Peptidic "Molecular Beacon" for Collagen.

Collagen-mimetic peptides (CMP) have been invaluable tools for understanding the structure and function of collagen, which is the most abundant protein in animals. CMPs have also been developed as probes that detect damaged collagen because of the specificity required to form a collagen triple helix. These probes are not, however, ratiometric. Here, we used EPR spectroscopy to determine the end-to-end distances of CMPs that do not form stable homotrimeric helices. We found that those distances are shorter than the distances in the context of a collagen triple helix, suggesting their potential utility as a "molecular beacon" and guiding the choice and location of a pendant fluorophore-quencher pair. We then showed that a molecular beacon based on a glycine-(2S,4S)-4-fluoroproline-(2S,4R)-4-hydroxyproline tripeptide repeat and EDANS-DABCYL pair enabled the ratiometric detection of its binding to both other CMPs and natural mammalian collagen. These results provide guidance for the development of a new modality for detecting damaged collagen in physiological settings.

A full year of the COVID-19 pandemic with two infection waves and its impact on ischemic stroke patient care in Germany.

BACKGROUND AND PURPOSE: Many countries worldwide, including Germany, reported that the first wave of the coronavirus disease 2019 (COVID-19) pandemic in early 2020 influenced the care of acute ischemic stroke (AIS) patients, but data are lacking for further pandemic wave periods. METHODS: We conducted a nationwide, retrospective, cross-sectional study of all hospitalized patients with the main diagnosis of AIS in 2019 and 2020. Primary outcomes were the number of hospitalizations for AIS, the application of stroke unit care, intravenous thrombolysis (IVT), and mechanical thrombectomy (MT), as well as the in-hospital mortality during the different pandemic periods in 2020 compared to the corresponding periods in 2019. Secondarily, we analyzed differences in outcomes between patients with and without concurrent COVID-19. RESULTS: We included 429,841 cases with AIS, of which 1268 had concurrent COVID-19. Hospitalizations for AIS declined during both pandemic wave periods in 2020 (first wave: -10.9%, second wave: -4.6%). MT rates were consistently higher throughout 2020 compared to 2019, whereas the IVT rate dropped during the second wave period (16.0% vs. 17.0%, p < 0.001). AIS patients with concurrent COVID-19 frequently received recanalization treatments, with an overall MT rate of 8.4% and IVT rate of 15.9%. The in-hospital mortality was high (22.8% vs. 7.5% in noninfected AIS patients, p < 0.001). CONCLUSIONS: These findings demonstrate a smaller decline in hospitalizations for AIS in the more severe second wave of the COVID-19 pandemic. AIS patients with and without concurrent COVID-19 who did seek acute care continued to receive recanalization treatments in Germany.

Female Stroke: Sex Differences in Acute Treatment and Early Outcomes of Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Men and women are differently affected by acute ischemic stroke (AIS) in many aspects. Prior studies on sex disparities were limited by moderate sample sizes, varying years of data acquisition, and inconsistent inclusions of covariates leading to controversial findings. We aimed to analyze sex differences in AIS severity, treatments, and early outcome and to systematically evaluate the effect of important covariates in a large German stroke registry. METHODS: Analyses were based on the Stroke Registry of Northwestern Germany from 2000 to 2018. We focused on admission-stroke severity and disability, acute recanalization treatment, and early stroke outcomes. Potential sex divergences were investigated via odds ratio (OR) using logistic regression models. Covariates were introduced in 3 steps: (1) base models (age and admission year), (2) partially adjusted models (additionally corrected for acute stroke severity and recanalization treatment), (3) fully adjusted models (additionally adjusted for onset-to-admission time interval, prestroke functional status, comorbidities, and stroke cause). Models were separately fitted for the periods 2000 to 2009 and 2010 to 2018. RESULTS: Data from 761 106 patients with AIS were included. In fully adjusted models, there were no sex differences with respect to treatment with intravenous thrombolysis (2000-2009: OR, 0.99 [95% CI, 0.94-1.03]; 2010-2018: OR, 1.0 [0.98-1.02]), but women were more likely to receive intraarterial therapy (2010-2018: OR, 1.12 [1.08-1.15]). Despite higher disability on admission (2000-2009: OR, 1.10 [1.07-1.13]; 2010-2018: OR, 1.09 [1.07-1.10]), female patients were more likely to be discharged with a favorable functional outcome (2003-2009: OR, 1.05 [1.02-1.09]; 2010-2018: OR, 1.05 [1.04-1.07]) and experienced lower in-hospital mortality (2000-2009: OR, 0.92 [0.86-0.97]; 2010-2018: OR, 0.91 [0.88-0.93]). CONCLUSIONS: Female patients with AIS have a higher chance of receiving intraarterial treatment that cannot be explained by clinical characteristics, such as age, premorbid disability, stroke severity, or cause. Women have a more favorable in-hospital recovery than men because their higher disability upon admission was followed by a lower in-hospital mortality and a higher likelihood of favorable functional outcome at discharge after adjustment for covariates.

