Exocyclic DNA adducts and oxidative stress parameters: useful tools for biomonitoring exposure to aldehydes in smokers.

CONTEXT: Exocyclic DNA adducts have been shown to be potential biomarkers of cancer risk related to oxidative stress and exposure to aldehydes in smokers. In fact, aldehydes potentially arise from tobacco combustion directly and endogenously through lipid peroxidation. OBJECTIVE: This study aims to investigate the relationship between a profile of nine aldehydes-induced DNA adducts and antioxidant activities, in order to evaluate new biomarkers of systemic exposure to aldehydes. METHODS: Using our previously published UPLC-MS/MS method, adducts levels were quantified in the blood DNA of 34 active smokers. The levels of antioxidant vitamins (A, C and E), coenzyme Q10, ß-carotene, superoxide dismutase (SOD) and autoantibodies against oxidized low-density lipoprotein were measured. RESULTS: Adducts induced by tobacco smoking-related aldehydes were quantified at levels reflecting an oxidative production from lipid peroxidation. A significant correlation between SOD and crotonaldehyde-induced adducts (p = 0.0251) was also observed. ß-Carotene was negatively correlated with the adducts of formaldehyde (p = 0.0351) and acetaldehyde (p = 0.0413). Vitamin C tended to inversely correlate with acetaldehyde-induced adducts (p = 0.0584). CONCLUSION: These results are promising, and the study is now being conducted on a larger cohort with the aim of evaluating the impact of smoking cessation programs on the evolution of adducts profile and antioxidants activities.

Head and neck cancer patients under radiotherapy undergoing skin application of hydrogel dressing or hyaluronic acid: results from a prospective, randomized study.

PURPOSE: Acute radiodermatitis (ARD) is a frequent side effect of radiotherapy, a therapeutic option for head and neck squamous cell carcinoma (HNSCC). It is responsible for pain, quality of life (QoL) impairment, and increased risk of treatment discontinuation, which may compromise the prognosis for patients. Local therapies to prevent or alleviate ARD have been proposed without providing any high level of evidence to establish recommendations. METHODS: We implemented a prospective multicenter randomized study on patients with HNSCC treated with definitive radiotherapy to assess the impact on ear, nose, and throat (ENT) pain of the application of a hydrogel-based skin dressing (HydroTac®) compared with the application of hyaluronic acid (Ialuset®) during radiotherapy. RESULTS: Out of 130 enrolled patients, 48 patients per group were assessable for the main endpoint. No difference between groups was found: a worsening of ENT pain of 3 points or more on a visual analog scale from the initiation to 1 month after the end of the radiotherapy was observed for 8 patients (16.7%) who received HydroTac® compared to 13 patients (27%) who received Ialuset® (p = 0.342). The proportion of patients who experienced ARD and grades of ARD (CTCAE v4.0 criteria) were similar between groups. Patient compliance with radiodermatitis treatment was poor, with 56.1% of patients in the HydroTac® group having their treatment temporarily stopped. CONCLUSION: The application of a hydrogel dressing to prevent ARD during radiotherapy for HNSCC patients has failed to demonstrate a benefit. These results may be limited by the difficulties of applying the dressing.

Impact of lymphopenia on efficacy of nivolumab in head and neck cancer patients.

