Different Influence Pattern of Conventional and Alternative Sources of Smoking on Adhesion Molecules and Cytokine Secretion in THP-1 Monocytes.

BACKGROUND/AIM: Tobacco is a carcinogen that is closely associated with the occurrence of lung cancer and head and neck squamous cell carcinoma (HNSCC). The consumption of tobacco is also leading to alterations in different immune cell subtypes. However, the impact of different conventional and alternative smoking sources on human monocytes remains elusive. MATERIALS AND METHODS: In this study, we investigated the influence of aqueous extracts of different sources of smoking (cigarettes; heated tobacco product IQOS; e-cigarettes with and without nicotine; nicotine pouches) on different monocytic adhesion molecules, chemokine receptors and checkpoint molecule PD-L1 by flow cytometry. Cytokine expression patterns were evaluated using human cytokine arrays and the human monocyte leukemia cell line THP-1 as a model. RESULTS: Data revealed differential effects of the analyzed conventional and alternative smoking devices on monocyte adhesion molecules and cytokine secretion. The examined smoking devices can be assigned to two differential monocyte activation patterns. Monocytes stimulated with aqueous extracts of cigarettes, e-cigarette without nicotine, and heat not burn product IQOS revealed distinct alterations of surface markers and cytokines compared to the monocyte activation pattern in response to aqueous extracts of nicotine, nicotine pouches, and e-cigarette with nicotine. CONCLUSION: Our data indicate differential immunological consequences of different conventional and alternative smoking sources with and without nicotine. Further comprehensive analysis as well as in vivo investigations on peripheral blood monocyte subsets from smoking individuals using different smoking sources are required to better understand the impact on monocyte characteristics, especially with regard to the development of cancer.

Differential Effects of Anti-PD-1/PD-L1 Checkpoint Inhibitors on Adhesion Molecules and Cytokine Secretion by THP-1 Monocytes.

BACKGROUND/AIM: Immune checkpoint inhibitors have improved the treatment regimen for human cancers in recent years. Particularly, inhibitors of the checkpoint molecules PD-1/PD-L1 have emerged as promising therapeutic treatments by preventing T-cell anergy and exhaustion. However, the impact of different anti-PD-1/PD-L1 checkpoint inhibitors on human monocytes remains elusive. MATERIALS AND METHODS: In this study, using the human monocyte leukemia cell line THP-1 as a model, we investigated the influence of different therapeutic anti-PD-1/PD-L1 checkpoint inhibitors on monocytic adhesion molecule expression and cytokine secretion. THP-1 monocytes were treated with the anti-PD-1 checkpoint inhibitors Nivolumab and Pembrolizumab and anti-PD-L1 checkpoint inhibitors Atezolizumab and Durvalumab. Cytokine expression patterns were evaluated using cytokine arrays and enzyme-linked immunosorbent assays (ELISA) and analysis of adhesion molecules was addressed using flow cytometry. RESULTS: Our data show an overall moderate apoptosis induction upon checkpoint inhibitor treatment and significantly reduced expression levels of adhesion molecules CD29, CD49d, and CX3CR1 in response to anti-PD-1 treatment. Cytokine screening revealed overall decreased secretion levels of insulin-like growth factor binding protein 2 (IGFBP2), CD147 (basigin) and CD31 (PECAM-1) as well as elevated levels of interleukin 5 (IL-5) and interferon gamma (IFNγ) in response to checkpoint inhibitor treatment. CONCLUSION: Our data indicate differential effects of anti-PD-1/PD-L1 checkpoint inhibitors on THP-1 monocytes, both by specific anti-PD-1/PD-L1 binding and unspecific antibody IgG isotype recognition. Further investigations on peripheral blood monocyte subsets in terms of their expansion and function upon checkpoint inhibitor therapy are required to better understand the individual immunological balances in cancer patients in long-term observational studies.

