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PURPOSE We aimed to characterize long-term quality of life (QOL) trajectories among patients with breast cancer treated with adjuvant chemotherapy and to identify related patterns of health behaviors. METHODS Female stage I-III breast cancer patients receiving chemotherapy in CANTO (CANcer TOxicity; ClinicalTrials.gov identifier: NCT01993498 ) were included. Trajectories of QOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–C30 Summary Score) and associations with trajectory group membership were identified by iterative estimations of group-based trajectory models and multivariable multinomial logistic regression, respectively. RESULTS Four trajectory groups were identified (N = 4,131): excellent (51.7%), very good (31.7%), deteriorating (10.0%), and poor (6.6%) QOL. The deteriorating trajectory group reported fairly good baseline QOL (mean [95% CI], 78.3/100 [76.2 to 80.5]), which significantly worsened at year-1 (58.1/100 [56.4 to 59.9]) and never recovered to pretreatment values through year-4 (61.1/100 [59.0 to 63.3]) postdiagnosis. Healthy behaviors were associated with better performing trajectory groups. Obesity (adjusted odds ratio [aOR] v lean, 1.51 [95% CI, 1.28 to 1.79]; P < .0001) and current smoking (aOR v never, 1.52 [95% CI, 1.27 to 1.82]; P < .0001) at diagnosis were associated with membership to the deteriorating group, which was also characterized by a higher prevalence of patients with excess body weight and insufficient physical activity through year-4 and by frequent exposure to tobacco smoking during chemotherapy. Additional factors associated with membership to the deteriorating group included younger age (aOR, 1-year decrement 1.01 [95% CI, 1.01 to 1.02]; P = .043), comorbidities (aOR v no, 1.22 [95% CI, 1.06 to 1.40]; P = .005), lower income (aOR v wealthier households, 1.21 [95% CI, 1.07 to 1.37]; P = .002), and endocrine therapy (aOR v no, 1.14 [95% CI, 1.01 to 1.30]; P = .047). CONCLUSION This latent-class analysis identified some patients with upfront poor QOL and a high-risk cluster with severe, persistent postchemotherapy QOL deterioration. Screening relevant patient-level characteristics may inform tailored interventions to mitigate the detrimental impact of chemotherapy and preserve QOL, including early addressal of behavioral concerns and provision of healthy lifestyle support programs.

BACKGROUND: Regular physical activity is associated with improved symptom control in patients with breast cancer but its association with chemotherapy completion or response is unclear. METHODS: Using a prospective design, 1075 breast cancer patients receiving neoadjuvant chemotherapy between March 2012 and February 2017 were studied. Physical activity was assessed using the Global Physical Activity Questionnaire [GPAQ-16], quantified in standardised MET-h/wk. Chemotherapy completion was defined as the proportion of patients completing planned treatment course, requiring dose reduction, or requiring dose delay. Response was evaluated by pathologic complete response (pCR). Associations between physical activity and primary outcomes were assessed using multivariable logistic regression models. RESULTS: There was no differences between any chemotherapy completion outcome on the basis of physical activity classification. The percent of patients not completing planned treatment was 5.7% for ≦0.33 MET-h/wk, compared with 6.8% for 0.34–16.65 MET-h/wk, and 4.6% for ≥16.6 MET-h/wk (p = 0.52). No significant relationships were observed between physical activity dose classification and pCR for the overall cohort or upon stratification by clinical subtype. CONCLUSION: Future studies are required to further investigate the relationship between pre-treatment levels of physical activity and function on treatment completion and response in breast and other cancer populations. CLINICAL TRIAL REGISTRATION: NCT01993498.

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.

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.

The continuous technical improvement in sensitivity and specificity placed mass spectrometry as an alternative method for analyzing clinical samples. In parallel to the rapid development of discovery proteomics, targeted acquisition has been implemented as a complementary option for measuring a small set of proteins with high sensitivity and robustness in a large sample cohort. The combination of trapped ion mobility with a rapid time-of-flight (TOF) mass spectrometer improves the sensitivity even further and triggers the development of prm-PASEF.This article discusses the development of prm-PASEF and its advantages over the existing targeted and discovery methods for analyzing clinical samples. We are also highlighting the different requirements for the use of prm-PASEF on clinical samples.prm-PASEF takes advantage of a dual ion-mobility trap enabling highly multiplexed targeted acquisition. It allows the implementation of a short chromatographic separation setup without sacrificing the number of targeted peptides. Analyzing clinical samples by prm-PASEF holds the promise to significantly improve throughput while maintaining sensitivity to detect the selected target proteins.