INTRODUCTION: Lymphopenia has been correlated with poorer survival in patients with metastatic cancers treated with anti-PD-1 immunotherapy. Treatments such as chemotherapy, surgery or radiotherapy can induce lymphopenia. Radiation-induced lymphopenia is common and prolonged in head and neck cancer (HNSCC) patients. We evaluated the impact of lymphopenia, on efficacy of anti PD-1 nivolumab immunotherapy in HNSCC patients. METHODS: a multicenter retrospective study included consecutive patients treated with nivolumab for recurrent/metastatic (R/M) HNSCC between January 2017 and June 2019. Lymphopenia was defined as lymphocyte counts below 1000 cells/mm3 upon initiation of nivolumab. Logistical regression was performed on factors associated with lymphopenia and ROC analyses assessed association between lymphopenia and survival. RESULTS: median age was 65. Of the 100 included patients, 60% had been treated by surgery, 67% had had first-line chemotherapy, and 89% loco-regional radiotherapy, 65% had concurrent chemotherapy with radiotherapy. Lymphopenia occurred in 56 (56%) patients upon initiation of nivolumab, with 29 (29%) patients having radiation-related lymphopenia. Prior locoregional radiotherapy was the only factor associated with lymphopenia upon initiation of nivolumab by logistical regression (OR 0.144 [0.029-0.706], p - 0.017). Lymphopenia upon initiation of nivolumab did not affect progression-free survival (PFS) (p - 0.815), overall survival (OS) (p - 0.783) or disease control rate (DCR) (p - 0.125). Locoregional symptomatology (HR - 2.37 [1.24-4.54], p - 0.009), metastatic symptomatology (HR - 4.74 [2.21-10.15], and persistent lymphopenia under nivolumab (HR 3.96 [1.19-13.17] p - 0.034) were associated with poorer OS in multivariate analysis. CONCLUSIONS: Lymphopenia upon initiation of nivolumab was not associated with poorer survival in R/M HNSCC patients, but persistence of lymphopenia during immunotherapy might be a prognostic marker of patient survival.

Impact of adjuvant trastuzumab treatment on fatigue, emotional status and quality of personal and work life of patients with localised breast cancer: results of the 'HER-ception' study.

PURPOSE: The aim of this study was to analyse the impact of adjuvant trastuzumab on fatigue, emotional status, and quality of personal and work life of patients treated for localised breast cancer. METHODS: In a prospective setting, we recruited age-matched localised breast cancer patients, treated by adjuvant chemotherapy with (group 1) or without IV trastuzumab (group 2), between September 2011 and May 2014. Patients completed questionnaires on quality of life (FACT-G, FACT-B), fatigue (FACIT-F, ICQ), anxiety-depression (HADS), and work life (dedicated self-questionnaire) at inclusion then at 3, 6, 9, and 15 months. RESULTS: We included 35 patients in each group. No significant difference was found between the two groups concerning return to work, fatigue, and quality of life scores at each phase of the study. In total, 39 patients (72.2%) reported having returned to work at T15, with no significant difference between the two groups (p = 0.53). Significantly higher scores for'helplessness' outcomes were observed in group 1, 9, and 15 months (6.138 and 5.731; p = 0.047 and 0.048, respectively). Patients in group 1 reported higher score of anxiety-depression than group 2 at 3 months (p = 0.027) then no significant difference was observed at the other times of the study. CONCLUSION: Trastuzumab does not appear to affect fatigue and return to work in patients with localised breast cancer. The emotional well-being could be affected in patients treated by trastuzumab, with a more pronounced 'helplessness' feeling which could be more related to the additional follow-up imposed by the prescription of trastuzumab.

Impact of creative art therapy on fatigue and quality of life in patients treated for localized breast cancer: A randomized study.

BACKGROUND: Art therapy (AT) as supportive care may help patients cope with cancer treatments. This non-blinded randomized trial assessed the impact of creative AT on severe fatigue and quality of life (QoL) in localized breast cancer patients undergoing irradiation. MATERIAL AND METHODS: 320 patients were randomized to an AT group (ATG; 8 weekly sessions starting during irradiation) or to a standard group (SG). The primary endpoint was severe global fatigue (Functional Assessment of Chronic Therapy Fatigue subscale score <37) at 1 month post-irradiation. Quality of life (Fact-B), anxiety/depression (Hospital Anxiety and Depression Scale (HADS)) and different dimensions of fatigue 20-item Multidimensional Fatigue Inventory (MFI-20) were assessed at 1, 6 and 12 months post-irradiation. The secondary endpoints, fatigue among patients treated with chemotherapy, QoL (Fact-B), anxiety/depression (HADS) and different dimensions of fatigue (MFI-20) at 1, 6 and 12 months post-irradiation (with post hoc analysis in patients with treated with chemotherapy) were also assessed. RESULTS: 82% of patients completed ≥8 sessions. Severe initial global fatigue was observed in 43% of patients in each group, and among in 64% of patients whose treatment protocol contained chemotherapy. At 1 month post-irradiation, 45% in the ATG and 57% of patients in the SG reported severe global fatigue (p = 0.37); among patients with initial severe mental fatigue (MFF), 79% and 44% had improved MFF (p = 0.007) respectively; similarly 79% and 44% with initial poor motivation had better mental motivation (p = 0.03). At 6 and 12 months, social well-being scores in the ATG were higher (21.3 and 21.4 vs. 19.8 and 19.2, p = 0.05 and p < 0.01) with a significant improvement for patients who had chemotherapy (41% vs. 18%, p = 0.017). A positive association was observed between the number of AT sessions, fatigue and QoL (p < 0.01). CONCLUSION: AT did not significantly improve global severe fatigue among all cancer participants 1 month after radiation therapy, however it had a positive impact on social well-being and may improve MFF and motivation.

