Unraveling two distinct polymorph transition mechanisms in one n-type single crystal for dynamic electronics.

Cooperativity is used by living systems to circumvent energetic and entropic barriers to yield highly efficient molecular processes. Cooperative structural transitions involve the concerted displacement of molecules in a crystalline material, as opposed to typical molecule-by-molecule nucleation and growth mechanisms which often break single crystallinity. Cooperative transitions have acquired much attention for low transition barriers, ultrafast kinetics, and structural reversibility. However, cooperative transitions are rare in molecular crystals and their origin is poorly understood. Crystals of 2-dimensional quinoidal terthiophene (2DQTT-o-B), a high-performance n-type organic semiconductor, demonstrate two distinct thermally activated phase transitions following these mechanisms. Here we show reorientation of the alkyl side chains triggers cooperative behavior, tilting the molecules like dominos. Whereas, nucleation and growth transition is coincident with increasing alkyl chain disorder and driven by forming a biradical state. We establish alkyl chain engineering as integral to rationally controlling these polymorphic behaviors for novel electronic applications.

Sex differences in etiology and short-term outcome in young ischemic stroke patients receiving mechanical thrombectomy.

BACKGROUND: Although there are well known sex differences in older patients with ischemic stroke receiving acute reperfusion treatments, there is paucity of data in younger patients. METHODS: We investigated sex-related differences in clinical presentation, stroke etiology and short-term outcomes in consecutive young patients with acute ischemic stroke (AIS) below the age of 50 years receiving mechanical thrombectomy (MT) between January 2011 and May 2021 in a tertiary stroke center. RESULTS: We identified a total of 202 young ischemic stroke patients with MT, with 51% being female. Young female AIS patients were significantly younger (39 ± 8 vs. 43 ± 7 years, p < 0.001), and presented with a trend for more severe stroke on admission (median NIHSS 12 vs. 9, p = 0.065), compared to males, respectively. Young female AIS patients had higher rates of embolic strokes of determined or undetermined sources in the anterior circulation, while young male AIS patients suffered more often strokes of arterio-arterial embolism. Complete reperfusion (TICI score 3) was achieved significantly less often in young female AIS patients (69% vs. 83%, p = 0.006), and in-hospital mortality was 2-times higher (5% vs. 2%, p = 0.271) compared to males. CONCLUSIONS: Young female AIS patients receiving MT have higher rates of severe embolic strokes and less often complete reperfusion due to different occlusion sites and stroke etiology compared to males.

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.

The level of urbanization influences acute ischemic stroke care: A nationwide ecological study from Germany.

BACKGROUND AND PURPOSE: Regional differences in acute ischemic stroke (AIS) care are still reported for Germany but not fully understood. We aimed to analyze the impact of the level of urbanization on the application of proved treatment procedures and the incidence of hospitalized AIS cases in Germany. METHODS: The level of urbanization of the 401 districts and district-free cities in Germany was defined according to the Federal Institute for Building, Urban Affairs and Spatial Research classification. Using nationwide administrative data, the application of intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and the incidence of hospitalizations for AIS, were analyzed according to the place of residence of the patients. Data included all patients hospitalized for AIS in 2019 (n = 224,274) and sociodemographic information of 83,019,213 residents in Germany. RESULTS: Sparsely populated districts had a significantly higher incidence of hospitalizations for AIS than cities (age-standardized: 271.8 versus 242.3 per 100,000 inhabitants, P < 0.001), but a lower use of MT (5.7% versus 8.4%, P < 0.001). In the adjusted negative binomial regression model, rurality remained an independent predictor for MT use and the incidence of AIS hospitalizations. The proportion of IVT did not significantly differ between sparsely populated districts and cities (15.6% versus 17.2%, P = 0.021). CONCLUSIONS: Although there is a dense network of stroke units in Germany, the level of urbanization still influences AIS care, as we found a lower proportion of MT and a higher incidence of AIS hospitalizations in Germany's rural areas.

Letter to the Editor: Analysis of stroke patient migration for mechanical thrombectomy and changes in neurointerventional center size in Germany.

AIM AND METHODS: To analyse nationwide changes in neurointerventional center size of all German hospitals performing mechanical thrombectomy (MT) in stroke patients from 2016 to 2019. Furthermore, we assessed cross-district patient migration for MT for the first time using hospitals' structured quality reports and German Diagnosis-Related Groups data in 2019. FINDINGS: Number of hospitals performing more than 100 MT procedures/year doubled in Germany from 2016 (n = 36) to 2019 (n = 71), and these neurointerventional centers performed 71% of all MT procedures in 2019. The overall increase in MT procedures was largely driven by these high-volume neurointerventional centers with ability to perform MT 24/7 (121% increase as compared with 8% increase in hospitals performing less than 100 MT procedures/year). The highest cross-district patient mobility/transfer of stroke patients for MT was observed in districts adjacent to these high-volume neurointerventional centers with existing neurovascular networks. CONCLUSION: The substantial increase in MT procedures observed in Germany between 2016 and 2019 was almost exclusively delivered by high-volume stroke centers performing more than 100 MT procedures per year in established neurovascular networks. As there is still a reasonable number of districts with low MT rates, further structural improvement including implementation of new or expansion of existing neurovascular networks and regional tailored MT triage concepts is needed.

