metastatic disease, not amenable to surgery or radiation with curative intent. Patients with endocrine sensitive disease (no prior ET or relapse more than 12 months after completing adjuvant ET) as well as patients with endocrine resistant disease (relapse while on adjuvant ET or within 12 months of completing adjuvant ET) will be enrolled. ET can be prescribed alone or in combination with a targeted therapy. Nevertheless, we will recruit at least 25% of patients with exclusive ET in the endocrine sensitive group. Peripheral-blood samples, for analysis of ctDNA, will be obtained from participating patients at pre-specified time points: at start of ET to determine the baseline mutational status of ESR1, PIK3CA, AKT1 and other genes included in a panel of genes of interest in solid tumors, and then, at evaluation of response to therapy until disease progression or end of study. Patients will be followed for 36 months or until disease progression. Determination of progression will be done per local investigator. The primary objective is to describe the prevalence of activating ESR1 mutations affecting the LBD, using NGS, from the start of ET to progression or end of study. Secondary objectives include to describe the prevalence of ESR1 mutations affecting other domains, the prevalence of ESR1 mutations in patients with and without endocrine resistance at enrolment and the prevalence of PIK3CA and AKT1 mutations, to demonstrate that ESR1, PIK3CA and AKT1 mutations whatever their times of onset are predictors of progression free survival. As of June 2018, 8 sites were opened to recruitment and 18 pts were included; the target enrollment is 146. The trial is supported by AstraZeneca. Citation Format: Massard V, Uwer L, Salleron J, Deblock M, Kieffer A, Rios M, Gilson P, Lesur A, Harle A, Merlin JL. CICLADES: Monitoring of ESR1, PIK3CA and AKT1 ctDNA mutations during real-life follow-up of patients with advanced breast cancer treated with endocrine therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-03-02.

Radiation-induced pulmonary fibrosis (RIPF) is a debilitating side effect of radiation therapy (RT) of several cancers including lung and breast cancers. Current clinical methods to assess and monitor RIPF involve diagnostic computed tomography (CT) imaging, which is restricted to anatomical macroscopic changes. Confocal laser endomicroscopy (CLE) or fluorescence endomicroscopy (FE) in combination with a fibrosis-targeted fluorescent probe allows to visualize RIPF in real-time at the microscopic level. However, a major limitation of FE imaging is the lack of anatomical localization of the endomicroscope within the lung. In this work, we proposed and validated the use of x-ray fluoroscopy-guidance in a rat model of RIPF to pinpoint the location of the endomicroscope during FE imaging and map it back to its anatomical location in the corresponding CT image. For varying endomicroscope positions, we observed a positive correlation between CT and FE imaging as indicated by the significant association between increased lung density on CT and the presence of fluorescent fiber structures with FE in RT cases compared to Control. Combining multimodality imaging allows visualization and quantification of molecular processes at specific locations within the injured lung. The proposed image-guided FE method can be extended to other disease models and is amenable to clinical translation for assessing and monitoring fibrotic damage.

BEST PATHS (acronym for “BEyond State-of-the-art Technologies for rePowering ac corridors and multi-Terminal HVDC Systems”) is a collaborative project of 40 leading European organizations from science and industry, supported by the 7th Research Framework Programme of the European Commission. The project investigates the feasibility of technological innovations that could advance high-capacity transmission links. These innovations include a demonstrator project dedicated to superconducting electric lines, which aims to validate the novel MgB2 technology for GW-level HVDC power transmission. The four-year project will thus demonstrate the operation of a full-scale 320 kV MgB2 monopole cable system that can transfer up to 3.2 GW. This paper focuses on the design and development activities for the 10 kA cable conductor, which were carried out in the first two years of the project.

