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INTRODUCTION: The differences in vascular risk factors' and stroke burden across Europe are notable, however there is limited understanding of the influence of socioeconomic environment on the quality of secondary prevention and outcome after acute ischemic stroke. PATIENTS AND METHODS: In this observational multicenter cohort study, we analyzed baseline characteristics, reperfusion treatment, outcome and secondary prevention in patients with acute ischemic stroke from three tertiary-care teaching hospitals with similar service population size in different socioeconomic environments: Bern/CH/n = 293 (high-income), Gdansk/PL/n = 140 (high-income), and Lutsk/UA/n = 188 (lower-middle-income). RESULTS: We analyzed 621 patients (43.2% women, median age = 71.4 years), admitted between 07 and 12/2019. Significant differences were observed in median BMI (CH = 26/PL = 27.7/UA = 27.8), stroke severity [(median NIHSS CH = 4(0-40)/PL = 11(0-33)/UA = 7(1-30)], initial neuroimaging (CT:CH = 21.6%/PL = 50.7%/UA = 71.3%), conservative treatment (CH = 34.1%/PL = 38.6%/UA = 95.2%) (each p < 0.001), in arterial hypertension (CH = 63.8%/PL = 72.6%/UA = 87.2%), atrial fibrillation (CH = 28.3%/PL = 41.4%/UA = 39.4%), hyperlipidemia (CH = 84.9%/PL = 76.4%/UA = 17%) (each p < 0.001) and active smoking (CH = 32.2%/PL = 27.3%/UA = 10.2%) (p < 0.007). Three-months favorable outcome (mRS = 0-2) was seen in CH = 63.1%/PL = 50%/UA = 59% (unadjusted-p = 0.01/adjusted-p CH-PL/CH-UA = 0.601/0.981), excellent outcome (mRS = 0-1) in CH = 48.5%/PL = 32.1%/UA = 27% (unadjusted-p < 0.001/adjusted-p CH-PL/CH-UA = 0.201/0.08 and adjusted-OR CH-UA = 2.09). Three-months mortality was similar between groups (CH = 17.2%/PL = 15.7%/UA = 4.8%) (unadjusted-p = 0.71/adjusted-p CH-PL/CH-UA = 0.087/0.24). Three-months recurrent stroke/TIA occurred in CH = 3.1%/PL = 10.7%/UA = 3.1%, adjusted-p/OR CH-PL = 0.04/0.32). Three-months follow-up medication intake rates were the same for antihypertensives. Statin/OAC intake was lowest in UA = 67.1%/25.5% (CH = 87.3%/39.2%/unadjusted-p < 0.001/adjusted-p CH-UA = 0.02/0.012/adjusted-OR CH-UA = 2.33/2.18). Oral intake of antidiabetics was lowest in CH = 10.8% (PL = 15.7%/UA = 16.1%/unadjusted-p = 0.245/adjusted-p CH-PL/CH-UA = 0.061/0.002/adjusted-OR CH-UA = 0.25). Smoking rates decreased in all groups during follow-up. DISCUSSION AND CONCLUSION: Substantial differences in presentation, treatment and secondary prevention measures, are linked to a twofold difference in adjusted 3-months excellent outcome between Switzerland and Ukraine. This underscores the importance of socioeconomic factors that influence stroke outcomes, emphasizing the necessity for targeted interventions to address disparities in treatment and secondary prevention strategies.
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BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease in which autoimmune T conventional (Tconv) cells break the blood-brain barrier and destroy neurons of the central nervous system. It is hypothesized that CD4+CD25highCD127-FoxP3+ T regulatory (Treg) cells may inhibit this destruction through suppressive activity exerted on Tconv cells. METHODS: We present the results of a phase 1b/2a, open-label, two-arm clinical trial in 14 patients treated with autologous Treg cells for relapsing-remitting MS. The patients received either expanded ex vivo Treg cells intravenously (intravenous [IV] group, n = 11; dose 40 × 106 Treg cells/kg of body weight) or freshly isolated Treg cells intrathecally (intrathecal [IT] group, n = 3; dose 1.0 × 106 Treg cells). Importantly, patients were not treated with any other disease-modifying drugs for at least 6 months before the recruitment and during the follow-up. RESULTS: No severe adverse events were observed. Self-assessed quality of life (EuroQol-5 Dimensions [EQ-5D] form) did not change and did not differ significantly between the groups. A total of 12 relapses were noted in five intravenously treated patients, who had from one to three attacks per year. Three out of ten participants who completed the trial in the IV group deteriorated more than 1 point on the Expanded Disability Status Scale (EDSS) during the follow-up. At the same time, no patients in the IT group experienced a relapse or such a deterioration in the EDSS. No significant differences were found in the Multiple Sclerosis Functional Composite (MSFC) scale in both the IV and IT groups. Magnetic resonance imaging (MRI) scans revealed a significantly lower change in the T2 lesion volume in the IT group compared to the IV group. The increase in the number of new T2 lesions during the follow-up was significant for the IV group only. There were no significant changes in the level of Treg cells or Tconv cells in the peripheral blood throughout the follow-up or between the groups. Interestingly, Treg cells in all patients consisted of two different phenotypes: peripheral Treg cells Helios(-) (≈ 20%) and thymic Treg cells Helios(+) (≈ 80%). The analysis of the cytokine pattern revealed higher levels of transforming growth factor-α and proinflammatory factors MCP3, CXCL8, and IL-1RA in the IT group compared with the IV group. CONCLUSIONS: No serious adverse events were reported in the 14 patients with MS treated with Treg cells in this study. The results suggest that IT administration is more promising than IV administration. Because of the low number of patients recruited, the statistical results may be underpowered and further studies are necessary to reach conclusions on efficacy and safety. TRIAL REGISTRATION: EudraCT: 2014-004320-22; registered 18 November 2014.