Analysis of Nationwide Stroke Patient Care in Times of COVID-19 Pandemic in Germany.

BACKGROUND AND PURPOSE: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many countries have introduced strict hygiene measures of social distancing to prevent further spreading of the disease. This may have led to a decreased presentation to hospital of patients with acute medical conditions and time-dependent management, such as stroke. METHODS: We conducted a nationwide cohort study using administrative database of all hospitalized patients with main diagnosis of acute ischemic stroke (AIS), transient ischemic attack, or intracerebral hemorrhage. Data from a total of 1463 hospitals in Germany were included. We compared case numbers and treatment characteristics of pandemic (March 16 to May 15, 2020) and prepandemic (January 16 to March 15, 2020) cases and also with corresponding time period in 2019. RESULTS: We identified a strong decline for hospitalization of AIS (-17.4%), transient ischemic attack (-22.9%), and intracerebral hemorrhage (-15.8%) patients during the pandemic compared with prepandemic period. IVT rate in patients with AIS was comparable (prepandemic versus pandemic: 16.4% versus 16.6%, P=0.448), whereas mechanical thrombectomy rate was significantly higher during the pandemic (8.1% versus 7.7%, P=0.044). In-hospital mortality was significantly increased in patients with AIS during the pandemic period (8.1% versus 7.6%, P=0.006). CONCLUSIONS: Besides a massive decrease in absolute case numbers, our data suggest that patients with AIS who did seek acute care during the pandemic, continued to receive acute recanalization treatment in Germany.

[Neurovascular manifestations of COVID­19]. / Neurovaskuläre Manifestationen von COVID­19.

Even early at the beginning of the coronavirus disease 2019 (COVID­19) pandemic, stroke was described as a manifestation or complication of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current meta-analyses reported a stroke rate of approximately 1.5%. Stroke in COVID­19 positive patients occurs more frequently in severe courses of the infection and in older patients with cardiovascular comorbidities; however, young patients without cardiovascular risk factors are also not uncommonly affected. The mechanisms of stroke are predominantly embolic. The thrombi frequently occlude large intracranial vessels and in more than 20% affect multiple vascular territories, whereas infarctions due to small vessel disease are uncommon. The exact source of the embolism remains cryptogenic in more than 40% of patients. The mortality caused by the co-occurrence of a SARS-CoV­2 infection and a stroke exceeds 15-30%. While acute stroke treatment was severely affected in some European regions, the rates of recanalization treatment in Germany largely remained stable during the first pandemic wave; however, 20-30% fewer patients with minor stroke and transient ischemic attacks (TIA) presented to hospitals during the first wave in spring 2020. The present narrative review summarizes the current evidence regarding the epidemiology and pathogenesis of stroke associated with COVID­19 and describes the effect of the pandemic so far on the provision of acute stroke treatment.

Rapid-Scan Electron Paramagnetic Resonance of Highly Resolved Hyperfine Lines in Organic Radicals.

X-band (ca. 9 GHz) fluid solution rapid-scan electron paramagnetic resonance spectra are reported for radicals with multiline spectra and resolution of hyperfine lines as narrow as 30 mG. Highly-resolved spectra of 3-carbamoyl-2,2,5,5-tetramethylpyrrolidin-1-yloxy, diphenylnitroxide, galvinoxyl, and perylene cation radical with excellent signal-to-noise are shown, demonstrating the capabilities of the rapid-scan technique to characterize very small, well-resolved hyperfine couplings. To acquire high resolution spectra the signal bandwidth must be less than the resonator bandwidth. Signal bandwidth is inversely proportional to linewidth and proportional to scan rate. Resonator bandwidth is inversely proportional to resonator Q. Proper selection of scan rate and resonator Q is needed to achieve resolution of closely-spaced narrow EPR lines.

