Highly Variable Sialylation Status of Donor-Specific Antibodies Does Not Impact Humoral Rejection Outcomes

Clinical outcome in antibody-mediated rejection (AMR) shows high inter-individual heterogeneity. Sialylation status of the Fc fragment of IgGs is variable, which could modulate their ability to bind to C1q and/or Fc receptors. In this translational study, we evaluated whether DSA sialylation influence AMR outcomes. Among 938 kidney transplant recipients for whom a graft biopsy was performed between 2004 and 2012 at Lyon University Hospitals, 69 fulfilled the diagnosis criteria for AMR and were enrolled. Sera banked at the time of the biopsy were screened for the presence of DSA by Luminex. The sialylation status of total IgG and DSA was quantified using Sambucus nigra agglutinin-based chromatography. All patients had similar levels of sialylation of serum IgGs (~2%). In contrast, the proportion of sialylated DSA were highly variable (median = 9%; range = 0–100%), allowing to distribute the patients in two groups: high DSA sialylation (n = 44; 64%) and low DSA sialylation (n = 25; 36%). The two groups differed neither on the intensity of rejection lesions (C4d, ptc, and g; p > 0.05) nor on graft survival rates (Log rank test, p = 0.99). in vitro models confirmed the lack of impact of Fc sialylation on the ability of a monoclonal antibody to trigger classical complement cascade and activate NK cells. We conclude that DSA sialylation status is highly variable but has not impact on DSA pathogenicity and AMR outcome

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Mise en place et évaluation d’un protocole d’analgésie-sédation dans le service de réanimation pédiatrique du CHRU de Besançon

La sédation-analgésie fait partie intégrante de la prise en charge du patient ventilé en réanimation pédiatrique et doit être adaptée à chaque patient, afin d’éviter un sur dosage en drogues sédatives tout en limitant l’impact sur le comportement lié à la douleur et au stress. L’objectif de notre travail était de mettre en place un protocole d’analgésie-sédation dan s notre service de réanimation pédiatrique afin d’améliorer nos pratiques tout en évaluant son impact. La première partie de ce projet consistait en une étude rétrospective des données relatives à l’analgésie-sédation chez 55 patients ayant été hospitalisés avec une ventilation mécanique pendant plus de 24 heures dans notre service de réanimation pédiatrique. La deuxième partie de ce projet consistait en l’élaboration d’un protocole d’analgésie-sédation géré par les infirmières. La troisième partie sera l’évaluation de son impact sur la durée de ventilation mécanique, la durée d’hospitalisation, les posologies cumulées et les durées des drogues, la survenue de complications, telles qu’un syndrome de sevrage ou une pneumopathie acquise sous ventilation mécanique, après son implantation dans notre service, dans une étude prospective monocentrique. Mettre en place un protocole d’analgésie-sédation dans le service de réanimation pédiatrique de Besançon pourrait permettre une amélioration de nos pratiques et de la prise en charge de nos patients

Etude cas-témoin sur la mortalité des hémorragies intra abdominales sous anticoagulants et antiagrégants en réanimation

CAEN-BU Médecine pharmacie (141182102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Tribute to an exemplary man: Yves Couder

International audienc

Visual Agnosia and Posterior Cerebral Artery Infarcts: An Anatomical-Clinical Study

Background: To evaluate systematically the cognitive deficits following posterior cerebral artery (PCA) strokes, especially agnosic visual disorders, and to study anatomical-clinical correlations. Methods and Findings: We investigated 31 patients at the chronic stage (mean duration of 29.1 months post infarct) with standardized cognitive tests. New experimental tests were used to assess visual impairments for words, faces, houses, and objects. Forty-one healthy subjects participated as controls. Brain lesions were normalized, combined, and related to occipitotemporal areas responsive to specific visual categories, including words (VWFA), faces (FFA and OFA), houses (PPA) and common objects (LOC). Lesions were located in the left hemisphere in 15 patients, in the right in 13, and bilaterally in 3. Visual field defects were found in 23 patients. Twenty patients had a visual disorder in at least one of the experimental tests (9 with faces, 10 with houses, 7 with phones, 3 with words). Six patients had a deficit just for a single category of stimulus. The regions of maximum overlap of brain lesions associated with a deficit for a given category of stimuli were contiguous to the peaks of the corresponding functional areas as identified in normal subjects. However, the strength of anatomicalclinical correlations was greater for words than for faces or houses, probably due to the stronger lateralization of the VWFA, as compared to the FFA or the PPA. Conclusions: Agnosic visual disorders following PCA infarcts are more frequent than previously reported. Dedicate

The median effective analgesic dose (ED50) of ropivacaine in ultrasound-guided transversus abdominis plane block for analgesia in reversal of ileostomy: A double-blind up-down dose-finding study.

International audienceThe transversus abdominis plane block has become popular since it has been combined with ultrasound-guided techniques. In abdominal surgery, and especially in subumbilical surgery, it improves postoperative analgesia and reduces morphine consumption. Although it has been shown to be an effective technique, there are wide variations in reported doses and volumes of local anaesthetic used. The primary objective was to assess the median effective analgesic dose (ED50 = effective dose in 50% of patients) of ropivacaine in TAP blocks for patients undergoing reversal of ileostomy. A prospective double-blind study. French Teaching Hospital. Twenty-six colorectal patients were included. After standardised general anaesthesia, a unilateral ultrasound-guided TAP block was performed on patients undergoing elective reversal of ileostomy using 20 ml of ropivacaine. Doses were predefined according to the up-and-down method. The first patient received a dose of 1.6 mg kg. The dose adjustment interval was 0.2 ml kg. The potentially toxic dose of 3 mg kg was never exceeded. The primary endpoint was pain (defined as 3 or higher on a numerical pain scale of 0 to 10) at rest 6 h after TAP block. Out of the twenty-six patients who were included in the study, the ED50 of ropivacaine in TAP block for patients undergoing reversal of ileostomy was 2.70 mg kg [95% confidence interval (95% CI) 2.37 to 3.03 mg kg]. The ED50 of ropivacaine in TAP blocks in reversal of ileostomy is close to the toxic threshold. Anaesthesiologists should always be aware of the systemic toxicity risk and use weight-based doses when performing a TAP block

Fluorine 18 Fluorodeoxyglucose PET/CT Volume-based Indices in Locally Advanced Non–Small Cell Lung Cancer: Prediction of Residual Viable Tumor after Induction Chemotherapy

International audienceTo study whether volume-based indices of fluorine 18 fluorodeoxyglucose positron emission tomographic (PET)/computed tomographic (CT) imaging is an accurate tool to predict the amount of residual viable tumor after induction chemotherapy in patients with locally advanced non-small cell lung cancer (NSCLC)