Multidisciplinary and standardized management of patients with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

BACKGROUND: The appropriate management of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) remains uncertain. We aimed to evaluate the effect of implementing a standardized protocol for detection and management of DCI after aSAH on cerebral infarction and functional outcome. METHODS: We studied two cohorts of aSAH patients, one before (pre-implementation cohort: January 2012 to August 2014) and one after (post-implementation cohort: January 2016 to July 2018) implementation of a multidisciplinary approach, with standardized neurological and radiological assessment and risk-based medical treatment of DCI. We assessed the presence of new hypodensities on CT within 6 weeks after aSAH and categorized cerebral infarction into overall and DCI-related infarctions (hypodensities not within 48 h after IA repair and not attributable to aneurysm occlusion or intraparenchymal hematoma). Functional outcome was assessed at 3 months using the extended Glasgow outcome scale (eGOS), dichotomized into unfavorable (eGOS: 1-5) and favorable (eGOS: 6-8). We calculated odds ratios (OR) with corresponding 95% confidence intervals (CI's), and adjusted for age, WFNS grade, Fisher score, and treatment modality (aOR). RESULTS: In the post-implementation (n = 158) versus the pre-implementation (n = 143) cohort the rates for overall cerebral infarction were 29.1% vs 46.9% (aOR: 0.41 [0.24-0.69]), for DCI-related cerebral infarction 17.7% vs. 31.5% (aOR: 0.41 [0.23-0.76]), and for unfavorable functional outcome at 3 months 37.3% vs. 53.8% (aOR: 0.30 [0.17-0.54]). For patients with DCI, the rates for unfavorable functional outcomes at 3 months in the post-implementation versus the pre-implementation cohort were 42.3% vs. 77.8% (aOR: 0.1 [0.03-0.27]). CONCLUSIONS: A multidisciplinary approach with more frequent and standardized neurological assessment, standardized CT and CT perfusion monitoring, as well as tailored application of induced hypertension and invasive rescue therapy strategies, is associated with a significant reduction of cerebral infarction and unfavorable functional outcome after aneurysmal aSAH.

Plasma-based S100B testing for management of traumatic brain injury in emergency setting.

BACKGROUND: Serum biomarker S100B has been explored for its potential benefit to improve clinical decision-making in the management of patients suffering from traumatic brain injury (TBI), especially as a pre-head computed-tomography screening test for patients with mild TBI. Although being already included into some guidelines, its implementation into standard care is still lacking. This might be explained by a turnaround time (TAT) too long for serum S100B to be used in clinical decision-making in emergency settings. METHODS: S100B concentrations were determined in 136 matching pairs of serum and lithium heparin blood samples. The concordance of the test results was assessed by linear regression, Passing Pablok regression and Bland-Altman analysis. Bias and within- and between-run imprecision were determined by a 5 × 4 model using pooled patient samples. CT scans were performed as clinically indicated. RESULTS: Overall, S100B levels between both blood constituents correlated very well. The suitability of S100B testing from plasma was verified according to ISO15189 requirements. Using a cut-off of 0.105 ng/ml, a sensitivity and negative predictive value of 100% were obtained for identifying patients with pathologic CT scans. Importantly, plasma-based testing reduced the TAT to 26 min allowing for quicker clinical decision-making. The clinical utility of integrating S100B in TBI management is highlighted by two case reports. CONCLUSIONS: Plasma-based S100B testing compares favorably with serum-based testing, substantially reducing processing times as the prerequisite for integrating S100B level into management of TBI patients. The proposed new clinical decision algorithm for TBI management needs to be validated in further prospective large-scale studies.

Tissue Sodium Concentration within White Matter Correlates with the Extent of Small Vessel Disease.

INTRODUCTION: Sodium MRI (23Na MRI) derived biomarkers such as tissue sodium concentration (TSC) provide valuable information on cell function and brain tissue viability and has become a reliable tool for the assessment of brain tumors and ischemic stroke beyond pathoanatomical morphology. Patients with major stroke often suffer from different degrees of underlying white matter lesions (WMLs) attributed to chronic small vessel disease. This study aimed to evaluate the WM TSC in patients with an acute ischemic stroke and to correlate the TSC with the extent of small vessel disease. Furthermore, the reliability of relative TSC (rTSC) compared to absolute TSC in these patients was analyzed. METHODOLOGY: We prospectively examined 62 patients with acute ischemic stroke (73 ± 13 years) between November 2016 and August 2019 from which 18 patients were excluded and thus 44 patients were evaluated. A 3D 23Na MRI was acquired in addition to a T2-TIRM and a diffusion-weighted image. Coregistration and segmentation were performed with SPM 12 based on the T2-TIRM image. The extension of WM T2 hyperintense lesions in each patient was classified using the Fazekas scale of WMLs. The absolute TSC in the WM region was correlated to the Fazekas grades. The stroke region was manually segmented on the coregistered absolute diffusion coefficient image and absolute, and rTSC was calculated in the stroke region and compared to nonischemic WM region. Statistical significance was evaluated using the Student t-test. RESULTS: For patients with Fazekas grade I (n = 25, age: 68.5 ± 15.1 years), mean TSC in WM was 55.57 ± 7.43 mM, and it was not statistically significant different from patients with Fazekas grade II (n = 7, age: 77.9 ± 6.4 years) with a mean TSC in WM of 53.9 ± 6.4 mM, p = 0.58. For patients with Fazekas grade III (n = 9, age: 81.4 ± 7.9 years), mean TSC in WM was 68.7 ± 10.5 mM, which is statistically significantly higher than the TSC in patients with Fazekas grade I and II (p < 0.001 and p = 0.05, respectively). There was a positive correlation between the TSC in WM and the Fazekas grade with r = 0.48 p < 0.001. The rTSC in the stroke region was statistically significant difference between low (0 and I) and high (2 and 3) Fazekas grades (p = 0.0353) whereas there was no statistically significant difference in absolute TSC in the stroke region between low (0 and I) and high (2 and 3) Fazekas grades. CONCLUSION: The significant difference in absolute TSC in WM in patients with severe small vessel disease; Fazekas grade 3 can lead to inaccuracies using rTSC quantification for evaluation of acute ischemic stroke using 23 Na MRI. The study, therefore, emphasizes the importance of absolute tissue sodium quantification.

