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The Minto pharmacokinetic model is used for target-controlled infusion of remifentanil. The reliability of this model has never been evaluated during normothermic cardiac surgery with cardiopulmonary bypass (CPB). The aim of this study was to assess the predictive performance of the model during CPB to determine its reliability during cardiac surgery.This was a single-centre observational study. Arterial blood samples were drawn at five time points: T1, after tracheal intubation; T2, immediately before CPB; T3, 10 min after starting CPB; T4, 45 min after starting CPB; T5, 10 min after weaning off CPB. Prediction error (PE) and absolute prediction error (APE) were calculated for each sample and used to determine median prediction error (MDPE) and median absolute prediction error (MDAPE) per patient. Risk factors for APE30% were assessed using multivariable analysis. Results are presented as medians with inter-quartile ranges.Fifty-eight patients with 283 blood samples (110 during CPB) were included. In the pre-CPB period, MDPE and MDAPE were -17.3 [-32.9 to 2.3] and 24.6 [12-37.7]%, whereas during CPB, they were -1.8 [-15.6 to 11.1] and 14.0 [6.74-27.1]%, respectively. There was no statistically significant difference between measured and predicted remifentanil plasma concentrations during CPB. Age, preoperative albumin concentrations, temperature, and haemodilution were not independently associated with MDAPE30%.The Minto model accurately predicts plasma remifentanil concentrations during cardiac surgery with CPB.2017-A03153-50.

BACKGROUND: We previously reported that CEA kinetics are a marker of progressive disease (PD) in metastatic colorectal cancer (mCRC). This study was specifically designed to confirm CEA kinetics for predicting PD and to evaluate CA19-9, cell-free DNA (cfDNA), circulating tumour DNA (ctDNA) and circulating tumour cell (CTC) kinetics. METHODS: Patients starting a chemotherapy (CT) with pre-treatment CEA > 5 ng/mL and/or CA19.9 > 30 UI/mL were prospectively included. Samples were collected from baseline to cycle 4 for CEA and CA19-9 and at baseline and the sixth week for other markers. CEA kinetics were calculated from the first to the third or fourth CT cycle. RESULTS: A total of 192 mCRC patients were included. CEA kinetics based on the previously identified >0.05 threshold was significantly associated with PD (p

Background No long-term maintenance therapy has been tested in patients with seborrheic dermatitis (SD). Objective We sought to compare the efficacy and tolerance of tacrolimus 0.1% ointment versus ciclopiroxolamine 1% cream as maintenance therapy for severe SD. Methods This double-blind randomized controlled study was conducted from 2014 to 2017 in 5 Dermatology Departments and 15 dermatology practices in France. Consecutive patients with severe and chronic facial SD were included. Patients were initially treated with desonide 0.05% cream twice daily for 7 days. Patients cleared after this open phase were randomized to receive tacrolimus 0.1% or ciclopiroxolamine 1% cream 2 times a week 24 weeks. The primary endpoint was disease-free-duration, defined as the time from randomization to first relapse. Results One hundred fourteen patients were randomized (tacrolimus, n = 57; ciclopiroxolamine, n = 57). Twelve patients relapsed in the tacrolimus group after a median delay of 91.5 days (range 15-195 days) versus 23 patients in the ciclopiroxolamine group (median delay, 27 days [range 13-201 days]). Comparison of disease-free duration curves showed that patients in the tacrolimus group had a longer duration of complete remission than those in the ciclopiroxolamine group (P = .018), corresponding to a hazard ratio of relapse of 0.44 (95% confidence interval 0.22-0.89; P = .022). Limitations The theoretical sample size was not reached. Conclusion Tacrolimus 0.1% is more effective than ciclopiroxolamine 1% as maintenance therapy for patients with facial SD.