Age and Sex Differences in Ischemic Stroke Treatment in a Nationwide Analysis of 1.11 Million Hospitalized Cases.

Background and Purpose- To date, there is still uncertainty about age and sex differences in access to stroke unit treatment and use of intravenous thrombolysis (IVT), while age and sex differences have not been investigated for the new treatment option of mechanical thrombectomy (MT). We, therefore, undertook a complete nationwide analysis of all hospitalized ischemic stroke patients in Germany from 2013 to 2017. Methods- We used the nationwide administrative database of the German Federal Statistical Office and investigated access to stroke unit treatment, IVT, MT, and in-hospital mortality. Patients were subdivided into 6 predefined age groups (20-44, 45-59, 60-69, 70-79, 80-89, and >90 years). Pooled overall and age group estimates were calculated using the random-effects model. To evaluate potential sex disparities, we estimated odds ratios (ORs) with 95% CIs. Results- A total of 1 112 570 patients were hospitalized for first or recurrent ischemic stroke from 2013 to 2017. Overall, stroke unit treatment increased significantly from 66.8% in 2013 to 73.5% in 2017, as did IVT (from 12.4% to 15.9%) and MT (from 2.4% to 5.8%; all P<0.001). Although the difference became smaller over time, patients ≥80 years of age still received significantly less often treatments. Men of all age groups had a significantly higher probability receiving stroke unit treatment (OR, 1.11; 95% CI, 1.09-1.12) and lower in-hospital mortality (OR, 0.91; 95% CI, 0.89-0.93). No disparity was observed in the use of IVT (OR, 1.00; 95% CI, 0.98-1.01), while women of all ages were treated more often with MT (OR, 1.26; 95% CI, 1.22-1.30). Conclusions- Access to stroke unit treatment has to be increased in both older patients and women of all ages. While there was no sex difference in IVT use, it is important to further investigate the significantly higher frequency of MT in women with ischemic stroke irrespective of age.

Direct Mechanical Intervention Versus Bridging Therapy in Stroke Patients Eligible for Intravenous Thrombolysis: A Pooled Analysis of 2 Registries.

BACKGROUND AND PURPOSE: Randomized controlled trials have shown that mechanical thrombectomy (MT) plus best medical treatment improves outcome in stroke patients with large-vessel occlusion in the anterior circulation. Whether direct MT is equally effective as bridging thrombolysis (intravenous thrombolysis plus MT) in intravenous thrombolysis eligible patients remains unclear. METHODS: We compared clinical and radiological outcomes at 3 months in 249 bridging patients with 111 patients receiving direct MT for large-vessel occlusion anterior circulation stroke from 2 prospective registries (study period Essen: June 2012 to August 2013, Bern February 2009 to August 2014). We matched all patients from the direct MT group who would have qualified for intravenous thrombolysis with controls from the bridging group, using multivariate and propensity score methods. Subgroup analyses for internal carotid artery occlusions were performed. RESULTS: Baseline characteristics did not differ between the direct MT group and bridging cohort, except for higher rates of coronary heart disease (P=0.029) and shorter intervals from onset to endovascular therapy (P<0.001) in the MT group. Functional outcome, mortality, and intracerebral hemorrhage did not differ, neither in univariate nor after multivariate and propensity score matching. However, in patients with internal carotid artery occlusion, mortality in the direct cohort was significantly lower. CONCLUSIONS: In this matched-pair analysis, there was no difference in outcome in patients with large-vessel occlusion anterior circulation stroke treated with direct MT compared with those treated with bridging thrombolysis; however, mortality in patients with internal carotid artery occlusion treated with direct MT was significantly lower than after bridging thrombolysis. Randomized trials comparing direct MT with bridging therapy are needed.

Efficacy and safety of a single occipital nerve blockade in episodic and chronic cluster headache: A prospective observational study.