23 Na MRI in ischemic stroke: Acquisition time reduction using postprocessing with convolutional neural networks.

Quantitative 23 Na magnetic resonance imaging (MRI) provides tissue sodium concentration (TSC), which is connected to cell viability and vitality. Long acquisition times are one of the most challenging aspects for its clinical establishment. K-space undersampling is an approach for acquisition time reduction, but generates noise and artifacts. The use of convolutional neural networks (CNNs) is increasing in medical imaging and they are a useful tool for MRI postprocessing. The aim of this study is 23 Na MRI acquisition time reduction by k-space undersampling. CNNs were applied to reduce the resulting noise and artifacts. A retrospective analysis from a prospective study was conducted including image datasets from 46 patients (aged 72 ± 13 years; 25 women, 21 men) with ischemic stroke; the 23 Na MRI acquisition time was 10 min. The reconstructions were performed with full dataset (FI) and with a simulated dataset an image that was acquired in 2.5 min (RI). Eight different CNNs with either U-Net-based or ResNet-based architectures were implemented with RI as input and FI as label, using batch normalization and the number of filters as varying parameters. Training was performed with 9500 samples and testing included 400 samples. CNN outputs were evaluated based on signal-to-noise ratio (SNR) and structural similarity (SSIM). After quantification, TSC error was calculated. The image quality was subjectively rated by three neuroradiologists. Statistical significance was evaluated by Student's t-test. The average SNR was 21.72 ± 2.75 (FI) and 10.16 ± 0.96 (RI). U-Nets increased the SNR of RI to 43.99 and therefore performed better than ResNet. SSIM of RI to FI was improved by three CNNs to 0.91 ± 0.03. CNNs reduced TSC error by up to 15%. The subjective rating of CNN-generated images showed significantly better results than the subjective image rating of RI. The acquisition time of 23 Na MRI can be reduced by 75% due to postprocessing with a CNN on highly undersampled data.

MRI Detection of Changes in Tissue Sodium Concentration in Brain Metastases after Stereotactic Radiosurgery: A Feasibility Study.

BACKGROUND AND PURPOSE: To date, treatment response to stereotactic radiosurgery (SRS) in brain metastases (BM) can only be determined by MRI evaluation of contrast-enhancing lesions in a long-time follow-up. Sodium MRI has been a subject of immense interest in imaging research as the measure of tissue sodium concentration (TSC) can give valuable quantitative information on cell viability. We aimed to analyze the longitudinal changes of TSC in BM measured with 23 Na MRI before and after SRS for assessment of early local tumor effects. METHODS: Seven patients with a total of 12 previously untreated BM underwent SRS with 22 Gy. In addition to a standard MRI protocol including dynamic susceptibility-weighted contrast-enhanced perfusion, a 23 Na MRI was performed at three time points: (I) 2 days before, (II) 5 days, and (III) 40 days after SRS. Nine BMs were evaluated. The absolute TSC in the BM, the respective peritumoral edemas, and the normal-appearing corresponding contralateral brain area were assessed and the relative TSC were correlated to the changes in BM longest axial diameters. RESULTS: TSC was elevated in nine BM at baseline before SRS with a mean of 73.4 ± 12.3 mM. A further increase in TSC was observed 5 days after SRS in all the nine BM with a mean of 86.9 ± 13 mM. Eight of nine BM showed a mean 60.6 ± 13.3% decrease in the longest axial diameter 40 days after SRS; at this time point, the TSC also had decreased to a mean 65.1 ± 7.9 mM. In contrast, one of the nine BM had a 13.4% increase in the largest axial diameter at time point III. The TSC of this BM showed a further TSC increase of 80.1 mM 40 days after SRS. CONCLUSION: Changes in TSC using 23 Na MRI shows the possible capability to detect radiobiological changes in BM after SRS.