Background: The different waves of SARS-CoV-2 infection have strained hospital resources and, notably, intensive care units (ICUs). Identifying patients at risk of developing a critical condition is essential to correctly refer patients to the appropriate structure and to spare limited resources. The soluble form of RAGE (sRAGE), the endoplasmic stress response and its surrogates, GRP78 and VEGF-A, may be interesting markers. Methods: This was a prospective monocenter cohort study of adult patients admitted to the ICU for severe COVID-19 pneumonia. The plasma levels of sRAGE, GRP78 and VEGF-A were measured within the first 24 h. Patients were classified as critical if they further needed vasopressor therapy, renal replacement therapy, or invasive mechanical ventilation, or died during their ICU stay, and were otherwise classified as not critical. Results: A total of 98 patients were included and 39 developed a critical condition. Critical patients presented higher sRAGE (626 [450–1043] vs. 227 [137–404] pg/mL, p < 0.0001), interleukin-6 (43 [15–112] vs. 11 [5–20] pg/mL, p < 0.0001), troponin T (17 [9–39] vs. 10 [6–18] pg/mL, p = 0.003) and NT-pro-BNP (321 [118–446] vs. 169 [63–366] pg/mL, p = 0.009) plasma levels. No difference was observed for VEGF-A and GRP78. The variables independently associated with worsening in the ICU were sRAGE (1.03 [1.01–1.05] per 10 pg/mL) and age (1.7 [1.2–2.4] per 5 years). An sRAGE value of 449.5 pg/mL predicted worsening with a sensitivity of 77% and a specificity of 80%. Conclusion: sRAGE may allow the identification of patients at risk of developing a critical form of COVID-19 pneumonia, and thus may be useful to correctly refer patients to the appropriate structure of care.

BackgroundElectroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD). However, due to response delay and cognitive impairment, ECT remains an imperfect treatment. Compared to ECT, repetitive transcranial magnetic stimulation (rTMS) is less effective at treating severe depression, but has the advantage of being quick, easy to use, and producing almost no side effects. In this study, our objective was to assess the priming effect of rTMS sessions before ECT on clinical response in patients with TRD.MethodsIn this multicenter, randomized, double-blind, sham-controlled trial, 56 patients with TRD were assigned to active or sham rTMS before ECT treatment. Five sessions of active/sham neuronavigated rTMS were administered over the left dorsolateral prefrontal cortex (20 Hz, 90% resting motor threshold, 20 2 s trains with 60-s intervals, 800 pulses/session) before ECT (which was active for all patients) started. Any relative improvements were then compared between both groups after five ECT sessions, in order to assess the early response to treatment.ResultsAfter ECT, the active rTMS group exhibited a significantly greater relative improvement than the sham group [43.4% (28.6%) v. 25.4% (17.2%)]. The responder rate in the active group was at least three times higher. Cognitive complaints, which were assessed using the Cognitive Failures Questionnaire, were higher in the sham rTMS group compared to the active rTMS group, but this difference was not corroborated by cognitive tests.ConclusionsrTMS could be used to enhance the efficacy of ECT in patients with TRD. ClinicalTrials.gov: NCT02830399.

BACKGROUND AND OBJECTIVE Probe-based confocal laser endomicroscopy (pCLE) enables in vivo microimaging of the distal lung, during bronchoscopy. This study aims at identifying pCLE descriptors of chronic interstitial lung diseases (ILD), their correlations with chest HRCT and assessing inter-observer agreement. METHODS pCLE was performed in 21 healthy volunteers (HV) and 59 non-smoking ILD patients, including 19 patients with idiopathic pulmonary fibrosis (IPF) or asbestosis, 15 with connective tissue disease-associated ILD (CTD-ILD), 17 with sarcoidosis and 8 with hypersensitivity pneumonitis (HP). pCLE descriptors were identified in ILD on the basis of comparison with HV. RESULTS Nine pCLE descriptors were more frequent in ILD compared to HV, with good inter-observer agreement, including fluorescent bronchiolar cells (sarcoidosis, CTD-ILD and HP), fluorescent alveolar cells (CTD-ILD and HP), small alveolar entrance rings (IPF or asbestosis and CTD-ILD), enlarged axial elastic fibres (IPF or asbestosis), septal fibres (IPF or asbestosis, CTD-ILD and HP), disorganized acinar network and rigid acinar network (IPF or asbestosis and CTD-ILD), dense elastic network (IPF or asbestosis) and alveolar fluorescent nodular structures (in sarcoidosis) (P

