Controlling Plasmonic Chemistry Pathways through Specific Ion Effects

Plasmon-driven dehalogenation of brominated purines has been recently explored as a model system to understand fundamental aspects of plasmon-assisted chemical reactions. Here, it is shown that divalent Ca2+ ions strongly bridge the adsorption of bromoadenine (Br-Ade) to Ag surfaces. Such ion-mediated binding increases the molecule's adsorption energy leading to an overlap of the metal energy states and the molecular states, enabling the chemical interface damping (CID) of the plasmon modes of the Ag nanostructures (i.e., direct electron transfer from the metal to Br-Ade). Consequently, the conversion of Br-Ade to adenine almost doubles following the addition of Ca2+. These experimental results, supported by theoretical calculations of the local density of states of the Ag/Br-Ade complex, indicate a change of the charge transfer pathway driving the dehalogenation reaction, from Landau damping (in the lack of Ca2+ ions) to CID (after the addition of Ca2+). The results show that the surface dynamics of chemical species (including water molecules) play an essential role in charge transfer at plasmonic interfaces and cannot be ignored. It is envisioned that these results will help in designing more efficient nanoreactors, harnessing the full potential of plasmon-assisted chemistry

Inhouse Bridging Thrombolysis Is Associated With Improved Functional Outcome in Patients With Large Vessel Occlusion Stroke: Findings From the German Stroke Registry

Background: Endovascular treatment (EVT) for large vessel occlusion stroke (LVOS) is highly effective. To date, it remains controversial if intravenous thrombolysis (IVT) prior to EVT is superior compared with EVT alone. The aim of our study was to specifically address the question, whether bridging IVT directly prior to EVT has additional positive effects on reperfusion times, successful reperfusion, and functional outcomes compared with EVT alone.Methods: Patients with LVOS in the anterior circulation eligible for EVT with and without prior IVT and direct admission to endovascular centers (mothership) were included in this multicentric, retrospective study. Patient data was derived from the German Stroke Registry (an open, multicenter, and prospective observational study). Outcome parameters included groin-to-reperfusion time, successful reperfusion [defined as a Thrombolysis in Cerebral Infarction (TICI) scale 2b-3], change in National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and mortality at 90 days.Results: Of the 881 included mothership patients with anterior circulation LVOS, 486 (55.2%) received bridging therapy with i.v.-rtPA prior to EVT, and 395 (44.8%) received EVT alone. Adjusted, multivariate linear mixed effect models revealed no difference in groin-to-reperfusion time between the groups (48 ± 36 vs. 49 ± 34 min; p = 0.299). Rates of successful reperfusion (TICI ≥ 2b) were higher in patients with bridging IVT (fixed effects estimate 0.410, 95% CI, 0.070; 0.750, p = 0.018). There was a trend toward a higher improvement in the NIHSS during hospitalization [ΔNIHSS: bridging-IVT group 8 (IQR, 9.8) vs. 4 (IQR 11) points in the EVT alone group; fixed effects estimate 1.370, 95% CI, −0.490; 3.240, p = 0.149]. mRS at 90 days follow-up was lower in the bridging IVT group [3 (IQR, 4) vs. 4 (IQR, 4); fixed effects estimate −0.350, 95% CI, −0.680; −0.010, p = 0.041]. There was a non-significantly lower 90 day mortality in the bridging IVT group compared with the EVT alone group (22.4% vs. 33.6%; fixed effects estimate 0.980, 95% CI −0.610; 2.580, p = 0.351). Rates of any intracerebral hemorrhage did not differ between both groups (4.1% vs. 3.8%, p = 0.864).Conclusions: This study provides evidence that bridging IVT might improve rates of successful reperfusion and long-term functional outcome in mothership patients with anterior circulation LVOS eligible for EVT

Bridging thrombolysis in atrial fibrillation stroke is associated with increased hemorrhagic complications without improved outcomes