Resume Introduction La chirurgie du cancer du sein est adaptee a une pratique ambulatoire car il s’agit d’une chirurgie programmee, a faible risque operatoire. L’objectif de cette etude a ete d’evaluer les indicateurs de reussite reconnus : taux de conversion en hospitalisation conventionnelle, taux de complications et de re-hospitalisations dans le mois suivant l’intervention. Methodes Analyse descriptive des cas consecutifs de patientes operees d’un cancer du sein en ambulatoire entre le 25 novembre 2012 et le 31 decembre 2013, a partir d’une base de donnees constituee prospectivement. Les caracteristiques sociodemographiques des patientes et clinico-biologiques des tumeurs ont ete relevees ainsi que le type de chirurgie et les actes preoperatoires. Resultats Trois cent quatre-vingt-seize patientes ont ete incluses. L’âge moyen des patientes etait de 54 ans [2–84], ont ete effectuees : 382 chirurgies conservatrices du sein (98,2 %), 238 ganglions sentinelles (60,1 %) et 40 curages axillaires (10,1 %). Trente-neuf patientes prevues en chirurgie ambulatoire ont ete hospitalisees en chirurgie conventionnelle, soit un taux de conversion de 9,8 % IC 95 % [6,7–9,12], dont 24 pour drainage axillaire (61,5 %). Ont ete observees 15 complications dans le mois suivant l’intervention, soit 3,7 % IC 95 % [1,8–5,6], et 5 re-hospitalisations ont eu lieu dans le mois suivant l’intervention soit 1,2 % IC 95 % [0,1–2,3]. Conclusion Les taux de complication et de re-hopitalisation apres chirurgie du sein en ambulatoire sont tres faibles (

Neural network machine learning approaches are widely used for object classification or detection problems with significant success. A similar problem with specific constraints and challenges is object state estimation, dealing with objects that consist of several removable or adjustable parts. A system that can detect the current state of such objects from camera images can be of great importance for Augmented Reality (AR) or robotic assembly and maintenance applications. In this work, we present a CNN that is able to detect and regress the pose of an object in multiple states. We then show how the output of this network can be used in an automatically generated AR scenario that provides step-by-step guidance to the user in assembling an object consisting of multiple components.

Background: Standard clinical imaging of the acute respiratory distress syndrome (ARDS) lung lacks resolution and offers limited possibilities in the exploration of the structure−function relationship, and therefore cannot provide an early and clear discrimination of patients with unexpected diagnosis and unrepair profile. The current gold standard is open lung biopsy (OLB). However, despite being able to reveal precise information about the tissue collected, OLB cannot provide real-time information on treatment response and is accompanied with a complication risk rate up to 25%, making longitudinal monitoring a dangerous endeavor. Intravital probe-based confocal laser endomicroscopy (pCLE) is a developing and innovative high-resolution imaging technology. pCLE offers the possibility to leverage multiple and specific imaging probes to enable multiplex screening of several proteases and pathogenic microorganisms, simultaneously and longitudinally, in the lung. This bedside method will ultimately enable physicians to rapidly, noninvasively, and accurately diagnose degrading lung and/or fibrosis without the need of OLBs. Objectives and Methods: To extend the information provided by standard imaging of the ARDS lung with a bedside, high-resolution, miniaturized pCLE through the detailed molecular imaging of a carefully selected region-of-interest (ROI). To validate and quantify real-time imaging to validate pCLE against OLB. Results: Developments in lung pCLE using fluorescent affinity- or activity-based probes at both preclinical and clinical (first-in-man) stages are ongoing—the results are promising, revealing correlations with OLBs in problematic ARDS. Conclusion: It can be envisaged that safe, high-resolution, noninvasive pCLE with activatable fluorescence probes will provide a “virtual optical biopsy” and will provide decisive information in selected ARDS patients at the bedside.

The apelinergic pathway has been generating increasing interest in the past few years for its potential as a therapeutic target in several conditions associated with the cardiovascular and metabolic systems. Indeed, preclinical and, more recently, clinical evidence both point to this G protein-coupled receptor as a target of interest in the treatment of not only cardiovascular disorders such as heart failure, pulmonary arterial hypertension, atherosclerosis, or septic shock, but also of additional conditions such as water retention/hyponatremic disorders, type 2 diabetes, and preeclampsia. While it is a peculiar system with its two classes of endogenous ligand, the apelins and Elabela, its intricacies are a matter of continuing investigation to finely pinpoint its potential and how it enables crosstalk between the vasculature and organ systems of interest. In this perspective article, we first review the current knowledge on the role of the apelinergic pathway in the above systems, as well as the associated therapeutic indications and existing pharmacological tools. We also offer a perspective on the challenges and potential ahead to advance the apelinergic system as a target for therapeutic intervention in several key areas.