Side-chain-constrained amino acids are useful tools to modulate the biological properties of peptides. In this study, we applied side-chain constraints to apelin-13 (Ape13) by substituting the Pro12 and Phe13 positions, affecting the binding affinity and signaling profile on the apelin receptor (APJ). The residues 1Nal, Trp, and Aia were found to be beneficial substitutions for Pro12, and the resulting analogues displayed high affinity for APJ (Ki 0.08-0.18 nM vs Ape13 Ki 0.7 nM). Besides, constrained (d-Tic) or α,α-disubstituted residues (Dbzg; d-α-Me-Tyr(OBn)) were favorable for the Phe13 position. Compounds 47 (Pro12-Phe13 replaced by Aia-Phe, Ki 0.08 nM) and 53 (Pro12-Phe13 replaced by 1Nal-Dbzg, Ki 0.08 nM) are the most potent Ape13 analogues activating the Gα12 pathways (53, EC50 Gα12 2.8 nM vs Ape13, EC50 43 nM) known to date, displaying high affinity, resistance to ACE2 cleavage as well as improved pharmacokinetics in vitro (t1/2 5.8-7.3 h in rat plasma) and in vivo.

Targeted proteomics allows the highly sensitive detection of specific peptides and proteins in complex biological samples. Here, we describe a methodology for targeted peptide quantification using a trapped ion mobility quadrupole time-of-flight mass spectrometer (timsTOF Pro). The prm-PASEF method exploits the multiplexing capability provided by the trapped ion mobility separation, allowing more than 200 peptides to be monitored over a 30 min liquid chromatography separation. Compared to conventional parallel reaction monitoring (PRM), precursor ions are accumulated in the trapped ion mobility spectrometry (TIMS) cells and separated according to their shape and charge before eluting into the quadrupole time-of-flight (QTOF) part of the mass spectrometer. The ion mobility trap allows measuring up to six peptides from a single 100 ms ion mobility separation with the current setup. Using these improved mass spectrometric capabilities, we detected and quantified 216 isotope-labeled synthetic peptides (AQUA peptides) spiked in HeLa human cell extract with limits of quantification of 17.2 amol for some peptides. The acquisition method is highly reproducible between injections and enables accurate quantification in biological samples, as demonstrated by quantifying KRas, NRas, and HRas as well as several Ras mutations in lung and colon cancer cell lines on fast 10 min gradient separations.

The French National Cancer Institute has developed, in partnership with the French National Authority for Health, breast cancer-specific Care Quality, and Safety Indicators (BC QIs). With regard to the most common form of cancer, our aim is to support local and national quality initiatives, to improve BC pathways and outcomes, reduce heterogeneity of practice and regional inequities. In this study, we measure the BC QIs available in the French National medico-administrative cancer database, the French Cancer Cohort, for 2018.BC QIs are developed according to the RAND method. QIs are based on good clinical practice and care pathway recommendations. QI computation should be automatable without any additional workload for data collection. They will be published annually for all stakeholders, and especially hospitals.Finally, ten feasible and pertinent QIs were selected. In France, BC care was found to be close to compliance with most QIs: proportion of patients undergoing biopsy prior to first treatment (94.5%), proportion of patients undergoing adjuvant radiotherapy after breast-conserving surgery for BC (94.5%), proportion of women undergoing radiotherapy within 12 weeks after surgery and without chemotherapy (86.2%), proportion of DCIS patients undergoing immediate breast reconstruction (54.3%) and proportion of women with NMIBC undergoing breast reintervention (14.4%). However, some are still far from their recommended rate. In particular, some QIs vary considerably from one region, or one patient, to another.Each result needs to be analyzed locally to find care quality leverage. This will strengthen transparency actions aimed at the public.

Heparan sulfate (HS), a glycosaminoglycan related to heparin, is a linear polysaccharide, consisting of repeating disaccharide units. This compound is involved in multiple biological processes such as inflammation, coagulation, angiogenesis and viral infections. Our work focuses on the synthesis of simple HS analogs for the study of structure-activity relationships, with the aim of modulating these biological activities. Thioglycoside analogs, in which the interglycosidic oxygen is replaced by a sulfur atom, are very interesting compounds in terms of therapeutic applications. Indeed, the thioglycosidic bond leads to an improvement of their stability and can allow the inhibition of enzymes involved in physiological and pathological processes. In our previous work, we developed a synthetic sequence which led to a non-sulfated thiodisaccharide analog of HS. In this paper, we report our results of the development of a new synthetic method allowing access to the novel sulfated

