Peripheral Eosinophil Trends and Clinical Outcomes After Non-traumatic Subarachnoid Hemorrhage

Background/objective Uncontrolled systemic inflammation after non-traumatic subarachnoid hemorrhage (SAH) is associated with worse outcomes. Changes in the peripheral eosinophil count have been linked to worse clinical outcomes after ischemic stroke, intracerebral hemorrhage, and traumatic brain injury. We aimed to investigate the association of eosinophil counts with clinical outcomes after SAH. Methods This retrospective observational study included patients with SAH admitted from January 2009 to July 2016. Variables included demographics, modified Fisher scale (mFS), Hunt–Hess Scale (HHS), global cerebral edema (GCE), and the presence of any infection. Peripheral eosinophil counts were examined as part of routine clinical care on admission and daily for 10 days after aneurysmal rupture. Outcome measures included dichotomized discharge mortality, modified Ranked Scale (mRS) score, delayed cerebral ischemia (DCI), vasospasm, and need for ventriculoperitoneal shunt (VPS). Statistical tests included the chi-square test, Student\u27s t-test, and multivariable logistic regression (MLR) model. Results A total of 451 patients were included. The median age was 54 (IQR 45, 63) years, and 295 (65.4%) were female patients. On admission, 95 patients (21.1%) had a high HHS (\u3e4), and 54 (12.0%) had GCE. A total of 110 (24.4%) patients had angiographic vasospasm, 88 (19.5%) developed DCI, 126 (27.9%) had an infection during hospitalization, and 56 (12.4%) required VPS. Eosinophil counts increased and peaked on days 8–10. Higher eosinophil counts on days 3–5 and day 8 were seen in patients with GCE (p \u3c 0.05). Higher eosinophil counts on days 7–9 (p \u3c 0.05) occurred in patients with poor discharge functional outcomes. In multivariable logistic regression models, higher day 8 eosinophil count was independently associated with worse discharge mRS (OR 6.72 [95% CI 1.27, 40.4], p = 0.03). Conclusion This study demonstrated that a delayed increase in eosinophils after SAH occurs and may contribute to functional outcomes. The mechanism of this effect and the relationship with SAH pathophysiology merit further investigation

Early Systemic Glycolytic Shift After Aneurysmal Subarachnoid Hemorrhage is Associated with Functional Outcomes

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) leads to a robust systemic inflammatory response. We hypothesized that an early systemic glycolytic shift occurs after aSAH, resulting in a unique metabolic signature and affecting systemic inflammation. METHODS: Control patients and patients with aSAH were analyzed. Samples from patients with aSAH were collected within 24 h of aneurysmal rupture. Mass spectrometry-based metabolomics was performed to assess relative abundance of 16 metabolites involved in the tricarboxylic acid cycle, glycolysis, and pentose phosphate pathway. Principal component analysis was used to segregate control patients from patients with aSAH. Dendrograms were developed to depict correlations between metabolites and cytokines. Analytic models predicting functional outcomes were developed, and receiver operating curves were compared. RESULTS: A total of 122 patients with aSAH and 38 control patients were included. Patients with aSAH had higher levels of glycolytic metabolites (3-phosphoglycerate/2-phosphoglycerate, lactate) but lower levels of oxidative metabolites (succinate, malate, fumarate, and oxalate). Patients with higher clinical severity (Hunt-Hess Scale score ≥ 4) had higher levels of glyceraldehyde 3-phosphate and citrate but lower levels of α-ketoglutarate and glutamine. Principal component analysis readily segregated control patients from patients with aSAH. Correlation analysis revealed distinct clusters in control patients that were not observed in patients with aSAH. Higher levels of fumarate were associated with good functional outcomes at discharge (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.15-2.82) in multivariable models, whereas higher levels of citrate were associated with poor functional outcomes at discharge (OR 0.36, 95% CI 0.16-0.73) and at 3 months (OR 0.35, 95% CI 0.14-0.81). No associations were found with delayed cerebral ischemia. Levels of α-ketoglutarate and glutamine correlated with lower levels of interleukin-8, whereas fumarate was associated with lower levels of tumor necrosis factor alpha. CONCLUSIONS: Aneurysmal subarachnoid hemorrhage results in a unique pattern of plasma metabolites, indicating a shift toward glycolysis. Higher levels of fumarate and lower levels of citrate were associated with better functional outcomes. These metabolites may represent targets to improve metabolism after aSAH

Efeito da talidomida sobre os níveis séricos de imunoglobulinas IgM e IgA, fator reumatóide e isohemaglutinina anti-A e anti-B em pacientes com lepra lepromatosa: um estudo duplo-cego

Um estudo duplo-cego foi conduzido em pacientes portadores de lepra lepromatosa estável, para avaliar a resposta à administração de talidomida 100 mg por dia, por 18 dias, dos níveis séricos de IgM e IgA e dos títulos de fator reumatóide e isohemaglutininas anti-A e anti-B. Nenhum efeito significativo foi detectado ao fim deste período

The role of neutralizing antibodies in prevention of HIV-1 infection: what can we learn from the mother-to-child transmission context?

International audienceIn most viral infections, protection through existing vaccines is linked to the presence of vaccine-induced neutralizing antibodies (NAbs). However, more than 30 years after the identification of AIDS, the design of an immunogen able to induce antibodies that would neutralize the highly diverse HIV-1 variants remains one of the most puzzling challenges of the human microbiology. The role of antibodies in protection against HIV-1 can be studied in a natural situation that is the mother-to-child transmission (MTCT) context. Indeed, at least at the end of pregnancy, maternal antibodies of the IgG class are passively transferred to the fetus protecting the neonate from new infections during the first weeks or months of life. During the last few years, strong data, presented in this review, have suggested that some NAbs might confer protection toward neonatal HIV-1 infection. In cases of transmission, it has been shown that the viral population that is transmitted from the mother to the infant is usually homogeneous, genetically restricted and resistant to the maternal HIV-1-specific antibodies. Although the breath of neutralization was not associated with protection, it has not been excluded that NAbs toward specific HIV-1 strains might be associated with a lower rate of MTCT. A better identification of the antibody specificities that could mediate protection toward MTCT of HIV-1 would provide important insights into the antibody responses that would be useful for vaccine development. The most convincing data suggesting that NAbs migh confer protection against HIV-1 infection have been obtained by experiments of passive immunization of newborn macaques with the first generation of human monoclonal broadly neutralizing antibodies (HuMoNAbs). However, these studies, which included only a few selected subtype B challenge viruses, provide data limited to protection against a very restricted number of isolates and therefore have limitations in addressing the hypervariability of HIV-1. The recent identification of highly potent second-generation cross-clade HuMoNAbs provides a new opportunity to evaluate the efficacy of passive immunization to prevent MTCT of HIV-1