Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial.

BACKGROUND: The standard of care for the treatment of locally advanced rectal cancer results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free and metastatic-free survival with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival is reported here. PATIENTS AND METHODS: The study design, participants, and primary endpoint disease-free survival (DFS) have been reported for this multicenter, randomized, open-label, phase 3 trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on MRI, and staged cT3/T4. Key secondary endpoints included overall survival (OS), metastasis-free survival (MFS), and local and metastatic recurrence rate. RESULTS: With a median follow-up of 82.2 months, the 7-year DFS were 67.6% (95% CI 60.7%-73.9%) and 62.5% (95% CI 55.6%-68.6%) (RMST difference 5.73 months; 95% CI 0.05-11.41; p=0.048) in the neoadjuvant chemotherapy and the standard of care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0%-84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8%-77.8%) in the standard of care group (RMST difference 6.1 months; 95% CI 0.93-11.37; p=0.021). The 7-year OS was 81.9% (95% CI 75.8%-86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7-81.2) in the standard of care group (RMST difference 4.37 months; 95% CI 0.35-8.38; p=0.033). The safety profile remained unchanged since the previous analysis. CONCLUSION(S): Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in locally advanced rectal cancer patients and should be considered as a one of the best options of care for these patients.

First-line trifluridine/tipiracil + bevacizumab in patients with unresectable metastatic colorectal cancer: final survival analysis in the TASCO1 study.

BACKGROUND: Therapeutic options are limited in patients with unresectable metastatic colorectal cancer (mCRC) ineligible for intensive chemotherapy. The use of trifluridine/tipiracil plus bevacizumab (TT-B) in this setting was evaluated in the TASCO1 trial; here, we present the final overall survival (OS) results. METHODS: TASCO1 was an open-label, non-comparative phase II trial. Patients (n = 153) were randomised 1:1 to TT-B (trifluridine/tipiracil 35 mg/m2 orally twice daily on days 1-5 and 8-12, and bevacizumab intravenously 5 mg/kg on days 1 and 15 of each 28-day cycle) or capecitabine plus bevacizumab (C-B; capecitabine, 1250 mg/m2 orally twice daily on days 1-14 and bevacizumab 7.5 mg/kg intravenously on day 1 of each 21-day cycle). Final OS was analysed when all patients had either died or withdrawn from the study. Adjusted multivariate regression was used to investigate the effects of pre-specified variables on OS. RESULTS: At 1 September 2020, median OS was 22.3 months (95% CI: 18.0-23.7) with TT-B and 17.7 months (95% CI: 12.6-19.8) with C-B (adjusted HR 0.78; 95% CI: 0.55-1.10). No variables negatively affected OS with TT-B. Safety results were consistent with prior findings. CONCLUSIONS: TT-B is a promising therapeutic regimen in mCRC patients ineligible for intensive chemotherapy. CLINICAL TRIAL INFORMATION: NCT02743221 (clinicaltrials.gov).

Age-related differences in self-reported disgust toward core disgust, sex-related, and food stimuli.

INTRODUCTION: While disgust is functional in preventing contagion from pathogens, it also plays a role in various psychopathologies. Disgust responses toward dirt, bodily secretions, certain types of food, and sexual stimuli typically emerge during (early) childhood. However, there is a lack of research on how disgust develops. This cross-sectional study investigated whether there are age-related differences in subjective, self-reported disgust between early and late adolescence and whether there are differences for distinctive types of disgust (core-disgust, sex-related, food-related). METHODS: Using an online survey, 240 Dutch children (116 female, 124 male) aged 9 through 16 years rated the extent to which they found the different types of stimuli disgusting or not on a VAS scale. RESULTS AND CONCLUSIONS: The results showed that only the disgust responses to sex-related stimuli decreased with age, whereas disgust toward the other categories did not show any age-related differences. Overall girls reported somewhat higher disgust ratings than boys for sex-related stimuli, but not for the other categories. The present study offers important new angles for future research, which might further disentangle the mechanisms through which the changes occur.

Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study.

BACKGROUND: The Immunoscore (IS), which prognostically classifies stage I-III colon cancer (CC) patients, was evaluated in the International Duration Evaluation of Adjuvant Therapy (IDEA) France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CC patients. PATIENTS AND METHODS: Densities of CD3+ and CD8+ T cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistochemistry or by pentaplex PCR. Prediction of disease-free survival (DFS) by IS was analyzed by a multivariable Cox regression model in each study arm. Harrell's C-statistics were used to investigate the IS performance. RESULTS: Samples of 1322 patients were available. IS Low, Intermediate (Int), and High were observed in 43.6%, 47.0%, and 9.4% of patients, respectively. IS Low identified patients at higher risk of relapse or death compared with Int + High [hazard ratio (HR) = 1.54; 95% confidence interval (CI) 1.24-1.93, P = 0.0001]. The 3-year DFS was 66.80% (95% CI 62.23-70.94) for IS Low and 77.14% (95% CI 73.50-80.35) for IS Int + High. In multivariable analysis, IS remained significantly independently associated with DFS (P = 0.003) when adjusted for sex, histological grade, T/N stage, and microsatellite instability. For mFOLFOX6-treated patients (91.6% of the cohort), a statistical significant interaction was observed for the predictive value of IS for treatment duration (3 versus 6 months) in terms of DFS (P = 0.057). IS Int + High significantly predicted benefit of 6 months of treatment (HR = 0.53; 95% CI 0.37-0.75; P = 0.0004), including clinically low- and high-risk stage III CC (all P < 0.001). Conversely, patients with IS Low (46.4%) did not significantly benefit from the 6-month mFOLFOX6 versus the 3-month mFOLFOX6. CONCLUSIONS: The prognostic value of IS for DFS was confirmed in patients with stage III CC treated with oxaliplatin-based chemotherapy. Its predictive value for DFS benefit of longer duration of mFOLFOX6 adjuvant treatment was found in IS Int + High. These results will be validated in an external independent cohort. CLINICALTRIALS. GOV REGISTRATION: NCT03422601; EudraCT Number: 2009-010384-16.

Trifluridine/tipiracil plus bevacizumab in patients with untreated metastatic colorectal cancer ineligible for intensive therapy: the randomized TASCO1 study.

BACKGROUND: We designed an open-label, noncomparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TT-B) and capecitabine plus bevacizumab (C-B) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies. PATIENTS AND METHODS: From 29 April 2016 to 29 March 2017, 153 patients were randomly assigned (1:1) to either TT-B (N = 77) or C-B (N = 76). The primary end point was progression-free survival (PFS). The primary PFS analysis was performed after 100 events (radiological progression or death) were observed. Secondary end points included overall survival (OS), quality of life (QoL; QLQ-C30 and QLQ-CR29 questionnaires), and safety. RESULTS: Median (range) duration of treatment was 7.8 (6.0-9.7) months and 6.2 (4.1-9.1) months in the TT-B and C-B groups, respectively. Median (range) PFS was 9.2 (7.6-11.6) and 7.8 (5.5-10.1) months, respectively. Median (range) OS was 18 (15.2 to NA) and 16.2 (12.5 to NA) months, respectively. QoL questionnaires showed no relevant changes over time for either treatment. Therapies were well tolerated. Patients receiving TT-B had more grade ≥3 neutropenia (47% versus 5% with C-B). Patients receiving C-B had more grade ≥3 hand-foot syndrome (12% versus 0% with TT-B) and grade ≥3 diarrhea (8% versus 1% with TT-B), consistent with the known safety profiles of these agents. CONCLUSION: TT-B treatment showed promising clinical activity in untreated patients with unresectable mCRC ineligible for intensive therapy, with an acceptable safety profile and no clinically relevant changes in QoL. CLINICAL TRIAL INFORMATION: NCT02743221 (ClinicalTrials.gov).

Spontaneous sensations reveal distorted body perception in complex regional pain syndrome (CRPS).