Background Elevated body mass index (BMI) represents a risk factor for cancer-related fatigue (CRF). Weight loss interventions are feasible and safe in cancer survivors, leading to improved cardio-metabolic and quality of life (QOL) outcomes and modulating inflammatory biomarkers. Randomized data are lacking showing that a lifestyle intervention aimed at weight loss, combining improved diet, exercise, and motivational counseling, reduces CRF. Motivating to Exercise and Diet, and Educating to healthy behaviors After breast cancer (MEDEA) is a multi-center, randomized controlled trial evaluating the impact of weight loss on CRF in overweight or obese survivors of breast cancer. Herein, we described the MEDEA methodology. Methods Patients (N = 220) with stage I–III breast cancer and BMI ≥ 25 kg/m2, within 12 months of primary treatment, and able to walk ≥ 400 m are eligible to enroll. Participants are randomized 1:1 to health education alone vs. a personalized telephone-based weight loss intervention plus health education. Both arms receive a health education program focusing on healthy living. Patients in the intervention arm are paired with an individual lifestyle coach, who delivers the intervention through 24 semi-structured telephone calls over 1 year. Intervention goals include weight loss ≥ 10% of baseline, caloric restriction of 500–1000 Kcal/day, and increased physical activity (PA) to 150 (initial phase) and 225–300 min/week (maintenance phase). The intervention is based on the social cognitive theory and is adapted from the Breast Cancer Weight Loss trial (BWEL, A011401). The primary endpoint is the difference in self-reported CRF (EORTC QLQ-C30) between arms. Secondary endpoints include the following: QOL (EORTC QLQ-C30, -BR45, -FA12), anxiety, and depression (HADS); weight and BMI, dietary habits and quality, PA, and sleep; health care costs (hospital-admissions, all-drug consumption, sick leaves) and cost-effectiveness (cost per quality-adjusted life-year); and patient motivation and satisfaction. The primary analysis of MEDEA will compare self-reported CRF at 12 months post-randomization between arms, with 80.0% power (two-sided α = 0.05) to detect a standardized effect size of 0.40. Discussion MEDEA will test the impact of a weight loss intervention on CRF among overweight or obese BC survivors, potentially providing additional management strategies and contributing to establish weight loss support as a new standard of clinical care. Trial registration ClinicalTrials.govNCT04304924

We previously reported a series of macrocyclic analogues of [Pyr

In body integrity dysphoria (BID), otherwise healthy individuals feel like a part of their physical body does not belong to them despite normal sensorimotor functioning. Theoretical and empirical evidence suggested a weakened integration of the affected body part into higher-order multisensory cortical body networks. Here, we used a multisensory stimulation paradigm in mixed reality to modulate and investigate multisensory processing underlying body (dis)ownership in individuals with BID of the lower limb. In 20 participants with BID, delay perception and body ownership were measured after introducing delays between the visual and tactile information of viewed stroking applied to affected and unaffected body parts. Unlike predicted, delay perception did not differ between the two body parts. However, specifically for the affected limb, ownership was lower and more strongly modulated by delay. These findings might be following the idea of a stronger dependency on online bottom up sensory signals in BID., Consciousness and cognition, 106, ISSN:1053-8100, ISSN:1090-2376

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.

Self-touch is considered important for bodily self-consciousness and self-other distinction and has been reported to improve clinical symptoms of disembodiment. To investigate the link between self-touch and disembodiment in healthy participants, we studied the effect of self-touch versus touch produced by another person (other-touch) on experimentally induced disembodiment. In a mixed reality paradigm, across two experiments, participants could see their own body and surroundings with a controllable visual delay and either stroked their own hand with a paintbrush or were stroked with it by the experimenter. Experiment 1 first assessed the sensitivity to temporal multimodal mismatches and delay-induced changes in the sense of body ownership in three conditions, namely self-touch, other-touch and hidden-self-touch (visually occluding the touching hand). In a second block, we compared phenomenological and physiological (threat response) measures of disembodiment between the self-touch and other-touch conditions. Experiment 2 roughly replicated the first block of Experiment 1 but included a condition in which participants performed the self-touch gesture without touching their hand. Such experiment attempted to control for the potential role of efferent signals. Our results show that increasing visual delay generally enhances the feeling of disembodiment, yet the decrease of body ownership is less pronounced during self-touch. For sensitivity to delay between conditions, however, diverging findings are discussed. This study provides evidence for the importance of self-touch in sustaining a healthy sense of body in the context of disembodiment.

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.