Revesz syndrome revisited.

BACKGROUND: Revesz syndrome (RS) is an extremely rare variant of dyskeratosis congenita (DKC) with only anecdotal reports in the literature. METHODS: To further characterize the typical features and natural course of the disease, we screened the English literature and summarized the clinical and epidemiological features of previously published RS cases. In addition, we herein describe the first recorded patient in central Europe. RESULTS: The literature review included 18 children. Clinical features are summarized, indicating a low prevalence of the classical DKC triad. All patients experienced early bone marrow failure, in most cases within the second year of life (median age 1.5 years; 95% CI 1.4-1.6). Retinopathy occurred typically between 6 and 18 months of age (median age 1.1 years; 95% CI 0.7-1.5). The incidence of seizures was low and was present in an estimated 20% of patients. The onset of seizures was exclusively during early childhood. The Kaplan-Meier estimate of survival was dismal (median survival 6.5 years; 95% CI 3.6-9.4), and none of the patients survived beyond the age of 12 years. Stem cell transplantation (SCT) was performed in eight children, and after a median of 22 months from SCT four of these patients were alive at the last follow up visit. CONCLUSION: RS is a severe variant of DKC with early bone marrow failure and retinopathy in all patients. Survival is dismal, but stem cell transplantation may be performed successfully and might improve prognosis in the future.

MOG antibody associated demyelinating syndrome presenting as aseptic meningitis in a 6-year-old boy.

We describe the case of a 6-year-old boy who developed myelin oligodendrocyte glycoprotein antibody (MOG-Ab) associated demyelinating syndrome, after initially presenting with aseptic meningitis. Magnetic resonance imaging showed cerebral and spinal lesions consistent with acute disseminating encephalomyelitis. Rapid clinical improvement occurred after intravenous high dose methylprednisolone. A small number of cases with MOG-Ab associated demyelinating syndrome presenting as aseptic meningitis have previously been reported in adults, but to our knowledge, this is the first pediatric case of this new clinical phenotype.

Outcome of Oral and Intra-arterial Nimodipine Administration After Aneurysmal Subarachnoid Haemorrhage - A Single-centre Study.

BACKGROUND: Oral nimodipine is administered to improve clinical outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). In this study, clinical outcome in patients with and without oral nimodipine administration was assessed. MATERIALS AND METHODS: A total of 105 patients did not receive oral nimodipine but did receive intra-arterial nimodipine in the occurrence of hemodynamically relevant vasospasm after aSAH, whereas 74 patients received applications of both. Demographic/radiological details and clinical presentation were abstracted from the case records. RESULTS: Patient baseline characteristics were comparable, a predominance of endovascular coiling was shown in cohort 2 (p=0.0135). Severity of initial aSAH and clinical status at admission (Hunt and Hess) was significantly higher in those receiving oral nimodipine. Incidence of angiographic vasospasm was significantly higher in patients not treated with oral nimodipine (p=0.0305); a significantly better outcome measured by the National Institute of Health Stroke Scale (p=0.0213), was noted in those receiving oral nimodipine. CONCLUSION: Oral nimodipine administration improved clinical outcome of patients after aSAH and should be administered routinely for such patients.

Influence of Gadolinium-Based Contrast Agents on Tissue Sodium Quantification in Sodium Magnetic Resonance Imaging.