This study aimed to compare the self-reported perceptions of the repercussions of the disease and its treatments and emotional distress in young women with breast cancer and their partners.Cross-sectional study using self-reported questionnaires.491 couples in which women were aged45 years when diagnosed with non-metastatic breast cancer in four different groups of treatment: during chemotherapy with or without Trastuzumab; under Trastuzumab with or without hormone therapy; during hormone therapy; and during the follow-up period.Patients and partners completed a questionnaire assessing their self-reported perceptions of the disease and treatments (Patient YW-BCI and Partner YW-BCI for the partners) and their emotional distress (CESD; STAI).Patients reported more difficulties than partners in the management of child(ren) and everyday life, body image and sexuality, negative affectivity about the disease and apprehension about the future, career management, and finances. While the difficulties were generally more marked in the chemotherapy and Trastuzumab groups than in the hormone therapy and follow-up groups, the negative affectivity about the disease and apprehension about the future was high in all four groups, especially in patients. The partners reported more difficulties in sharing with close relatives, and even more in those groups reflecting the latest treatment phases. No difference appeared between patients and partners in couple cohesion and deterioration of relationships with relatives. Partners were less anxious than patients but as depressed as them.Difficulties of patients and partners seem particularly severe in the early care pathway, maybe reflecting better adjustment in women under surveillance and their partners. A longitudinal study will substantiate this finding and enable a better identification of some explanatory processes of these differences and similarities in the daily self-reported repercussions of the disease throughout the cancer care pathway. Implications for psychosocial oncology: It seems important to support young women with breast cancer and their partners, as our results evidence distress in both and differences according to the type of treatment the woman is currently receiving. Healthcare providers need consistent methods to identify and respond to couples' distress and reduce significant disparities in support.

This article presents research activities for the development of Ka-band electronic scanning antenna array for SATCOM applications. The full system is composed of two antennas: a receive antenna (Rx) and a transmit antenna (Tx). This document is focused on the receive architecture and in particular on the design of a new topology for MMIC Variable Gain Low Noise Amplifier (VGLNA). The proposed LNA topology is composed of 2 common source cells and 2 cascode cells. The UMS PH15 process is used to design and manufacture the VGLNA. The simulated noise figure is below 1.4 dB and the gain maintained over 40 dB. The final circuit covers an area of $3.4\times 1.4\ \mathbf{mm}2$ .

