For a given severity, mHLA-DR proved not to a predictive marker of outcome, but a weak trend of mHLA-DR recovery was associated with an increased risk of secondary infection. Monitoring immune functions through mHLA-DR in intensive care unit patients therefore could be useful to identify a high risk of secondary infection.
Preliminary studies suggest that a subgroup of septic patients with severe immune alterations is at high risk of death or nosocomial infection and therefore could benefit from adjunctive immune stimulating therapies. There is thus an urgent need for robust biomarkers usable in routine conditions evaluating rapidly evolving immune status in patients. Although functional testing remains a gold standard, its standardisation remains challenging. Therefore, surrogate markers such as monocyte HLA-DR expression, are being developed. Such biomarkers of immune functionality will enable a novel approach in the design of clinical trials evaluating immunostimulating therapies in sepsis at the right time and in the right patient.
The somatosensory evoked potential negative components in the 100-150-ms range were studied under conditions where attention was directed either toward or away from the probe stimulus. An N120 component, not sensitive to spatial attention, appeared in all conditions, including the no-task condition. Its distribution was consistent with an origin in the second somatic area. A later N140 response, not recorded in neutral conditions, was highly sensitive to spatial attention and reached its maximum to stimulation of the attended hand; its behavior was consistent with that of a processing negativity. The N140 was bilaterally distributed, but the hemisphere contralateral to stimulation appeared to be involved earlier than the ipsilateral one. Although the exogenous N120 may be influenced by somatosensory awareness and perhaps tactile recognition, the N140 appears linked to the spatial components of attention and results from the activation of several areas in both hemispheres.
Background and Purpose: The efficiency of prehospital care chain response and the adequacy of hospital resources are challenged amid the coronavirus disease 2019 (COVID-19) outbreak, with suspected consequences for patients with ischemic stroke eligible for mechanical thrombectomy (MT). Methods: We conducted a prospective national-level data collection of patients treated with MT, ranging 45 days across epidemic containment measures instatement, and of patients treated during the same calendar period in 2019. The primary end point was the variation of patients receiving MT during the epidemic period. Secondary end points included care delays between onset, imaging, and groin puncture. To analyze the primary end point, we used a Poisson regression model. We then analyzed the correlation between the number of MTs and the number of COVID-19 cases hospitalizations, using the Pearson correlation coefficient (compared with the null value). Results: A total of 1513 patients were included at 32 centers, in all French administrative regions. There was a 21% significant decrease (0.79; [95%CI, 0.76–0.82]; P <0.001) in MT case volumes during the epidemic period, and a significant increase in delays between imaging and groin puncture, overall (mean 144.9±SD 86.8 minutes versus 126.2±70.9; P <0.001 in 2019) and in transferred patients (mean 182.6±SD 82.0 minutes versus 153.25±67; P <0.001). After the instatement of strict epidemic mitigation measures, there was a significant negative correlation between the number of hospitalizations for COVID and the number of MT cases ( R 2 −0.51; P =0.04). Patients treated during the COVID outbreak were less likely to receive intravenous thrombolysis and to have unwitnessed strokes (both P <0.05). Conclusions: Our study showed a significant decrease in patients treated with MTs during the first stages of the COVID epidemic in France and alarming indicators of lengthened care delays. These findings prompt immediate consideration of local and regional stroke networks preparedness in the varying contexts of COVID-19 pandemic evolution.
Neutrophils play a major role in inflammatory responses and immune defense against pathogens. Even though expression of inhibitory receptors has been reported on neutrophils, their role remains poorly defined. Here we show that primary human neutrophils expressed immunoglobulin-like transcript 4 (ILT4) inhibitory receptor and that this expression was induced during differentiation of the myelomonoblast PLB-985 cell line into "neutrophil-like" cells. Functional assays indicated that human leukocyte antigen G, the preferred ligand of ILT4, inhibited the phagocytic function of neutrophils. ILT4 engagement also impaired reactive oxygen species production induced through CD32a and both receptors were found colocalized into neutrophil lipid rafts. Moreover, neutrophil degranulation induced through inflammatory stimuli increased ILT4 expression as a result of the rapid translocation of an intracellular pool to the cell surface. Consequently to this ILT4 upregulation, the human leukocyte antigen G-mediated inhibition of neutrophil phagocytic function was enhanced. Finally, we found that ILT4 up-regulation induced on healthy donor neutrophils following stimulation was impaired in presence of plasma from patients with sepsis. Similarly, ILT4 up-regulation was inhibited in neutrophils from septic patients. Altogether, our results reveal a unique mechanism of regulation of neutrophil functions through ILT4 and its exocytosis that may have implications in inflammatory disorders.granulocytes |
BackgroundTo investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis.Methodology/Principal FindingsProspective multicenter observational study done in 4 intensive care units in two university hospitals. Severe sepsis and septic shock patients with at least 2 organ failures based on the SOFA score were classified: 1) "no AKI", 2) "mild AKI" (grouping stage 1 and 2 of AKIN score) and 3) "severe AKI" (stage 3 of AKIN score). Sequential measurements: The vasopressor dependency index (VDI; dose and types of drugs) to evaluate the association between hemodynamic status and the development of early AKI; plasma levels of IL-10, macrophage migration inhibitory factor (MIF), IL-6 and HLA-DR monocyte expression. Genotyping of the 13 HLA-DRB1 alleles with deduction of presence of HLA-DRB3, -DRB4 and -DRB5 genes. We used multivariate analysis with competitive risk model to study associations. Overall, 176 study patients (146 with septic shock) were classified from AKIN score as "no AKI" (n = 43), "mild AKI" (n = 74) or "severe AKI" (n = 59). The VDI did not differ between groups of AKI. After adjustment, "mild and severe AKI" were an independent risk factor for mortality (HR 2.42 95%CI[1.01-5.83], p = 0.048 and HR 1.99 95%CI[1.30-3.03], p = 0.001 respectively). "Severe AKI" had higher levels of plasma IL-10, MIF and IL-6 compared to “no AKI” and mild AKI (p<0.05 for each), with no difference in mHLA-DR at day 0. HLA-DRB genotyping showed a significantly lower proportion of 4 HLA-DRB alleles among patients requiring renal replacement therapy (RRT) (58%) than in patients with severe AKI who did not receive RRT (84%) (p = 0.004).ConclusionsAKI severity is independently associated with mortality and plasma IL-10, MIF or IL-6 levels. Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT.
• Stent retriever thrombectomy of tandem occlusion is efficient and safe. • Emergent carotid stenting during thrombectomy increase symptomatic intracranial haemorrhage without impact mortality. • Thrombectomy of tandem anterior circulation occlusion may be the first therapeutic option.
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