OBJECTIVES: Sodium magnetic resonance (MR) imaging provides noninvasive insights to cellular processes by measuring tissue sodium concentration (TSC). Many clinical studies combine sodium MR imaging with clinical standard MR procedures, in which contrast media is frequently administered. This work investigates the influence of gadolinium-based contrast agents on quantification of TSC. Thus, either scan pauses between early and late contrast-enhanced acquisitions can be used efficiently or sodium imaging can be performed as the final scan after dynamic contrast-enhanced acquisition. MATERIALS AND METHODS: For this study, 2 gadolinium-based contrast agents, Dotarem and Gadovist, were diluted with saline solution covering contrast agent concentrations in a clinical range. In addition, agarose-based sample series were created to simulate tissue relaxation time behavior. In vivo, the influence of Dotarem on sodium acquisition and TSC quantification was investigated in 1 ischemic stroke patient. RESULTS: Proton relaxation times decreased for increasing contrast agent concentrations as hyperbolic functions. Sodium relaxation times displayed a negative slope in regression analysis in most cases. The largest influence (-1.52 milliseconds per mmol/L contrast agent) was measured for sodium T1. Worst case calculations in ultrashort echo time sequence signal analysis showed a signal drop of (1.21% ± 0.56%) on tissue sodium quantification. In vivo sodium brain acquisitions of a stroke patient before and after Dotarem injection resulted in statistically nonsignificant differences in TSC quantification of relevant tissues and stroke areas (P > 0.05). CONCLUSIONS: Our study showed a quantitative influence of Dotarem and Gadovist on sodium relaxation times. However, quantification of TSC was not impaired, which was proven by worst case calculations and nonsignificant differences in vivo in an ischemic stroke patient. We suggest performing sodium imaging in useful clinical positions in protocols regardless of included Dotarem or Gadovist administrations. Being flexible in the study protocol design will strengthen ongoing sodium imaging investigations for various pathologies.

Off-label use of IV t-PA in patients with intracranial neoplasm and cavernoma.

BACKGROUND: The safety of systemic thrombolysis in patients with intracranial tumor and cavernoma are unknown. So far evidence is limited to a number of case reports and few case series or unspecified data based on population-based analysis. Our aim was to comprehend the risk of systemic thrombolysis in these patients. METHODS: Patients with additional evidence of intracranial tumor or cavernoma who received IV tissue plasminogen activator (t-PA) treatment at our comprehensive stroke center over a period of 7 years were identified in our stroke database and compared to the same number of matched control subjects without any evidence of intracranial tumor and cavernoma. Clinical history and imaging patterns before and after t-PA therapy were individually reviewed for each patient. RESULTS: Thirty-four patients with additional evidence of meningioma (19/34), cavernoma (13/34) or malignant intracranial neoplasm (2/34) were identified. The incidence of secondary intracranial hemorrhage observed showed no difference between control subjects (9/34, 26%) and patients (6/34, 18%; p = 0.56). Symptomatic hemorrhage in patients with meningioma or cavernoma could not be observed. Likewise, the prevalence of stroke mimics showed no difference between patients (8/34, 24%) and control subjects (5/34, 15%; p = 0.54). However, both patients with malignant intracranial neoplasm presented with a stroke mimic and intracranial hemorrhage was observed in one of them. CONCLUSIONS: In compliance with existing evidence, treatment in patients with meningioma and cavernoma appears to be safe and reasonable, while the therapy should be avoided in patients with malignant intracranial neoplasm with blood-brain barrier disruption.

Impact of pre-admission treatment with non-vitamin K oral anticoagulants on stroke severity in patients with acute ischemic stroke.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) have gained increasing importance for stroke prevention in patients with non-valvular atrial fibrillation (AF). With changing prescription practice, among other factors, clinicians can expect to see rising numbers of patients with ischemic stroke and pre-existing NOAC therapy. Few data exist regarding a potential impact of NOAC on stroke severity and outcome. AIMS: To evaluate the impact of pre-admission NOAC therapy on ischemic stroke severity. METHODS: Retrospective analysis of medical data of 376 patients with newly detected AF or known AF with either no pre-admission oral anticoagulation (n = 277) or existing NOAC therapy (n = 99; Apixaban, n = 33, Dabigatran, n = 16; Edoxaban, n = 1; Rivaroxaban, n = 49) consecutively admitted for acute ischemic stroke between January 2015 and December 2016. RESULTS: Patients with pre-admission NOAC had significantly more often experienced a prior stroke than patients not on NOAC therapy (45.5 vs. 18.4%, p < 0.001) and were significantly more frequently non-smokers (1.0 vs. 7.2%, p = 0.021). Significantly more patients without pre-admission NOAC received thrombolysis (33.8 vs. 8.1%, p < 0.001). Pre-admission NOAC therapy was associated with significantly lower NIHSS and mRS scores upon admission (median NIHSS score 6 vs. 10, p = 0.018, median mRS score 4 vs. 5, p = 0.035) and trend-level lower NIHSS scores at discharge (median NIHSS score 3 vs. 5, p = 0.057). There were no differences regarding the frequency of symptomatic intracerebral hemorrhage between NOAC and non-NOAC patients (p > 0.05). CONCLUSIONS: We report a positive impact of pre-admission NOAC on ischemic stroke severity, which is particularly remarkable in light of the increased prevalence of prior stroke and lower rates of thrombolysis in this patient population.

