Matrix metalloproteinase (MMP)-8 and myeloperoxidase (MPO) may contribute to cerebral damage in acute ischemic stroke. We tested the hypothesis that levels of MPO, MMP-8 and the ratio between MMP-8 ...and its regulator, tissue inhibitor of metalloproteinase (TIMP-1), are increased in acute ischemic stroke and its etiologic subgroups and they correlate with stroke severity.
In a cross-sectional case–control study, serum concentrations of MMP-8, MPO and TIMP-1 were assessed within 24 h after admission in 470 first-ever ischemic stroke patients and 809 age- and sex-matched controls, randomly selected from the population. Odds ratios (OR) per decade of log transformed dependent variables were calculated and adjusted for age, sex and vascular risk factors.
Levels of MMP-8 (OR 4.9; 95% CI 3.4–7.2), MMP-8/TIMP-1 ratio (3.0; 2.2–4.1) and MPO (6.6; 4.0–11.0) were independently associated with ischemic stroke. MMP-8 levels differed between etiologic stroke subgroups (p = 0.019, ANOVA), with higher levels in cardioembolic stroke and stroke due to large vessel disease, and lower levels in microangiopathic stroke. MMP-8, MMP-8/TIMP-1 ratio and MPO (p < 0.001) concentrations showed positive associations with stroke severity independent of stroke etiology.
Concentrations of serum neutrophil markers are increased after ischemic stroke and associate with stroke severity and etiology. The value of these biomarkers in diagnostics and prognostics is worth being evaluated.
•Serum concentrations of inflammatory biomarkers are significantly higher in acute ischemic stroke cases as compared to controls.•Serum levels of MMP-8 and MPO are strongly associated with stroke severity.•The value of these biomarkers in diagnostics and prognostics is worth being evaluated.
The association between socioeconomic status in adulthood and the risk of stroke is well established; however, the independent effects of socioeconomic conditions in different life phases are less ...understood.
Within a population-based stroke registry, we performed a case-control study with 470 ischemic stroke patients (cases) aged 18 to 80 years and 809 age- and sex-matched stroke-free controls, randomly selected from the population (study period October 2007 to April 2012). We assessed socioeconomic conditions in childhood, adolescence, and adulthood, and developed a socioeconomic risk score for each life period.
Socioeconomic conditions were less favorable in cases regarding paternal profession, living conditions and estimated family income in childhood, school degree, and vocational training in adolescence, last profession, marital status and periods of unemployment in adulthood. Using tertiles of score values, low socioeconomic conditions during childhood (odds ratio 1.77; 95% confidence interval 1.20-2.60) and adulthood (odds ratio 1.74; 95% confidence interval 1.16-2.60) but not significantly during adolescence (odds ratio 1.64; 95% confidence interval 0.97-2.78) were associated with stroke risk after adjustment for risk factors and other life stages. Medical risk factors attenuated the effect of childhood conditions, and lifestyle factors reduced the effect of socioeconomic conditions in adolescence and adulthood. Unfavorable childhood socioeconomic conditions were particularly associated with large artery atherosclerotic stroke in adulthood (odds ratio 2.13; 95% confidence interval 1.24-3.67).
This study supports the hypothesis that unfavorable childhood socioeconomic conditions are related to ischemic stroke risk, independent of established risk factors and socioeconomic status in adulthood, and fosters the idea that stroke prevention needs to begin early in life.
Antibodies against glutamic acid decarboxylase (GAD-abs) at high serum levels are associated with diverse autoimmune neurological syndromes (AINS), including cerebellar ataxia, epilepsy, limbic ...encephalitis and stiff-person syndrome. The impact of low serum GAD-ab levels in patients with suspected AINS remains controversial. Specific intrathecal GAD-ab synthesis may serve as a marker for GAD-ab-associated nervous system autoimmunity. We present characteristics of a multicentric patient cohort with suspected AINS associated with GAD antibodies (SAINS-GAD+) and explore the relevance of serum GAD-ab levels and intrathecal GAD-ab synthesis.
All patients with SAINS-GAD+ included in the registry of the German Network for Research on Autoimmune Encephalitis (GENERATE) from 2011 to 2019 were analyzed. High serum GAD-ab levels were defined as RIA>2000 U/mL, ELISA>1000 U/mL, or as a positive staining pattern on cell-based assays.