Background Treatment options for cluster headache (CH) include acute, transitional and prophylactic strategies. We assessed the efficacy and safety of a single occipital nerve block (ONB) in patients with episodic (eCH) and chronic CH (cCH). Methods In this prospective, observational study 101 CH were treated with a single ONB using triamcinolone 10 mg and bupivacaine. Attack frequency, pain intensity and side effects were assessed at days 1 and 7 after ONB and thereafter weekly for 60 days until recurrence of attacks. Results Baseline mean daily attack frequency was 2.9 ± 2.5 (eCH) and 3.3 ± 2.9 (cCH), which was reduced to 0.7 ± 1.2 (eCH) and 1.1 ± 1.4 (cCH) after one day ( p = 0.08 for group difference) and to 1.1 ± 1.6 (eCH) and 1.9 ± 2.3 (cCH) after seven days ( p = 0.01 for group difference). In patients with eCH the pain-free period lasted longer compared to cCH ( p = 0.004). There was no association between the presence of local anesthesia and treatment response ( p = 0.88). No serious adverse events occurred. Conclusion ONB is an easy, safe and effective transitional treatment option in case of insufficient response of CH to treatment both in patients with eCH and cCH. Patients with eCH have a better and more sustainable treatment response.

The association between collateral status, recanalization and long term outcome in stroke patients treated with stent retrievers - Are there indications not to perform thrombectomy based on CT angiography?

BACKGROUND AND PURPOSE: To investigate the association between baseline pial collateral status on computed tomography angiography (CTA) with recanalization and functional outcome in patients with acute anterior circulation stroke treated with stent retriever thrombectomy. MATERIAL AND METHODS: Retrospective analysis of 87 patients from a prospective thrombectomy registry. Collateral status on CTA source images was categorized into good, moderate, and poor with the Tan and Miteff scores by two-blinded readers. Association between CTA collateral status and successful recanalization was investigated with univariate regression analysis. Multivariate logistic regression was used to analyse the association between collateral score and favourable clinical outcome (mRS 0-2) and death at follow-up. RESULTS: Mean age was 72.5 years and baseline median NIHSS score was 15. Patients with poor collaterals on Tan score had a significant higher mortality compared with moderate or good collaterals during a mean follow-up period of 5.2 months (85.7% vs. 30.6% vs. 25.7%, P<0.001). Univariate logistic regression analysis did not show a significant association between Tan score (OR 1.681, 95% CI 0.683-4.140) and successful recanalization. Higher age (OR 1.067, 95% CI 1.013-1.124; P=0.015) and lower Tan score (OR 0.421, 95% CI 0.192-0.922; P=0.031) were independent predictors of death at follow-up on multivariate analysis. The Miteff collateral score could be assessed only in 65 of the 87 patients and the Tan collateral score had a higher interrater reliability. CONCLUSIONS: Poor collaterals on CTA were associated with a very high rate of fatal outcome in anterior circulation stroke patients despite a high rate of successful recanalization with stent retrievers.

Frequency-Swept Integrated Solid Effect.

The efficiency of continuous wave dynamic nuclear polarization (DNP) experiments decreases at the high magnetic fields used in contemporary high-resolution NMR applications. To recover the expected signal enhancements from DNP, we explored time domain experiments such as NOVEL which matches the electron Rabi frequency to the nuclear Larmor frequency to mediate polarization transfer. However, satisfying this matching condition at high frequencies is technically demanding. As an alternative we report here frequency-swept integrated solid effect (FS-ISE) experiments that allow low power sweeps of the exciting microwave frequencies to constructively integrate the negative and positive polarizations of the solid effect, thereby producing a polarization efficiency comparable to (±10 % difference) NOVEL. Finally, the microwave frequency modulation results in field profiles that exhibit new features that we coin the "stretched" solid effect.

Outcome After Thrombectomy and Intravenous Thrombolysis in Patients With Acute Ischemic Stroke: A Prospective Observational Study.

BACKGROUND AND PURPOSE: In patients with ischemic stroke, randomized trials showed a better functional outcome after endovascular therapy with new-generation thrombectomy devices compared with medical treatment, including intravenous thrombolysis. However, effects on mortality and the generalizability of results to routine clinical practice are uncertain. METHODS: In a prospective observational register-based study patients with ischemic stroke treated either with thrombectomy, intravenous thrombolysis, or their combination were included. Primary outcome was the modified Rankin scale score (0 [no symptoms] to 6 [death]) at 3 months. Ordinal logistic regression was used to estimate the common odds ratio as treatment effects (shift analysis). Propensity score matching was applied to compare patients treated either with intravenous thrombolysis alone or with intravenous thrombolysis plus thrombectomy. RESULTS: Among 2650 recruited patients, 1543 received intravenous thrombolysis, 504 underwent thrombectomy, and 603 received intravenous thrombolysis in combination with thrombectomy. Later time-to-treatment was associated with worse outcomes among patients treated with thrombectomy plus thrombolysis. In 241 pairs of propensity score-matched patients with a proximal intracranial occlusion, thrombectomy plus thrombolysis was associated with improved functional outcome (common odds ratio, 1.84; 95% confidence interval, 1.32-2.57), and reduced mortality (15% versus 33%; P<0.0001) compared with intravenous thrombolysis alone. Results were similar in various sensitivity analyses accounting for missing outcome data and different analytic methods. CONCLUSIONS: Results from this large prospective registry show that also in routine clinical care thrombectomy plus thrombolysis compared with thrombolysis alone improved functional outcome and reduced mortality in patients with ischemic stroke. Earlier treatment was associated with better outcomes.

