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BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is ongoing. The pathophysiology of SARS-CoV-2 infection is beginning to be elucidated but the role of microRNAs (miRNAs), small non-coding RNAs that regulate gene expression, remains incompletely understood. They play a role in the pathophysiology of viral infections with potential use as biomarkers. The objective of this study was to identify miRNAs as biomarkers of severe COVID-19 and to analyze their role in the pathophysiology of SARS-CoV-2 infection. MethodsmiRNA expression was measured in nasopharyngeal swabs from 20 patients with severe COVID-19, 21 patients with non-severe COVID-19 and 20 controls. Promising miRNAs to differentiate non-severe from severe COVID-19 patients were identified by differential expression analysis and sparse Partial Least Squares-Discriminant Analysis (sPLS-DA). ROC analysis, target prediction, GO enrichment and pathway analysis were used to analyze the role and the pertinence of these miRNAs in severe COVID-19. ResultsThe number of expressed miRNAs was lower in severe COVID-19 patients compared to non-severe COVID-19 patients and controls. Among the differentially expressed miRNAs between severe COVID-19 and controls, 5 miRNAs were also differentially expressed between severe and non-severe COVID-19. sPLS-DA analysis highlighted 8 miRNAs, that allowed to discriminate the severe and non-severe COVID-19 cases. Target and functional analysis revealed enrichment for genes involved in viral infections and the cellular response to infection as well as one miRNA, hsa-miR-15b-5p, that targeted the SARS-CoV-2 RNA. The comparison of results of differential expression analysis and discriminant analysis revealed three miRNAs, namely hsa-miR-125a-5p, hsa-miR-491-5p and hsa-miR-200b-3p. These discriminated severe from non-severe cases with areas under the curve ranging from 0.76 to 0.80. ConclusionsOur analysis of miRNA expression in nasopharyngeal swabs revealed several miRNAs of interest to discriminate severe and non-severe COVID-19. These miRNAs represent promising biomarkers and possibly targets for antiviral or anti-inflammatory treatment strategies.
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We quantified S1-specific IgG, neutralizing antibody titers, specific IFN{gamma} secreting T cells and functionality of specific CD4+ and CD8+ T cells in 130 young adults (median age 44.0 years) and 106 older residents living in a long-term care facility (86.5 years) after 2 doses of BNT162b2. Three months after the first injection, humoral and cellular memory responses were dramatically impaired in the 54 COVID-19-naive older compared to the 121 COVID-19-naive younger adults. Notably, older participants neutralizing antibodies, detected in 76.5% (versus 100% in young adults, P < 0.0001), were ten times lower than the youngers antibody titers (P < 0.0001). Antibody and T cell responses were greater among the 52 COVID-19-recovered than among the 54 COVID-19-naive older adults (P < 0.0001). Our study shows that 2 doses of BNT162b2 does not guarantee long-term protection against SARS-CoV-2 in the older. An additional dose should be considered to boost their specific memory response.
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Background@#and Purpose Despite the widespread adoption of mechanical thrombectomy (MT) for the treatment of large vessel occlusion stroke (LVOS) in the anterior circulation, the optimal strategy for the treatment tandem occlusion related to cervical internal carotid artery (ICA) dissection is still debated. This individual patient pooled analysis investigated the safety and efficacy of prior intravenous thrombolysis (IVT) in anterior circulation tandem occlusion related to cervical ICA dissection treated with MT. @*Methods@#We performed a retrospective analysis of two merged prospective multicenter international real-world observational registries: Endovascular Treatment in Ischemic Stroke (ETIS) and Thrombectomy In TANdem occlusions (TITAN) registries. Data from MT performed in the treatment of tandem LVOS related to cervical ICA dissection between January 2012 and December 2019 at 24 comprehensive stroke centers were analyzed. The primary endpoint was a favorable outcome defined as 90-day modified Rankin Scale (mRS) score of 0–2. @*Results@#The study included 144 patients with tandem occlusion LVOS due to cervical ICA dissection, of whom 94 (65.3%) received IVT before MT. Prior IVT was significantly associated with a better clinical outcome considering the mRS shift analysis (common odds ratio, 2.59; 95% confidence interval [CI], 1.35 to 4.93; P=0.004 for a 1-point improvement) and excellent outcome (90-day mRS 0–1) (adjusted odds ratio [aOR], 4.23; 95% CI, 1.60 to 11.18). IVT was also associated with a higher rate of intracranial successful reperfusion (83.0% vs. 64.0%; aOR, 2.70; 95% CI, 1.21 to 6.03) and a lower rate of symptomatic intracranial hemorrhage (4.3% vs. 14.8%; aOR, 0.21; 95% CI, 0.05 to 0.80). @*Conclusions@#Prior IVT before MT for the treatment of tandem occlusion related to cervical ICA dissection was safe and associated with an improved 90-day functional outcome.