One-hundred-one patients were analyzed. In descending order they presented with epilepsy/limbic encephalitis (39%), cerebellar ataxia (28%), stiff person syndrome (22%), and overlap syndrome (12%). Immunotherapy was administered in 89% of cases with improvements in 46%. 35% of SAINS-GAD+ patients had low GAD-ab serum levels. Notably, unmatched oligoclonal bands in CSF but not in serum were more frequent in patients with low GAD-ab serum levels. GAD-ab-levels (high/low) and intrathecal GAD-ab synthesis (present or not) did not impact clinical characteristics and outcome.
Overall, immunotherapy in SAINS-GAD+ was moderately effective. Serum GAD-ab levels and the absence or presence of intrathecal GAD-ab synthesis did not predict clinical characteristics or outcomes in SAINS-GAD+. The detection of unmatched oligoclonal bands might outweigh low GAD-ab serum levels.
•Immunotherapy is moderately effective neurological syndromes with GAD-antibodies.•Serum GAD-antibody levels does not predict clinical characteristics or outcomes.•The detection of oligoclonal bands might outweigh low GAD- antibody serum levels.
Abstract
Background
Risk diseases and risk factors for stroke include atrial fibrillation, hypertension, diabetes mellitus, smoking, and elevated LDL-cholesterol. Due to modern treatment options, the ...impact of these risk diseases on subsequent cardiovascular events or death after a first stroke is less clear and needs to be elucidated. We therefore aimed to get insights into the persistence of adverse prognostic effects of these risk diseases and risk factors on subsequent stroke or death events 1 year after the first stroke by using the new weighted all-cause hazard ratio.
Methods
This study evaluates the 1 year follow-up of 470 first ever stroke cases identified in the area of Ludwigshafen, Germany, with 23 deaths and 34 subsequent stroke events. For this purpose, the recently introduced “weighted all-cause hazard ratio” was used, which allows a weighting of the competing endpoints within a composite endpoint. Moreover, we extended this approach to allow an adjustment for covariates.
Results
None of these risk factors and risk diseases, most probably being treated after the first stroke, remained to be associated with a subsequent death or stroke weighted hazard ratios (95% confidence interval) for diabetes mellitus, atrial fibrillation, high cholesterol, hypertension, and smoking are 0.4 (0.2–0.9), 0.8 (0.4–2.2), 1.3 (0.5–2.5), 1.2 (0.3–2.7), 1.6 (0.8–3.6), respectively. However, when analyzed separately in terms of death and stroke, the risk factors and risk diseases under investigation affect the subsequent event rate to a variable degree.
Conclusions
Using the new weighted hazard ratio, established risk factors and risk diseases for the occurrence of a first stroke do not remain to be significant predictors for subsequent events like death or recurrent stroke. It has been demonstrated that the new weighted hazard ratio can be used for a more adequate analysis of cardiovascular risk and disease progress. The results have to be confirmed within a larger study with more events.
This study aimed at comparing clinical outcome, recanalization success and time metrics in the "drip and ship" (DS) vs. "drive the doctor" (DD) concept in a comparable setting.
This is a ...retrospective analysis of thrombectomy registries of a comprehensive stroke center (CSC) and a thrombectomy-capable stroke center (TSC). Patients, who were transferred from the TSC to the CSC, were classified as DS. Patients treated at the TSC by an interventionalist transferred from the CSC were classified as DD. Good outcome was defined as mRS 0-2 or equivalent to premorbid mRS at discharge. Recanalization (TICI 2b-3 or equivalent) and time metrics were compared in both groups.
In total, 295 patients were included, of which 116 (39.3%) were treated in the DS concept and 179 (60.7%) in the DD concept. Good clinical outcome was similarly achieved in DS and DD (DS 25.0% vs. DD 31.3%,
= 0.293). mRS on discharge (DS median 4, DD median 4,
= 0.686), NIHSS improvement (DS median 4, DD median 5,
= 0.582) and NIHSS on discharge (DS median 9, DD median 7,
= 0.231) were similar in both groups. Successful reperfusion was achieved similarly in DS (75.9%) and DD as well (81.0%,
= 0.375). Time from onset to reperfusion (median DS 379 vs. DD 286 min,
= 0.076) and time from initial imaging to reperfusion were longer in DS compared to DD (median DS 246 vs. DD 162 min,
< 0.001).
The DD concept is time saving while achieving similar clinical outcome and recanalization results.
Physical activity (PA) is associated with lower risk of stroke. We tested the hypothesis that lack of pre-stroke PA is an independent predictor of poor outcome after first-ever ischemic stroke.