Background/aims Apelin and its G protein-coupled receptor APJ (gene symbol Aplnr) are strongly expressed in magnocellular vasopressinergic neurons suggesting that the apelin/APJ system plays a key role at the central level in regulating salt and water balance by counteracting the antiduretic action of vasopressin (AVP). Likewise, recent studies revealed that apelin exerts opposite effects to those of vasopressin induced on water reabsorption via a direct action on the kidney collecting duct. However, the underlying mechanisms of the peripheral action of apelin are not clearly understood. Here, we thus investigated the role of the apelin/APJ system in the regulation of water balance in the kidney, and more specifically its involvement in modulating the function of aquaporin-2 (AQP2) in the collecting duct. Methods Mouse cortical collecting duct cells (mpkCCD) were incubated in the presence of dDAVP and treated with or without apelin-13. Changes in AQP2 expression and localization were determined by immunoblotting and confocal immunofluorescence staining. Results Herein, we showed that the APJ was present in mpkCCD cells. Treatment of mpkCCD with apelin-13 reduced the cAMP production and antagonized the AVP-induced increase in AQP2 mRNA and protein expressions. Immunofluorescent experiments also revealed that the AVP-induced apical cell surface expression of AQP2, and notably its phosphorylated isoform AQP2-pS269, was considerably reduced following apelin-13 application to mpkCCD cells. Conclusion Our data reinforce the aquaretic role of the apelin/APJ system in the fine regulation of body fluid homeostasis at the kidney level and its physiological opposite action to the antiduretic activity of AVP.

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.

Middle Stone Age humans in high-altitude Africa Recent archaeological research has produced evidence of the earliest human occupation of high-altitude habitats in the Andes and the Tibetan Plateau. Ossendorf et al. now present the oldest evidence of human settlement and adaptation to areas above 4000-meter elevation in Africa (see the Perspective by Aldenderfer). Their excavations at a rock shelter in the Bale Mountains of Ethiopia reveal obsidian artifacts and faunal remains, including abundant burnt bones, mostly of giant mole-rats. The findings reveal the environmental conditions and show how Late Pleistocene humans adapted to the harsh environments of these glaciated high-altitude African landscapes. Science , this issue p. 583 ; see also p. 541

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.

ELABELA (ELA) is the second endogenous ligand of the apelin receptor (APJ). Although apelin-13 and ELA both target APJ, there is limited information on structure-activity relationship (SAR) of ELA. In the present work, we identified the shortest bioactive C-terminal fragment ELA23-32, which possesses high affinity for APJ (Ki 4.6 nM) and produces cardiorenal effects in vivo similar to those of ELA. SAR studies on conserved residues (Leu25, His26, Val29, Pro30, Phe31, Pro32) show that ELA and apelin-13 may interact differently with APJ. His26 and Val29 emerge as important for ELA binding. Docking and binding experiments suggest that Phe31 of ELA may bind to a tight groove distinct from that of Phe13 of Ape13, while the Phe13 pocket may be occupied by Pro32 of ELA. Further characterization of signaling profiles on the Gαi1, Gα12, and β-arrestin2 pathways reveals the importance of aromatic residue at the Phe31 or Pro32 position for receptor activation.

In this work hyaluronic acid (HA) oligosaccharides with degree of polymerization (DP) 4, 6 and 8, obtained by enzymatic depolymerization of HA, were conjugated to a PEG-phospholipid moiety. The products (HA-DP4, HA-DP6 and HA-DP8) were used to prepare decorated liposomes. The cellular uptake of HA-DP4, HA-DP6 and HA-DP8-decorated fluorescently labelled liposomes was significantly higher (12 to 14-fold) in lung cancer cell lines with high CD44 expression than in those with low CD44 expression, suggesting a receptor-mediated entry of HA-conjugated formulations. Competition assays showed that the uptake followed this rank order: HA-DP8>HA-DP6>HA-DP4 liposomes. Moreover, they are capable of a faster interaction with CD44, followed by phagocytosis, than HA liposomes obtained from HA of higher molecular weight (4800 and 14800 Da). HA-DP4, HA-DP6 and HA-DP8-liposomes did not show cytotoxicity or inflammatory effects. Overall, we propose our new HA-DP oligosaccharides as biocompatible and effective tools for a potential drug delivery to CD44-positive cells.

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.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.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.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.

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.

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.

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.

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.

Breast cancer of young women has medico-psychological issues, particularly in the perspective of "after cancer" period. The objective of the study was to analyze the changes in management, in a decade including the publication of Cancer Plans I and II.This retrospective unicentric study involved two populations of women aged 40 and treated at the "Institut de cancérologie de Lorraine" in 2002-2004 (P1) and 2012-2014 (P2). Epidemiological-demographic, histological, diagnostic and therapeutic sequences were analyzed.216 patients were included. The mean age was 35.7 years (range 22-40), with no significant epidemiological difference, except for an increased rate of obesity in P2. Preoperative biopsies became almost systematic and the pre-therapeutic care plan rate increased over the decade from 3.8% to 8% (p0.001). The rate of breast-conserving treatment remained stable. The sentinel lymph node rate increased from 4.4% in P1 to 31.9% in P2 (p0.001), while the rate of lymph node dissection decreased (p0.001) between the two periods. Resort to breast nurses, psycho-oncologists, fertility experts and oncogenetic consultations has also increased.There is an improvement in the care and management of young women under 40 because of the first Cancer Plans. A study about the impact on the prognosis and a reflection to improve the experience of illness for these women are to lead.

