Publicaciones: febrero 2023

Influence of Temperature Chronobiology on Stroke Outcome

Alonso-Alonso ML, Sampedro-Viana A, Rodríguez-Yáñez M et al. Int J Mol Sci. 2023 Feb 13;24(4):3746. doi: 10.3390/ijms24043746. PMID: 36835156

https://pubmed.ncbi.nlm.nih.gov/36835156/

Abstract: : The circadian system regulates numerous physiological variables, including body temperature. Additionally, a circadian patter has been described in stroke onset. Considering this, we hypothesised that the chronobiology of temperature may have an impact on stroke onset and functional outcomes. We also studied the variation of blood biomarkers according to stroke onset time. This is a retrospective observational study. Of the patients included, 2763 had a stroke between midnight and 8:00 h; 1571 between 8:00–14:00 h; and 655 between 14:00 h and midnight. Axillary temperature was measured at admission. At this time, blood samples were collected for biomarker analysis (TNF-α, IL-1β, IL-6, IL-10, and glutamate). Temperature was higher in patients admitted from 8:00 h to midnight (p < 0.0001). However, the percentage of poor outcome at 3 months was highest in patients from midnight to 8:00 h (57.7%, p < 0.001). The association between temperature and mortality was highest during night time (OR: 2.79; CI 95%: 2.36–3.28; p < 0.001). These patients exhibited high glutamate (220.2 ± 140.2 µM), IL-6 (32.8 ± 14.3 pg/mL) and low IL-10 (9.7 ± 14.3 pg/mL) levels. Therefore, temperature chronobiology could have a significant impact on stroke onset and functional outcome. Superficial body hyperthermia during sleep seems to be more dangerous than during wakefulness. Further studies will be necessary to confirm our data. 

Funding: This research was funded by Spanish Ministry of Science and Innovation (SAF2017-84267- R), PDC2021-121455-I00, Xunta de Galicia (Consellería de Educación: IN607A2022-03), Instituto de Salud Carlos III (ISCIII) (PI17/00540, PI17/01103), ISCIII/PI21/01256/Co-financed by the European Union, Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS PLUS (RD16/0019/0001), RICORS-ICTUS (Cerebrovascular diseases) D21/0006/0003. M. Bazarra-Barreiros is a PFIS Researcher (FI22/00200) of Instituto de Salud Carlos III. T. Sobrino (CPII17/00027), F. Campos (CPII19/00020) and R. Iglesias-Rey (CP22/00061) from the Miguel Servet Program of Instituto de Salud Carlos III and Co-financed by the EU. Sponsors did not participate in the study design, collection, analysis, or interpretation of the data, or in writing the report.

Direct Mechanical Thrombectomy vs. Bridging Therapy in Stroke Patients in A «Stroke Belt» Region of Southern Europe

Del Toro-Pérez C, Amaya-Pascasio L, Guevara-Sánchez E. et al. J Pers Med. 2023 Feb 28;13(3):440. doi: 10.3390/jpm13030440. PMID: 36983622

https://pubmed.ncbi.nlm.nih.gov/36983622/

Abstract: The aim of this 4-year observational study is to analyze the outcomes of stroke patients treated with direct mechanical thrombectomy (dMT) compared to bridging therapy (BT) (intravenous thrombolysis [IVT] + BT) based on 3-month outcomes, in real clinical practice in the «Stroke Belt» of Southern Europe. In total, 300 patients were included (41.3% dMT and 58.6% BT). The frequency of direct referral to the stroke center was similar in the dMT and BT group, whereas the time from onset to groin was longer in the BT group (median 210 [IQR 160–303] vs. 399 [IQR 225–675], p = 0.001). Successful recanalization (TICI 2b-3) and hemorrhagic transformation were similar in both groups.
The BT group more frequently showed excellent outcomes at 3 months (32.4% vs. 15.4%, p = 0.004). Multivariate analysis showed that BT was independently associated with excellent outcomes (OR 2.7. 95% CI,1.2–5.9, p = 0.02) and lower mortality (OR 0.36. 95% CI 0.16–0.82, p = 015). Conclusions: Compared with dMT, BT was associated with excellent functional outcomes and lower 3-month mortality in this real-world clinical practice study conducted in a region belonging to the “Stroke Belt” of Southern Europe. Given the disparity of results on the benefit of BT in the current evidence, it is of vital importance to analyze the convenience of its use in each health area.