Acute ischemic stroke care in Germany - further progress from 2016 to 2019.

BACKGROUND: Stroke Unit Care (SUC), intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatment options for acute ischemic stroke (AIS). Using nationwide comprehensive administrative data from Germany, we recently reported nationwide development of AIS admissions, SUC rates, IVT rates and MT rates in Germany between 2010 and 2016. In this update paper, we analyze data on the further development of these data to 2019 after publication of time window extensions for recanalization therapies. METHODS: We considered all hospitalized cases with the main diagnosis of the ICD-10-GM code I63 (AIS) for the year 2019. We identified stroke therapies by using the corresponding Operating and Procedure Keys for IVT, MT and SUC out of the DRG statistics. Regional analyses are based on data from the 412 German administrative districts and cities. We compared the results with those from 2016. RESULTS: Number of hospitalized AIS patients showed a mild decrease in 2019 (n = 225,531) compared with 2016 (n = 227,687), with significant more AIS patients treated on a stroke unit in 2019 (n = 167,799; 74.4% vs. n = 164,270; 72.1%, p < 0.001). The rate of IVT further increased from 14.9% (n = 33,916) in 2016 to 16.3% (n = 36,745) in 2019 (p < 0.001). Similarly, the MT rate increased from 4.3% (n = 9795) in 2016 to 7.2% (n = 16,135) in 2019 (p < 0.001). There was still a high regional variability for MT (1.4 to 15.2%) according to the place of residence of the AIS patients. CONCLUSIONS: In Germany, the rates of recanalization therapies in patients with AIS continued to increase from 2016 to 2019. Compared to IVT-rates and numbers, the respective data for MT procedures showed an even more pronounced increase.

[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.

Photoinduced formation of persistent free radicals, hydrogen radicals, and hydroxyl radicals from catechol on atmospheric particulate matter.

Catechol is speculated to be a potential precursor of environmentally persistent free radicals (EPFRs) in the atmosphere. EPFRs absorbed on PM2.5 have attracted public attention because their toxicity is similar to cigarette smoke. In this study, we found that catechol could produce EPFRs, which were oxygen-centered phenoxy and semiquinone radicals. These free radical species had half-lives of up to 382 days. CaO, CuO, and Fe2O3 markedly promoted EPFR formation from catechol. The valence states of Cu and Fe changed during the photochemical reactions of catechol but no valence state changed for Ca. Alkaline nature of CaO is possibly the key for promoting the free radical formations through acid-base reactions with catechol. In addition to hydroxyl free radicals, hydrogen free radicals and superoxide anions formed from the photochemical reactions of catechol were first discovered. This is of concern because of the adverse effects of these free radicals on human health.

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.

Effectiveness of very low profile thrombectomy device in primary distal medium vessel occlusion, as rescue therapy after incomplete proximal recanalization or following iatrogenic thromboembolic events.

BACKGROUND: Recent progress with smaller retrievers has expanded the ability to reach distal brain arteries. We herein report recanalization, bleeding complications and short-term clinical outcomes with the smallest currently known low profile thrombectomy device in patients with primary or secondary distal medium vessel occlusion (DMVO). METHODS: We performed a retrospective analysis of 115 patients receiving mechanical thrombectomy (MT) in DMVO using the extended Thrombolysis in Cerebral Infarction (eTICI), European Cooperative Acute Stroke Study (ECASS) II classification, The National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores at admission and discharge to evaluate outcomes. Patients were stratified into three groups: (1) primary isolated distal occlusion (n=34), (2) secondary distal occlusion after MT of a proximal vessel occlusion (n=71), or (3) during endovascular treatment of aneurysms or arteriovenous malformations (AVMs) (n=10). RESULTS: Successful distal recanalization, defined as an eTICI score of 2b67, 2c and 3, was achieved in 74.7% (86/115) of patients. More specifically, it was 70.5% (24/34), 73.2% (52/71), and 100% (10/10) of primary DMVO, secondary DMVO after proximal MT, and rescue MT during aneurysm or AVM embolization, respectively. Symptomatic intraparenchymal bleeding occurred in 6.9% (eight patients). In-hospital mortality occurred in 18.1% (19/105) of patients with stroke. The most common cause of death was large infarct, old age, and therapy limitation. CONCLUSION: Direct or rescue MT of DMVO using a very low profile thrombectomy device is associated with a high rate of successful recanalization and a reasonable rate of symptomatic hemorrhagic complication, despite a risk of 18.1% hospital mortality in elderly patients. Further trials are needed to confirm our results and assess long-term clinical outcomes.

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.

Comparison of stroke care parameters in acute ischemic stroke patients with and without concurrent Covid-19. A Nationwide analysis.