BACKGROUND: Atrial fibrillation (AF) associated ischemic stroke is associated with worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Conversely, AF is not associated with hemorrhagic complications or functional outcomes in patients undergoing mechanical thrombectomy (MT). This differential effect of MT and IVT in AF associated stroke raises the question of whether bridging thrombolysis increases hemorrhagic complications in AF patients undergoing MT. METHODS: This international cohort study of 22 comprehensive stroke centers analyzed patients with large vessel occlusion (LVO) undergoing MT between June 1, 2015 and December 31, 2020. Patients were divided into four groups based on comorbid AF and IVT exposure. Baseline patient characteristics, complications, and outcomes were reported and compared. RESULTS: 6461 patients underwent MT for LVO. 2311 (35.8%) patients had comorbid AF. In non-AF patients, bridging therapy improved the odds of good 90 day functional outcomes (adjusted OR (aOR) 1.29, 95% CI 1.03 to 1.60, p=0.025) and did not increase hemorrhagic complications. In AF patients, bridging therapy led to significant increases in symptomatic intracranial hemorrhage and parenchymal hematoma type 2 (aOR 1.66, 1.07 to 2.57, p=0.024) without any benefit in 90 day functional outcomes. Similar findings were noted in a separate propensity score analysis. CONCLUSION: In this large thrombectomy registry, AF patients exposed to IVT before MT had increased hemorrhagic complications without improved functional outcomes, in contrast with non-AF patients. Prospective trials are warranted to assess whether AF patients represent a subgroup of LVO patients who may benefit from a direct to thrombectomy approach at thrombectomy capable centers

Outcomes of Mechanical Thrombectomy for Patients With Stroke Presenting With Low Alberta Stroke Program Early Computed Tomography Score in the Early and Extended Window

Importance: Limited data are available about the outcomes of mechanical thrombectomy (MT) for real-world patients with stroke presenting with a large core infarct. Objective: To investigate the safety and effectiveness of MT for patients with large vessel occlusion and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 2 to 5. Design, setting, and participants: This retrospective cohort study used data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combines the prospectively maintained databases of 28 thrombectomy-capable stroke centers in the US, Europe, and Asia. The study included 2345 patients presenting with an occlusion in the internal carotid artery or M1 segment of the middle cerebral artery from January 1, 2016, to December 31, 2020. Patients were followed up for 90 days after intervention. The ASPECTS is a 10-point scoring system based on the extent of early ischemic changes on the baseline noncontrasted computed tomography scan, with a score of 10 indicating normal and a score of 0 indicating ischemic changes in all of the regions included in the score. Exposure: All patients underwent MT in one of the included centers. Main outcomes and measures: A multivariable regression model was used to assess factors associated with a favorable 90-day outcome (modified Rankin Scale score of 0-2), including interaction terms between an ASPECTS of 2 to 5 and receiving MT in the extended window (6-24 hours from symptom onset). Results: A total of 2345 patients who underwent MT were included (1175 women [50.1%]; median age, 72 years [IQR, 60-80 years]; 2132 patients [90.9%] had an ASPECTS of ≥6, and 213 patients [9.1%] had an ASPECTS of 2-5). At 90 days, 47 of the 213 patients (22.1%) with an ASPECTS of 2 to 5 had a modified Rankin Scale score of 0 to 2 (25.6% [45 of 176] of patients who underwent successful recanalization [modified Thrombolysis in Cerebral Ischemia score ≥2B] vs 5.4% [2 of 37] of patients who underwent unsuccessful recanalization; P = .007). Having a low ASPECTS (odds ratio, 0.60; 95% CI, 0.38-0.85; P = .002) and presenting in the extended window (odds ratio, 0.69; 95% CI, 0.55-0.88; P = .001) were associated with worse 90-day outcome after controlling for potential confounders, without significant interaction between these 2 factors (P = .64). Conclusions and relevance: In this cohort study, more than 1 in 5 patients presenting with an ASPECTS of 2 to 5 achieved 90-day functional independence after MT. A favorable outcome was nearly 5 times more likely for patients with low ASPECTS who had successful recanalization. The association of a low ASPECTS with 90-day outcomes did not differ for patients presenting in the early vs extended MT window

Association of Noncontrast Computed Tomography and Perfusion Modalities With Outcomes in Patients Undergoing Late-Window Stroke Thrombectomy

