Conjugation of small ubiquitin-like modifier (SUMO) to substrates is involved in a large number of cellular processes. Typically, SUMO is conjugated to lysine residues within a SUMO consensus site; ...however, an increasing number of proteins are sumoylated on non-consensus sites. To appreciate the functional consequences of sumoylation, the identification of SUMO attachment sites is of critical importance. Discovery of SUMO acceptor sites is usually performed by a laborious mutagenesis approach or using MS. In MS, identification of SUMO acceptor sites in higher eukaryotes is hampered by the large tryptic fragments of SUMO1 and SUMO2/3. MS search engines in combination with known databases lack the possibility to search MSMS spectra for larger modifications, such as sumoylation. Therefore, we developed a simple and straightforward database search tool (“ChopNSpice”) that successfully allows identification of SUMO acceptor sites from proteins sumoylated in vivo and in vitro. By applying this approach we identified SUMO acceptor sites in, among others, endogenous SUMO1, SUMO2, RanBP2, and Ubc9.
Nocebo effects describe all negative outcomes for well-being brought about by negative health-related expectations. Media coverage of drug side effects can fuel nocebo effects and lead to increased ...symptom reports. This retrospective observational analysis of emergency reports at the neurological emergency room at University Hospital Essen, Germany, examines whether media communication about a cumulation of very rare cases of cerebral venous sinus thrombosis (CVST) after COVID-19 vaccination with the AstraZeneca compound (ChAdOx-1 nCoV-19) was followed by an increase in weekly presentation rates of patients with the main complaint of headache, a symptom commonly occurring as a vaccination reaction but also communicated as a warning symptom for CVST. The rate of headache presentations increased by 171.7% during the five weeks after the first announcement of CVSTs in Germany on 11 March 2021, compared to the five weeks immediately prior. Furthermore, more young women sought consultation for headache, reflecting the communicated at-risk profile for CVST. The increased rate of headache presenters contributed to a 32.1% rise in total neurological emergency cases, causing an increased strain on the emergency facility after the side effect risk was publicized. We discuss a causal role of negative side effect expectations after vaccination with AstraZeneca as a driver for this increase. While transparent communication about benefits and potential side effects is crucial for vaccination acceptance, increased vigilance toward nocebo effects in health-related media communication is needed due to its potential harm to the individual and society, especially when emergency medical resources are stretched thin.
Multimodal endovascular therapy (EVT) of carotid cavernous fistula (CCF) with different approaches and a variety of available embolization material enable high occlusion rates with good clinical and ...functional outcome but until now there is still little evidence available. This retrospective single-center study aims to evaluate EVT of CCF with different neuroendovascular techniques regarding occlusion rates, complications and outcomes.
From 2001 to 2021 59 patients with CCF were treated at our tertiary university hospital. Patient records and all imaging data including angiograms were reviewed for demographic and epidemiological data, symptoms, fistula type, number of EVTs, complications of EVT, type of embolic materials, occlusion rates and recurrences.
Etiology of the CCF were spontaneous (41/59, 69.5%) post-traumatic (13/59, 22%) and ruptured cavernous aneurysms (5/59, 8.5%). Endovascular therapy was completed in one session in 74.6% (44/59). Transvenous access was most frequent (55.9% 33/59) followed by transarterial catheterization in 33.9% (20/59) and a combination of both (6/59, 10.2%). Exclusively coils were used in 45.8% (27/59), a combination of ethylene vinyl alcohol (EVOH) copolymer (Onyx) and coils in 42.4% (25/59). Complete obliteration was achieved in 96.6% of patients (57/59) with an intraprocedural-related complication rate of 5.1% (3/59) and no mortality.
Endovascular therapy of CCF has been shown to be safe and effective with high cure rates and low rates of intraprocedural complications and morbidity even in complex scenarios.
We report a case of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated encephalomyelitis following vector-based vaccination against SARS-CoV-2 that mimicked bacterial meningomyelitis ...upon initial presentation. A 43-year-old woman who had received a first dose of ChAdOx1 nCoV-19 (Vaxzevria; Astra Zeneca, UK Limited) 9 days earlier presented with subacute sensorimotor paraparesis, urinary retention, headache, meningism, and fever. Clinical findings and cerebrospinal fluid (CSF) features were highly suggestive of bacterial infection; however, despite receiving broad anti-infective treatment alongside with high-dose glucocorticoids, symptoms deteriorated. Imaging findings and the detection of immunoglobulin G against MOG substantiated diagnosis of an anti-MOG associated disorder. Treatment with high-dose intravenous (IV) methylprednisolone and plasma exchange resulted in substantial clinical improvement, which sustained under monthly regimen of IV Tocilizumab at 3-month follow-up. Awareness of this post-vaccinal presentation of a rare autoimmune disorder is important to not miss potential treatment options.