Distortions of body representation have been reported in Complex Regional Pain Syndrome (CRPS). The perception of sensations arising without external triggers (spontaneous sensations or SPS) was assessed here as a means of investigating distortions of body representation and awareness in CRPS. To avoid confounds between CRPS symptoms and SPS, lower-limb CRPS patients were included, whereas SPS were tested on the hands. Patients and controls were required to focus on their hands and to report the spatial and qualitative characteristics of SPS arising there. We found an ipsilateral decrease in the perception of thermal, pain-related and surface/mechanical SPS, as well as in the number of SPS-sensitive areas. The latter finding was predicted by decreased body awareness as assessed through questionnaires. A bilateral decrease in the perception of paresis-like SPS was also observed. Finally, the ipsilateral spatial distribution of SPS frequency and intensity underwent a shift from the fingers towards the lower parts of the palm. CRPS is likely to distort patient's body perception and awareness of the entire half-body ipsilateral to the affected limb, and even of both sides. Such disturbances are not manifested solely as a decrease in sensitivity, but sometimes as shifts in the spatial distribution of sensitivity.

Morbidity and oncological outcomes of rectal cancer impaired by previous prostate malignancy.

BACKGROUND: Specific surgical and oncological outcomes in patients with rectal cancer surgery after a previous diagnosis of prostate cancer have not been well described. The aim of this study was to compare surgical outcomes in patients with rectal cancer with or without a history of prostate cancer. METHODS: Patients who had surgery for rectal cancer with (PC group) or without (no-PC group) previous curative treatment for prostate cancer were enrolled between January 2001 and December 2015. Comparisons between the two groups were performed by multivariable Cox analysis, and after propensity score matching in a 3 : 1 ratio for demographic and tumour characteristics, and surgical and oncological outcomes. RESULTS: A total of 944 patients with rectal cancer were enrolled, of whom 10·8 per cent had a history of prostate cancer. After matching, 83 patients who had received treatment for prostate cancer were compared with 249 who had not. The PC and no-PC groups were similar regarding patient characteristics. Extended total mesorectal excision, conversion to open surgery, transfusion and tumour perforation were more frequent in the PC group than in the no-PC group. Major surgical morbidity (28 versus 17·2 per cent; P = 0·036), anastomotic leakage (25 versus 13·7 per cent; P = 0·019) and permanent stoma (41 versus 12·4 per cent; P < 0·001) occurred more frequently in the PC group. Local recurrence was increased significantly in the PC group (17 versus 8·0 per cent; P = 0·019), and resulted in a significant decrease in disease-free and overall survival. CONCLUSION: Prostate cancer treatment increases short- and long-term surgical morbidity in patients with rectal cancer, and impairs oncological outcomes.

Does an observer's empathy influence my pain? Effect of perceived empathetic or unempathetic support on a pain test.

The physiological and behavioural effects of empathy for other's pain have been widely investigated, while the opposite situation, i.e. the influence on one's pain of empathetic feedback from others, remains largely unexplored. Here, we assessed whether and how empathetic and unempathetic comments from observers modulate pain and associated vegetative reactions. In Study 1, conversations between observers of a pain study were recorded by professional actors. Comments were prepared to be perceived as empathetic, unempathetic or neutral, and were validated in 40 subjects. In a subsequent pain experiment (Study 2), changes in subjective pain and heart rate were investigated in 30 naïve participants who could overhear the empathetic or unempathetic conversations pre-recorded in study 1. Subjective pain was significantly attenuated when hearing empathetic comments, as compared to both unempathetic and neutral conditions, while unempathetic comments failed to significantly modulate pain. Heart rate increased when hearing unempathetic remarks and when receiving pain stimuli, but heart acceleration to nociceptive stimulation was not correlated with pain ratings. These results suggest that empathetic feedback from observers has a positive influence on pain appraisal and that this effect may surpass the negative effect of unempathetic remarks. Negative remarks can either trigger feelings of guilt or induce irritation/anger, with antagonistic effects on pain that might explain inter-individual variation. As in basal conditions heart rate and pain perception are positively correlated, their dissociation here suggests that changes in subjective pain were linked to a cognitive bias rather than changes in sensory input.