Background: Thrombosis is frequent during COVID-19 disease, and thus, identifying predictive factors of hemostasis associated with a poor prognosis is of interest. The objective was to explore coagulation disorders as early predictors of worsening critical conditions in the intensive care unit (ICU) using routine and more advanced explorations. Materials: Blood samples within 24 h of ICU admission for viscoelastic point-of-care testing, (VET), advanced laboratory tests: absolute immature platelet count (A-IPC), von Willebrand-GPIb activity (vWF-GpIb), prothrombin fragments 1 + 2 (F1 + 2), and the thrombin generation assay (TGA) were used. An association with worse outcomes was explored using univariable and multivariable analyses. Worsening was defined as death or the need for organ support. Results: An amount of 85 patients with 33 in critical condition were included. A-IPC were lower in worsening patients (9.6 [6.4–12.5] vs. 12.3 [8.3–20.7], p = 0.02) while fibrinogen (6.9 [6.1–7.7] vs. 6.2 [5.4–6.9], p = 0.03), vWF-GpIb (286 [265–389] vs. 268 [216–326], p = 0.03) and F1 + 2 (226 [151–578] vs. 155 [129–248], p = 0.01) were higher. There was no difference observed for D-dimer, TGA or VET. SAPS-II and A-IPC were independently associated with worsening (OR = 1.11 [1.06–1.17] and OR = 0.47 [0.25–0.76] respectively). The association of a SAPS-II ≥ 33 and an A-IPC ≤ 12.6 G/L predicted the worsening of patients (sensitivity 58%, specificity 89%). Conclusions: Immature platelets are early predictors of worsening in severe COVID-19 patients, suggesting a key role of thrombopoiesis in the adaption of an organism to SARS-CoV-2 infection.

Introduction Les dermatites seborrheiques (DS) severes sont affichantes et parfois source de corticodependance. But Comparer l’efficacite et la tolerance du ciclopiroxolamine (Cipro) et du tacrolimus (Tacro) comme traitement d’entretien des DS severes. Materiel et methodes Etude randomisee realisee dans 22 centres hospitaliers et liberaux, financee par l’AO liberal de la SFD. Critere inclusion : DS severe (definie par un score prenant en compte l’intensite de l’erytheme et la desquamation), d’evolution chronique, n’ayant pas repondu aux traitements locaux ou systemiques prealables. L’etude comportait 2 phases : 1) traitement d’attaque : application de creme Tridenosit®, 2/jour pendant 7 jours ; 2) traitement d’entretien : randomisation 1 : 1 Tacro vs Cipo, une application × 2 jours/semaine pendant 6 mois. L’insu etait assure par des surtubes identiques et un engagement signe des patients de ne pas parler a l’investigateur de la consistance des produits, ni de la tolerance avant l’evaluation d’efficacite. Le critere de jugement principal etait la duree de la remission clinique complete (RC) obtenue a l’issue du traitement d’attaque (delai entre la randomisation et la 1ere rechute). Le traitement dermocorticoide etait ensuite repris pendant 7 jours, puis les produits a l’essai reappliques 2/semaine jusqu’a la prochaine rechute ou la fin de l’etude. Resultats Cent quatorze patients ayant une DS severe ont ete inclus et randomises (Tacro n = 57, Cipro n = 57). La duree d’evolution moyenne de la DS avant l’inclusion etait de 113 ± 117 mois (Tacro : 101 ± 107,6 mois ; Cipro : 125 ± 125,9). Douze patients ont rechute dans le groupe Tacro apres un delai moyen de 3,2 ± 2,4 mois versus 22 patients dans le groupe Cipro (delai 1,9 ± 2 mois). La comparaison de courbes de DFS montrait une plus longue duree de RC dans le groupe Tacro que dans le groupe Cipro (Logrank test, p = 0,02 ( Figure 1 )). Le nombre total de rechutes pendant les 6 mois de l’etude a ete de 14 (0,24 rechute/malade) dans le bras Tacro vs 23 (0,40 rechute/malade) dans le bras Cipro (p = 0,071). Le nombre de jours pendant lesquels les patients ont du appliquer du Tridesonit® pendant l’etude etait de 15,9 ± 13 jours (Cipro) vs 16,8 ± 14,5 jours (Tacro), (p = 0,77). Six effets secondaires (ES) severes et 34 ES non severes ont ete observes dans le bras Tacro vs 2 et 17 dans le bras Cipro. Les ES les plus frequents etaient : sensation de brulure (35 %) dans le bras Tacro et prurit (29 %) dans le bras Cipro. Des ES ayant conduit a l’arret du traitement ont ete observes chez 5 (12 %) patients du groupe Tacro et 1 (5 %) du groupe Cipro. Conclusion Le tacrolimus topique applique 2 fois/semaine est superieur au ciclopiroxolamine comme traitement d’entretien des DS severes.

