Short- and long-term impact of adapted physical activity and diet counseling during adjuvant breast cancer therapy: the “APAD1” randomized controlled trial

International audienceBACKGROUND:Patients with breast cancer undergoing chemotherapy and radiotherapy experience fatigue and other treatment side effects. Integrative therapies combining physical activity and dietary counseling are recommended; however to date no large randomized controlled trial has been conducted during adjuvant therapy. The Adapted Physical Activity and Diet (APAD) intervention was evaluated for its ability to decrease fatigue (primary outcome), anxiety, depression, body mass index (BMI), and fat mass, and enhance muscular and cognitive performances, and quality-of-life (QoL).METHODS:Women diagnosed with early breast cancer (N = 143, mean age = 52 ± 10 years) were randomized to APAD or usual care (UC). APAD included thrice-weekly moderate-intensity mixed aerobic and resistance exercise sessions and 9 dietetic consultations. Patient-reported outcomes (PROs) and anthropometric, muscular, and cognitive variables were measured at baseline, 18 weeks (end of chemotherapy), and 26 weeks (end of radiotherapy and intervention), and at 6- and 12-month post-intervention follow-ups. Multi-adjusted linear mixed-effects models were used to compare groups over time.RESULTS:Significant beneficial effects of the APAD intervention were observed on all PROs (i.e., fatigue, QoL, anxiety, depression) at 18 and 26 weeks. The significant effect on fatigue and QoL persisted up to 12-month follow-up. Significant decreases in BMI, fat mass, and increased muscle endurance and cognitive flexibility were observed at 26 weeks, but did not persist afterward. Leisure physical activity was enhanced in the APAD group vs UC group at 18 and 26 weeks. No significant effect of the intervention was found on major macronutrients intake.CONCLUSIONS:A combined diet and exercise intervention during chemotherapy and radiotherapy in patients with early breast cancer led to positive changes in a range of psychological, physiological and behavioral outcomes at the end of intervention. A beneficial effect persisted on fatigue and QoL at long term, i.e., 1 year post-intervention. Diet-exercise supportive care should be integrated into the management of early breast cancer patients.TRIAL REGISTRATION:The APAD study was prospectively registered on ClinicalTrials.gov (NCT01495650; date of registration: December 20, 2011)

Kinematic angular parameters in PD: reliability of joint angle curves and comparison with healthy subjects,”

Abstract Background: Most previous biomechanical studies of Parkinson's disease (PD) have been restricted to the description of spatiotemporal parameters and certain peak values for angular parameters. The reliability of joint angle curves and comparisons with control data are of major interest in PD, since variability in gait cycle timing is a feature of this pathology. Methods: We used a video motion analysis system to record kinematic, spatiotemporal and angular parameters in 32 'off-drug' PD patients. The reliability of the patients' lower limb joint angle curves in the sagittal plane were analysed using the intra-class correlation coefficient (ICC), together with fast Fourier transform (FFT) analysis and hierarchical classification for discarding deviant curves. Lastly, we compared average curves (using a mixed model and the bootstrap method) for the less-affected and more-affected sides of PD patients and then compared the patient data with the results from 30 age-matched controls. Results: The ICC-based procedure was easily applicable. Only 9.4% and 12.5% of the patients' hip and knee curves (respectively) were deemed to be unreliable. However, the PD patients' very high cycle-to-cycle variability in the sagittal plane ankle curves prevented us from applying to this joint. For the knee joint, the curves for the most disabled patients (who walked at below 0.5 m/s) were not reliable. We did not find any differences between the less and more disabled sides. The differences between patient and control curves concerned the doublesupport time during the stance phase and the time point for maximum knee flexion during the swing phase. Patients and controls differed in terms of the hip extension phase, with lower values in PD. Conclusion: We have developed the use of validated statistic tools for unambiguously comparing PD patients and controls in terms of joint angle curve differences.

