Key message
The strong genetic structure observed in Mediterranean oats affects the predictive ability of genomic prediction as well as the performance of training set optimization methods.
In this ...study, we investigated the efficiency of genomic prediction and training set optimization in a highly structured population of cultivars and landraces of cultivated oat (
Avena sativa
) from the Mediterranean basin, including white (subsp.
sativa
) and red (subsp.
byzantina
) oats, genotyped using genotype-by-sequencing markers and evaluated for agronomic traits in Southern Spain. For most traits, the predictive abilities were moderate to high with little differences between models, except for biomass for which Bayes-B showed a substantial gain compared to other models. The consistency between the structure of the training population and the population to be predicted was key to the predictive ability of genomic predictions. The predictive ability of inter-subspecies predictions was indeed much lower than that of intra-subspecies predictions for all traits. Regarding training set optimization, the linear mixed model optimization criteria (prediction error variance (PEVmean) and coefficient of determination (CDmean)) performed better than the heuristic approach “partitioning around medoids,” even under high population structure. The superiority of CDmean and PEVmean could be explained by their ability to adapt the representation of each genetic group according to those represented in the population to be predicted. These results represent an important step towards the implementation of genomic prediction in oat breeding programs and address important issues faced by the genomic prediction community regarding population structure and training set optimization.
Background and purpose
In patients with acute ischaemic stroke (AIS), haemorrhagic transformation (HT) following endovascular treatment (EVT) is associated with poor functional outcome. However, the ...impact of asymptomatic HT, not linked to neurological deterioration in the acute phase, is unknown. We aimed to investigate the impact of asymptomatic PH1 (aPH1) and PH2 (aPH2) subtypes of HT on the functional outcome of patients treated with EVT.
Methods
We conducted a retrospective study of patients with AIS who were consecutively admitted to our comprehensive stroke centre between January 2019 and December 2022, and who underwent EVT. We collected clinical, radiological, and procedural data. HTs were categorized according to the Heidelberg classification. The primary outcome was the shift on the modified Rankin Scale (mRS) at 3 months of follow‐up. We performed bivariate and multivariable ordinal regression analyses to test the association between aPH1/aPH2 and the primary outcome.
Results
We included 314 patients (mean age = 72.5 years SD = 13.6, 171 54.5% women). We detected 54 (17.2%) patients with HT; 23 (7.3%) were classified as PH2 (11 asymptomatic) and 17 (5.4%) as PH1 (16 asymptomatic). The adjusted common odds ratio for aPH2 of worsening 1 point on the 3‐month mRS was 3.32 (95% confidence interval = 1.16–9.57, p = 0.026). No association was observed for aPH1. aPH2 was also independently associated with lower odds of achieving a favourable outcome (mRS = 0–2). Neither aPH1 nor aPH2 was associated with mortality.
Conclusions
In patients with AIS treated with EVT, aPH2 is independently associated with unfavourable functional outcome.
There are no generally accepted criteria for the etiologic classification of intracerebral hemorrhage (ICH). For this reason, we have developed a set of etiologic criteria and have applied them to a ...large number of patients to determine their utility.
The H-ATOMIC classification includes 7 etiologic categories: Hypertension, cerebral Amyloid angiopathy, Tumour, Oral anticoagulants, vascular Malformation, Infrequent causes and Cryptogenic. For each category, the etiology is scored with three degrees of certainty: Possible(3), Probable(2) and Definite(1). Our aim was to perform a basic study consisting of neuroimaging, blood tests, and CT-angio when a numerical score (SICH) suggested an underlying structural abnormality. Combinations of >1 etiologic category for an individual patient were acceptable. The criteria were evaluated in a multicenter and prospective study of consecutive patients with spontaneous ICH.
Our study included 439 patients (age 70.8 ± 14.5 years; 61.3% were men). A definite etiology was achieved in 176 (40.1% of the patients: Hypertension 28.2%, cerebral Amyloid angiopathy 0.2%, Tumour 0.2%, Oral anticoagulants 2.2%, vascular Malformation 4.5%, Infrequent causes 4.5%). A total of 7 patients (1.6%) were cryptogenic. In the remaining 58.3% of the patients, ICH was attributable to a single (n = 56, 12.7%) or the combination of ≥2 (n = 200, 45.5%) possible/probable etiologies. The most frequent combinations of etiologies involved possible hypertension with possible CAA (H3A3, n = 38) or with probable CAA (H3A2, n = 29), and probable hypertension with probable OA (H2O2, n = 27). The most frequent category with any degree of certainty was hypertension (H1+2+3 = 80.6%) followed by cerebral amyloid angiopathy (A1+2+3 = 30.9%).
