Fluid challenge (FC) is one of the most common practices in Intensive Care Unit (ICU). The present study aimed to evaluate whether echocardiographic assessment of the response to FC at the end of the infusion or 20 min later could affect the results of the FC. This is a prospective, observational, multicenter study including all ICU patients in septic shock requiring a FC of 500 mL crystalloids over 10 min. Fluid responsiveness was defined as a > 15% increase in stroke volume (SV) assessed by velocity-time integral (VTI) measurements at baseline (T0), at the end of FC (T10), then 10 (T20) and 20 min (T30) after the end of FC. From May 20, 2014, to January 7, 2016, a total of 143 patients were enrolled in 11 French ICUs (mean age 64 ± 14 years, median IGS II 53 [43–63], median SOFA score 10 [8–12]). Among the 76/143 (53%) patient responders to FC at T10, 37 patients were transient responders (TR), i.e., became non-responders (NR) at T30 (49%, 95%CI = [37–60]), and 39 (51%, 95%CI = [38–62]) patients were persistent responders (PR), i.e., remained responders at T30. Among the 67 NR at T10, 4 became responders at T30, (6%, 95%CI = [1.9–15.3]). In the subgroup analysis, no statistical difference in hemodynamic and echocardiographic parameters was found between groups. This study shows that 51.3% of initial responders have a persistent response to fluid 30 min after the beginning of fluid infusion and only 41.3% have a transient response highlighting that fluid responsiveness is time dependent. ClinicalTrials.gov , NCT02116413 . Registered on April 16, 2014

The aim of this study was to identify novel biomarkers for multiple sclerosis (MS) diagnosis and prognosis, addressing the critical need for specific and prognostically valuable markers in the field. We conducted an extensive proteomic investigation, combining analysis of (1) CSF proteome from symptomatic controls, fast and slow converters after clinically isolated syndromes, and patients with relapsing-remitting MS (n = 10 per group) using label-free quantitative proteomics and (2) oligodendrocyte secretome changes under proinflammatory or proapoptotic conditions using stable isotope labeling by amino acids in cell culture. Proteins exhibiting differential abundance in both proteomic analyses were combined with other putative MS biomarkers, yielding a comprehensive list of 87 proteins that underwent quantification through parallel reaction monitoring (PRM) in a novel cohort, comprising symptomatic controls, inflammatory neurologic disease controls, and patients with MS at various disease stages (n = 10 per group). The 11 proteins that passed this qualification step were subjected to a new PRM assay within an expanded cohort comprising 158 patients with either MS at different disease stages or other inflammatory or noninflammatory neurologic disease controls. This study unveiled a promising biomarker signature for MS, including previously established candidates, such as chitinase 3-like protein 1, chitinase 3-like protein 2, chitotriosidase, immunoglobulin kappa chain region C, neutrophil gelatinase-associated lipocalin, and CD27. In addition, we identified novel markers, namely cat eye syndrome critical region protein 1 (adenosine deaminase 2, a therapeutic target in multiple sclerosis) and syndecan-1, a proteoglycan, also known as plasma cell surface marker CD138 and acting as chitinase 3-like protein 1 receptor implicated in inflammation and cancer signaling. CD138 exhibited good diagnostic accuracy in distinguishing MS from inflammatory neurologic disorders (area under the curve [AUC] = 0.85, CI 0.75-0.95). CD138 immunostaining was also observed in the brains of patients with MS and cultured oligodendrocyte precursor cells but was absent in astrocytes. These findings identify CD138 as a specific CSF biomarker for MS and suggest the selective activation of the chitinase 3-like protein 1/CD138 pathway within the oligodendrocyte lineage in MS. They offer promising prospects for improving MS diagnosis and prognosis by providing much-needed specificity and clinical utility. This study provides Class II evidence that CD138 distinguishes multiple sclerosis from other inflammatory neurologic disorders with an AUC of 0.85 (95% CI 0.75-0.95).

A revised classification of cerebellar infarctions (CI) may uncover unrecognized associations with etiologic stroke subtypes. We hypothesized that obliquely oriented small cortical cerebellar infarction (SCCI) representing end zone infarctions on MRI would be associated with cardiac embolism. We retrospectively analyzed consecutive stroke patients recruited between January–December 2016 in our center. Analyzed baseline characteristics: sex, age, cardiovascular risk factors, history of stroke or atrial fibrillation (AF). TOAST classification was used for determining stroke subtype. Acute infarction location (anterior/posterior/mixed anterior-posterior circulation), acute uni- or multiterritorial infarction, and acute or chronic CI/SCCI/non-SCCI were assessed by MRI, and vertebrobasilar stenosis/occlusion by vessel imaging. Pre-specified analysis was also performed in patients without known high cardioembolic risk (known AF history or acute multiterritorial infarction). We included 452 patients (CI in 154, isolated SCCI in 55, isolated non-SCCI in 50, and mixed SCCI/non-SCCI in 49). Both SCCI and non-SCCI were associated with AF history (SCCI, p = 0.021; non-SCCI, p = 0.004), additional acute posterior circulation infarction (p < 0.001 both CI-subtypes), multiterritorial infarctions (SCCI, p = 0.003; non-SCCI, p < 0.001) and cardioembolic more frequent than large-artery atherosclerosis origin (p < 0.001 for both CI-subtypes). SCCI was associated with older age (p < 0.001), whereas non-SCCI was associated with stroke history (p = 0.036) and vertebrobasilar stenosis/occlusion (p = 0.002). SCCI were older (p = 0.046) than non-SCCI patients, had less frequently prior stroke (p < 0.001), and more frequent cardioembolic infarction (p = 0.025). In patients without known high cardioembolic risk (n = 348), SCCI was strongly associated with subsequent cardioembolism diagnosis (OR 3.00 [CI 1.58–5.73, p < 0.001]). No such association was present in non-SCCI. Acute or chronic SCCI are strongly associated with a cardioembolic origin.