Populations of segetal species are facing sharp declines in Europe due to agricultural intensification. To better conserve them, it is important to assess the effect of intensification in extensive mixed crop-livestock systems, which are considered hotspots for segetal species. The aim of this study was to evaluate how certain key farming practices and land-use intensity affect the composition, species richness and abundance of segetal species, taking into account spatial heterogeneity within the studied fields. To do this, we sampled 94 winter cereal fields - 41 farmed organically and 53 farmed conventionally - along a gradient of land-use intensity. At field scale, we found that both the species richness and the abundance of segetal taxa decreased with an increase in land-use intensity. The results also showed significant differences in segetal taxa composition, species richness and abundance between the edges and the inner-fields location and these differences significantly increased with land-use intensity. The species richness and abundance of both common and threatened segetal taxa were significantly higher at the edges of fields than within them. Herbicide treatments had a significant negative impact on segetal taxa species richness and abundance, while mechanical weeding had a positive impact on abundance. Nitrogen inputs had a significant detrimental effect only on the abundance of common segetal taxa. Crop seed origin and the ratio of cereal crops in the rotational cycle had no effect on segetal taxa species richness and abundance. Despite these impacts, we found that segetal species richness and abundance were better explained by farm identity (random factor) than by current management (fixed factors). Variation in segetal species richness and abundance between fields of the same farm and between farms reflect the long-term effects of farming practices and the history of seed transfer between farms more than by current management practices. In our study area, the production of cereals is destined for the consumption of the farm's sheep and the fact the cereals are not marketed makes it possible to tolerate the presence of segetal species in higher proportions than in intensive farming systems.

Purpose: The aims were to compare peak oxygen uptake (VO2peak) predicted from four standard equations to actual V O2peak measured from a cardiopulmonary exercise test (CPET) in obese patients with metabolic syndrome (MetS), and develop a new equation to estimate V O2peak in obese women with MetS. Methods: Seventy-five obese patients with MetS performed a CPET. Anthropometric data were also collected for each participant. V O2peak was predicted from four prediction equations (from Riddle, Hansen, Wasserman or Glaser) and then compared with the actual VO2peak measured during the CPET. The accuracy of the predictions was determined with the Bland–Altman method. When accuracy was low, a new prediction equation including anthropometric variables was proposed. Results: VO2peak predicted from the equation of Wasserman was not significantly different from actual VO2 peak in women. Moreover, a significant correlation was found between the predicted and actual values (p r = 0.69). In men, no significant difference was noted between actual VO2peak and VO2peak predicted from the prediction equation of Glaser, and these two values were also correlated (p = 0.03, r = 0.44). However, the LoA95% was wide, whatever the prediction equation or gender. Regression analysis suggested a new prediction equation derived from age and height for obese women with MetS. Conclusions: The methods of Wasserman and Glaser are valid to predict VO2peak in obese patient with MetS, respectively. However, the accuracy of the predictions was low for both methods. Consequently, a new prediction equation including age and height was developed for obese women with MetS. However, new prediction equation remains to develop in obese men with MetS.

Aspergillus species are the main cause of invasive fungal disease for patients with severe and prolonged neutropenia. Building or renovation works have been shown as one of the major causes of outbreaks of aspergillosis.This study aimed to assess the effectiveness of introduction and adaptation by air sampling of mechanical preventive measures on the incidence of invasive pulmonary aspergillosis in neutropenic patients during hospital renovation.All of the patients admitted for prolonged and severe neutropenia during a renovation period from 2003 to 2008 were prospectively enrolled. Invasive pulmonary aspergillosis (IPA) cases were classified as possible, probable, and proven, according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group criteria. The effectiveness of preventive measures was determined by air sampling.We recorded 705 hospitalizations for neutropenia concerning 438 patients. The majority of hospitalized neutropenic patients was treated for acute leukemia (38.3 %), followed by patients suffering from non-Hodgkin and Hodgkin lymphomas (33 %). The total cumulative incidence of probable and proven IPA was 4.1 %. Risk factors for developing IPA were underlying disease, treatment course at the time of hospitalization, and the mean duration of hospitalization and of neutropenia.In this prospective study, the incidence of invasive pulmonary aspergillosis did not increase in neutropenic patients during a renovation period because of efficient mechanical preventive measures systematically adjusted using the results of air sampling.

3560Background: CEA, cDNA and CTC have been reported as useful markers in mCRC pts treated with chemotherapy (CT)-based regimen. We previously reported that CEA kinetic (threshold 0.05) was associa...