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Background The SAME device (i-SEP, France) is an innovative filtration-based autotransfusion device able to salvage and wash both red blood cells and platelets. This study evaluated the device performances using human whole blood with the hypothesis that the device will be able to salvage platelets while achieving a erythrocyte yield of 80% and removal ratios of 90% for heparin and 80% for major plasma proteins without inducing signification activation of salvaged cells. Methods Thirty healthy human whole blood units (median volume, 478 ml) were diluted, heparinized, and processed by the device in two consecutive treatment cycles. Samples from the collection reservoir and the concentrated blood were analyzed. Complete blood count was performed to measure blood cell recovery rates. Flow cytometry evaluated the activation state and function of platelets and leukocytes. Heparin and plasma proteins were measured to assess washing performance. Results The global erythrocyte yield was 88.1% (84.1 to 91.1%; median [25th to 75th]) with posttreatment hematocrits of 48.9% (44.8 to 51.4%) and 51.4% (48.4 to 53.2%) for the first and second cycles, respectively. Ektacytometry did not show evidence of erythrocyte alteration. Platelet recovery was 36.8% (26.3 to 43.4%), with posttreatment counts of 88 × 109/l (73 to 101 × 109/l) and 115 × 109/l (95 to 135 × 109/l) for the first and second cycles, respectively. Recovered platelets showed a low basal P-selectin expression at 10.8% (8.1 to 15.2%) and a strong response to thrombin-activating peptide. Leukocyte yield was 93.0% (90.1 to 95.7%) with no activation or cell death. Global removal ratios were 98.3% (97.8 to 98.9%), 98.2% (96.9 to 98.8%), and 88.3% (86.6 to 90.7%) for heparin, albumin, and fibrinogen, respectively. The processing times were 4.4 min (4.2 to 4.6 min) and 4.4 min (4.2 to 4.7 min) for the first and second cycles, respectively. Conclusions This study demonstrated the performance of the SAME device. Platelets and red blood cells were salvaged without significant impact on cell integrity and function. In the meantime, leukocytes were not activated, and the washing quality of the device prevented reinfusion of high concentrations of heparin and plasma proteins. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

INTRODUCTION Myositis are systemic diseases, in which heart damage is possible. Cardiac troponin T is often found to be defective to detect cardiac involvement. OBSERVATION We report cases of two patients with a myositis. Diagnosis was retained based on muscle pain, increase in serum creatinine kinase, and inflammatory muscle damage on MRI. Histology confirmed the diagnosis for one of the two patients. Cardiac troponin T was measured in both patients, to detect myocardial involvement. Despite a serum elevation of this marker, cardiological assessment remained negative (electrocardiogram, cardiac ultrasound, cardiac MRI). Cardiac troponin I was normal in serum because of the absence of correlation with peripheral muscle involvement. CONCLUSION Cardiac troponin T is correlated with muscle involvement in patients with myositis. Cardiac troponin I should be preferred because of a better specificity.

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The search of substrates for solute carriers (SLCs) constitutes a major issue, owing notably to the role played by some SLCs, such as the renal electrogenic organic cation transporter (OCT) 2 (SLC22A2), in pharmacokinetics, drug–drug interactions and drug toxicity. For this purpose, substrates have been proposed to be identified by their cis-inhibition and trans-stimulation properties towards transporter activity. To get insights on the sensitivity of this approach for identifying SLC substrates, 15 various exogenous and endogenous OCT2 substrates were analysed in the present study, using 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (DiASP) as a fluorescent OCT2 tracer substrate. All OCT2 substrates cis-inhibited DiASP uptake in OCT2-overexpressing HEK293 cells, with IC50 values ranging from 0.24 µM (for ipratropium) to 2.39 mM (for dopamine). By contrast, only 4/15 substrates, i.e., acetylcholine, agmatine, choline and metformin, trans-stimulated DiASP uptake, with a full suppression of the trans-stimulating effect of metformin by the reference OCT2 inhibitor amitriptyline. An analysis of molecular descriptors next indicated that trans-stimulating OCT2 substrates exhibit lower molecular weight, volume, polarizability and lipophilicity than non-trans-stimulating counterparts. Overall, these data indicated a rather low sensitivity (26.7%) of the trans-stimulation assay for identifying OCT2 substrates, and caution with respect to the use of such assay may therefore be considered.

International audience; The recent development of a humanized, bi-specific, and monoclonal antibody mimicking the function of activated factor VIII was a revolution in the management of patients suffering from severe hemophilia A with inhibitors. The phase III randomized studies have shown a more efficient prophylaxis of this subcutaneous administered drug in these patients compared with recombinant FVIIa (rFVIIa) and activated prothrombin complex concentrates (aPCC). Nonetheless, there are “real life” matters that need to be explored in this new era of managing hemophilia patients, such as surgery management under emicizumab, especially in children. Here, we report the first case, to our knowledge, of major orthopedic surgery managed with factor VIII infusions in a child with inhibitor receiving emicizumab.