Objectives: the purpose of this study is to assess TAM safety in terms of side effects and hormonal status, the persistence of the treatment over a five years time-frame and to report the remote follow-up data.Fifty five patients were included patients between January 2001 and November 2002 at the Institut de cancérologie de Lorraine. The subjects were aged 50 years or less, premenopausal at diagnosis and treated with adjuvant TAM therapy at a daily dose of 20 mg, for an expected duration of 5 years, at a daily. After 2 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in the institution (1x/year). All data were retrospectively evaluated in 2019.In these 55 patients, the cumulative incidences of cysts and hot flushes 5 years after treatment were 68.5 % and 77.6 %, respectively. Of the 33 patients with chemoreactive amenorrhea, half had cycles which resumed within a median of 9 months. In the 10 patients without chemotherapy-induced amenorrhea, 4 had a cycle stop. Of these, 3 patients had cycles that, resumed within 1, 4 and 8 months. 34 patients (61.3 %) had taken Tamoxifen for at least 5 years. After 15 years of treatment, overall and progression-free survival was 90.7 % and 67.4 %, respectively.The observation of the tolerance to the treatment for 5 years and beyond, contributes to the quality of information delivered to future patients starting the treatment, allowing a better understanding and in the long term a better observance.

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

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.

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.

International audience; Glycan-protein interactions control numerous biological events from cell-cell recognition and signaling to pathogen host cell attachment for infections. To infect cells, some viruses bind to immune cells with the help of DC-SIGN (dendritic cell [DC]-specific ICAM3-grabbing nonintegrin) C-type lectin expressed on dendritic and macrophage cell membranes, via their envelope protein. Prevention of this infectious interaction is a serious therapeutic option. Here, we describe the synthesis of the first water-soluble tetravalent fucocluster pseudopeptide-based 1,3-alternate thiacalixarenes as viral antigen mimics designed for the inhibition of DC-SIGN, to prevent viral particle uptake. Their preparation exploits straightforward convergent strategies involving one-pot Ugi four-component (Ugi-4CR) and azido-alkyne click chemistry reactions as key steps. Surface plasmon resonance showed strong inhibition of DC-SIGN interaction properties by tetravalent ligands designed with high relative potencies and β avidity factors. All ligands block DC-SIGN active sites at nanomolar IC50 preventing cis-cell infection by Ebola viral particles pseudotyped with EBOV glycoprotein (Zaire species of Ebola virus) on Jurkat cells that express DC-SIGN. In addition, we observed strong inhibition of DC-SIGN/human cytomegalovirus (HCMV)-gB recombinant glycoprotein interaction. This finding opens the way to the simple development of new models of water-soluble glycocluster-based thia-calixarenes with wide-ranging antimicrobial activities.

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 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).

ELABELA (ELA) was recently discovered as a novel endogenous ligand of the apelin receptor (APJ), a G protein-coupled receptor. ELA signaling was demonstrated to be crucial for normal heart and vasculature development during embryogenesis. We delineate here ELA's structure- activity relationships and report the identification of analogue 3 (ELA(19-32)), a fragment of ELA that binds to APJ, activates the G alpha(i1) and beta-arrestin-2 signaling pathways, and induces receptor internalization similarly to its parent endogenous peptide. An alanine scan performed on 3 revealed that the C-terminal residues are critical for binding to APJ and signaling. Finally, using isolated-perfused hearts and in vivo hemodynamic and echocardiographic measurements, we demonstrate that ELA and 3 both reduce arterial pressure and exert positive inotropic effects on the heart. Altogether, these results present ELA and 3 as potential therapeutic options in managing cardiovascular diseases