According to our etiologic criteria, only about 40% patients received a definite diagnosis, while in the remaining patients ICH was attributable to a single possible/probable etiology or to more than one possible/probable etiology. The use of these criteria would likely help in the management of patients with ICH.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We evaluated whether stroke severity, functional outcome, and mortality are different in patients with ischemic stroke with or without coronavirus disease 2019 (COVID-19) infection.
A prospective, ...observational, multicentre cohort study in Catalonia, Spain. Recruitment was consecutive from mid-March to mid-May 2020. Patients had an acute ischemic stroke within 48 hours and a previous modified Rankin Scale (mRS) score of 0 to 3. We collected demographic data, vascular risk factors, prior mRS score, National Institutes of Health Stroke Scale score, rate of reperfusion therapies, logistics, and metrics. Primary end point was functional outcome at 3 months. Favourable outcome was defined depending on the previous mRS score. Secondary outcome was mortality at 3 months. We performed mRS shift and multivariable analyses.
We evaluated 701 patients (mean age 72.3±13.3 years, 60.5% men) and 91 (13%) had COVID-19 infection. Median baseline National Institutes of Health Stroke Scale score was higher in patients with COVID-19 compared with patients without COVID-19 (8 3-18 versus 6 2-14,
=0.049). Proportion of patients with a favourable functional outcome was 33.7% in the COVID-19 and 47% in the non-COVID-19 group. However, after a multivariable logistic regression analysis, COVID-19 infection did not increase the probability of unfavourable functional outcome. Mortality rate was 39.3% among patients with COVID-19 and 16.1% in the non-COVID-19 group. In the multivariable logistic regression analysis, COVID-19 infection was a risk factor for mortality (hazard ratio, 3.14 95% CI, 2.10-4.71;
<0.001).
Patients with ischemic stroke and COVID-19 infection have more severe strokes and a higher mortality than patients with stroke without COVID-19 infection. However, functional outcome is comparable in both groups.
Oat,
, is an important crop traditionally grown in cool-temperate regions. However, its cultivated area in the Mediterranean rim steadily increased during the last 20 years due to its good adaptation ...to a wide range of soils. Nevertheless, under Mediterranean cultivation conditions, oats have to face high temperatures and drought episodes that reduce its yield as compared with northern regions. Therefore, oat crop needs to be improved for adaptation to Mediterranean environments. In this work, we investigated the influence of climatic and edaphic variables on a collection of 709 Mediterranean landraces and cultivars growing under Mediterranean conditions. We performed genotype-environment interaction analysis using heritability-adjusted genotype plus genotype-environment biplot analyses to determine the best performing accessions. Further, their local adaptation to different environmental variables and the partial contribution of climate and edaphic factors to the different agronomic traits was determined through canonical correspondence, redundancy analysis, and variation partitioning. Here, we show that northern bred elite cultivars were not among the best performing accessions in Mediterranean environments, with several landraces outyielding these. While all the best performing cultivars had early flowering, this was not the case for all the best performing landraces, which showed different patterns of adaption to Mediterranean agroclimatic conditions. Thus, higher yielding landraces showed adaptation to moderate to low levels of rain during pre- and post-flowering periods and moderate to high temperature and radiation during post-flowering period. This analysis also highlights landraces adapted to more extreme environmental conditions. The study allowed the selection of oat genotypes adapted to different climate and edaphic factors, reducing undesired effect of environmental variables on agronomic traits and highlights the usefulness of variation partitioning for selecting genotypes adapted to specific climate and edaphic conditions.
Owing to the high risk of recurrence, identifying indicators of carotid plaque vulnerability in atherothrombotic ischemic stroke is essential. In this study, we aimed to identify modified LDLs and ...antioxidant enzymes associated with plaque vulnerability in plasma from patients with a recent ischemic stroke and carotid atherosclerosis. Patients underwent an ultrasound, a CT-angiography, and an
F-FDG PET. A blood sample was obtained from patients (n = 64, 57.8% with stenosis ≥50%) and healthy controls (n = 24). Compared to the controls, patients showed lower levels of total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B (apoB), apoA-I, apoA-II, and apoE, and higher levels of apoJ. Patients showed lower platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase-1 (PON-1) enzymatic activities in HDL, and higher plasma levels of oxidized LDL (oxLDL) and electronegative LDL (LDL(-)). The only difference between patients with stenosis ≥50% and <50% was the proportion of LDL(-). In a multivariable logistic regression analysis, the levels of LDL(-), but not of oxLDL, were independently associated with the degree of carotid stenosis (OR: 5.40, CI: 1.15-25.44,
< 0.033), the presence of hypoechoic plaque (OR: 7.52, CI: 1.26-44.83,
< 0.027), and of diffuse neovessels (OR: 10.77, CI: 1.21-95.93,
< 0.033), indicating that an increased proportion of LDL(-) is associated with vulnerable atherosclerotic plaque.