The search of substrates for solute carriers (SLCs) constitutes a major issue, owing notably to the role played by some SLCs, such as the renal electrogenic organic cation transporter (OCT) 2 (SLC22A2), in pharmacokinetics, drug–drug interactions and drug toxicity. For this purpose, substrates have been proposed to be identified by their cis-inhibition and trans-stimulation properties towards transporter activity. To get insights on the sensitivity of this approach for identifying SLC substrates, 15 various exogenous and endogenous OCT2 substrates were analysed in the present study, using 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (DiASP) as a fluorescent OCT2 tracer substrate. All OCT2 substrates cis-inhibited DiASP uptake in OCT2-overexpressing HEK293 cells, with IC50 values ranging from 0.24 µM (for ipratropium) to 2.39 mM (for dopamine). By contrast, only 4/15 substrates, i.e., acetylcholine, agmatine, choline and metformin, trans-stimulated DiASP uptake, with a full suppression of the trans-stimulating effect of metformin by the reference OCT2 inhibitor amitriptyline. An analysis of molecular descriptors next indicated that trans-stimulating OCT2 substrates exhibit lower molecular weight, volume, polarizability and lipophilicity than non-trans-stimulating counterparts. Overall, these data indicated a rather low sensitivity (26.7%) of the trans-stimulation assay for identifying OCT2 substrates, and caution with respect to the use of such assay may therefore be considered.

Introduction. Even though Corynebacterium aurimucosum has been described in 2002, this species has long been underestimated due to the unreliability of conventional identification methods and only a few cases of infections have been reported. Hypothesis/Gap Statement. Little is known about clinical significance and antimicrobial susceptibility profile of this uncommon species. Aim. To evaluate the clinical relevance of C. aurimucosum and its antimicrobial susceptibility profile. Methodology. All C. aurimucosum isolates, collected from 2010 to 2019 in 10 French university hospitals, were retrospectively included. Demographic, clinical and microbiological data were collected for all cases. Antimicrobial susceptibility testing was performed according to the 2019 EUCAST guidelines. Results. Fifty-seven clinical isolates of C. aurimucosum were collected in 57 patients (median age, 65.8 years; male/female sex ratio, 1.1), mostly from urine (28 %), blood culture (28 %) and bone/synovial fluid (19 %) samples. Of them, 14 cases of infection were confirmed, mainly bone and joint infections (50 %) followed by urinary tract infections (UTIs) (21 %), bacteremia (14 %), skin and soft-tissue infections (14 %). C. aurimucosum was recovered in pure culture in 36 % of cases (UTIs and bacteremia) while mixed cultures were observed for other infections. By testing 52 clinical isolates in vitro, this species appeared to be fully susceptible to linezolid and vancomycin while most isolates (>80 %) were susceptible to amoxicillin (MIC90, 2 µg ml−1), gentamicin, tetracycline and rifampicin. Both cefotaxime and ciprofloxacin seemed to have a limited activity (ca. 50 % of susceptible strains). The MIC distribution for ciprofloxacin showed a bimodal profile with a population of highly-resistant strains with MICs >2 µg ml−1. Most isolates (>90 %) were categorized as resistant to penicillin G and clindamycin. Conclusion. C. aurimucosum should be considered as an actual opportunistic pathogen, and treatment with amoxicillin, vancomycin or linezolid should be preferred.

International audience; Very-high-dose biotin therapy is sometimes prescribed in newborns with pharmacoresistant neonatal epileptic encephalopathy or with suspicion of inherited metabolic disorders such as biotinidase deficiency, holocarboxylase synthetase deficiency, or Leigh syndrome (in biotin-thiamine-responsive basal ganglia disease due to SLC19A3 mutation).1,2 Regardless of the child’s weight (2-10 kg), tremendous doses of biotin are administrated (10-300 mg/day, e.g., 3-100 mg/kg/day for a 3-kg newborn).

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International audience; Ketosis is a metabolic situation involving an increase in blood and urine concentrations of ketones that, when prolonged, leads to acidosis. Moderate ketosis usually appears after a fast of a few hours, but its prolongation exposes to hyperketosis. Observation A 25-year-old woman presented to the emergency department for cohercitive vomiting. She was fasting for a long time in a spiritual setting and had a restricted diet limited to water and vitamin supplements. Clinical and biological assessment was in favour of fasting ketoacidosis. Evolution was favorable with intravenous hydration, poly-ionic and micronutrient supplementation and a gradual resumption of oral feeding. Conclusion We report the case of a patient with fasting ketoacidosis. Besides consequences of this ketoacidosis, the challenge was also in resuming oral feeding in order to avoid a potentially fatal inappropriate renutrition syndrome.