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Background@#and Purpose Despite the widespread adoption of mechanical thrombectomy (MT) for the treatment of large vessel occlusion stroke (LVOS) in the anterior circulation, the optimal strategy for the treatment tandem occlusion related to cervical internal carotid artery (ICA) dissection is still debated. This individual patient pooled analysis investigated the safety and efficacy of prior intravenous thrombolysis (IVT) in anterior circulation tandem occlusion related to cervical ICA dissection treated with MT. @*Methods@#We performed a retrospective analysis of two merged prospective multicenter international real-world observational registries: Endovascular Treatment in Ischemic Stroke (ETIS) and Thrombectomy In TANdem occlusions (TITAN) registries. Data from MT performed in the treatment of tandem LVOS related to cervical ICA dissection between January 2012 and December 2019 at 24 comprehensive stroke centers were analyzed. The primary endpoint was a favorable outcome defined as 90-day modified Rankin Scale (mRS) score of 0–2. @*Results@#The study included 144 patients with tandem occlusion LVOS due to cervical ICA dissection, of whom 94 (65.3%) received IVT before MT. Prior IVT was significantly associated with a better clinical outcome considering the mRS shift analysis (common odds ratio, 2.59; 95% confidence interval [CI], 1.35 to 4.93; P=0.004 for a 1-point improvement) and excellent outcome (90-day mRS 0–1) (adjusted odds ratio [aOR], 4.23; 95% CI, 1.60 to 11.18). IVT was also associated with a higher rate of intracranial successful reperfusion (83.0% vs. 64.0%; aOR, 2.70; 95% CI, 1.21 to 6.03) and a lower rate of symptomatic intracranial hemorrhage (4.3% vs. 14.8%; aOR, 0.21; 95% CI, 0.05 to 0.80). @*Conclusions@#Prior IVT before MT for the treatment of tandem occlusion related to cervical ICA dissection was safe and associated with an improved 90-day functional outcome.
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BACKGROUND AND PURPOSE: Recent single-center series and meta-analyses suggest that mechanical thrombectomy (MT) without prior intravenous thrombolysis (IVT) might be equally effective to bridging therapy. We analyzed, within the Endovascular Treatment in Ischemic Stroke (ETIS) prospective observational registry, the angiographic and clinical outcomes after IVT+MT versus MT alone. METHODS: From December 2012 to December 2016, a total of 1,507 consecutive patients with a proximal arterial occlusion of the anterior circulation were treated by MT. Of these, 975 (64.7%) received prior IVT. Immediate angiographic and clinical outcomes at 90 days (modified Rankin Scale [mRS]) were compared between the two groups while checking for propensity score, matched-propensity score and by inverse probability of treatment weighting (IPTW) propensity score method. RESULTS: Favorable outcome (mRS 0 to 2) was more frequently achieved after IVT+MT (n=523, 53.6%) than after MT alone (n=222, 41.8%) with an unadjusted odds ratio (OR) for bridging therapy of 1.61 (95% confidence interval [CI], 1. 29 to 2.01). This difference remained not significant in matched-propensity score cohort (OR, 1.21; 95% CI, 0.90 to 1.63) although it remained according to adjusted propensity score (OR, 1.31; 95% CI, 1.02 to 1.68) and IPTW (OR, 1.37; 95% CI, 1.09 to 1.73) analyses. A significant difference was found in terms of excellent outcome (mRS 0 to 1) (adjusted OR, 1.63; 95% CI, 1.25 to 2.11) and successful reperfusion (adjusted OR, 1.58; 95% CI, 1.33 to 2.15). No differences in intracerebral hemorrhage or in allcause mortality within 90 days were found between groups. CONCLUSIONS: IVT prior to MT is associated with increased excellent outcome and successful reperfusion rates. These findings support the use of bridging therapy.
Subject(s)
Humans , Cerebral Hemorrhage , Cohort Studies , Methods , Mortality , Odds Ratio , Propensity Score , Prospective Studies , Reperfusion , Silver , Stroke , Thrombectomy , Tissue Plasminogen ActivatorABSTRACT
On page 271, in Table 1, the value ‘1115 (65??51)’ of subgroup ‘Imaging to groin puncture’ and column heading ‘SVS (??’ was input incorrectly. The correct value is ‘115 (65??51).’
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BACKGROUND AND PURPOSE: In the Aspiration vs. Stent Retriever for Successful Revascularization (ASTER) trial, which evaluated contact aspiration (CA) versus stent retriever (SR) use as first-line technique, the impact of the susceptibility vessel sign (SVS) on magnetic resonance imaging (MRI) was studied to determine its influence on trial results. METHODS: We included patients having undergone CA or SR for M1 or M2 occlusions, who were screened by MRI with T2* gradient recalled echo. Occlusions were classified as SVS (+) or SVS (–) in each randomization arm. Modified thrombolysis in cerebral infarction (mTICI) 2b, 2c, or 3 revascularization rates were recorded and clinical outcomes assessed by the overall distribution of modified Rankin scale (mRS) at 90 days. RESULTS: Among the 202 patients included, 143 patients were SVS (+) (70.8%; 95% confidence interval [CI], 64.5% to 77.1%). Overall, there was no difference in angiographic and clinical outcomes according to SVS status. However, compared to SR, CA achieved a lower mTICI 2c/3 rate in SVS (+) patients (risk ratio [RR] for CA vs. SR, 0.60; 95% CI, 0.51 to 0.71) but not in SVS (–) (RR, 1.11; 95% CI, 0.69 to 1.77; P for interaction=0.018). A significant heterogeneity in favor of superiority of first-line SR strategy in SVS (+) patients was also found regarding the overall mRS distribution (common odds ratio for CA vs. SR, 0.40 vs. 1.32; 95% CI, 0.21 to 0.74 in SVS (+) vs. 95% CI, 0.51 to 3.35 in SVS (–); P for interaction=0.038). CONCLUSIONS: As a first line strategy, SR achieved higher recanalization rates and a more favourable clinical outcome at 3 months compared to CA when MRI shows SVS within the thrombus.