How health-related quality of life assessment should be used in advanced colorectal cancer clinical trials.

Traditionally, the efficacy of cancer treatment in patients with advance or metastatic disease in clinical studies has been studied using overall survival and more recently tumor-based end points such as progression-free survival, measurements of response to treatment. However, these seem not to be the relevant clinical end points in current situation if such end points were no validated as surrogate of overall survival to demonstrate the clinical efficacy. Appropriate, meaningful, primary patient-oriented and patient-reported end points that adequately measure the effects of new therapeutic interventions are then crucial for the advancement of clinical research in metastatic colorectal cancer to complement the results of tumor-based end points. Health-related quality of life (HRQoL) is effectively an evaluation of quality of life and its relationship with health over time. HRQoL includes the patient report at least of the way a disease or its treatment affects its physical, emotional and social well-being. Over the past few years, several phase III trials in a variety of solid cancers have assessed the incremental value of HRQoL in addition to the traditional end points of tumor response and survival results. HRQoL could provide not only complementary clinical data to the primary outcomes, but also more precise predictive and prognostic value. This end point is useful for both clinicians and patients in order to achieve the dogma of precision medicine. The present article examines the use of HRQoL in phase III metastatic colorectal cancer clinical trials, outlines the importance of HRQoL assessment methods, analysis, and results presentation. Moreover, it discusses the relevance of including HRQoL as a primary/co-primary end point to support the progression-free survival results and to assess efficacy of treatment in the advanced disease setting.

Clinical utility of circulating DNA analysis for rapid detection of actionable mutations to select metastatic colorectal patients for anti-EGFR treatment.

BACKGROUND: While tumor-tissue remains the 'gold standard' for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care. PATIENTS AND METHODS: Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients). Results are presented according to STARD criteria and were discussed in regard with clinical outcomes of patients. RESULTS: Much more mutations were found by ctDNA analysis: 59%, 11.8% and 14.4% of the patients were found KRAS, NRAS and BRAF mutant by ctDNA analysis instead of 44%, 8.8% and 7.2% by tumor-tissue analysis. Median tumor-tissue data turnaround-time was 16 days while 2 days for ctDNA analysis. Discordant samples analysis revealed that use of biopsy, long delay between tumor-tissue and blood collection and resection of the tumor at time of blood draw, tumor site, or type of tissue analyzed seem to affect concordance. Altogether, the clinical data with respect to the anti-epidermal growth factor receptor response (RAS status) and the prognosis (BRAF status) of those discordant patients do not appear contradictory to the mutational status as determined by plasma analysis. Lastly, we present the first distribution profile of the RAS and BRAF hotspot mutations as determined by ctDNA analysis (n = 119), revealing a high proportion of patients with multiple mutations (45% of the population and up to 5 mutations) and only 24% of WT scored patients for both genes. Mutation profile as determined from ctDNA analysis with using various detection thresholds highlights the importance of the test sensitivity. CONCLUSION: Our study showed that ctDNA could replace tumor-tissue analysis, and also clinical utility of ctDNA analysis by considerably reducing data turnaround time.

Exposure to hypomethylating agent, 5-azacytidine, may improve iCasp9 suicide gene therapy for treating GvHD in allografts.