Tailoring of Polarizing Agents in the bTurea Series for Cross-Effect Dynamic Nuclear Polarization in Aqueous Media.

A series of 18 nitroxide biradicals derived from bTurea has been prepared, and their enhancement factors ɛ ((1)H) in cross-effect dynamic nuclear polarization (CE DNP) NMR experiments at 9.4 and 14.1 T and 100 K in a DNP-optimized glycerol/water matrix ("DNP juice") have been studied. We observe that ɛ ((1)H) is strongly correlated with the substituents on the polarizing agents, and its trend is discussed in terms of different molecular parameters: solubility, average e-e distance, relative orientation of the nitroxide moieties, and electron spin relaxation times. We show that too short an e-e distance or too long a T1e can dramatically limit ɛ ((1)H). Our study also shows that the molecular structure of AMUPol is not optimal and its ɛ ((1)H) could be further improved through stronger interaction with the glassy matrix and a better orientation of the TEMPO moieties. A new AMUPol derivative introduced here provides a better ɛ ((1)H) than AMUPol itself (by a factor of ca. 1.2).

Probing the Noninnocent π-Bonding Influence of N-Carboxyamidoquinolate Ligands on the Light Harvesting and Redox Properties of Ruthenium Polypyridyl Complexes.

Electronic and photophysical characterization is presented for a series of bis-heteroleptic [Ru(bpy)2(R-CAQN)](+) complexes where CAQN is a bidentate N-(carboxyaryl)amidoquinolate ligand and the aryl substituent R = p-tolyl, p-fluorobenzene, p-trifluoromethylbenzene, 3,5-bis(trifluoromethyl)benzene, or 4-methoxy-2,3,5,6-tetrafluorobenzene. Characterized by a strong noninnocent Ru(dπ)-CAQN(π) bonding interaction, density functional theory (DFT) analysis is used to estimate the contribution of both atomic Ru(dπ) and ligand CAQN(π) manifolds to the frontier molecular orbitals of these complexes. UV-vis absorption and emission studies are presented where the noninnocent Ru(dπ)-CAQN(π) bonding scheme plays a major role in defining complex electronic and photophysical properties. Oxidation potentials are tuned over a range of 0.92 V with respect to the [Ru(bpy)3](2+) reference system, hereafter referred to as 1(2+), by varying the degree of R-CAQN fluorination while maintaining consistently strong and panchromatic visible absorption properties. Electron paramagnetic resonance (EPR) spectroscopy is employed to experimentally map delocalization of the unpaired electron/electron-hole within the delocalized Ru(dπ)-CAQN(π) singly occupied valence molecular orbital of the one-electron oxidized complexes. EPR data is complemented experimentally by UV-vis-NIR spectroelectrochemistry, and computationally by molecular orbital Mulliken contributions and spin-density analysis. It is ultimately demonstrated that the CAQN ligand framework provides a simple yet broad synthetic platform in the design of redox-active transition metal chromophores with a range of electronic and spectroscopic characteristics hinting at the diversity and potential of these complexes toward photochemical and catalytic applications.

A novel copper(II) complex identified as a potent drug against colorectal and breast cancer cells and as a poison inhibitor for human topoisomerase IIα.

A novel complex, [Cu(acetylethTSC)Cl]Cl•0.25C2H5OH 1 (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide), was shown to have anti-proliferative activity against various colon and aggressive breast cancer cell lines. In vitro studies showed that complex 1 acted as a poison inhibitor of human topoisomerase IIα, which may account for the observed anti-cancer effects.