Rationale: Overweight and obesity are highly prevalent among BC patients and are linked to poorer prognosis and worse patient-reported outcomes (PROs). Weight loss interventions, based on caloric restriction, increased physical activity (PA) and behavioral counselling, are safe and feasible among BC survivors and hold the promise to improve BC-specific outcomes. MEDEA: Motivating to Exercise and Diet, and Educating to healthy behaviors After breast cancer (ClinicalTrials.gov NCT04304924) will evaluate the impact of weight loss on CRF. Trial design: French multi-center 1:1 randomized controlled trial comparing a 12-month personalized, telephone-based weight loss program + health education intervention vs health education alone in overweight or obese BC patients. Endpoints and measures: Primary endpoint: difference in self-reported CRF 12 months post-randomization between arms, measured using the EORTC QLQ-C30 CRF subscale. Secondary endpoints: 1) PROs (EORTC QLQ-C30, -B45, -FA12), anxiety and depression (Hospital Anxiety and Depression Scale); 2) weight and body mass index (BMI), diet habits and quality, PA, sleep; 3) cost-effectiveness (number and length of hospital-admissions, all-drug consumption, number and duration of sick leaves). Accelerometer data will be collected to track PA and sleep measures. Qualitative analyses will evaluate patient motivation and satisfaction. Main eligibility criteria: stage I-II-III BC, primary BC treatment completed within the prior 12 months (definitive surgery, adjuvant chemo-, and/or radio-therapy, if administered), BMI ≥25 kg/m2, ability to walk at least 400 meters at any pace, ECOG PS 0-1, not participating in another weight loss, dietary or PA intervention clinical trial. Intervention and Control arms: The intervention and health education program are adapted from the BWEL: Breast Cancer WEight Loss study (ClinicalTrials.gov NCT02750826; PI Ligibel JA). The behavior change program is based on the Social Cognitive Theory. Patients in the intervention arm are paired with an individual lifestyle coach, who delivers the intervention through 24 semi-structured telephone calls of 30-60 minutes, supplemented by a detailed participant workbook and scheduled as follows: 1) intensive phase (weeks 1-12), 12 weekly calls; 2) consolidation phase (weeks 13-24), 6 bi-weekly calls; 3) maintenance phase (weeks 25-52), 1 monthly call. Coaches were hired and trained specifically for MEDEA, they are located at a centralized call center and receive support from coordinating nutrition, PA, and behavioral experts. Regular meetings with study team and investigators assure standardized delivery of the intervention and troubleshooting. Intervention goals include weight loss ≥10% of baseline weight, caloric restriction of 500-1000 Kcal/day, increased PA to 150 minutes/week in the initial phase and 225-300 minutes/week in the maintenance phase. Toolbox solutions are offered to tailor the intervention and meet the needs of specific ethnic, socioeconomic or other patient populations with difficulties in achieving intervention goals. All participants in both arms receive a health education program focusing on healthy living. Accrual: MEDEA will enroll 220 patients overall. Recruitment started in June 2020. Statistical considerations: The primary analysis of MEDEA will compare the primary endpoint of CRF scores at the 12-month post-randomization time point between arms. The study has 90.0% power at two-sided α=0.05 to detect a standardized effect size of 0.40 (sample size inflated for drop outs). For interpreting the clinical significance of effects, 0.2, 0.5 and 0.8 standard deviation effects will be considered as small, moderate, and large (Cohen, 1988). All other measures, time points and analyses will be considered secondary or exploratory. Citation Format: Antonio Di Meglio, Elise Martin, Stefan Michiels, Cecile Charles, Tracy E. Crane, Aude Barbier, Bruno Raynard, Anthony Mangin, Olivier Tredan, Paul H. Cottu, Laurence Vanlemmens, Carine Segura-Djezzar, Anne Lesur, Barbara Pistilli, Florence Joly, Thomas Ginsbourger, Bernadette Coquet, Guillemette Jacob, Aude Sirven, Julia Bonastre, Jennifer A. Ligibel, Ines Vaz-Luis. MEDEA: A randomized trial of weight loss to reduce cancer-related fatigue (CRF) among overweight and obese breast cancer (BC) patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-38-01.

To meet the challenges of sustainability in agricultural system design, reducing the dependency on synthetic plant protection products has become a core issue. There are currently two major reasons for farmers' decision to reduce their use of synthetic products: public policies, and the extralegal requirements of food supply chains. To reduce or eliminate synthetic plant protection products, agroecological crop protection (ACP) relying on the development of agroecology science and practices is a promising holistic approach focused on crop health overall. ACP requires a consistent combination of various agronomic practices at different spatiotemporal and trophic levels. Vegetable crops are minor crops facing the major challenges of producing high-quality produce and of controlling sanitary pressure on yields. Thus, agroecological vegetable systems must not only be adapted to official regulations and environmental parameters but must also comply with the specifications of the targeted food value chains (FVC), which are variable: marketing standards regarding cosmetic issues are very strict in long value chains, whereas they are more flexible in local short chains. Whereas fresh vegetable production is strongly challenged by the reduction of synthetic plant protection products, there are few studies that show how to design, manage and assess agroecological crop protection strategies for such systems, considering the main specifications and criteria of the FVC as a whole. This article reports on the challenges of complying with both FVC specifications and agroecology principles in protected vegetable crop protection. This study relies on four cropping systems implemented in an experimental station for 4.5 years, each of which had a specific strategy of crop protection management and was devoted to a particular FVC. The four FVCs are “local direct sale in low-pesticide farming”, “local direct sale in organic farming”, “super- and hypermarket value chain in low-pesticide farming” and “super- and hypermarkets value chain in organic farming”. Results consist in the description of combination of agronomic practices used, as well as the corresponding decision-making processes. They then present the performance of the four systems tested, showing that agroecological crop protection strategies are successful in reducing or eliminating synthetic plant protection products. We then discuss failure and success factors highlighted by this multi-year experiment. It illustrates that agroecological crop protection and compliance with the FVC's expectations can be compatible but involve specific trade-offs, depending on the targeted food value chain. We finally stress key areas to investigate further in order to achieve still challenging objectives in vegetable systems.