IMPORTANCE: Prehospital transfer protocols are based on rapid access to reperfusion therapies for patients with ischemic stroke. The effect of different protocols among patients receiving a final ...diagnosis of intracerebral hemorrhage (ICH) is unknown. OBJECTIVE: To determine the effect of direct transport to an endovascular treatment (EVT)–capable stroke center vs transport to the nearest local stroke center. DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of RACECAT, a multicenter, population-based, cluster-randomized clinical trial conducted from March 2017 to June 2020 in Catalonia, Spain. Patients were evaluated by a blinded end point assessment. All consecutive patients suspected of experiencing a large vessel occlusion stroke (Rapid Arterial Occlusion Evaluation Scale RACE score in the field >4 on a scale of 0 to 9, with lower to higher stroke severity) with final diagnosis of ICH were included. A total of 1401 patients were enrolled in RACECAT with suspicion of large vessel occlusion stroke. The current analysis was conducted in October 2022. INTERVENTION: Direct transport to an EVT-capable stroke center (n = 137) or to the closest local stroke center (n = 165). MAIN OUTCOMES AND MEASURES: The primary outcome was tested using cumulative ordinal logistic regression to estimate the common odds ratio (OR) and 95% CI of the shift analysis of disability at 90 days as assessed by the modified Rankin Scale (mRS) score (range, 0 no symptoms to 6 death) in the intention-to-treat population. Secondary outcomes, included 90-day mortality, death or severe functional dependency, early neurological deterioration, early mortality, ICH volume and enlargement, rate of neurosurgical treatment, rate of clinical complications during initial transport, and rate of adverse events until day 5. RESULTS: Of 1401 patients enrolled, 1099 were excluded from this analysis (32 rejected informed consent, 920 had ischemic stroke, 29 had transient ischemic attack, 12 had subarachnoid hemorrhage, and 106 had stroke mimic). Thus, 302 patients were included (204 67.5% men; mean SD age 71.7 12.8 years; and median IQR RACE score, 7 6-8). For the primary outcome, direct transfer to an EVT-capable stroke center (mean SD mRS score, 4.93 1.38) resulted in worse functional outcome at 90 days compared with transfer to the nearest local stroke center (mean SD mRS score, 4.66 1.39; adjusted common OR, 0.63; 95% CI, 0.41-0.96). Direct transfer to an EVT-capable stroke center also suggested potentially higher 90-day mortality compared with transfer to the nearest local stroke center (67 of 137 48.9% vs 62 of 165 37.6%; adjusted hazard ratio, 1.40; 95% CI, 0.99-1.99). The rates of medical complications during the initial transfer (30 of 137 22.6% vs 9 of 165 patients 5.6%; adjusted OR, 5.29; 95% CI, 2.38-11.73) and in-hospital pneumonia (49 of 137 patients 35.8% vs 29 of 165 patients 17.6%; OR, 2.61; 95% CI, 1.53-4.44) were higher in the EVT-capable stroke center group. CONCLUSIONS AND RELEVANCE: In this secondary analysis of the RACECAT randomized clinical trial, bypassing the closest stroke center resulted in reduced chances of functional independence at 90 days for patients who received a final diagnosis of ICH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02795962
Stroke onset in women occurs later in life compared with men. The underlying mechanisms of these differences have not been established. Epigenetic clocks, based on DNA methylation (DNAm) profiles, ...are the most accurate biological age estimate. Epigenetic age acceleration (EAA) measures indicate whether an individual is biologically younger or older than expected. Our aim was to analyze whether sexual dichotomy at age of stroke onset is conditioned by EAA.
We used 2 DNAm datasets from whole blood samples of case-control genetic studies of ischemic stroke (IS), a discovery cohort of 374 IS patients (N women=163, N men=211), from GRECOS (Genotyping Recurrence Risk of Stroke) and SEDMAN (Dabigatran Study in the Early Phase of Stroke, New Neuroimaging Markers and Biomarkers) studies and a replication cohort of 981 IS patients (N women=411, N men=570) from BASICMAR register. We compared chronological age, 2 DNAm-based biomarkers of aging and intrinsic and extrinsic epigenetic age acceleration EAA (IEAA and extrinsic EAA, respectively), in IS as well as in individual IS etiologic subtypes. Horvath and Hannum epigenetic clocks were used to assess the aging rate. A proteomic study using the SOMAScan multiplex assay was performed on 26 samples analyzing 1305 proteins.