Background In patients treated with cardiotoxic chemotherapies, the presence of cardiovascular risk factors and previous cardiac disease have been strongly correlated to the onset of cardiotoxicity. The influence of overweight and obesity as risk factors in the development of treatment-related cardiotoxicity in breast cancer (BC) was recently suggested. However, due to meta-analysis design, it was not possible to take into account associated cardiac risk factors or other classic risk factors for anthracycline (antineoplastic antibiotic) and trastuzumab (monoclonal antibody) cardiotoxicity. Methods and findings Using prospective data collected from 2012–2014 in the French national multicenter prospective CANTO (CANcer TOxicities) study of 26 French cancer centers, we aimed to examine the association of body mass index (BMI) and cardiotoxicity (defined as a reduction in left ventricular ejection fraction [LVEF] > 10 percentage points from baseline to LVEF < 50%). In total, 929 patients with stage I–III BC (mean age 52 ± 11 years, mean BMI 25.6 ± 5.1 kg/m2, 42% with 1 or more cardiovascular risk factors) treated with anthracycline (86% epirubicin, 7% doxorubicin) and/or trastuzumab (36%), with LVEF measurement at baseline and at least 1 assessment post-chemotherapy were eligible in this interim analysis. We analyzed associations between BMI and cardiotoxicity using multivariate logistic regression. At baseline, nearly 50% of the study population was overweight or obese. During a mean follow-up of 22 ± 2 months following treatment completion, cardiotoxicity occurred in 29 patients (3.2%). The obese group was more prone to cardiotoxicity than the normal-weight group (9/171 versus 8/466; p = 0.01). In multivariate analysis, obesity (odds ratio [OR] 3.02; 95% CI 1.10–8.25; p = 0.03) and administration of trastuzumab (OR 12.12; 95% CI 3.6–40.4; p < 0.001) were independently associated with cardiotoxicity. Selection bias and relatively short follow-up are potential limitations of this national multicenter observational cohort. Conclusions In BC patients, obesity appears to be associated with an important increase in risk-related cardiotoxicity (CANTO, ClinicalTrials.gov registry ID: NCT01993498). Trial registration ClinicalTrials.gov NCT01993498., Charles Guenancia and colleagues investigate the association of obesity to breast cancer treatment related cardiotoxicity., Author summary Why was this study done? Anthracyclines remain a cornerstone of breast cancer therapy, in combination with new-generation targeted drugs such as trastuzumab, and represent the major culprit in chemotherapy-induced heart disease. In a recent meta-analysis, we showed that overweight and obesity increased cardiotoxicity, but it was not possible to take into account associated cardiac risk factors or other classic risk factors for anthracycline and trastuzumab cardiotoxicity. We examined the association of body mass index (BMI) and cardiotoxicity using prospective data collected in the CANTO study, a French national cohort. What did the researchers do and find? In patients treated for stage I–III breast cancer with anthracyclines and/or trastuzumab, being obese was associated with increased risk of developing cardiotoxicity, regardless of other predictors of cardiotoxicity. Among all the classic risk factors for cardiotoxicity, overweight and obesity were by far the most common risk factors in this breast cancer population. What do these findings mean? Obesity appears to be a risk factor for cardiotoxicity in breast cancer patients. Overweight and obese patients may benefit from careful cardiac screening and follow-up during and after chemotherapy.

The systematic second opinion review in cancer centers after breast cancer detection is currently under development. The purposes were the evaluation of review's consequences, in particularly of the axillary staging and the evolution of the delays.A retrospective study was conducted on patients who consulted a clinician at Cancer Center of Lorraine in Nancy from January 1st, 2016 to December 31th, 2016. We analyzed from their medical charts: the outside exams, the initial therapeutic plan, the second opinion review, the additional exams, the multidisciplinary consultation conclusions, the first treatment, the multidisciplinary consultation after surgery.In all, 251 patients were analyzed. Second opinion review discrepancies were seen in 72.5%. As a result, 43.4% of all patients had new breast-axillary biopsies. New malignancies lesions were identified in 19.9% of patients. Modifications in therapeutic plan were recommended in 19.9% of patients (including patients with and without new malignancies lesions diagnosed). Before a second opinion review, 9.8% of axillary ultrasound lead to a positive fine-needle biopsy. The additional exams identified 9.6% additional lesions. After a positive sentinel lymph node excision biopsy, the multidisciplinary consultation recommended a revision surgery of axillary lymph node dissection for 27% of patients with axillary ultrasound performed in our cancer center, and for 70% of patients without ultrasound (P=0.023).The systematic second opinion at cancer center allows the detection of new malignancies lesions and significant modifications in the therapeutic plan. A systematic evaluation of axillary ultrasound in cancer center could be considered.