Reversible cerebral vasoconstriction syndrome associated with fingolimod treatment in relapsing-remitting multiple sclerosis three months after childbirth.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by acute thunderclap headache, evidence of vasoconstriction in conventional angiography or magnetic resonance angiography and reversibility of these phenomena within 12 weeks. Some triggering factors, for example drugs such as selective serotonin reuptake inhibitors, sumatriptan, tacrolimus, cyclophosphamide and cocaine, or states such as pregnancy, puerperium or migraine have been described. We describe the case of a 29-year-old woman with RCVS associated with fingolimod three months after childbirth. This case represents the first report of RCVS in fingolimod treatment.

EPR detection of two protein-associated ubiquinone components (SQ(Nf) and SQ(Ns)) in the membrane in situ and in proteoliposomes of isolated bovine heart complex I.

The success of Sazanov's group in determining the X-ray structure of the whole bacterial complex I is a great contribution to the progress of complex I research. In this mini-review of 35years' history of my laboratory and collaborators, we characterized the function of protein-associated semiquinone molecules in the proton-pumping mechanism in complex I (NADH-quinone oxidoreductase). We have constructed most of the frame work of our hypothesis, utilizing EPR techniques before the X-ray structures of complex I were reported by Sazanov's and Brandt's groups. One of the semiquinones (SQ(Nf)) is extremely sensitive to a proton motive force imposed on the energy-transducing membrane, while the other (SQ(Ns)) is insensitive. Their sensitivity to rotenone inhibition also differs. These differences were exploited using tightly coupled bovine heart submitochondrial particles with a high respiratory control ratio (>8). We determined the distance between SQ(Nf) and iron-sulfur cluster N2 on the basis of their direct spin-spin interaction. We are extending this line of work using reconstituted bovine heart complex I proteoliposomes which shows a respiratory control ratio >5. Two frontier research groups support our view point based on their mutagenesis studies. High frequency (33.9GHz; Q-band) EPR experiments appear to favor our two-semiquinone model. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).

Discontinuation of antiplatelet study medication and risk of recurrent stroke and cardiovascular events: results from the PRoFESS study.

BACKGROUND: Several case control studies have reported an increased risk of cardiovascular events following discontinuation of antiplatelet agents in high-risk patients. We therefore sought to investigate the risk of recurrent stroke and cardiovascular events following discontinuation of antiplatelet study medication in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial, a large randomized secondary stroke prevention study. METHODS: The recurrent stroke and cardiovascular event rates following discontinuation of aspirin plus extended-release dipyridamole (ASA + ERDP) or clopidogrel were compared to the event rates in the on-treatment populations (patients who had discontinued their antiplatelet medication due to an outcome event were kept in the on-treatment population in order not to underestimate the on-treatment stroke rate). RESULTS: In 7,212 treated ASA + ERDP patients, the stroke incidence rate for the on-treatment group was 729 strokes with an average exposure of 17,048 person-years (0.12 per 1,000 person-days). For 7,864 treated clopidogrel patients, the stroke incidence rate for the on-treatment group was 737 strokes with an average exposure of 18,715 person-years (0.11 per 1,000 person-days). ASA + ERDP was discontinued in 2,843 patients (in 57.7% due to an adverse event, 28.2% noncompliance, 1.4% loss to follow-up, 4.5% withdrawal of consent and 8.1% other/nonspecified reasons) and clopidogrel was permanently discontinued in 2,176 patients (49.0% due to an adverse event, 34.2% noncompliance, 1.8% loss to follow-up, 5.3% withdrawal of consent and 9.7% other/nonspecified reasons). Within 30 days, a recurrent stroke occurred in 31 patients (0.37 per 1,000 person-days) after discontinuation of ASA + ERDP and in 15 patients (0.24 per 1,000 person-days) after discontinuation of clopidogrel. This corresponds to an absolute excess risk of 0.77% within 30 days after discontinuation of ASA + ERDP and 0.40% within 30 days after discontinuation of clopidogrel compared with the on-treatment study populations. A combined vascular endpoint (stroke, myocardial infarction, vascular death) occurred in 68 patients (0.82 per 1,000 person-days) within 30 days after discontinuation of ASA + ERDP and in 47 patients (0.75 per 1,000 person-days) within 30 days after discontinuation of clopidogrel. This corresponds to an absolute excess risk of 2.02% within 30 days after discontinuation of ASA + ERDP and 1.83% within 30 days after discontinuation of clopidogrel compared with the on-treatment study populations. CONCLUSION: Discontinuation of antiplatelet medication after ischemic stroke should be advocated only when the risk and severity of bleeding clearly outweigh the risk of cardiovascular events.