We ...assessed recent self-reported PA and other potential predictors for loss of functional independence - modified Rankin Scale (mRS) > 2 - one year after first-ever ischemic stroke in 1370 patients registered between 2006 and 2010 in the Ludwigshafen Stroke Study, a population-based stroke registry.
After 1 year, 717 (52.3%) of patients lost their independence including 251 patients (18.3%) who had died. In multivariate logistic regression analysis lack of regular PA prior to stroke (Odds Ratio (OR) 1.7, Confidence Interval (CI) 1.1-2.5), independently predicted poor outcome together with higher age (65-74: OR 1.7; CI 1.1-2.8, 75-84 years: OR 3.3; CI 2.1-5.3; ≥85 years OR 14.5; CI 7.4-28.5), female sex (OR 1.5; CI 1.1-2.1), diabetes mellitus (OR 1.8; CI 1.3-2.5), stroke severity (OR 1.2; CI 1.1-1.2), probable atherothrombotic stroke etiology (OR 1.8; CI 1.1-2.8) and high leukocyte count (> 9.000/mm
; OR 1.4; CI 1.0-1.9) at admission. Subclassifying unknown stroke etiology, embolic stroke of unknown source (ESUS; n = 40, OR 2.2; CI 0.9-5.5) tended to be associated with loss of independence.
In addition to previously reported factors, lack of PA prior to stroke as potential indicator of worse physical condition, high leukocyte count at admission as indicator of the inflammatory response and probable atherothrombotic stroke etiology might be independent predictors for non-functional independence in first-ever ischemic stroke.
At present, "severe acute respiratory syndrome new coronavirus" (SARS-CoV-2) affects the whole world and has led to a pandemia with almost 2.000.000 infected patients in the mid of April 2020 (WHO). ...Thus, health care specialists primarily focus on therapy of corona disease 2019 (COVID-19) and a lot of effort has been undertaken to get more manpower on intensive care units. However, the number of patients with life threatening diseases other than COVID-19 like heart attacks or strokes has not changed at all. With a strong focus on COVID-19, there is a marked risk of diagnostic and therapeutic delays or misdiagnoses, potentially harming those patients. In this respect, we present two of those cases with the intent to improve the medical management of
" diseases in times of corona pandemia.
We present two patients with diseases others than SARS-CoV-2. Both cases were treated in our institution, a tertiary care hospital in the Southwest of Germany.
One patient had a prolonged treatment on intensive care unit (ICU) because of heart failure following voluntary isolation because of fearing COVID-19 and subsequent shortage of medication. Another patient with hypothesis of COVID-19 of primary care physician because of fever and a history of skiing in a high risk region for SARS-CoV-2 was sent home for isolation. After disease progression, the patient presented in an external hospital with fever, pain in the right ear and tachypnea. Immediately, antibiotics were started at same day, but nevertheless, he developed a septic shock, leading to multi organ failure. In blood samples, bacteria
was found, without any signs of SARS-CoV-2-infection. Despite adequate antibiosis, the patient developed fixed pupils, brain edema and died because of massive brain edema.
Focusing only on COVID-19 may lead to delayed diagnosis and therapy in patients with "traditional diseases". These two cases impressively clarify medical challenges in times of SARS-CoV-2 pandemia. It is important to emphasize that physicians and health care professionals have not only to focus on COVID-19 and virus associated diseases, but also on adequate drug supply, intake and monitoring and differential diagnoses, respectively.
Stroke is among the most common causes of death and persisting disability and therefore represents a great social and economic burden worldwide. In order to lower this burden it is essential to ...identify risk factors and respective preventive strategies. Besides the established stroke risk factors (e.g. hypertension, diabetes, hypercholesterolemia, atrial fibrillation) both acute and chronic infectious diseases have emerged as risk factors for stroke. Mainly acute respiratory tract infection but also urinary tract infections independently increase the risk of ischemic stroke. Such additional risk was shown to be highest for infection within 3 days before ischemia and the risk steadily declines with increasing time intervals between infection and stroke. Associations between stroke incidence and mortality and influenza epidemics have been demonstrated. Observational studies showed an inverse association between influenza vaccination and stroke risk; however, interventional studies in this field have not been performed so far. Chronic infections, presently discussed as stroke risk factors mainly include periodontitis and infections with Helicobacter pylori (Hp) and Chlamydia pneumoniae (Cp). Although most respective studies identified these infectious diseases as independent stroke risk factors interventional trials have not been performed so far and causality is not proven, yet. There is preliminary evidence that the number of pathogens to which a subject had been exposed to rather than single pathogens are associated with the risk of stroke or other cardiovascular diseases. Chronic infectious diseases are treatable conditions and their identification as causal contributors to stroke risk could offer new avenues in stroke prevention.