Importance: There is substantial controversy with regards to the adequacy and use of noncontrast head computed tomography (NCCT) for late-window acute ischemic stroke in selecting candidates for mechanical thrombectomy. Objective: To assess clinical outcomes of patients with acute ischemic stroke presenting in the late window who underwent mechanical thrombectomy stratified by NCCT admission in comparison with selection by CT perfusion (CTP) and diffusion-weighted imaging (DWI). Design, setting, and participants: In this multicenter retrospective cohort study, prospectively maintained Stroke Thrombectomy and Aneurysm (STAR) database was used by selecting patients within the late window of acute ischemic stroke and emergent large vessel occlusion from 2013 to 2021. Patients were selected by NCCT, CTP, and DWI. Admission Alberta Stroke Program Early CT Score (ASPECTS) as well as confounding variables were adjusted. Follow-up duration was 90 days. Data were analyzed from November 2021 to March 2022. Exposures: Selection by NCCT, CTP, or DWI. Main outcomes and measures: Primary outcome was functional independence (modified Rankin scale 0-2) at 90 days. Results: Among 3356 patients, 733 underwent late-window mechanical thrombectomy. The median (IQR) age was 69 (58-80) years, 392 (53.5%) were female, and 449 (65.1%) were White. A total of 419 were selected with NCCT, 280 with CTP, and 34 with DWI. Mean (IQR) admission ASPECTS were comparable among groups (NCCT, 8 [7-9]; CTP, 8 [7-9]; DWI 8, [7-9]; P = .37). There was no difference in the 90-day rate of functional independence (aOR, 1.00; 95% CI, 0.59-1.71; P = .99) after adjusting for confounders. Symptomatic intracerebral hemorrhage (NCCT, 34 [8.6%]; CTP, 37 [13.5%]; DWI, 3 [9.1%]; P = .12) and mortality (NCCT, 78 [27.4%]; CTP, 38 [21.1%]; DWI, 7 [29.2%]; P = .29) were similar among groups. Conclusions and relevance: In this cohort study, comparable outcomes were observed in patients in the late window irrespective of neuroimaging selection criteria. Admission NCCT scan may triage emergent large vessel occlusion in the late window

Colony formation and colony size do not reflect the onset of replicative senescence in human fibroblasts

Replicative senescence of human fibroblasts in vitro has been used as a model for in vivo aging. The onset of replicative senescence varies between several months to years. A colony formation assay, critically dependent on growth speed, can be performed within weeks, and has been reported being an indicator for the onset of replicative senescence. Earlier we could not find a correlation between growth speed in mass cultures and onset of replicative senescence of human fibroblast strains. Therefore, we studied the colony formation assay in 23 fibroblast strains that varied widely in their replicative capacity. Neither the number nor the size of colonies was related to the onset of replicative senescence. The number of cells within the colonies was modestly correlated to the growth speed of the mass cultures. We conclude that the colony formation assay does not reflect the onset of replicative senescence in human fibroblasts

Doppler flow morphology characteristics of epiaortic arteries in aortic valve pathologies: a retrospective study on a cohort of patients with ischemic stroke