Funding: This study is part of the Spanish Health Outcomes-Oriented Cooperative Research Networks (RICORS-ICTUS), Instituto de Salud Carlos III (Carlos III Health Institute), Ministerio de Ciencia e Innovación (Ministry of Science and Innovation), RD21/0006/0010.

Factors associated with migraine aura mimicking stroke in code stroke

Macias-Gómez A, Suárez-Pérez A, Rodríguez-Campello A, Giralt-Steinhauer E, Moreira A, Guisado-Alonso D, Capellades J, Fernández-Pérez I, Jiménez-Conde J, Rey L, Jiménez-Balado J, Roquer J, Ois Á, Cuadrado-Godia E. Neurol Sci. 2023 Feb 7. doi: 10.1007/s10072-023-06641-y. Epub ahead of print. PMID: 36749530.

https://pubmed.ncbi.nlm.nih.gov/36749530/

Conclusions: In code stroke, a model including age, sex, NIHSS, and fbrinogen showed a good discrimination capability to diferentiate between MA and Ischemic stroke. Whether these variables can be implemented in a diagnostic rule should be tested in future studies.

Funding: This work was supported in part by Spain’s Ministry ofHealth (Instituto de Salud Carlos III, Fondos FEDER, RICORS-ICTUS(RD21/0006/0021)).

Machine Learning Approximations to Predict Epigenetic Age Acceleration in Stroke Patients

Fernández-Pérez I, Jiménez-Balado J, Lazcano U, Giralt-Steinhauer E, et al. Int J Mol Sci. 2023 Feb 1;24(3):2759. doi: 10.3390/ijms24032759. PMID: 36769083; PMCID: PMC9917369

https://pubmed.ncbi.nlm.nih.gov/36769083/

Abstract: Age acceleration (Age-A) is a useful tool that is able to predict a broad range of health outcomes. It is necessary to determine DNA methylation levels to estimate it, and it is known that Age-A is influenced by environmental, lifestyle, and vascular risk factors (VRF). The aim of this study is to estimate the contribution of these easily measurable factors to Age-A in patients with cerebrovascular disease (CVD), using different machine learning (ML) approximations, and try to find a more accessible model able to predict Age-A.We studied a CVD cohort of 952 patients with information about VRF, lifestyle habits, and target organ damage. We estimated Age-A using Hannum’s epigenetic clock, and trained six different models to predict Age-A: a conventional linear regression model, four ML models (elastic net regression (EN), K-Nearest neighbors, random forest, and support vector machine models), and one deep learning approximation (multilayer perceptron (MLP) model). The best-performing models were EN and MLP; although, the predictive capability was modest (R2 0.358 and 0.378, respectively). In conclusion, our results support the influence of these factors on Age-A; although, they were not enough to explain most of its variability.

Funding: This work was supported by grants from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III with the grants “Registro BASICMAR” Funding for Research in Health (PI051737), Fondos de Investigación Sanitaria ISC III (PI12/01238), (PI15/00451), (PI18/00022), (PI21/00593); Sara Borrell program, funded by Instituto de Salud Carlos III (CD22/00001, J.J.-B.); and Fondos FEDER/EDRF Spanish stroke research network INVICTUS+ (RD16/0019/0002) and Grant “RICORS-ICTUS” (RD21/0006/0021) funded by Instituto de Salud Carlos III (ISCIII), and by Int. J. Mol. Sci. 2023, 24, 2759 13 of 15 the European Union NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR). Additional support was provided by Recercaixa’13 (JJ086116).