This article introduces a spatio-temporal distance which allows the extension of the spatial cluster detection methods of Demattei et al. ( 2007 Demattei , C. , Molinari , N. , Daures , J. P. ( 2007 ). Arbitrarily shaped multiple spatial cluster detection for case event data . Computat. Statist. Data Anal. 51 ( 8 ): 3931 – 3945 . [Google Scholar] ) and Cucala ( 2009 Cucala , L. ( 2009 ). A flexible spatial scan test for case event data . Computat. Statist. Data Anal. 53 ( 8 ): 2843 – 2850 . [Crossref], [Web of Science ®] [Google Scholar] ). A review of these methods is given before we define a spatio-temporal distance. Then this distance is used for detecting spatio-temporal clusters. These ordering-based methods are compared to the scan statistic by a simulation study. The scan procedure is more powerful but it detects fewer true positives due to its lack of flexibility. Those techniques are applied to a seismic data set. This article highlights two advantages of the ordering-based methods: their flexibility and their low computational demand.

Background: Although wisdom-tooth extraction is a routine intervention, the postoperative period remains marked by local inflammation classically manifesting as pain, edema and trismus. Furthermore, there is no consensus on the best operative techniques, particularly for the mucosal closure stage on impacted mandibular wisdom teeth. Methods: This parallel, randomized, non-blinded study compared pain following removal of impacted third molars, with and without sutures. Patients were electronically allocated 1:1 to extraction with versus without sutures. Patients ≥ 14 years’ old scheduled for extraction of four impacted wisdom teeth under general anesthesia at three French hospitals were eligible for inclusion. Exclusion criteria included taking antiplatelet agents or anticoagulants, coagulation disorders or immunosuppression, and planned orofacial surgical procedures or emergency pain/infection. The primary objective was pain evaluated by Visual Analogue Scale on Day 3. Secondary outcomes were edema, trismus, healing, complications, painkiller consumption and quality of life on Day 3 and 31. Results: Between June 2016 and November 2018, 100 patients were randomized. Finally, 44 patients in the Suture group and 50 patients in the Without Suture group were analyzed. Mean age was 16.5 years and 66.6% of patients were female. After adjustment on center, age and smoking, no statistical difference was seen between groups for pain on Day 3 (p = 0.904). No differences were seen for swelling, trismus, consumption of painkillers, healing, complications or quality of life. Smokers had a 3.65 times higher complications rate (p = 0.0244). Conclusions: Sutureless removal of third molars is thus a reliable technique without negative consequence on outcomes, and allows shorter operating time. Smoking is a risk factor for postoperative complications. Trial registration www.clinicaltrials.gov (NCT02583997), registered 22/10/2015

The objective of this study was to investigate the link between gut microbiota (GM) dysbiosis, gut inflammation, and bacterial translocation (BT) in recently diagnosed rheumatoid arthritis (RA). This case-control, observational study prospectively recruited recently diagnosed (<12 months) RA patients and age-matched healthy controls (HC) from two French hospitals between July 2014 to March 2018. The primary objective was to investigate GM composition in each group using 16S rRNA sequencing and metaproteomics approaches. Three plasmatic BT markers (sCD14, LPS-binding protein, and number of 16S rRNA gene copies) and one intestinal permeability marker (I-FABP) were quantified in blood samples. Twenty-five were included in each group, and 50 stools and blood samples were analyzed. 16S rRNA gene analysis showed an decrease in Coprococcus in RA patients after Body Mass Index and HLA status. Circulating bacterial DNA (number of copies of the 16S rRNA gene) and plasmatic I-FABP were higher in RA patients compared to HCs (p < 0.01), indicating increased BT and intestinal permeability in these patients. Metaproteomics from stool samples highlighted an increased host humoral immune response in RA, with elevated levels of inflammatory proteins (azurocidin, cathepsin G, neutrophil defensing 1). Gut inflammation may contribute to increased intestinal permeability, leading to BT into the systemic circulation and thus chronic inflammation.