Background Breast cancer diagnosed during pregnancy (BCP) is rare, but the prevalence is expected to rise. Long-term follow-up data regarding this clinically challenging condition are scarce. The main objective of this multicentre case-control French study was to compare the survival between pregnant patients and matched controls. Methods Patients from 27 centres diagnosed between 2000 and 2009 with histologically proven invasive breast cancer occurring during pregnancy were retrospectively included. Controls were matched to BCP patients on age, clinical T stage, hormone receptor, HER2, administration of neo-adjuvant chemotherapy and pathological node involvement in the absence of neo-adjuvant chemotherapy. Five-year overall survival (OS), disease-free survival (DFS) and metastasis-free survival (MFS) rates were estimated using the Kaplan–Meier method. Results One hundred and eleven BCP patients and 253 controls were included. Median age was 33 and 35 years, respectively. Both populations were managed similarly, except for less frequent sentinel node dissection (p = 0.026) and taxane administration (p = 0.03) among BCP patients. Median follow-up was 7.5 years. Survival rates were similar between both BCP and control patients: 5-year OS rates were 83.1% (95% CI: 74.5–89.0) vs 85.5% (95% CI: 80.4–89.4), respectively, p = 0.31; 5-year DFS rates 60.0% (95% CI: 50.1–68.6) vs 68.5% (95% CI: 62.3–73.9), respectively, p = 0.12 and 5-year MFS rates 71.0% (95% CI: 61.3–78.6) and 74.5% (95% CI: 68.6–79.5), respectively, p = 0.21. Conclusion Our study showed that the survival outcomes of patients diagnosed with BCP were not significantly different as compared to those of matched non-pregnant controls. A proper management of women diagnosed with BCP is crucial.

Purpose: Endometrial cancer (EC) diagnosis relies on the observation of tumor cells in endometrial biopsies obtained by aspiration (i.e., uterine aspirates), but it is associated with 22% undiagnosed patients and up to 50% of incorrectly assigned EC histotype and grade. We aimed to identify biomarker signatures in the fluid fraction of these biopsies to overcome these limitations. Experimental Design: The levels of 52 proteins were measured in the fluid fraction of uterine aspirates from 116 patients by LC-PRM, the latest generation of targeted mass-spectrometry acquisition. A logistic regression model was used to assess the power of protein panels to differentiate between EC and non-EC patients and between EC histologic subtypes. The robustness of the panels was assessed by the "leave-one-out" cross-validation procedure performed within the same cohort of patients and an independent cohort of 38 patients. Results: The levels of 28 proteins were significantly higher in patients with EC (n = 69) compared with controls (n = 47). The combination of MMP9 and KPYM exhibited 94% sensitivity and 87% specificity for detecting EC cases. This panel perfectly complemented the standard diagnosis, achieving 100% of correct diagnosis in this dataset. Nine proteins were significantly increased in endometrioid EC (n = 49) compared with serous EC (n = 20). The combination of CTNB1, XPO2, and CAPG achieved 95% sensitivity and 96% specificity for the discrimination of these subtypes. Conclusions: We developed two uterine aspirate-based signatures to diagnose EC and classify tumors in the most prevalent histologic subtypes. This will improve diagnosis and assist in the prediction of the optimal surgical treatment. Clin Cancer Res; 23(21); 6458–67. ©2017 AACR.

International audience; AIM: Evaluate the influence of emotional distress of young women with breast cancer and their spouses on their daily subjective experience of the disease, through application of the Actor-Partner Interdependence Model. PATIENTS & METHODS: A total of 112 women under 45 years of age were diagnosed with nonmetastatic breast cancer and their spouses answered self-reported measures of anxiety, depression and subjective experience of the disease and its treatment. RESULTS: The patient's emotional distress influenced more the subjective experience of her spouse than the spouse's emotional distress influenced the patient. The spouse's difficulties depended as much on his own distress level as on the patient's distress level. CONCLUSION: These data confirm the importance of implementing couple-focused interventions.

Objective To devise and validate a system to categorize GreenLight photoselective vaporization of prostate (PVP) complications according to Clavien score (CS), to report complications of PVP using this categorization, and to determine risk factors. Materials and Methods A survey questionnaire was distributed to all participants of the second meeting of the Group of GreenLight Users. They were asked to grade PVP complications according to CS. We calculated the mode CS for each complication from the survey data to propose a categorization system for complications of PVP. Complications encountered in a large single-center cohort of 370 patients were reported according to this system. We assessed the reproducibility of CS by estimating inter-rater agreement by the Fleiss kappa. We performed univariate and multivariate analyses to determine risk factors for complications. Results Of the 67 meeting participants, 42 (62.7%) completed the survey. Overall agreement between urologists was fair (Fleiss kappa = 0.356). Among the 370 patients, 21 (5.7%) had intraoperative complications, 147 (39.7%) had postoperative complications, and 70 (18.9%) had long-term complications. Among the postoperative complications, 125 patients (33.8%) were classified as Clavien grade I, 58 (15.7%) as Clavien grade II, 4 (1.1%) as Clavien grade IIIb, 5 (1.3%) as Clavien grade IVa, 1 (0.3%) as Clavien grade IVb, and 1 (0.3%) as Clavien grade V. In multivariate analysis, the only predictor of overall complications was a polymicrobial preoperative urine culture. Conclusion The grading of PVP complications by CS is fairly reproducible. We are the first to propose a system for the categorization of PVP complications. PVP complications are frequent but most often minor.