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Resume Objectif Depuis les dernieres recommandations nationales elaborees par l’Institut national du cancer (INCa) et la Societe francaise de senologie et de pathologie mammaire (SFSPM) sur l’ensemble de la prise en charge diagnostique et therapeutique des carcinomes canalaires in situ (CCIS), de nouvelles publications ont fait emerger des interrogations en termes de bonnes pratiques et sur les possibilites de desescalade therapeutique dans la prise en charge des CCIS. L’actualisation de ces recommandations intervient dans un contexte de questionnement sur le surdiagnostic et son corollaire le surtraitement. Elle met a la disposition des professionnels des informations sur les bonnes pratiques correspondant a l’etat le plus recent des connaissances scientifiques et etudie notamment les possibilites de desescalade therapeutique. Methode Le processus d’elaboration est base sur une revue systematique de la litterature et sur le jugement argumente d’experts cliniciens au sein d’un groupe de travail multidisciplinaire. Avant publication, les recommandations sont revues par plus de cent experts cliniciens independants du groupe de travail. Resultats Cet article presente les recommandations nationales relatives a l’indication de l’IRM, la place de la macrobiopsie en cas de microcalcifications et la conduite a tenir en cas de CCIS de bas grade identifie par biopsie, dans le diagnostic des CCIS.

The growing number of breast cancer survivors challenges healthcare organizations, particularly oncology specialty and primary care providers. Currently, in France, the follow-up care is based on detection of recurrences, of second primary contralateral breast cancer, of long-term treatment sequelae, in addition to psychosocial consequences of cancer and its treatment. This review will discuss the evidence base and intents of breast cancer survivorship care plans (CSCPs) as a wellness model for cancer survivors in clinical setting, mainly providing health promotion recommendations such as regular exercise. The CPCPs involve multidisciplinary approach and patient–physician communication. Therefore, this comprehensive care will improve their quality of life, treatment compliance, and general health care maintenance. This article offers innovative guidance to implement the post-cancer patient care and includes the relevant templates to be submitted to the patients.

The period between breast cancer diagnosis (suspected or certain) and the first treatment is an agonizing transition period, characterized by distress, emotional experiences, and biographical disruption. The breast cancer diagnosis is a key turning point in a woman’s life, associated with fear, anxiety, and loss of hope. Health care providers must help the patient not only by shortening but also by recognizing psychological distress symptoms to propose adaptive behaviors. As it is known that the level of adjustment to diagnosis in the earliest period is associated with future adjustment, it is important to consider this period with empathic behavior and help women to alleviate anxiety and reduce loneliness. Specialized diagnosis assessment units can help because it includes a multidisciplinary health care team with a nurse navigator and a care pathway physician responsible.