BACKGROUND: Comparing health care parameters of acute ischemic stroke (AIS) patients with and without concurrent coronavirus disease 2019 (Covid-19, SARS-CoV-2 infection), may be helpful in terms of optimizing clinical and public health care during pandemic. METHODS: We evaluated a nationwide administrative database of all hospitalized patients with main diagnosis of acute ischemic stroke with/without diagnosis of Covid-19 who were hospitalized during the time period from January 16th to May 15th, 2020. Data from a total of 1463 hospitals in Germany were included. We compared case numbers, treatment characteristics (intravenous thrombolysis, IVT; mechanical thrombectomy, MT; treated on an intensive care unit, stroke unit or regular ward) and in-hospital mortality of AIS with and without concurrent diagnosis of Covid-19. RESULTS: From a total of 30,864 hospitalized Covid-19 patients during the evaluation period in Germany, we identified a subgroup of 213 patients with primary diagnosis of AIS. Compared to the 68,700 AIS patients without Covid-19, this subgroup showed a similar rate of IVT (16.4% vs. 16.5%, p = 0.985) but a significantly lower rate of MT (3.8% vs. 7.9%, p = 0.017). In-hospital mortality rate was significantly higher in patients with AIS and concurrent Covid-19 compared to non-infected AIS patients (22.5% vs. 7.8%, p < 0.001). CONCLUSION: These nationwide data point out differences in mortality and medical treatment regime between AIS patients with and without concurrent Covid-19. Since the pandemic is still ongoing, these data draw attention to AIS as a less frequent but often fatal comorbidity in Covid-19 patients.

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.

Adiabatic Solid Effect.

The solid effect (SE) is a two spin dynamic nuclear polarization (DNP) mechanism that enhances the sensitivity in NMR experiments by irradiation of the electron-nuclear spin transitions with continuous wave (CW) microwaves at ω0S ± ω0I, where ω0S and ω0I are electron and nuclear Larmor frequencies, respectively. Using trityl (OX063), dispersed in a 60/40 glycerol/water mixture at 80 K, as a polarizing agent, we show here that application of a chirped microwave pulse, with a bandwidth comparable to the EPR line width applied at the SE matching condition, improves the enhancement by a factor of 2.4 over the CW method. Furthermore, the chirped pulse yields an enhancement that is ∼20% larger than obtained with the ramped-amplitude NOVEL (RA-NOVEL), which to date has achieved the largest enhancements in time domain DNP experiments. Numerical simulations suggest that the spins follow an adiabatic trajectory during the polarization transfer; hence, we denote this sequence as an adiabatic solid effect (ASE). We foresee that ASE will be a practical pulsed DNP experiment to be implemented at higher static magnetic fields due to the moderate power requirement. In particular, the ASE uses only 13% of the maximum microwave power required for RA-NOVEL.

Incidence of Acute Kidney Injury After Computed Tomography Angiography±Computed Tomography Perfusion Followed by Thrombectomy in Patients With Stroke Using a Postprocedural Hydration Protocol.

Background The risk of contrast-induced acute kidney injury (AKI) in patients with stroke receiving both computed tomography (CT) angiography and mechanical thrombectomy has been investigated only in small case series. No studies have investigated whether additional CT perfusion or chronic kidney disease (CKD) are associated with higher rates of AKI. Methods and Results Retrospective analysis of the AKI incidence in 1089 consecutive patients receiving CT angiography and mechanical thrombectomy from 2015 to 2017 and in subgroups with CKD (n=99) and CT perfusion (n=104) was performed. Patients received a standardized hydration protocol. Data on kidney function after mechanical thrombectomy were available in 1017 patients. A total of 59 (5.8%) patients developed AKI, and only 4 (6.8%) patients needed hemodialysis, all with known CKD. Patients with AKI significantly more often had known CKD (20.3% versus 8.4%, P=0.002), diabetes mellitus (33.9% versus 20.9%, P=0.018), and tandem occlusion (32.2% versus 16.2%, P=0.003) and a significantly higher in-hospital mortality (20.3% versus 7.0%, P<0.001) compared with patients without AKI. However, there were no significant independent predictors for AKI in multivariable logistic regression analysis. Sex (odds ratio [OR], 2.03; 95% CI, 1.17-3.52 [P=0.012]), higher National Institutes of Health Stroke Scale (OR, 1.10; 95% CI, 1.05-1.14 [P<0.001]), AKI (OR, 3.52; 95% CI, 1.63-7.64 [P=0.001]), diuretic use (OR, 1.80; 95% CI, 1.02-3.19), futile or incomplete recanalization (OR, 0.19; 95% CI, 0.09-0.40 [P<0.001]), and total volume of contrast agent volume (OR, 1.007; 95% CI, 1.002-1.011 [P=0.004]) were independently associated with in-hospital death. Two thirds of the patients with AKI died of severe brain damage and not AKI itself. Conclusions Post-contrast AKI rarely occurs in patients with stroke receiving a contrast agent for CT angiography/CT perfusion and subsequent mechanical thrombectomy. Patients with known CKD had higher rates of AKI and only these patients needed hemodialysis, but CKD was not independently associated with AKI or in-hospital mortality.

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.