High-Order Nanowire Resonances for High-Frequency, Large-Coupling-Strength Quantum Dot Hybrid Nanomechanics

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Dual targeting of HER1/EGFR and HER2 with cetuximab and trastuzumab in patients with metastatic pancreatic cancer after gemcitabine failure: results of the "THERAPY"phase 1-2 trial

International audienceTo improve treatment efficacy, we decided to simultaneously target HER1 and HER2 with trastuzumab and cetuximab. Following promising preclinical results, we conducted a phase 1-2 trial in advanced pancreatic cancer patients after first-line gemcitabine-based chemotherapy failure. In this single-arm, non-randomized, multicenter trial, patients received weekly cetuximab (400mg/m², then 250mg/m²). They were sequentially included in two trastuzumab dose levels: 3.0 or 4.0mg/kg, then 1.5 or 2.0mg/kg/weekly. Endpoints were the objective response rate, safety, progression-free (PFS) and overall survival (OS). During phase 1 (n=10 patients), toxicities were evenly distributed except for skin toxicities that frequently caused compliance issues. The higher dose level was defined as the trastuzumab recommended dose. During phase 2 (n=39 patients), toxicities were mainly cutaneous reactions and asthenia. No objective response was observed. Nine patients were stabilized but arrested treatment due to toxicity. Median PFS was 1.8 months (95%CI: 1.7-2.0 months) and median OS was 4.6 months (95%CI: 2.7-6.6 months). Both were positively correlated with skin toxicity severity (P=0.027 and P=0.001, respectively). Conventional phase 1 dose-escalation schedules are unsuitable for targeted therapies because most cutaneous toxicities are not considered dose-limiting toxicities. The compliance issues caused by skin toxicities were particularly detrimental because of the toxicity-response correlation

Subchondral involvement in osteonecrosis of the femoral head: insight on local composition, microstructure and vascularization.

To determine changes of subchondral bone composition, micro-structure, bone marrow adiposity and micro-vascular perfusion in end-stage osteonecrosis of the femoral head (ONFH) compared to osteoarthritis (OA) using a combined in vivo and ex vivo approach. Male patients up to 70 years old referred for total hip replacement surgery for end-stage ONFH were included (n=14). Fifteen patients with OA were controls. Pre-operative MRI was used to assess bone perfusion (dynamic contrast-enhanced (DCE) sequences) and marrow fat content (chemical shift imaging). Three distinct zones of femoral head subchondral bone - necrotic, sclerotic, distant - were compared between groups. After surgery, plugs were sampled in these zones and Raman spectroscopy was applied to characterize bone mineral and organic components (old and newly-formed), and contrast-enhanced micro-computed tomography (CE-μCT) to determine bone micro-structural parameters and volume of bone marrow adipocytes, using conventional 2D histology as a reference. In the necrotic zone of ONFH patients compared to OA patients: i) the subchondral plate did not exhibit significant changes in composition nor structure; ii) the volume fraction of subchondral trabecular bone was significantly lower; iii) type-B carbonate substitution was less pronounced, iv) collagen maturity was more pronounced; and v) bone marrow adipocytes were significantly depleted. The sclerotic zone from the ONFH group showed greater trabecular thickness, and higher DCE-MRI AUC and K. Volume fraction of subchondral bone, trabecular number, and K were significantly lower in the distant zone of the ONFH group. This study demonstrated alterations of subchondral bone microstructure, composition, perfusion and/or adipose content in all zones of the femoral head

Effects of a Hypnosis Session Before General Anesthesia on Postoperative Outcomes in Patients Who Underwent Minor Breast Cancer Surgery

