Detection of decreased glomerular filtration rate in intensive care units: serum cystatin C versus serum creatinine

Peer reviewe

Multiple-center evaluation of mortality associated with acute kidney injury in critically ill patients: a competing risks analysis

International audienceINTRODUCTION: In this study, we aimed to assess the association between acute kidney injury (AKI) and mortality in critically ill patients using an original competing risks approach. METHODS: Unselected patients admitted between 1997 and 2009 to 13 French medical or surgical intensive care units were included in this observational cohort study. AKI was defined according to the RIFLE criteria. The following data were recorded: baseline characteristics, daily serum creatinine level, daily Sequential Organ Failure Assessment (SOFA) score, vital status at hospital discharge and length of hospital stay. Patients were classified according to the maximum RIFLE class reached during their ICU stay. The association of AKI with hospital mortality with "discharge alive" considered as a competing event was assessed according to the Fine and Gray model. RESULTS: Of the 8,639 study patients, 32.9% had AKI, of whom 19.1% received renal replacement therapy. Patients with AKI had higher crude mortality rates and longer lengths of hospital stay than patients without AKI. In the Fine and Gray model, independent risk factors for hospital mortality were the RIFLE classes Risk (sub-hazard ratio (SHR) 1.58 and 95% confidence interval (95% CI) 1.32 to 1.88; P < 0.0001), Injury (SHR 3.99 and 95% CI 3.43 to 4.65; P < 0.0001) and Failure (SHR 4.12 and 95% CI 3.55 to 4.79; P < 0.0001); nonrenal SOFA score (SHR 1.19 per point and 95% CI 1.18 to 1.21; P < 0.0001); McCabe class 3 (SHR 2.71 and 95% CI 2.34 to 3.15; P < 0.0001); and respiratory failure (SHR 3.08 and 95% CI 1.36 to 7.01; P < 0.01). CONCLUSIONS: By using a competing risks approach, we confirm in this study that AKI affecting critically ill patients is associated with increased in-hospital mortality

Predictive test of therapeutic response of breast cancer

Method for ex vivo testing of the effects of (candidate) pharmaceuticals for treatment of breast cancer. Method for ex vivo testing of the effects of (candidate) pharmaceuticals for treatment of breast cancer comprises: (A) culturing cancer cells from a breast sample in a basal medium that contains the following growth factors/ingredients: hydrocortisone (HC) 0.3-0.5 mg/l; triiodothyronine (T3) 0.0004-0.0008 mg/l; insulin 5-15 mg/l; transferrin 4-10 mg/l; recombinant human epidermal growth factor (EGF) 0.05-0.15 mg/l and 17beta -estradiol (E) 0.2-0.3 mg/l, until a culture of cancer cells, essentially free of stromal cells, is produced; (B) contacting the culture with one or more (candidate) pharmaceuticals and (C) identifying, and selecting, one or more of the test compounds that show antiproliferative activity. Independent claims are included for the following: (1) culture medium (CM) that contains growth factors/ingredients specified above; (2) cell culture containing CM and breast cancer cells; and (3) kit for performing the new method comprising CM, transport medium and dissociation medium. - ACTIVITY : Cytostatic. - MECHANISM OF ACTION : None given

Etude du récepteur pro-apoptotique Fas dans des cellules neuronales et lymphocytaires T humaines

Cette étude porte sur le récepteur pro-apoptotique Fas dans le système nerveux et immunitaire. La sclérose latérale amyotrophique (SLA) est une maladie neurogénérative avec une destruction sélective des neurones moteurs. Nous avons montré que 26 % des sérums de malades atteints de SLA présentaient des taux élevés d'autoanticorps dirigés contre Fas qui induisaient l'apoptose d'une lignée neuroblastique humaine et des motoneurones de rat. L'expression du récepteur Fas a été mise en évidence in vitro et ex vivo dans les neurones moteurs murins et humains. Les cellules de la lignée neuroblastique SH-SY5Y sont hétérogènes. Le tri des cellules par SdFFF a permis d'obtenir 3 populations présentant des stades distincts de différenciation. Nous avons mis en évidence dans la lignée lymphocytaire T Jurkat la phosphorylation extracellulaire des agrégats de Fas de 116 kDa par des ectokinases C qui inhibent ainsi l'oligomérisation membranaire de Fas à la surface cellulaire et l'apoptose.LIMOGES-BU Sciences (870852109) / SudocSudocFranceF

Oncogramme, a new promising method for individualized breast tumour response testing for cancer treatment.

International audienceBACKGROUND:Breast cancer is the most widely spread cancer in the world, attracting much research and individualized tumour response testing (ITRT) methods are now used to individualize patient chemotherapeutic administrations. A new ITRT method was developed with optimized processing.MATERIALS AND METHODS:Breast tumour fragments were separated and the cells seeded in a foetal calf serum-free defined medium. After various chemotherapeutic treatments, cytotoxicity was determined by cell death detection with calcein acetoxymethyl and ethidium homodimer labelling.RESULTS:The culture medium allowed breast tumour cell proliferation in culture, while preventing fibroblastic cell survival. Moreover, the cell death analysis gave rise to a chemoresistance profile called an Oncogramme, with statistically significant values.CONCLUSION:The Oncogramme is a new ITRT method which can predict patient cell sensitivities to chemotherapeutics and should be validated by a new phase I clinical trial

Response to Ventilator Adjustments for Predicting Acute Respiratory Distress Syndrome Mortality. Driving Pressure versus Oxygenation

International audienceAbstract Background There is wide variability between intensivists in the decisions to forgo life-sustaining treatment (DFLST). Advance directives (ADs) allow patients to communicate their end-of-life wishes to physicians. We assessed whether ADs reduced variability in DFLSTs between intensivists. Methods We conducted a multicenter, prospective, simulation study. Eight patients expressed their wishes in ADs after being informed about DFLSTs by an intensivist-investigator. The participating intensivists answered ten questions about the DFLSTs of each patient in two scenarios, referring to patients’ characteristics without ADs (round 1) and then with (round 2). DFLST score ranged from 0 (no-DFLST) to 10 (DFLST for all questions). The main outcome was variability in DFLSTs between intensivists, expressed as relative standard deviation (RSD). Results A total of 19,680 decisions made by 123 intensivists from 27 ICUs were analyzed. The DFLST score was higher with ADs than without (6.02 95% CI [5.85; 6.19] vs 4.92 95% CI [4.75; 5.10], p < 0.001). High inter-intensivist variability did not change with ADs (RSD: 0.56 (round 1) vs 0.46 (round 2), p = 0.84). Inter-intensivist agreement on DFLSTs was weak with ADs (intra-class correlation coefficient: 0.28). No factor associated with DFLSTs was identified. A qualitative analysis of ADs showed focus on end-of-life wills, unwanted things and fear of pain. Conclusions ADs increased the DFLST rate but did not reduce variability between the intensivists. In the decision-making process using ADs, the intensivist’s decision took priority. Further research is needed to improve the matching of the physicians’ decision with the patient’s wishes. Trial registration ClinicalTrials.gov Identifier: NCT03013530. Registered 6 January 2017; https://clinicaltrials.gov/ct2/show/NCT03013530

Sedimentation field flow fractionation monitoring of in vitro enrichment in cancer stem cells by specific serum-free culture medium

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