[Prevention of Post-Stroke Depression]. / Prävention der Post-Stroke-Depression.

Post-stroke depression (PSD) is a clinically relevant complication of ischemic and hemorrhagic cerebral infarction that affects about 30% of all stroke survivors. It is associated with reduced quality of life as well as delayed recovery from neurological deficits and functional impairment, frequently leading to impeded rehabilitation. Suitable screening methods allow early detection of PSD. Timely initiation of treatment in patients with manifest PSD as well as implantation of effective prevention strategies can help reduce medical and socioeconomic burden associated with the disease. We reviewed the current literature on pharmacological and non-pharmacological prevention of PSD.

Operando Spatial and Temporal Tracking of Axial Stresses and Interfaces in Solid-state Batteries.

Solid-state batteries have the potential to replace the current generation of liquid electrolyte batteries. However, the major limitation resulting from their solid-state architecture is the gradual loss of ionic conductivity due to the loss of physical contact between the individual battery components during charging/discharging. This is mainly due to mechanical stresses caused by volume changes in the cathode and anode during lithiation and delithiation. To date, limited research has been devoted to understanding the spatio-temporal distribution of stresses during battery operation. Here, operando scanning high-energy X-ray diffraction to quantify cross-sectional axial stresses with a spatial resolution of 10 µm is used. It is shown how a non-monotonous stress distribution evolves over time during the cycling of the solid-state battery. In addition, degradation of the solid-state electrolyte in the vicinity of the lithium anode is observed and tracked periodic changes in the unit cell volume in the cathode. The presented methodology of tracking the chemo-mechanically induced stresses and interface morphology in real time in correlation with other battery parameters is believed, can provide a valuable platform for the future optimization of solid-state batteries.

Evidence from UK Research Ethics Committee members on what makes a good research ethics review, and what can be improved.

The rapid development of vaccines and other innovative medical technologies in response to the COVID-19 pandemic required streamlined and efficient ethics and governance processes. In the UK the Health Research Authority (HRA) oversees and coordinates a number of the relevant research governance processes including the independent ethics review of research projects. The HRA was instrumental in facilitating the rapid review and approval of COVID-19 projects, and following the end of the pandemic, have been keen to integrate new ways of working into the UK Health Departments' Research Ethics Service. In January 2022 the HRA commissioned a public consultation that identified strong public support for alternative ethics review processes. Here we report feedback from 151 current research ethics committee members conducted at three annual training events, where we asked members to critically reflect on their ethics review activities, and to share new ideas or ways of working. The results showed a high regard for good quality discussion among members with diverse experience. Good chairing, organisation, feedback and the opportunity for reflection on ways of working were considered key. Areas for improvement included the consistency of information provided to committees by researchers, and better structuring of discussions by allowing signposting of the key issues that ethics committee members might need to consider.

Clinical and Imaging Phenotypes and Outcomes in a Costa Rican Cohort of Acute Ischemic Stroke Survivors: A Retrospective Study.

BACKGROUND: We characterized clinical and imaging phenotypes and their association with clinical outcomes in acute ischemic stroke (AIS) survivors in the understudied region of Costa Rica. METHODS: We conducted a retrospective cohort study in AIS patients treated at a tertiary stroke center in Costa Rica from 2011-2015. Participants underwent detailed phenotyping for cardiovascular risk factors and stroke etiology. We assessed the association of ischemic brain lesion features and clinical outcomes using the Oxfordshire Community Stroke Project (OCSP) classification. RESULTS: We included 684 AIS survivors (60.2% males, aged 68.1 ± 13.6 years, mean ± SD). While the cardiovascular risk profiles and mortality rates of our patients were similar to populations in European and North American countries, only 20.2% of patients with atrial fibrillation (AF) received anticoagulation. On multivariable analysis, patients with total anterior circulation infarct (TACI) displayed an increased risk of complications (OR: 4.2; 95% CI: 2.2-7.8; p < 0.001), higher mortality (OR: 6.9; 95% CI: 2.9-16.1; p < 0.001) and lower chance of functional independence at discharge (OR: 8.9; 95% CI: 4.1-19; p < 0.001) compared to non-TACI. The comorbidity of bronchopneumonia increased the probability of death by 14.5 times. CONCLUSIONS: Our observations in a Costa Rican cohort of AIS survivors might help improve local measures for preventing and managing AIS.

Impact of Transcatheter Aortic Valve Implantation Among Patients With Co-existing Mild to Moderate Mitral Regurgitation.