Anti-tumor cellular immunotherapies that implement a suicide gene system can limit potential undesirable effects. In a haplo-identical bone marrow transplant clinical trial, over 90% of iCaspase-9-expressing cells were eradicated after AP1903 exposure, and signs of graft-versus-host disease disappeared. Nevertheless, low numbers of genetically modified T cells survived this treatment. We studied genetically modified cell lines (GMCL) that carried a dual iCaspase-9/ΔCD19 DNA construct (ΔCD19=truncated CD19). With AP1903 exposure, a low percentage of cells (1.47±0.67%; n=5 replications) persisted in vitro. Repeated exposures to increasing AP1903 doses generated low (GMCLLR) and high AP1903-responders (GMCLHR), which expressed different levels of surface ΔCD19 and intracellular iCaspase-9. Compared with GMCLHR, GMCLLR exhibited higher methylation of 5'-long-terminal repeat (LTR) promoters, both in the number of sequences with at least one methylated CpG (16 vs 51.5%, respectively) and in the number of CpG islands (1.2 vs 8.9%, respectively). Four days of 5-azacytidine exposure reduced methylation and increased ΔCD19 and iCaspase-9 expression. Interestingly, LTR demethylation restored GMCLLR sensitivity to AP1903 by 24.3-fold (1.8 vs 43.8%) without affecting GMCLHR. We showed that 5'-LTR-methylation inhibited transgene expression and caused AP1903 hypo-responsiveness. Treating with a hypomethylating agent restored AP1903 sensitivity. This approach can be applied in further clinical trials to improve iCaspase-9 response if low response is detected.

Pathological response and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: a randomized, noncomparative phase II study.

BACKGROUND: In T3 rectal cancer (RC), preoperative chemoradiotherapy [5-fluorouracil (5-FU-RT)] reduces local recurrences, but does not affect overall survival. New therapeutic options are still necessary to improve clinical outcomes. PATIENTS AND METHODS: This randomized, noncomparative, open-label, multicenter, two arms, phase II study was conducted in MRI-defined locally advanced T3 resectable RC. In arm A, patients received 12-week bevacizumab plus 5-FU, leucovorin and oxaliplatin (Folfox-4) followed with bevacizumab-5-FU-RT before total mesorectal excision (TME). In arm B, patients received only bevacizumab-5-FU-RT before TME. Primary end point was pathological complete response (pCR) rate. RESULTS: Forty-six patients were randomized in arm A and 45 patients in arm B. In arm A, the rate of pCR was 23.8% [95% confidence interval (CI) 12.1% to 39.5%] statistically superior to the defined standard rate of 10%, P = 0.015. In arm B, the rate of pCR of 11.4% (95% CI 3.8% to 24.6%) was not different from 10%, P = 0.906. No death occurred during the study period, from the start until 8 weeks following surgery. Postoperative fistulas were reported for 16 patients (7 in arm A and 9 in arm B). CONCLUSION: Even if the addition of bevacizumab induced manageable toxicities including an increased risk of postoperative fistula and no treatment-related death, arm B did not achieve the expected pCR rate in the population of patients included. Induction bevacizumab-Folfox-4 followed by bevacizumab-5-FU-RT is promising. It is however necessary to continue investigations in the management of locally advanced RC. ClinicalTrials.gov Identifier: NCT 00865189.

[Post anoxia impairment of autobiographical memory and time estimation]. / Déficit de mémoire autobiographique et d'estimation du temps après une anoxie cérébrale.

A case of episodic amnesia with impairment of time perception is described; it illustrates the link between time perception and autobiographical memory. This woman suffered from a Sheehan syndrome with anoxia at the age of 36 and since that date has had a strong and isolated difficulty to estimate the date and duration of events in a range of weeks, months or years. Conversely, short duration time spans are correctly evaluated. The patient's complaints also involve episodic memory. She reports many events from her biography very imprecisely while the semantic autobiographical data are preserved. The patient has difficulty in recalling the date of public events and the period of celebrity of well-known people. That observation confirms the specificity of time organization for long periods and the link with the episodic memory where the context of the dating task is crucial. The results are discussed in reference to autobiographical memory that involves mental wandering in time-space and the constitution of self over a time continuum.

DCF (docetaxel, cisplatin and 5-fluorouracil) chemotherapy is a promising treatment for recurrent advanced squamous cell anal carcinoma.

BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare disease, mostly diagnosed at early stage. After concurrent chemoradiation (CRT) with mitomycin C and 5-fluorouracil (5FU), local or metastatic recurrences occur in >20% of the patients. After treatment failure, cisplatin (CDDP)-based chemotherapy is the standard option, but complete response (CR) is a rare event and the prognosis remains poor. PATIENTS AND METHODS: Eight consecutive patients with advanced recurrent SCCA after CRT were treated with DCF regimen (docetaxel 75 mg/m(2) day 1, CDDP 75 mg/m(2) day 1 and 5FU at 750 mg/m(2)/day for 5 days every 3 weeks). Tumour samples were analysed for human papillomavirus (HPV) genotyping, as well as p16 and p53 expression. RESULTS: After a median follow-up of 41 months, the overall survival rate at 12 months was 62.5% (95% CI 22.9-86.1 months). Four patients achieved a complete remission and remain relapse-free at the time of analysis with a progression-free survival of 19, 33, 43 and 88 months. Three of these patients underwent surgery for all involved metastatic sites. For all of them, pathological CR was confirmed. DCF regimen appeared feasible in these patients previously exposed to pelvic CRT, and no grade IV toxicity occurred. All patients in complete remission had HPV-16-positive SCCA, while HPV could only be detected among 50% of the non-responding patients. Of interest, immunohistochemical study revealed a p16(+)/p53(-) phenotype in these patients, while none of non-responders expressed p16. CONCLUSION: The high level of complete and long-lasting remission among SCCA patients treated with DCF regimen supports the assessment of this strategy in prospective cohorts.

Exploration of verbal and non-verbal semantic knowledge and autobiographical memories starting from popular songs in Alzheimer's disease.

BACKGROUND: In mild Alzheimer's disease (AD), a deficit in episodic memory, particularly autobiographical memory, is clearly established. Several recent studies have also shown impaired semantic memory from the onset of the disease. Musical memory capacities may be especially preserved and listening to music might encourage autobiographical recall. The aim of this study was to explore recall of popular songs in AD. METHODS: We tested 12 patients with mild AD and 12 control subjects. We created a tool made up of old French popular songs: POP 10. This tool is a questionnaire composed of several subtests: melodic free recall, chorus free recall, melodic recognition, chorus recognition, semantic knowledge, autobiographical recall about the song, and autobiographical recall about the interpreter. RESULTS: We used non-parametric tests, the Mann-Whitney test (M-W), the Friedman test, and the a posteriori Wilcoxon test. Results of AD patients were rather similar to those of control participants for melodic memory. Concerning chorus memory (except recognition), semantic knowledge, and autobiographical recall about the interpreter, results of AD patients were significantly weaker than those of control participants. The most important result concerned autobiographical recall about the song: we found no impairment-related differences between the two groups. CONCLUSION: Our findings demonstrate that popular songs can be excellent stimuli for reminiscence, such as the ability to produce an autobiographical memory related to a song. Thus, we confirm that musical semantic knowledge associated with a song may be relatively preserved in the early stages of AD. This leads to new possibilities for cognitive stimulation.

Economic impact of prescribing error prevention with computerized physician order entry of injectable antineoplastic drugs.

UNLABELLED: A cost-benefit analysis was carried out to determine the potential economic costs and benefits of pharmaceutical analysis in preventing prescribing errors for full standardized injectable antineoplastic drugs computerized physician order entry, in a pharmaceutical unit (University teaching hospital), compared with theoretical setting with no pharmaceutical analysis. The viewpoint is that of the payer or the French national Public Health Insurance system, and is limited to hospital cost (only direct medical costs related to net cost and net benefit. A decision analysis model was performed to compare two strategies: with pharmaceutical analysis (± pharmacy intervention) and without pharmaceutical analysis. RESULTS: are expressed in terms of benefit-to-cost ratio and total benefit. The robustness of the results was assessed through a series of one-way sensitivity analyses. Over 1 year, prescribing error incidence was estimated at 1.5% [1.3-1.7], i.e. 218 avoided prescribing errors. Potential avoidance of hospital stay was estimated at 419 days or 1.9 ± 0.3 days per prescribing error. Cost-benefit analysis could estimate a net benefit-to-cost ratio of 33.3 (€17.34/€0.52) and a total benefit at €16.82 per pharmaceutical analysis or €249,844 per year. The sensitivity analysis showed robustness of results. Our study shows a substantial economic benefit of pharmaceutical analysis and intervention in the prevention of prescribing errors. The clinical pharmacist adds both value and economic benefit, making it possible to avoid additional use of expensive antineoplastic drugs and hospitalization. Computerized physician order entry of antineoplastic drugs improves the relevance of clinical pharmacist interventions, expanding pharmaceutical analysis and also the role of the pharmacist.