Abstract
Background
The modified Rankin scale (mRS) at 3 months is established as the primary outcome measure in clinical stroke trials. Traditionally, the mRS is assessed through an unstructured ...face-to-face interview. This approach can be labor-intensive and lead to suboptimal inter-rater reliability. Recently, the Covid-19 pandemic made face-to-face contact even more challenging. To address these issues, we developed and validated a structured German-language questionnaire for mRS testing by telephone.
Methods
In this prospective cohort study, we compared the mRS testing results of the standard face-to-face interview with those obtained in a structured interview by telephone using Cohen’s Kappa.
Results
At our tertiary care stroke center, we included 108 patients who underwent both assessments. In 80.6% of cases (87/108) face-to-face and telephone interview reached identical scores. Linear weighted Kappa was 0.82 (
p
< 0.001). Unweighted Kappa for dichotomized mRS between fair (0–2) and poor (3–6) functional outcome was κ = 0.97 (
p
< 0.001).
Conclusions
Our study validates the use of the German-language structured telephone interview as a reliable instrument for the use in clinical trials. We encourage others to utilize the questionnaire. It is available as an Appendix (Additional file 1) to this publication.
Background and Purpose:
Large vessel occlusion (LVO) recognition scales were developed to identify patients with LVO-related acute ischemic stroke (AIS) on the scene of emergency. Thus, they may ...enable direct transport to a comprehensive stroke centre (CSC). In this study, we aim to validate a smartphone app-based stroke triage with a shortened form of the Field Assessment Stroke Triage for Emergency Destination (FAST-ED).
Methods:
This retrospective validation study included 2815 patients with confirmed acute stroke and suspected acute stroke but final diagnosis other than stroke (stroke mimics) who were admitted by emergency medical service (EMS) to the CSC of the Neurological University Hospital Essen, Germany. We analysed the predictive accuracy of a shortened digital app-based FAST-ED ( ‘FAST-ED App’) for LVO-related AIS and yield comparison to various other LVO recognition scales.
Results:
The shortened FAST-ED App had comparable test quality (Area under ROC = 0.887) to predict LVO-related AIS to the original FAST-ED (0.889) and RACE (0.883) and was superior to Cincinnati Prehospital Stroke Severity (CPSS), 3-Item Stroke Scale (3-ISS) and National Institute of Health Stroke Scale (NIHSS). A FAST-ED App ⩾ 4 revealed very good accuracy to detect LVO related AIS (sensitivity of 77% and a specificity 87%) with an area under the curve c-statistics of 0.89 (95% CI: 0.87–0.90). In a hypothetical triage model, the number needed to screen in order to avoid one secondary transportation in an urban setting would be five.
Conclusion:
This validation study of a shortened FAST-ED assessment for a smartphone-app guided stroke triage yields good quality to identify patients with LVO.
This paper shows characteristics of mental illness and its economic impact, as well as various cost-estimating approaches and insights in missed economic opportunities. To assess the burden of ...economic diseases, there are three different ways: the human capital, the economic growth and the value of statistical life approach. The first focuses on indirect and direct costs. Direct costs are frequently associated with care and recovery, indirect costs apply to the "invisible costs" correlated with revenue loss due to death, injury, treatment and a fading productivity. The global financial costs of mental illness were evaluated at US$2.5 trillion, with a significantly bigger impact of indirect costs. Moreover, the effect of mental illness on economic development can only be approximated implicitly. Thus, the lack of production is primary estimated for somatic conditions compared to their corresponding quantity of disability-adjusted life years (DALYs). According to some research, the total economic productivity drop associated with mental illnesses between 2011 and 2030 is estimated to be US$16.3 trillion globally. Furthermore, the value of statistical life (VSL) method suggests that trade-offs between risks and capital should be used to assess the probability of injury or death due to psychiatric illness. This computation, like the economic increase effect, is equivalent to that of cardiovascular disease and bigger than that of chronic respiratory disease, cancer, and diabetes. However, greater activism is required to better the existing condition. This involves a shift in thinking away from stigmatizing mentally ill people and supports the activation of financial resources.
Purpose
This study retrospectively examined the extent to which computed tomography angiography (CTA) and digital subtraction angiography (DSA) can help identify the cause of lobar intracerebral ...bleeding.