Background:Drugs are suspected when obvious causes of intensive care unit (ICU)-acquired thrombocytopenia have been excluded. It has been estimated that 10% to 25% of cases may be drug induced. Objectives: The objectives of this study were to evaluate the risk of thrombocytopenia associated with drug classes commonly used in the ICU. Methods: Data concerning patients admitted for more than 48 hours between 1997 and 2011 were extracted from a research-purpose database. Patients with thrombocytopenia within the first 72 hours of admission and with diagnoses or interventions considered strongly associated with thrombocytopenia were excluded. Drug exposures were compared and adjusted for confounders using conditional logistic regression. Results: A total of 238 cases were identified after exclusions. Each case was matched according to sex, age, admission year, and admission unit with 1 control. In univariate analysis, quinolones (odds ratio [OR] = 1.56; 95% CI = 1.01-2.40) and extended spectrum β-lactams (OR = 1.71; 95% CI = 1.00-2.93) were significantly associated with an increased risk of thrombocytopenia. After adjusting for confounders, exposure to quinolones was the only drug class with a statistically significant increase in risk of thrombocytopenia (OR = 1.697; 95% CI = 1.002-2.873; P = 0.049). Conclusion: In this study of ICU-acquired thrombocytopenia, we found no association between the exposures to several antibiotic classes, anticonvulsants, antiplatelet agents, nonsteroidal anti-inflammatory agents, and heparins and thrombocytopenia. As linezolid was not studied, no conclusions can be drawn concerning this agent. The statistically significant association between quinolones and thrombocytopenia warrants further investigation.

Aspiration of secretions toward lower airways potentially occurs during endotracheal tube (ETT) repositioning in mechanically ventilated patients in the intensive care unit and may be a risk factor for developing ventilator-associated pneumonia (VAP). This case-control study confirms that repositioning of the ETT is an independent risk factor for VAP.

Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomic dominant disorder, which is characterized by the development of multiple arteriovenous malformations in either the skin, mucous membranes, and/or visceral organs. Pulmonary arteriovenous malformations (PAVMs) may either rupture, and lead to life-threatening hemoptysis/hemothorax or be responsible for a right-to-left shunting leading to paradoxical embolism, causing stroke or cerebral abscess. PAVMs patients should systematically be screened as the spontaneous complication rate is high, by reaching almost 50%. Neurological complications rate is considerably higher in patients presenting with diffuse pulmonary involvement. PAVM diagnosis is mainly based upon transthoracic contrast echocardiography and CT scanner examination. The latter also allows the planification of treatments to adopt, which consists of percutaneous embolization, having replaced surgery in most of the cases. The anchor technique consists of percutaneous coil embolization of the afferent pulmonary arteries of the PAVM, by firstly placing a coil into a small afferent arterial branch closely upstream the PAVM. Enhanced contrast CT scanner is the key follow-up examination that depicts the PAVM enlargement, indicating the various mechanisms of PAVM reperfusion. When performed by experienced operators as the prime treatment, percutaneous embolization of PAVMs, is a safe, efficient and sustained therapy in the great majority of HHT patients.

Purpose: To evaluate the impact of slow-tempo music listening periods in mechanically ventilated intensive care unit patients. Methods: A randomized crossover study was performed in a 16-bed, adult critical care unit at a tertiary care hospital. Still-sedated patients, mandating at least 3 more days of mechanical ventilation, were included. The interventionconsistedintwo1-hourdailyperiodsofmusic-vs-sham-MP3listeningwhichwereperformedon Day 1 or 3 post-inclusion, with a Day 2 wash-out. “Before-after” collection of vital signs, recording of daily sedative drug consumption and measurement of stress and inflammatory blood markers were performed. Results: Of 55 randomized patients, 49 were included in the final analyses. Along with music listening, (i) vital signs did not consistently change, whereas narcotic consumption tended to decrease to a similar sedation (P= .06 vs sham-MP3); (ii) cortisol and prolactin bloodconcentrationsdecreased, whereasAdreno Cortico Trophic Hormone (ACTH)/cortisol ratio increased (P =. 02;P = .038; and P = .015 vs sham-MP3, respectively), (iii) cortisol responders exhibited reversed associated changes in blood mehionine (MET)enkephalin content (P =. 01). Conclusions: In the present trial, music listening is a more sensitive stress-reliever in terms of biological vs clinical response. The hypothalamus-pituitary adrenal axis stress axis is a quick sensor of music listening in responding mechanically ventilated intensive care unit patients, through a rapid reduction in blood cortisol.