Cellular Cytotoxicity and Oxidative Potential of Recurrent Molds of the Genus Aspergillus Series Versicolores.

Molds are ubiquitous biological pollutants in bioaerosols. Among these molds, the genus Aspergillus is found in the majority of indoor air samples, and includes several species with pathogenic and toxigenic properties. Aspergillus species in the series Versicolores remain little known despite recurrence in bioaerosols. In order to investigate their toxicity, we studied 22 isolates of clinical and environmental origin, corresponding to seven different species of the series Versicolores. Spore suspensions and ethyl acetate extracts prepared from fungal isolates were subjected to oxidative potential measurement using the dithiothreitol (DTT) test and cell survival measurement. The DTT tests showed that all species of the series Versicolores had an oxidative potential, either by their spores (especially for Aspergillus jensenii) or by the extracts (especially from Aspergillus amoenus). Measurements of cell survival of A549 and HaCaT cell lines showed that only the spore suspension containing 105 spores/mL of Aspergillus jensenii caused a significant decrease in survival after 72 h of exposure. The same tests performed with mixtures of 105 spores/mL showed a potentiation of the cytotoxic effect, with a significant decrease in cell survival for mixtures containing spores of two species (on A549 cells, p = 0.05 and HaCaT cells, p = 0.001) or three different species (on HaCaT cells, p = 0.05). Cell survival assays after 72 h of exposure to the fungal extracts showed that Aspergillus puulaauensis extract was the most cytotoxic (IC50 < 25 µg/mL), while Aspergillus fructus caused no significant decrease in cell survival.

Impact of taxane-based chemotherapy among older women with breast cancer on cognition and quality of life: a longitudinal pooled analysis.

PURPOSE: Older cancer patients are susceptible to long-term effects of chemotherapy, including cancer-related cognitive decline and impairments to quality of life. Taxane-based chemotherapies are associated with physical declines among older women and may negatively impact cognitive performance. We sought to examine whether changes in objective and subjective measures of cognitive performance and well-being differ among older breast cancer survivors as a function of taxane-based chemotherapy treatment regimens. METHODS: Individual-level data were pooled and harmonized from two large prospective studies of older (greater than 60 years) breast cancer survivors. Assessments were conducted prior to systemic therapy and up to 36 months after. Cognitive performance was assessed with objective (working memory, processing speed, and executive functions) and subjective tests and physical, emotional, and functional well-being were also assessed. RESULTS: One hundred and sixty-seven (M age = 67.3 years) women with 116 receiving chemotherapy with taxanes and 51 without taxanes contributed data. Declines in subjective cognition for both groups were significant between pre-treatment and 12-month follow-up. Significant improvements were seen on a measure of objective cognition (working memory) from 12 to 36 months. Measures of well-being improved from prior to systemic therapy to 12 months. Longitudinal changes across all measures did not vary as a function of receipt of taxane-based treatment. CONCLUSION: Older women who received treatment with taxanes did not have greater declines in cognitive performance or well-being than women receiving other chemotherapy regimens. Despite older cancer survivors being at greater risk for negative outcomes, treatment with taxane-based chemotherapies does not appear to exacerbate these health consequences.