Background: Breast cancer (BC) during pregnancy (BCP) is a rare situation that requires collaboration between oncologists, surgeons and obstetricians. The main objectives of this study were to compare the overall survival (OS) and disease free survival (DFS) of a multicenter cohort of pregnant patients (pts) with those of matched control pts. Methods: Patients from 27 centers and diagnosed between 2000 and 2006 with histological confirmed M0 invasive BC were included in this retrospective study. For the cohort of BCP, pts whose pregnancy was interrupted were not eligible. Controls were matched to BCP pts on 5 criteria: clinical T (of TNM), hormonal receptor (HR) status, HER2 status, administration of neo-adjuvant chemotherapy and pathological nodal status in the absence of neo-adjuvant chemotherapy. Survival times were estimated from the date of diagnosis using Kaplan-Meier method. OS was calculated until death from every cause, DFS was calculated until relapse or death from every cause; patients alive were censored at the date of last news. Results: 100 BCP pts were identified. Their clinical and pathological characteristics were described on a previous presentation (SABCS 2013 P6-06-07). Matched controls could not be found for 12 BCP pts. 88 BCP pts were matched with 204 controls. The only differences between the 2 populations in terms of characteristics or treatment were more radical mastectomy (p=0.036) and fewer taxane administrations in the BCP group (p=0.06). The median duration of follow-up was 8.2 years for cases and 7.7 years for controls. There were no differences between BCP pts and controls in 5-year OS: 83.4%, IC 95% (73.5-89.8) vs 83.8%, IC 95% (77.9-88.3) nor 7-year OS: 76.5% (65.5-84.4) vs 78.1% (71.5-83.3) (p=0.52). The 5-year DFS was 58.6% IC 95% (47.3-68.3) vs 67.2% IC 95% (60.2-73.2) (p= 0.16). However, 5-year DFS was lower in HR+ BCP pts subgroup than in HR+ control group (56.7% IC 95% (40.7-69.8) vs 70.9% IC 95% (61.4-78.5) (p=0.023). Conclusion: This multicenter French large study confirmed that there are no differences on OS and DFS between pregnant and no pregnant pts, though this might not be true for HR subgroup. Citation Format: Vanlemmens L, Ploquin A, Delaloge S, Rouzier R, Lesur A, Frenel J-S, Loustalot C, Bachelot T, Provansal M, Ferrero J-M, Coussy F, Debled M, Kerbrat P, Vinceneux A, Djelila A, Baron M, Jebert S, Decoupigny E, Tresch E, Bonneterre J. 5-year overall survival of early breast cancer during pregnancy: A multicenter French case control study. [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 P1-07-02.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the removal of foreign bodies in the upper gastrointestinal tract in adults. Recommendations Nonendoscopic measures 1 ESGE recommends diagnostic evaluation based on the patient's history and symptoms. ESGE recommends a physical examination focused on the patient's general condition and to assess signs of any complications (strong recommendation, low quality evidence). 2 ESGE does not recommend radiological evaluation for patients with nonbony food bolus impaction without complications. We recommend plain radiography to assess the presence, location, size, configuration, and number of ingested foreign bodies if ingestion of radiopaque objects is suspected or type of object is unknown (strong recommendation, low quality evidence). 3 ESGE recommends computed tomography (CT) scan in all patients with suspected perforation or other complication that may require surgery (strong recommendation, low quality evidence). 4 ESGE does not recommend barium swallow, because of the risk of aspiration and worsening of the endoscopic visualization (strong recommendation, low quality evidence). 5 ESGE recommends clinical observation without the need for endoscopic removal for management of asymptomatic patients with ingestion of blunt and small objects (except batteries and magnets). If feasible, outpatient management is appropriate (strong recommendation, low quality evidence). 6 ESGE recommends close observation in asymptomatic individuals who have concealed packets of drugs by swallowing ("body packing"). We recommend against endoscopic retrieval. We recommend surgical referral in cases of suspected packet rupture, failure of packets to progress, or intestinal obstruction (strong recommendation, low quality evidence). Endoscopic measures 7 ESGE recommends emergent (preferably within 2 hours, but at the latest within 6 hours) therapeutic esophagogastroduodenoscopy for foreign bodies inducing complete esophageal obstruction, and for sharp-pointed objects or batteries in the esophagus. We recommend urgent (within 24 hours) therapeutic esophagogastroduodenoscopy for other esophageal foreign bodies without complete obstruction (strong recommendation, low quality evidence). 8 ESGE suggests treatment of food bolus impaction in the esophagus by gently pushing the bolus into the stomach. If this procedure is not successful, retrieval should be considered (weak recommendation, low quality evidence). The effectiveness of medical treatment of esophageal food bolus impaction is debated. It is therefore recommended, that medical treatment should not delay endoscopy (strong recommendation, low quality evidence). 9 In cases of food bolus impaction, ESGE recommends a diagnostic work-up for potential underlying disease, including histological evaluation, in addition to therapeutic endoscopy (strong recommendation, low quality evidence). 10 ESGE recommends urgent (within 24 hours) therapeutic esophagogastroduodenoscopy for foreign bodies in the stomach such as sharp-pointed objects, magnets, batteries and large/long objects. We suggest nonurgent (within 72 hours) therapeutic esophagogastroduodenoscopy for medium-sized blunt foreign bodies in the stomach (strong recommendation, low quality evidence). 11 ESGE recommends the use of a protective device in order to avoid esophagogastric/pharyngeal damage and aspiration during endoscopic extraction of sharp-pointed foreign bodies. Endotracheal intubation should be considered in the case of high risk of aspiration (strong recommendation, low quality evidence). 12 ESGE suggests the use of suitable extraction devices according to the type and location of the ingested foreign body (weak recommendation, low quality evidence). 13 After successful and uncomplicated endoscopic removal of ingested foreign bodies, ESGE suggests that the patient may be discharged. If foreign bodies are not or cannot be removed, a case-by-case approach depending on the size and type of the foreign body is suggested (weak recommendation, low quality evidence).