Women present lower Hannum-extrinsic EAA values, whereas men have higher Hannum-extrinsic EAA values (women=-0.64, men=1.24,
=1.34×10
); the same tendency was observed in the second cohort (women=-0.57, men=0.79,
=0.02). These differences seemed to be specific to cardioembolic and undetermined stroke subtypes. Additionally, 42 blood protein levels were associated with Hannum-extrinsic EAA (
<0.05), belonging to the immune effector process (
=1.54×10
) and platelet degranulation (
<8.74×10
) pathways.
This study shows that sex-specific underlying biological mechanisms associated with stroke onset could be due to differences in biological age acceleration between men and women.
Introduction
We aimed to determine whether the degree of collateral circulation is associated with blood pressure at admission in acute ischemic stroke patients treated with endovascular treatment ...and to determine its prognostic value.
Methods
We evaluated patients with anterior large vessel occlusion treated with endovascular treatment in a single-center prospective registry. We collected clinical and radiological data. Automated and validated software (Brainomix Ltd., Oxford, UK) was used to generate the collateral score (CS) from the baseline single-phase CT angiography: 0, filling of ≤10% of the occluded MCA territory; 1, 11–50%; 2, 51–90%; 3, >90%. When dichotomized, we considered that CS was good (CS = 2–3), or poor (CS = 0–1). We performed bivariate and multivariable ordinal logistic regression analysis to predict CS categories in our population. The secondary outcome was to determine the influence of automated CS on functional outcome at 3 months. We defined favorable functional outcomes as mRS 0–2 at 3 months.
Results
We included 101 patients with a mean age of 72.1 ± 13.1 years and 57 (56.4%) of them were women. We classified patients into 4 groups according to the CS: 7 patients (6.9%) as CS = 0, 15 (14.9%) as CS = 1, 43 (42.6%) as CS = 2 and 36 (35.6%) as CS = 3. Admission systolic blood pressure aOR per 10 mmHg increase 0.79 (95% CI 0.68–0.92) and higher baseline NIHSS aOR 0.90 (95% CI, 0.84–0.96) were associated with a worse CS. The OR of improving 1 point on the 3-month mRS was 1.63 (95% CI, 1.10–2.44) favoring a better CS (
p
= 0.016).
Conclusion
In acute ischemic stroke patients with anterior large vessel occlusion treated with endovascular treatment, admission systolic blood pressure was inversely associated with the automated scoring of CS on baseline CT angiography. Moreover, a good CS was associated with a favorable outcome.
Mechanical thrombectomy (MT) is effective for acute ischemic stroke (AIS) in selected patients with large intracranial vessel occlusion. A minority of patients with AIS receive MT. We aimed to ...describe the reasons for excluding patients with AIS for MT.
We evaluated patients with AIS in a prospective population-based multicenter registry (Codi Ictus Catalunya registry) that includes all stroke code activations from January to June 2018 in Catalonia, Spain. We analyzed the major reasons for not treating with MT.
Stroke code was activated in 3060 patients. Excluding 355 intracranial hemorrhages and 502 stroke mimics, resulted in 2203 patients with AIS (mean age 72.8±13.8 years; 44.6% were women). Of the patients with AIS, 405 (18.4%) were treated with MT. We analyzed the reasons for not treating with MT. The following reasons were considered not modifiable: absence of large intracranial vessel occlusion (922, 41.9%), transient ischemic attack (206, 9.4%), and more than one cause (124, 5.6%). The potentially modifiable reasons for not performing MT by changing selection criteria were as follows: an intracranial artery occlusion that was considered inaccessible or not indicated (48, 2.2%); clinical presentation that was considered too mild to be treated (222, 10.1%); neuroimaging criteria (129, 5.9%), age/prior modified Rankin Scale score/medical comorbidities (129, 5.9%), and therapeutic time window >8 hours (16, 0.7%).
In our area, considering all potentially modifiable causes for not performing MT, the percentage of patients with AIS eligible for MT could increase from 18.4% to a maximum of 43.1%. The clinical benefit of this increase is still uncertain and should be confirmed in future trials. Criteria for stroke code activation must be considered for the generalizability of these results.
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