First Characterization and Description of Aspergillus Series Versicolores in French Bioaerosols.

Air quality can be altered by fungal contaminants suspended in the air, forming bioaerosols. Aspergilli section Nidulantes series Versicolores are recurrent in bioaerosols and are mainly responsible for allergies and asthma aggravation. Phylogenetic studies recently identified 12 new species within this series. This study is the first to identify species of Aspergillus series Versicolores in French bioaerosols and to characterize them macroscopically, microscopically and molecularly. Bioaerosols were collected in a cancer treatment center, in contaminated homes and in agricultural environments. A total of 93 isolates were cultured on selective media, observed by optical microscopy and identified by benA amplification before sequencing. The field data (temperature and relative humidity) were statistically tested to explore the ecology of these species. Eight species were identified from bioaerosols: Aspergillus creber and A. jensenii, which represent more than 80% of the isolates, and A. protuberus, A. puulaauensis, A. sydowii, A. tabacinus, A. amoenus and A. fructus. Aspergilli series Versicolores are distributed differently depending on the sampling site and climatic determinants. Aspergillus protuberus was found in bioaerosols collected under significantly lower relative humidity (p = 3.899 × 10-4). Characterization and repartition of these isolates belonging to the Versicolores series constitute an important step to better assess exposure to fungal bioaerosols.

Evaluation of long-term living conditions in patients treated for localised prostate cancer.

PURPOSE: To evaluate the evolution of living conditions (LC) in long-term survivors of localised prostate cancer 10 years after treatment compared with those of a same-age control group from the general population. METHODS: Two hundred and eighty-seven patients diagnosed with prostate cancer in 2001 were selected in 11 French cancer registries. They were matched with controls randomly selected for age and residency. Both patients and controls completed a self-administered LC questionnaire concerning their familial, social and professional life, and general and specific quality of life (QoL) and anxiety and depression questionnaires. RESULTS: Compared with controls, patients reported more sexual modifications (p < .0001), but without any difference in marital status. Patients' circle of friends was more stable than that of the controls (91% vs. 63%; p < .0001) and patients reported fewer friendship modifications than controls (p < .0006). Their professional and physical activities were also preserved. They reported more anxiolytic intake (p = .002) but did not consult their general practitioner more often. Type of specialist consulted differed in the two groups. CONCLUSION: Patients treated for localised prostate cancer had the same living conditions as men of the same age. Their social life was satisfying on the whole, albeit they reported more sexual difficulties than their counterparts.

Tumor burden of persistent disease in patients with differentiated thyroid cancer: correlation with postoperative risk-stratification and impact on outcome.

BACKGROUND: In patients with differentiated thyroid cancer (DTC), tumor burden of persistent disease (PD) is a variable that could affect therapy efficiency. Our aim was to assess its correlation with the 2015 American Thyroid Association (ATA) risk-stratification system, and its impact on response to initial therapy and outcome. METHODS: This retrospective cohort study included 618 consecutive DTC patients referred for postoperative radioiodine (RAI) treatment. Patients were risk-stratified using the 2015 ATA guidelines according to postoperative data, before RAI treatment. Tumor burden of PD was classified into three categories, i.e. very small-, small- and large-volume PD. Very small-volume PD was defined by the presence of abnormal foci on post-RAI scintigraphy with SPECT/CT or 18FDG PET/CT without identifiable lesions on anatomic imaging. Small- and large-volume PD were defined by lesions with a largest size < 10 or ≥ 10 mm respectively. RESULTS: PD was evidenced in 107 patients (17%). Mean follow-up for patients with PD was 7 ± 3 years. The percentage of large-volume PD increased with the ATA risk (18, 56 and 89% in low-, intermediate- and high-risk patients, respectively, p < 0.0001). There was a significant trend for a decrease in excellent response rate from the very small-, small- to large-volume PD groups at 9-12 months after initial therapy (71, 20 and 7%, respectively; p = 0.01) and at last follow-up visit (75, 28 and 16%, respectively; p = 0.04). On multivariate analysis, age ≥ 45 years, distant and/or thyroid bed disease, small-volume or large-volume tumor burden and 18FDG-positive PD were independent risk factors for indeterminate or incomplete response at last follow-up visit. CONCLUSIONS: The tumor burden of PD correlates with the ATA risk-stratification, affects the response to initial therapy and is an independent predictor of residual disease after a mean 7-yr follow-up. This variable might be taken into account in addition to the postoperative ATA risk-stratification to refine outcome prognostication after initial treatment.

