Impact of Vaccination Status on Outcome of Patients With COVID-19 and Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

BACKGROUND: Data on impact of COVID-19 vaccination and outcomes of patients with COVID-19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience. METHODS AND RESULTS: This was a retrospective analysis of patients with COVID-19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID-19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients; P=0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group (P=0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome (P=0.957). However, acute COVID-19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007-1.417]; P=0.041). CONCLUSIONS: Our study demonstrated no impact of COVID-19 vaccination on angiographic or clinical outcome of COVID-19-positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID-19 was confirmed.

In vivo effects of the anti-interleukin-6 receptor inhibitor tocilizumab on the B cell compartment.

OBJECTIVE: Interleukin-6 (IL-6) receptor inhibition by tocilizumab was recently licensed for the treatment of rheumatoid arthritis (RA). IL-6 induces in vitro differentiation of B cells into antibody-forming cells; however, the in vivo effects of IL-6 inhibition on the B cell compartment are currently not known. The purpose of this study was to examine this feature. METHODS: Sixteen patients with active RA were treated in an open-label study with tocilizumab (8 mg/kg every 4 weeks). Immunophenotyping was performed at baseline, week 12, and week 24. RESULTS: Memory B cell subsets declined significantly during tocilizumab therapy. Preswitch memory B cells decreased from a median of 19.6% to 12.3% at week 24 and postswitch memory B cells declined from a median of 18.6% to 15.0% at week 24 (P = 0.04). In parallel, CD19+IgA+ and CD19+IgG+ B cells decreased significantly. The proportion of IgA-expressing B cells fell from a median of 9.2% at baseline to 4.3% at week 12 and to 3.6% at week 24 (P = 0.01). IgG+ B cells declined from a median of 6.7% at baseline to 4.9% at week 12 (P = 0.007) and 2.8% at week 24 (P = 0.01). In parallel, serum levels of IgA and IgG were significantly diminished at week 24 (P < 0.05). There was a good correlation between relative and absolute numbers of IgA+ B cells with serum IgA at week 24. CONCLUSION: Tocilizumab induced a significant reduction in the frequency of peripheral preswitch and postswitch memory B cells. In addition, the number of IgG+ and IgA+ B cells declined and correlated well with reduced serum immunoglobulin levels. The data indicate that IL-6 blockade affects the B cell hyperreactivity in RA patients.

Mechanical thrombectomy for acute ischemic stroke in COVID-19 patients: multicenter experience in 111 cases.

BACKGROUND: Data on the frequency and outcome of mechanical thrombectomy (MT) for large vessel occlusion (LVO) in patients with COVID-19 is limited. Addressing this subject, we report our multicenter experience. METHODS: A retrospective cohort study was performed of consecutive acute stroke patients with COVID-19 infection treated with MT at 26 tertiary care centers between January 2020 and November 2021. Baseline demographics, angiographic outcome and clinical outcome evaluated by the modified Rankin Scale (mRS) at discharge and 90 days were noted. RESULTS: We identified 111 out of 11 365 (1%) patients with acute or subsided COVID-19 infection who underwent MT due to LVO. Cardioembolic events were the most common etiology for LVO (38.7%). Median baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score were 16 (IQR 11.5-20) and 9 (IQR 7-10), respectively. Successful reperfusion (mTICI ≥2b) was achieved in 97/111 (87.4%) patients and 46/111 (41.4%) patients were reperfused completely. The procedure-related complication rate was 12.6% (14/111). Functional independence was achieved in 20/108 (18.5%) patients at discharge and 14/66 (21.2%) at 90 days follow-up. The in-hospital mortality rate was 30.6% (33/108). In the subgroup analysis, patients with severe acute COVID-19 infection requiring intubation had a mortality rate twice as high as patients with mild or moderate acute COVID-19 infection. Acute respiratory failure requiring ventilation and time interval from symptom onset to groin puncture were independent predictors for an unfavorable outcome in a logistic regression analysis. CONCLUSION: Our study showed a poor clinical outcome and high mortality, especially in patients with severe acute COVID-19 infection undergoing MT due to LVO.

Biochemical frequency control by synchronisation of coupled repressilators: an in silico study of modules for circadian clock systems.

Exploration of chronobiological systems emerges as a growing research field within bioinformatics focusing on various applications in medicine, agriculture, and material sciences. From a systems biological perspective, the question arises whether biological control systems for regulation of oscillatory signals and their technical counterparts utilise similar mechanisms. If so, modelling approaches and parameterisation adopted from building blocks can help to identify general components for frequency control in circadian clocks along with gaining insight into mechanisms of clock synchronisation to external stimuli like the daily rhythm of sunlight and darkness. Phase-locked loops could be an interesting candidate in this context. Both, biology and engineering, can benefit from a unified view resulting from systems modularisation. In a first experimental study, we analyse a model of coupled repressilators. We demonstrate its ability to synchronise clock signals in a monofrequential manner. Several oscillators initially deviate in phase difference and frequency with respect to explicit reaction and diffusion rates. Accordingly, the duration of the synchronisation process depends on dedicated reaction and diffusion parameters whose settings still lack to be sufficiently captured analytically.