A subset of patients with severe aortic stenosis (AS) who are who underwent transcatheter aortic valve implantation (TAVI) also has mitral regurgitation (MR). Clinical outcomes in these patients with combined MR and AS have varied. The purpose of this study was to assess clinical outcomes and echocardiographic outcomes after TAVI in patients with preprocedural MR. A retrospective chart review from March 2018 to June 2020 identified all TAVI patients. Patients were assigned an MR class of mild, moderate, or severe based upon pre-TAVI transthoracic echocardiogram (TTE). Patients were excluded if they were discharged from the hospital and did not have a 6-month follow-up after TAVI. Clinical outcomes at 6 months included all-cause mortality, major adverse cardiovascular events, clinically significant bleeding, changes in ejection fraction (EF) category, and changes in MR severity. Of 118 included patients (age 76 ± 10 years, 79% male, 46% White), 33% had MR, with 26% being mild and 7% moderate MR. Before TAVI, AS + MR patients were more likely to have a reduced EF (<50%) by category compared with those with AS only (33.3% vs 8.8%, p = 0.01) but were more likely to show an increase in EF by category after TAVI (19.4% vs 5.5%, p = 0.039). No significant differences were observed between the 2 groups in terms of all-cause mortality (12.8 vs 5.1%, p = 0.14), major adverse cardiovascular events (17.9 vs 8.9%, p = 0.15), or clinically significant bleeding (10.3 vs 6.3%, p = 0.45). Patients with AS and co-existing MR experienced similar clinical outcomes at 6 months to those with AS only after TAVI. They were more likely to show increases in EF category 6 months after valve implantation. Our results support the conclusion that in addition to treating the aortic valve, TAVI also potentially benefits left ventricular function in the setting of mild or moderate MR.

Global intercompany assessment of ICIEF platform comparability for the characterization of therapeutic proteins.

An international team spanning 19 sites across 18 biopharmaceutical and in vitro diagnostics companies in the United States, Europe, and China, along with one regulatory agency, was formed to compare the precision and robustness of imaged CIEF (ICIEF) for the charge heterogeneity analysis of the National Institute of Standards and Technology (NIST) mAb and a rhPD-L1-Fc fusion protein on the iCE3 and the Maurice instruments. This information has been requested to help companies better understand how these instruments compare and how to transition ICIEF methods from iCE3 to the Maurice instrument. The different laboratories performed ICIEF on the NIST mAb and rhPD-L1-Fc with both the iCE3 and Maurice using analytical methods specifically developed for each of the molecules. After processing the electropherograms, statistical evaluation of the data was performed to determine consistencies within and between laboratory and outlying information. The apparent isoelectric point (pI) data generated, based on two-point calibration, for the main isoform of the NIST mAb showed high precision between laboratories, with RSD values of less than 0.3% on both instruments. The SDs for the NIST mAb and the rhPD-L1-Fc charged variants percent peak area values for both instruments are less than 1.02% across different laboratories. These results validate the appropriate use of both the iCE3 and Maurice for ICIEF in the biopharmaceutical industry in support of process development and regulatory submissions of biotherapeutic molecules. Further, the data comparability between the iCE3 and Maurice illustrates that the Maurice platform is a next-generation replacement for the iCE3 that provides comparable data.

Coronary Stent Placement in an Interarterial Anomalous Right Coronary Artery: An Alternative Approach in a Multimorbid High-risk Surgical Patient.

Anomalous aortic origin of a coronary artery is a rare congenital anomaly and potential aetiology for sudden cardiac death. However, the mere presence of this anomaly does not portend clinical significance, and there are many factors that contribute to limiting coronary blood flow in these patients. The standard of care for symptomatic individuals is surgical management with coronary unroofing although not all cases are amenable to surgery. We report the case of an anomalous right coronary artery with interarterial course managed by percutaneous coronary intervention due to surgical contraindication secondary to comorbidities. The proposed mechanism of action culminating in aborted sudden cardiac death is unique and involves aggravated pulmonary hypertension in an individual with severe comorbid pulmonary disease.

Intravenous Thrombolysis by Telestroke in the 3- to 4.5-h Time Window.