Analysis of medico-social factors for return to work among patients presenting with haematological malignancy (adamantine): results of a 'pilot study'.

OBJECTIVE: The aim of this study was to describe return to work determinants in patients with haematological malignancy. RESULTS: This medico-social pilot study included patients with haematological malignancy in the département of Calvados, aged 18 to 55 years, diagnosed between 1st January and 31st December 2010 and alive at 1st January 2015. Patients were identified via consultation of the Lower Normandy haematological malignancy Registry. They completed a specially developed self-questionnaire, in addition to validated questionnaires for anxiety-depression, quality of life and fatigue. Of the patients contacted, 50% accepted to participate. The mean age at diagnosis was 49.8 years, and the majority of patients (79.2%) was professionally active at the time of diagnosis. Only 64.9% of subjects had stopped work due to illness. The psychological impact (demonstrated anxiety) was significantly greater in men (p = 0.01). The majority of subjects returned to work after treatment (80.7%) and among them, the mean duration of absence from work was 16.1 months. Only 52.6% of subjects had informed their occupational physician and 56.7% had benefited from a pre-return visit. The satisfactory response rate obtained is promising for the extension of the present project as a prospective multicentric study.

Comparative Toxigenicity and Associated Mutagenicity of Aspergillus fumigatus and Aspergillus flavus Group Isolates Collected from the Agricultural Environment.

The mutagenic patterns of A. flavus, A. parasiticus and A. fumigatus extracts were evaluated. These strains of toxigenic Aspergillus were collected from the agricultural environment. The Ames test was performed on Salmonella typhimurium strains TA98, TA100 and TA102, without and with S9mix (exogenous metabolic activation system). These data were compared with the mutagenicity of the corresponding pure mycotoxins tested alone or in reconstituted mixtures with equivalent concentrations, in order to investigate the potential interactions between these molecules and/or other natural metabolites. At least 3 mechanisms are involved in the mutagenic response of these aflatoxins: firstly, the formation of AFB1-8,9-epoxide upon addition of S9mix, secondly the likely formation of oxidative damage as indicated by significant responses in TA102, and thirdly, a direct mutagenicity observed for higher doses of some extracts or associated mycotoxins, which does not therefore involve exogenously activated intermediates. Besides the identified mycotoxins (AFB1, AFB2 and AFM1), additional "natural" compounds contribute to the global mutagenicity of the extracts. On the other hand, AFB2 and AFM1 modulate negatively the mutagenicity of AFB1 when mixed in binary or tertiary mixtures. Thus, the evaluation of the mutagenicity of "natural" mixtures is an integrated parameter that better reflects the potential impact of exposure to toxigenic Aspergilli.

Genotoxicity of aldehyde mixtures: profile of exocyclic DNA-adducts as a biomarker of exposure to tobacco smoke.