Abstract Background and aims Neurovascular ultrasound (nvUS) of the epiaortic arteries is an integral part of the etiologic workup in patients with ischemic stroke. Aortic valve disease shares similar vascular risk profiles and therefore not only presents a common comorbidity, but also an etiologic entity. The aim of this study is to investigate the predictive value of specific Doppler curve flow characteristics in epiaortic arteries and the presence of aortic valve disease. Methods Retrospective, single-center analysis of ischemic stroke patients, both receiving full nvUS of the extracranial common- (CCA), internal- (ICA) and external carotid artery (ECA) and echocardiography (TTE/TEE) during their inpatient stay. A rater blinded for the TTE/TEE results investigated Doppler flow curves for the following characteristics: ‘pulsus tardus et parvus’ for aortic valve stenosis (AS) and ‘bisferious pulse’, ‘diastolic reversal’, ‘zero diastole’ and ‘no dicrotic notch’ for aortic valve regurgitation (AR). Predictive value of these Doppler flow characteristics was investigated using multivariate logistic regression models. Results Of 1320 patients with complete examination of Doppler flow curves and TTE/TEE, 75 (5.7%) showed an AS and 482 (36.5%) showed an AR. Sixty-one (4.6%) patients at least showed a moderate-to-severe AS and 100 (7.6%) at least showed a moderate-to-severe AR. After adjustment for age, coronary artery disease, arterial hypertension, diabetes mellitus, smoking, peripheral arterial disease, renal failure and atrial fibrillation, the following flow pattern predicted aortic valve disease: ‘pulsus tardus et parvus’ in the CCA and ICA was highly predictive for a moderate-to-severe AS (OR 1158.5, 95% CI 364.2–3684.8, p < 0.001). ‘No dicrotic notch’ (OR 102.1, 95% CI 12.4–839.4, p < 0.001), a ‘bisferious pulse’ (OR 10.8, 95% CI 3.2–33.9, p < 0.001) and a ‘diastolic reversal’ (OR 15.4, 95% CI 3.2–74.6, p < 0.001) in the CCA and ICA predicted a moderate-to-severe AR. The inclusion of Doppler flow characteristics of the ECA did not increase predictive value. Conclusions Well defined, qualitative Doppler flow characteristics detectable in the CCA and ICA are highly predictive for aortic valve disease. The consideration of these flow characteristics can be useful to streamline diagnostic and therapeutic measures, especially in the outpatient setting

Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial

(1) Background: Bile acids, known as aids in intestinal fat digestion and as messenger molecules in serum, can be detected in cerebrospinal fluid (CSF), although the blood–brain barrier is generally an insurmountable obstacle for bile acids. The exact mechanisms of the occurrence, as well as possible functions of bile acids in the central nervous system, are not precisely understood. (2) Methods: We conducted a single-center observational trial. The concentrations of 15 individual bile acids were determined using an in-house LC-MS/MS method in 54 patients with various acute and severe disorders of the central nervous system. We analyzed CSF from ventricular drainage taken within 24 h after placement, and blood samples were drawn at the same time for the presence and quantifiability of 15 individual bile acids. (3) Results: At a median time of 19.75 h after a cerebral insult, the concentration of bile acids in the CSF was minute and almost negligible. The CSF concentrations of total bile acids (TBAs) were significantly lower compared to the serum concentrations (serum 0.37 µmol/L [0.24, 0.89] vs. 0.14 µmol/L [0.05, 0.43]; p = 0.033). The ratio of serum-to-CSF bile acid levels calculated from the respective total concentrations were 3.10 [0.94, 14.64] for total bile acids, 3.05 for taurocholic acid, 14.30 [1.11, 27.13] for glycocholic acid, 0.0 for chenodeoxycholic acid, 2.19 for taurochenodeoxycholic acid, 1.91 [0.68, 8.64] for glycochenodeoxycholic acid and 0.77 [0.0, 13.79] for deoxycholic acid; other bile acids were not detected in the CSF. The ratio of CSF-to-serum S100 concentration was 0.01 [0.0, 0.02]. Serum total and conjugated (but not unconjugated) bilirubin levels and serum TBA levels were significantly correlated (total bilirubin p = 0.031 [0.023, 0.579]; conjugated bilirubin p = 0.001 [0.193, 0.683]; unconjugated p = 0.387 [−0.181, 0.426]). No correlations were found between bile acid concentrations and age, delirium, intraventricular blood volume, or outcome measured on a modified Rankin scale. (4) Conclusions: The determination of individual bile acids is feasible using the current LC-MS/MS method. The results suggest an intact blood–brain barrier in the patients studied. However, bile acids were detected in the CSF, which could have been achieved by active transport across the blood–brain barrier

Effect of beta-blocker therapy on post-stroke infections stratified by statin therapy.

<p>*p-value for interaction based on a Likelihood Ratio Test comparing a model with interaction term with the corresponding model without interaction term</p><p>Effect of beta-blocker therapy on post-stroke infections stratified by statin therapy.</p