Background: While intravenous thrombolysis (IVT) in ischemic stroke can be safely applied in telestroke networks within 3 h from symptom onset, there is a lack of evidence for safety in the expanded 3- to 4. 5-h time window. We assessed the safety and short-term efficacy of IVT in acute ischemic stroke (AIS) in the expanded time window delivered through a hub-and-spoke telestroke network. Methods: Observational study of patients with AIS who received IVT at the Stroke Eastern Saxony Telemedical Network between 01/2014 and 12/2015. We compared safety data including symptomatic intracerebral hemorrhage (sICH; according to European Cooperative Acute Stroke Study II definition) and any intracerebral hemorrhage (ICH) between patients admitted to telestroke spoke sites and patients directly admitted to a tertiary stroke center representing the hub of the network. We also assessed short-term efficacy data including favorable functional outcome (i.e., modified Rankin Scale ≤ 2) and National Institutes of Health Stroke Scale (NIHSS) at discharge, hospital discharge disposition, and in-hospital mortality. Results: In total, 152 patients with AIS were treated with IVT in the expanded time window [spoke sites, n = 104 (26.9%); hub site, n = 48 (25.9%)]. Patients treated at spoke sites had less frequently a large vessel occlusion [8/104 (7.7) vs. 20/48 (41.7%); p < 0.0001], a determined stroke etiology (p < 0.0001) and had slightly shorter onset-to-treatment times [210 (45) vs. 228 (58) min; p = 0.02] than patients who presented to the hub site. Both cohorts did not display any further differences in demographics, vascular risk factors, median baseline NIHSS scores, or median baseline Alberta stroke program early CT score (p > 0.05). There was no difference in the frequency of sICH (4.9 vs. 6.3%; p = 0.71) or any ICH (8.7 vs. 16.7%; p = 0.15). Neither there was a difference regarding favorable functional outcome (44.1 vs. 39.6%; p = 0.6) nor median NIHSS [3 (5.5) vs. 2.5 (5.75); p = 0.92] at discharge, hospital discharge disposition (p = 0.28), or in-hospital mortality (9.6 vs. 8.3%; p = 1.0). Multivariable modeling did not reveal an association between telestroke and sICH or favorable functional outcome (p > 0.05). Conclusions: Delivery of IVT in the expanded 3- to 4.5-h time window through a telestroke network appears to be safe with equivalent short-term functional outcomes for spoke-and-hub center admissions.

Video-Oculography-Assisted Head Impulse Test and Caloric Testing for Detecting Stroke in Acute Vertigo Patients via Modified HINTS Plus.

BACKGROUND: We assessed whether detection of stroke underlying acute vertigo using HINTS plus (head-impulse test, nystagmus type, test of skew, hearing loss) can be improved by video-oculography for automated head-impulse test (V-HIT) analysis. METHODS: We evaluated patients with acute vestibular syndrome (AVS) presenting to the emergency room using HINTS plus and V-HIT-assisted HINTS plus in a randomized sequence followed by cranial MRI and caloric testing. Image-confirmed posterior circulation stroke or vertebrobasilar TIA were the reference standards to calculate diagnostic accuracy. We repeated statistical analysis for a third protocol that was composed post hoc by replacing the head-impulse test with caloric testing in the HINTS plus protocol. RESULTS: We included 30 AVS patients (ages 55.4 ± 17.2 years, 14 females). Of these, 11 (36.7%) had posterior circulation stroke (n = 4) or TIA (n = 7). Acute V-HIT-assisted HINTS plus was feasible and displayed tendentially higher accuracy than conventional HINTS plus (sensitivity: 81.8%, 95% CI 48.2-97.7%; specificity 31.6%, 95% CI 12.6-56.6% vs. sensitivity 72.7%, 95% CI 39.0-94.0%; specificity 36.8%, 95% CI 16.3-61.6%). The new caloric-supported algorithm showed high accuracy (sensitivity 100%, 95% CI 66.4-100%; specificity 66.7%, 95% CI 41-86.7%). CONCLUSIONS: Our study provides pilot data on V-HIT-assisted HINTS plus for acute AVS assessment and indicates the diagnostic value of integrated acute caloric testing.

Serum neurofilament light chain levels are associated with stroke severity and functional outcome in patients undergoing endovascular therapy for large vessel occlusion.

BACKGROUND: We aimed to analyze serum neurofilament light chain (sNfL) levels in patients undergoing endovascular therapy (EVT) for anterior circulation large vessel occlusion (acLVO). METHODS: Prospective study of consecutive patients with acLVO receiving EVT (12/2020-01/2021). sNfL was serially measured prior to and at 30-min, 6-h, 12-h, 24-h, 48-h and 7-days following EVT. ANOVA and Spearman correlation were run to assess sNfL levels (ie, absolute values) and ΔsNfL levels (ie, absolute values subtracted by baseline value) and their association with clinical (ie, NIHSS), imaging (ie, ASPECTS) surrogates of stroke severity as well as functional outcome (ie, mRS) at 90-days. RESULTS: 175 sNfL samples were retrieved from 25 patients. While there were no differences among serial sNfL levels in the first 12-h post-EVT, a constant increase was observed afterwards (maximum day 7, median: 383 [IQR, 209-907] pg/mL, p < 0.001). ΔsNfL showed a constant increase from 30-min measurement onwards peaking after 7 days (median 363.5 [IQR, 114.3-851.1] pg/mL). sNfL levels at 7 days correlated with ASPECTS post-EVT (r = -0.59, p < 0.001), NIHSS at discharge (r = -0.50, p = 0.011) and mRS at 90-days (r = 0.45, p = 0.027). CONCLUSIONS: Serum NFL may complement established clinical and imaging predictors of treatment response and functional outcome in stroke patients undergoing EVT for acLVO.