Electrophilic compounds present in humans, originating from endogenous processes or pollutant exposures, pose a risk to health though their reaction with nucleophilic sites in protein and DNA. Among this chemical class, aldehydes are mainly present in indoor air and they can also be produced by endogenous lipid peroxidation arising from oxidative stress. Known to be very reactive, aldehydes have the ability to form exocyclic adducts to DNA that, for the most if not repaired correctly, are mutagenic and by consequence potential agents involved in carcinogenesis. The aim of this work was to establish profiles of exocyclic DNA adducts induced by aldehyde mixtures, which could ultimately be considered as a genotoxic marker of endogenous and environmental aldehyde exposure. Adducts were quantified by an accurate, sensitive and validated ultra high performance liquid chromatography-electrospray ionization analytical method coupled to mass spectrometry in the tandem mode (UHPLC-ESI-MS/MS). We simultaneously measured nine exocyclic DNA adducts generated during the exposure in vitro of calf thymus DNA to different concentrations of each aldehyde along, as well as, to an equimolar mixture of these aldehydes. This approach has enabled us to establish dose-response relationships that allowed displaying the specific reactivity of aldehydes towards corresponding adducts formation. Profiles of these adducts determined in DNA of current smokers and non-smokers blood samples supported these findings. These first results are encouraging to explore genotoxicity induced by aldehyde mixtures and can furthermore be used as future reference for adductomic approaches.

Use of soil fungi in the biosorption of three trace metals (Cd, Cu, Pb): promising candidates for treatment technology?

Trace metal contamination is a widespread and complex environmental problem. Because fungi are capable of growing in adverse environments, several fungal species could have an interesting potential in remediation technologies for metal contaminated environments. This study proposes to test the ability to tolerate and biosorb three trace metals (Cd, Cu and Pb) of 28 fungal isolates collected from different soils. First, a tolerance assay in agar medium was performed. Each isolate was grown in the presence of Cd, Cu, and Pb at different concentrations. Then, we exposed each soil fungus to 50 mg L-1 of Cd, Cu, or Pb during 3 days in liquid medium. Parameters such as biomass production, pH, and biosorption were evaluated. The results showed that responses to metal exposure are very diverse even with fungi isolated from the same soil sample, or belonging to the same genera. Several isolates could be considered as good metal biosorbents and could be used in future mycoremediation studies. Among the 28 fungi tested, Absidia cylindrospora biosorbed more than 45% of Cd and Pb, Chaetomium atrobrunneum biosorbed more than 45% of Cd, Cu, Pb, and Coprinellus micaceus biosorbed 100% of Pb.

Convergent Validity and Minimal Clinically Important Difference of the Maugeri Foundation Respiratory Failure Questionnaire (MRF-28) and the Chronic Obstructive Pulmonary Disease-Specific Health-Related Quality of Life questionnaire (VQ11).

Purpose: Short and easy questionnaires have been developed to assess the health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD), such as the Maugeri Foundation Respiratory Failure Questionnaire (MRF-28) and the COPD-specific HRQoL Questionnaire (VQ11). Both are valid, reliable, and sensitive, but their minimal clinically important differences (MCID) are unknown. Consequently, this study aimed to confirm the convergent validities of the MRF-28 and VQ11 and establish their MCID. A retrospective design was used to evaluate the effect of individual home-based pulmonary rehabilitation (PR) in 400 COPD patients. Patients and methods: Exercise tolerance, anxiety and depression based on the Hospital Anxiety and Depression Scale (HADS), and HRQoL using three questionnaires (MRF-28, VQ11, and the Visual Simplified Respiratory Questionnaire: VSRQ) were assessed before and after an individualized home-based PR program (5 sessions of 30-45 mins/week for 8 weeks, including a weekly session supervised by a team member). Results: PR improved all measured variables (p < 0.0001). The correlations were significant (p < 0.0001) between VSRQ and MRF-28 (r = -0.685 at baseline and r = -0.686 after the PR program), and between VSRQ and VQ11 (r = -0.691 at baseline and r = -0.753 after the PR program). Moreover, changes in score (delta between after and before PR program) of VSRQ were also significantly correlated (p < 0.0001) to changes in score of MRF-28 (r = -0.372) and VQ11 (r = -0.423). Last, we calculated MCID of -5.2 and -2.0 units for MRF-28 and VQ11, respectively. Conclusion: The MRF-28 and VQ11 can be used in routine practice to evaluate the effects of PR on the HRQoL of COPD patients, with MCID of -5.2 and -2.0, respectively.

Effectiveness of a therapeutic patient education program in improving cancer pain management: EFFADOL, a stepped-wedge randomised controlled trial.