Materials and methods
In the period from 2002 to 2020, data from patients who were >18 years at a university and an academic teaching hospital with lobar intracerebral bleeding were evaluated retrospectively. The CTA DSA data were reviewed separately by two neuroradiologists, and differences in opinion were resolved by consensus after discussion. A positive finding was defined as an underlying vascular etiology of lobar bleeding.
Results
The data of 412 patients were retrospectively investigated. DSA detected a macrovascular cause of bleeding in 125/412 patients (33%). In total, sixty patients had AVMs (15%), 30 patients with aneurysms (7%), 12 patients with vasculitis (3%), and 23 patients with dural fistulas (6%). The sensitivity, specificity, positive and negative predictive values, and accuracy of CTA compared with DSA were 93, 97, 100, and 97%. There were false-negative CTA readings for two AVMs and one dural fistula.
Conclusion
The DSA is still the gold standard diagnostic modality for detecting macrovascular causes of ICH; however, most patients with lobar ICH can be investigated first with CTA, and the cause of bleeding can be found. Our results showed higher sensitivity and specificity than those of other CTA studies.
Baseline values and the change of platelet count (PLT) during disease were reported to be associated with prognosis of patients with cancer and intensive care treatment. We aimed to evaluate the ...association between PLT with the course and prognosis of aneurysmal subarachnoid hemorrhage (SAH).
Admission (AdmPLT) and the 14-days mean PLT (MeanPLT) values of 763 SAH patients treated between 01/2005 and 06/2016 were recorded and, for further analysis, divided into four categories: <150, 150–260, 261–400 and > 400 × 109/L. Primary endpoints were cerebral infarcts in follow-up computed tomography scans, in-hospital mortality and unfavorable outcome at 6-months follow-up defined as modified Rankin scale>3. Adverse events during SAH were assessed as secondary endpoints.
Higher PLT values were independently associated with lower risk of cerebral infarction (MeanPLT: aOR = 0.65 per-PLT-category-increase, p = 0.001), in-hospital mortality (AdmPLT: aOR = 0.64, p = 0.017; MeanPLT: aOR = 0.23, p < 0.0001) and unfavorable outcome (AdmPLT: aOR = 0.70, p = 0.031; MeanPLT: aOR = 0.35, p < 0.0001). Moreover, individuals with poorer outcome were less prone to PLT increase during SAH (mean values: -+20.3 vs + 30.5 × 109/L for cerebral infarction; +9.3 vs + 32.8 × 109/L for in-hospital mortality; +14.4 vs + 31.1 × 109/L for unfavorable outcome). The following adverse events during SAH were related to AdmPLT and/or MeanPLT: non-aneurysm related secondary rebleeding, intracranial hypertension requiring conservative treatment or decompressive craniectomy, sepsis and acute kidney failure.
Low PLT at admission and their less prominent increase during SAH were strongly linked with poor outcome of SAH. Further analysis is required to clarify the background of this association and potential therapeutic implications.
Background:
Despite the high incidence of acute ischemic stroke (AIS) in cancer patients, there is still no consensus about the safety of recanalization therapies in this cohort.
Objectives:
In this ...observational study, our aim was to investigate the bleeding risk after acute recanalization therapy in AIS patients with active malignancy.
Methods and Study Design:
We retrospectively analyzed observational data of 1016 AIS patients who received intravenous thrombolysis with rtPA (IVT) and/or endovascular therapy (EVT) between January 2017 and December 2020 with a focus on patients with active malignancy. The primary safety endpoint was the occurrence of stroke treatment-related major bleeding events, that is, symptomatic intracranial hemorrhage (SICH) and/or relevant systemic bleeding. The primary efficacy endpoint was neurological improvement during hospital stay (NI).
Results:
None of the 79 AIS patients with active malignancy suffered from stroke treatment-related systemic bleeding. The increased rate (7.6% versus 4.7%) of SICH after therapy compared to the control group was explained by confounding factors. A total of nine patients with cerebral tumor manifestation received acute stroke therapy, two of them suffered from stroke treatment-related intracranial hemorrhage remote from the tumor, both asymptomatic. The group of patients with active malignancy and the control group showed comparable rates of NI.
Conclusion:
Recanalization therapy in AIS patients with active malignancy was not associated with a higher risk for stroke treatment-related systemic or intracranial bleeding. IVT and/or EVT can be regarded as a safe therapy option for AIS patients with active malignancy.
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