Randomized Sham-Controlled Pilot Study of Neurocardiac Function in Patients With Acute Ischaemic Stroke Undergoing Heart Rate Variability Biofeedback.

Background: Neurocardiac dysfunction worsens clinical outcome and increases mortality in stroke survivors. We hypothesized that heart rate variability (HRV) biofeedback improves neurocardiac function by modulating autonomic nervous system activity after acute ischaemic stroke (AIS). Methods: We randomly allocated (1:1) 48 acute ischaemic stroke patients to receive nine sessions of HRV- or sham biofeedback over 3 days in addition to comprehensive stroke unit care. Before and after the intervention patients were evaluated for HRV via standard deviation of normal-to-normal intervals (SDNN, primary outcome), root mean square of successive differences between normal heartbeats (RMSSD), a predominantly parasympathetic measure, and for sympathetic vasomotor and sudomotor function. Severity of autonomic symptoms was assessed via survey of autonomic symptom scale total impact score (TIS) at baseline and after 3 months. Results: We included 48 patients with acute ischaemic stroke [19 females, ages 65 (4.4), median (interquartile range)]. Treatment with HRV biofeedback increased HRV post intervention [SDNN: 43.5 (79.0) ms vs. 34.1 (45.0) ms baseline, p = 0.015; RMSSD: 46.0 (140.6) ms vs. 29.1 (52.2) ms baseline, p = 0.015] and alleviated autonomic symptoms after 3 months [TIS 3.5 (8.0) vs. 7.5 (7.0) baseline, p = 0.029], which was not seen after sham biofeedback (SDNN: p = 0.63, RMSSD: p = 0.65, TIS: 0.06). There were no changes in sympathetic vasomotor and sudomotor function (p = ns). Conclusions: Adding HRV biofeedback to standard stroke unit care led to improved neurocardiac function and sustained alleviation of autonomic symptoms after acute ischaemic stroke, which was likely mediated by a predominantly parasympathetic mechanism. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03865225.

Simple and Eco-Friendly Route from Agro-Food Waste to Water Pollutants Removal.

The current study reflects the demand to mitigate the environmental issues caused by the waste from the agriculture and food industry. The crops that do not meet the supply chain requirements and waste from their processing are overfilling landfills. The mentioned wastes contain cellulose, which is the most abundant carbon precursor. Therefore, one of the possibilities of returning such waste into the life cycle could be preparing the activated carbon through an eco-friendly and simple route. Herein, the carrot pulp from the waste was used. Techniques such as thermogravimetric analysis (TGA), elemental analysis (EA), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and x-ray diffraction (XRD) were used to investigate the thermal treatment effect during the carbon material preparation. The development of microstructure, phase formation, and chemical composition of prepared material was evaluated. The obtained carbon material was finally tested for water cleaning from a synthetic pollutant such as rhodamine B and phloxine B. An adsorption mechanism was proposed on the base of positron annihilation lifetime spectroscopy (PALS) results and attributed to the responsible interactions. It was shown that a significant carbon sorbent from the organic waste for water purification was obtained.

Measuring inconsistency in research ethics committee review.

BACKGROUND: The review of human participant research by Research Ethics Committees (RECs) or Institutional Review Boards (IRBs) is a complex multi-faceted process that cannot be reduced to an algorithm. However, this does not give RECs/ IRBs permission to be inconsistent in their specific requirements to researchers or in their final opinions. In England the Health Research Authority (HRA) coordinates 67 committees, and has adopted a consistency improvement plan including a process called "Shared Ethical Debate" (ShED) where multiple committees review the same project. Committee reviews are compared for consistency by analysing the resulting minutes. METHODS: We present a description of the ShED process. We report an analysis of minutes created by research ethics committees participating in two ShED exercises, and compare them to minutes produced in a published "mystery shopper" exercise. We propose a consistency score by defining top themes for each exercise, and calculating the ratio between top themes and total themes identified by each committee for each ShED exercise. RESULTS: Our analysis highlights qualitative differences between the ShED 19, ShED 20 and "mystery shopper" exercises. The quantitative measure of consistency showed only one committee across the three exercises with more than half its total themes as top themes (ratio of 0.6). The average consistency scores for the three exercises were 0.23 (ShED19), 0.35 (ShED20) and 0.32 (mystery shopper). There is a statistically significant difference between the ShED 19 exercise, and the ShED 20 and mystery shopper exercises. CONCLUSIONS: ShED exercises are effective in identifying inconsistency between ethics committees and we describe a scoring method that could be used to quantify this. However, whilst a level of inconsistency is probably inevitable in research ethics committee reviews, studies must move beyond the ShED methodology to understand why inconsistency occurs, and what an acceptable level of inconsistency might be.