BACKGROUND: Despite numerous guidelines, nearly one of two patients with cancer pain remains undertreated, thereby affecting their quality of life. Active patient involvement through Therapeutic Patient Education (TPE) is considered as a relevant strategy to overcoming hurdles in pain management. The aim of the EFFADOL study is to assess the effectiveness of a TPE program in improving cancer pain management. METHODS/DESIGN: The EFFADOL study is a stepped-wedge randomised controlled trial. A total of 260 cancer patients with unbalanced background pain will be randomised over the institutional level, i.e. stepped-wedge cluster design. Six clusters will be formed, one at the regional level of "Basse-Normandie" for patients receiving the educational approach by health providers already trained to TPE. Then, five additional centers will be gradually included at the national level, making it possible to compare the "conventional" management of pain (before medical staff training to TPE) with the educational approach (after being trained). The main study parameter is pain interference on daily life assessed with the self-administrated and validated Brief Pain Inventory questionnaire. Secondary objectives comprised the evaluation of patients' adherence to pain education program, the description of pain intensity, pain relief, analgesic adherence and pain emotional impact. Educational dimension of the program will be evaluated through the patients' acquisition of knowledge and skills about their pain and treatment as well as their self-efficacy to participate actively in pain management. The patient's feeling of pain changes will be measured. Finally, the satisfaction of participants and educators will be reported. We hypothetise active involvement of patients in TPE will lead to an improved pain management compared to standard care. DISCUSSION: Analyzing the impact of a TPE program in cancer pain patients will improve their pain management and quality of life. We expect that the dissemination of our project educational approach through the French territory will be accompanied by long term change in clinical practices with mutual benefit to patients and caregiver-educators. TRIAL REGISTRATION: NCT03297723 , registered: 09/28/2017. Protocol version: Version n°1.1 dated from 2016/09/08.

Long-Term In vitro Cultivation of Plasmodium falciparum in a Novel Cell Culture Device.

The standard in vitro cultivation procedure for Plasmodium falciparum requires gas exchange and a microaerophilic atmosphere. A novel system using a commercially available cell culture device (Petaka G3™; Celartia Ltd., Powell, OH) was assessed for long-term cultivation of a P. falciparum reference laboratory clone in normal air. Parasite growth during 30 days was similar, or better, in Petaka G3 than that in the standard cultivation method with gas exchange in a CO2 incubator. The successful cultivation of P. falciparum in the Petaka G3 device suggests that low O2 content available in hemoglobin and dissolved gas in the blood is sufficient for long-term cultivation. This finding may open the way to novel methods to cultivate and adapt P. falciparum field isolates to in vitro conditions with more ease.

French Therapeutic Education Programme Aimed at Improving the Quality of Life of Laryngectomised Patients and their Close Relations: the Three Stages (Observational and Interventional Randomised) of the Study "PETAL".

The therapeutic education of patients and their close relations is, as yet, poorly developed in France in the field of oncology. Total laryngectomy is a mutilating surgical procedure having a major impact on the patient's life, due to its physical and functional sequelae. Its psychosocial consequences are also important and alter the quality of life of patients and their close relations. Currently, care for laryngectomised patients consists essentially in informing and educating them on some technical procedures during hospital admission. The intervention of a speech therapist, often serves as the link between the patient and the hospital care team. These healthcare modalities often insufficiently account for the social, environmental and personal factors that interact in health-related problems. This report presents the therapeutic education programme protocol "PETAL" for laryngectomised patients and their close relations to improve their quality of life. The trial will be conducted over three phases: (1) the "pilot" phase aims at developing knowledge on the consequences of laryngectomy on the quality of life of patients and their close relations and developed a pluridisciplinary therapeutic education program, (2) the prospective intervention "replication" phase aims at evaluating the programme's transferability in three centres and (3) the cluster-randomised multicentric comparative intervention phase, will assess the benefits of the developed programme. Phase I identified nine themes of workshops related to therapeutic education, training and coordination of care. The developed programme should reinforce town-hospital links to improve help, follow-up and support for patients and their close relations.

Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.

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