Safety and efficacy of intra-arterial bone marrow mononuclear cell transplantation in patients with acute ischaemic stroke in Spain (IBIS trial): a phase 2, randomised, open-label, standard-of-care controlled, multicentre trial

Moniche F, Cabezas-Rodriguez JA, Valverde R et al. Lancet Neurol. 2023 Feb;22(2):137-146. doi: 10.1016/S1474-4422(22)00526-9. PMID: 36681446

https://pubmed.ncbi.nlm.nih.gov/36681446/

Summary:

Background Pilot clinical trials have shown the safety of intra-arterial bone marrow mononuclear cells (BMMNCs) in stroke. However, the efficacy of different doses of intra-arterial BMMNCs in patients with acute stroke has not been tested in a randomised clinical trial. We aimed to show safety and efficacy of two different doses of autologous intraarterial BMMNC transplantation in patients with acute stroke.
Methods The IBIS trial was a multicentre phase 2, randomised, controlled, investigator-initiated, assessor-blinded, clinical trial, in four stroke centres in Spain. We included patients (aged 18–80 years) with a non-lacunar, middle cerebral artery ischaemic stroke within 1–7 days from stroke onset and with a National Institutes of Health Stroke Scale score of 6–20. We randomly assigned patients (2:1:1) with a computer-generated randomisation sequence to standard of care (control group) or intra-arterial injection of autologous BMMNCs at one of two different doses (2×10⁶ BMMNCs/kg or 5×10⁶ BMMNCs/kg). The primary efficacy outcome was the proportion of patients with modified Rankin Scale scores of 0–2 at 180 days in the intention-to-treat population, comparing each BMMNC dose group and the pooled BMMNC group versus the control group. The primary safety endpoint was the proportion of serious adverse events. This trial was registered at ClinicalTrials.gov, NCT02178657 and is completed.
Findings Between April 1, 2015, and May 20, 2021, we assessed 114 patients for eligibility. We randomly assigned 77 (68%) patients: 38 (49%) to the control group, 20 (26%) to the low-dose BMMNC group, and 19 (25%) the highdose BMMNC group. The mean age of participants was 62·4 years (SD 12·7), 46 (60%) were men, 31 (40%) were women, all were White, and 63 (82%) received thrombectomy. The median NIHSS score before randomisation was 12 (IQR 9–15), with intra-arterial BMMNC injection done a median of 6 days (4–7) after stroke onset. The primary efficacy outcome occurred in 14 (39%) patients in the control group versus ten (50%) in the low-dose group (adjusted odds ratio 2·08 [95% CI 0·55–7·85]; p=0·28), eight (44%) in the high-dose group (1·89 [0·52–6·96]; p=0·33), and 18 (47%) in the pooled BMMNC group (2·22 [0·72–6·85]; p=0·16). We found no differences in the proportion of patients who had adverse events or dose-related events, but two patients had a groin haematoma after cell injection in the low-dose BMMNC group.
Interpretation Intra-arterial BMMNCs were safe in patients with acute ischaemic stroke, but we found no significant improvement at 180 days on the mRS. Further clinical trials are warranted to investigate whether improvements might be possible at different timepoints.

Funding: The Andalusian Network for the Design and Translation of Advanced Therapies through the Andalusian Progress and Health Public Foundation is the study sponsor. We acknowledge all the participants of the trial and the investigators. We thank the funding bodies Instituto de Salud Carlos III through the projects PI18/01414, PI15/01197,
RD16/0019/0015 (INVICTUS+), and RD21/0006/0015 (co-funded by the European Regional Development Fund “A way to make Europe” and by the European Social Fund [FSE] “The FSE invests in your future”), Mutua Madrileña grant, and the Regional Ministry of Health of Andalusia, who financed the costs incurred by participating hospitals and the Andalusian Network for the Design and Translation of Advanced Therapies through the Andalusian Progress and Health Public Foundation. MM-R has a Rio Hortega grant (CM21/00096). We acknowledge the Methodological and Statistical Support Unit from the Andalusian Public Foundation for Health Research Management in Seville (FISEVI) for their support in the statistical analysis.