The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age.

Purpose: Cancer patients are at risk of severe COVID-19 infection, and vaccination is recommended. Nevertheless, we observe a failure of COVID-19 vaccines in this vulnerable population. We hypothesize that senescent peripheral T-cells alter COVID-19 vaccine-induced immunity. Methods: We performed a monocentric prospective study and enrolled cancer patients and healthy donors before the COVID-19 vaccination. The primary objective was to assess the association of peripheral senescent T-cells (CD28-CD57+KLRG1+) with COVID-19 vaccine-induced immunity. Results: Eighty cancer patients have been included, with serological and specific T-cell responses evaluated before and at 3 months post-vaccination. Age ≥ 70 years was the principal clinical factor negatively influencing the serological (p=0.035) and specific SARS-CoV-2 T-cell responses (p=0.047). The presence of senescent T-cells was correlated to lower serological (p=0.049) and specific T-cell responses (p=0.009). Our results sustained the definition of a specific cut-off for senescence immune phenotype (SIP) (≥ 5% of CD4 and ≥ 39.5% of CD8 T-cells), which was correlated to a lower serological response induced by COVID-19 vaccination for CD4 and CD8 SIPhigh (p=0.039 and p=0.049 respectively). While CD4 SIP level had no impact on COVID-19 vaccine efficacy in elderly patients, our results unraveled a possible predictive role for CD4 SIPhigh T-cell levels in younger cancer patients. Conclusions: Elderly cancer patients have a poor serological response to vaccination; specific strategies are needed in this population. Also, the presence of a CD4 SIPhigh affects the serological response in younger patients and seems to be a potential biomarker of no vaccinal response.

[Semantic knowledge in MCI and Alzheimer's disease: the French version of the New Words Interview]. / Connaissance des nouveaux mots de la langue française dans les troubles cognitifs légers de type amnésique et la maladie d'Alzheimer.

INTRODUCTION: The first decline in cognitive performance in Alzheimer's disease can appear when assessing semantic memory and can be detected long before the typical symptoms of Alzheimer's disease (AD), appearing with Mild Cognitive Impairment (MCI). PATIENTS AND METHOD: We propose the French version of the New Words Interview (fNWI) using 22 words to investigate semantic knowledge. The fNWI uses 11 words, which entered the French dictionary between 1996 and 1997, and 11 other words, which entered between 2006 and 2007. Words were paired according to orthographic and semantic criteria. Each word was associated with three sub-tests: free evocation, discrimination of the best definition from three propositions, and recognition of the accurate word context (two sentences were proposed). Regarding evocation, we distinguished conceptual definition, life situation examples or examples by use. We tested 12 patients with AD, 12 patients with amnesic Mild Cognitive Impairment (aMCI) and 72 controls (12 were paired with patients for age and education level). RESULTS: MCI patients and AD patients exhibited lower performance than controls in the three sub-tests and for the words of both periods. From the early stage of MCI, the patients were more impaired in the fNWI than in the context recognition task, and they failed to provide conceptual definitions of new words. Therefore, MCI patients suffer from semantic impairments before obvious clinical signs of AD. CONCLUSION: In patients with AD, performance worsened on all subtests, and more strongly in the definition discrimination task, which suggests the impairment of stored semantic knowledge. They provided fewer conceptual definitions and failed to use the strategy observed in MCI patients, who compensated for conceptual difficulties by providing examples.