Disadvantageous socioeconomic conditions (SEC) in both childhood and adulthood increase the risk of stroke. We investigated whether intergenerational and lifetime social advancement decreases and/or ...social descent increases stroke risk.
In a case-control study with 466 patients with first-ever ischemic stroke and 807 controls randomly selected from the general population, we compared paternal profession to subjects' professional education in adolescence and their last profession in adulthood. Furthermore, we constructed a socioeconomic risk score for childhood (based on paternal and maternal profession and occupation, familial, living and material conditions), adolescence (based on highest school degree and professional education), and adulthood (based on last profession, periods of unemployment, and marital status), and compared subjects´ positions at different life stages. Odds ratios were derived based on conditional logistic regression conditioning on age and sex only, after adjustment for medical and lifestyle risk factors, and after additional adjustment for socioeconomic risk score values.
Intergenerational upward mobility between paternal profession and subject's professional education was associated with lower ischemic stroke risk independent of medical and lifestyle risk factors (odds ratio (OR) 0.58; 95% confidence interval (CI) 0.41-0.81) and after additional adjustment for socioeconomic conditions in all three life stages (OR 0.67; 95% CI 0.45-0.99). Advancement between fathers´ profession and subject's last profession was associated with reduced odds of stroke after adjustment for risk factors (OR 0.65; 95% CI 0.47-0.89), but not significantly after additional adjustment for SEC (OR 0.77; 95% CI 0.52-1.13). Social descent between adolescence and adulthood indicated by the transition into a more disadvantageous tertile of socioeconomic risk score was associated with increased odds of stroke after adjustment for all risk factor (OR 2.93; 95% CI 1.21-7.13). Analyses by sex revealed mostly similar results in men and women with only few potential differences.
Our study results indicate that aspects of social downward mobility during adulthood may be associated with increased risk of stroke, whereas intergenerational upward mobility may be linked to a lower stroke risk. If confirmed by future studies, such results may help to focus stroke prevention measures at high risk populations.
Socioeconomic conditions may strongly influence the risk of stroke. We tested the hypotheses that indexes of social status in different life periods including childhood are inversely associated with ...stroke risk and that there is a cumulative effect of social conditions during lifetime on the risk of stroke. Furthermore, we investigated whether social advancement compared to the parental generation is associated with reduced stroke risk.
In a case-control study, we assessed parental professional status, highest school degree, professional education and the last professional activity in 370 consecutive patients with ischemic or hemorrhagic stroke or transient ischemic attack TIA; age 60.7 ± 12.8 years (mean ± standard deviation); 31.1% women and 370 age- and sex-matched control subjects randomly selected from the general population of the same area.
Higher level of school exams odds ratio (OR) 0.58, 95% confidence interval (CI) 0.39-0.86, university or polytechnic high school degrees (OR 0.39, 95% CI 0.24-0.63), nonmanual (last or current) professional activity (OR 0.51, 95% CI 0.37-0.71) and father's nonmanual professional activity (OR 0.64, 95% 0.43-0.97) were associated with a lower risk of stroke/TIA. Adjustment for vascular risk factors including current smoking and alcohol consumption reduced the strength of these associations and rendered them nonsignificant except for university or polytechnic high school degrees (OR 0.49, 95% CI 0.27-0.87). Additional adjustment for regular sports activity further attenuated the association between academic degrees and risk of stroke/TIA (OR 0.56, 95% CI 0.31-1.02). A score summarizing 4 lifetime social indexes was not independently associated with stroke risk (OR 0.67, 95% CI 0.39-1.16). Social advancement as assessed by changes from paternal manual work to nonmanual work in the index generation was more common among control subjects (23.5%) than patients (15.3%; p = 0.0097), but such advancement was not independently associated with stroke/TIA after adjustment for all covariables (OR 0.82, 95% CI 0.50-1.33).
Socioeconomic conditions were inversely linked to the risk of stroke/TIA. These associations were strongly influenced by lifestyle factors such as smoking, alcohol consumption and mainly sports activity. Stroke preventive strategies may have a particularly large potential if they focus on such lifestyle habits in socially disadvantaged groups.
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