International audienceImportance: Hypnosis is now widespread in medical practice and is emerging as an alternative technique for pain management and anxiety. However, its effects on postoperative outcomes remain unclear.Objective: To evaluate the efficacy of a preoperative hypnosis session for reducing postoperative breast pain in patients who underwent minor breast cancer surgery.Design, Setting, and Participants: The HYPNOSEIN prospective randomized clinical trial was conducted from October 7, 2014, to April 5, 2016. In this multicenter study in France, 150 women scheduled for minor breast cancer surgery were randomized between control and hypnosis arms, and 148 (71 control and 77 hypnosis) were included in the intent-to-treat analysis.Intervention: On the day of surgery, eligible patients were randomly assigned (1:1) to the control arm or the hypnosis arm. Patients (but not the care teams) were blinded to the arm to which they were assigned. A 15-minute hypnosis session before general anesthesia in the operating room was performed in the hypnosis arm.Main Outcomes and Measures: The primary end point was breast pain reduction (by 2 on a visual analog scale), assessed immediately before discharge from the postanesthesia care unit (PACU). Secondary end points were nausea/vomiting, fatigue, comfort/well-being, anxiety, and PACU length of stay, assessed at different times until postoperative day 30.Results:T he median patient age was 57 years (range, 33-79 years) in the control arm and 53 years (range, 20-84 years) in the hypnosis arm. Baseline characteristics were similar in the 2 arms. The median duration of the hypnosis session was 6 minutes (range, 2-15 minutes). The use of intraoperative opioids and hypnotics was lower in the hypnosis arm. The mean (SD) breast pain score (range, 0-10) was 1.75 (1.59) in the control arm vs 2.63 (1.62) in the hypnosis arm (P = .004). At PACU discharge and with longer follow-up, no statistically significant difference in breast pain was reported. Fatigue was significantly lower in the hypnosis arm on the evening of surgery (mean [SD] score, 3.81 [2.15] in the control arm vs 2.99 [2.56] in the hypnosis arm; P = .03). The median PACU length of stay was 60 minutes (range, 20-290 minutes) in the control arm vs 46 minutes (range, 5-100 minutes) in the hypnosis arm (P = .002). Exploratory analyses according to patient perception of whether she received hypnosis showed significantly lower fatigue scores in the perceived hypnosis subgroup on the evening of surgery (mean [SD], 4.13 [2.26] for no perceived hypnosis vs 2.97 [2.42] for perceived hypnosis; P = .01). Anxiety was also significantly lower on the evening of surgery in the perceived hypnosis subgroup (mean [SD], 0.75 [1.64] for perceived hypnosis vs 1.67 [2.29] for no perceived hypnosis; P = .03).Conclusions and Relevance: The results of this study do not support a benefit of hypnosis on postoperative breast pain in women undergoing minor breast cancer surgery. However, other outcomes seem to be improved, which needs to be confirmed by further studies.Trial Registration: EudraCT Identifier: 2014-A00681-46 and ClinicalTrials.gov Identifier: NCT03253159

High-Order Nanowire Resonances for High-Frequency, Large-Coupling-Strength Quantum Dot Hybrid Nanomechanics

Hybrid nanomechanical systems embedding a quantum light emitter, such as a semiconductor quantum dot (QD), are actively investigated both for their fundamental interest and for potential applications to quantum information technologies. Here, we explore the high-order vibration modes of a conical GaAs nanowire that embeds a few self-assembled InAs QDs. On-chip electrodes generate a 3D force field that can drive flexural and longitudinal vibration modes. Mechanical vibrations are detected optically by measuring the microphotoluminescence spectrum of the QDs. The latter also provides a fingerprint of the mode nature. Starting from the sub-MHz fundamental flexural mode, we show that higher-order resonances enable a dramatic increase in both mechanical frequency and hybrid coupling strength. In particular, we identify a low-loss flexural mode that resonates at 190 MHz. This frequency exceeds the QD radiative rate, which constitutes an important step toward the resolved-sideband regime. For a QD located at the stress maximum, the hybrid coupling strength reaches 3.9 MHz, the highest value reported so far for a QD hybrid system. These results demonstrate the potential of the QD-nanowire platform for high-frequency hybrid nanomechanics