The Burden of Diabetes and the Chance of a Previous Stroke: Thrombolysis for Recurrent Stroke in Diabetics.

BACKGROUND: Intravenous thrombolysis with recombinant tissue plasminogen activator is still not approved by the European Medicines Agency for patients with diabetes mellitus and previous stroke. We assessed functional benefit and potential risk of thrombolysis in patients with diabetes and previous stroke and the influence of age, preexisting diabetic damage, as well as acute and chronic hyperglycemia on outcome, symptomatic intracranial hemorrhage, and in-hospital mortality. METHODS: We analyzed 527 consecutive patients treated with thrombolysis for acute stroke. Poor outcome was defined as deterioration of prestroke modified Rankin Scale (mRS) to 3 or greater at discharge. Symptomatic intracranial hemorrhage was defined according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria. RESULTS: Of the patients, 35.9% were diabetic and 33.2% had previous stroke. Of these patients, 14.4% were diabetics with previous stroke (index group). The rate of patients with poor functional outcome at discharge, symptomatic intracranial hemorrhage, or mortality did not differ between the index group and patients with either diabetes or previous stroke in 2 × 2 comparisons. Diabetics with first-ever stroke showed significantly more symptomatic intracranial hemorrhage (9.7%, P < .001) than the other groups, poorer functional recovery (P = .036), and the highest rate of mortality (12.4%, P < .001). Significant predictors for poor outcome were age (P < .001) and HbA1c (P = .013), for symptomatic intracranial hemorrhage HbA1c (P = .006) and for mortality acute hyperglycemia (P = .001) and age (P = .004). CONCLUSION: Diabetics with previous stroke should not be withheld from intravenous thrombolysis. The risk of complications derives primarily from poor long-term metabolic control rather than from acute hyperglycemia or from previous stroke.

Regional Differences in Thrombectomy Rates : Secondary use of Billing Codes in the MIRACUM (Medical Informatics for Research and Care in University Medicine) Consortium.

BACKGROUND AND PURPOSE: Mechanical thrombectomy, in addition to intravenous (i.v.) thrombolysis is recommended for treatment of acute stroke in patients with large vessel occlusions (LVO) in the anterior circulation up to 6 h after symptom onset. We compared thrombectomy rates of eight university hospitals of the MIRACUM consortium to analyze the implementation of this guideline in clinical routine. METHODS: Anonymized billing data in a standardized format were loaded into a local i2b2 data warehouse by applying already existing extract, transform and load (ETL) routines. A locally executed uniform SQL (structured query language) query delivered aggregated site data for all inpatients with a discharge diagnosis of ischemic stroke (ICD-10 I63) containing counts for type of acute treatment, type of admission and age groups, which were centrally analyzed with R. RESULTS: From 2014 to 2016, the thrombectomy rate almost doubled from a mean of 4.7% to 9.6%, although significant differences between centers exist (range in 2016: 5.8-17%). The number of drip-and-ship procedures increased in 3 out of 8 centers. There was no evidence for a decrease in thrombectomy rates during weekends/holiday or among patients older than 80 years, but this age group is more likely to receive i.v. recombinant tissue plasminogen activator (rtPA). CONCLUSION: The observed increase of thrombectomy rates and drip-and-ship procedures without a significant difference between weekdays and weekends or patients of different ages is substantiating a rapid implementation of stroke guidelines within the analyzed neurovascular centers. The prototype of the MIRACUM Data Integration Center already contributes to health services research in Germany.

A double-tuned (1) H/(23) Na resonator allows (1) H-guided (23) Na-MRI in ischemic stroke patients in one session.

BACKGROUND: Established imaging methods are still not confident in the determination of stroke onset. Sodium imaging in animal models and lately in humans implicates that the sodium signal intensity within the ischemic lesion increases in a time-dependent fashion. Sodium imaging usually requires a time-consuming change of resonators or magnetic resonance imaging systems. To avoid this, we used a double-tuned (1) H/(23) Na birdcage head coil in combination with a protocol minimizing T1 - and T2 *-weighting effects for measurement of sodium intensity in acute stroke patients. METHODS: Multinuclear (1) H/(23) Na data sets were obtained from 16 stroke patients [75 ± 9·9 (standard deviation) years old] 4-130 h after symptom onset. The protocol was acquired on a clinical 3T magnetic resonance imaging site using a double-tuned (1) H/(23) Na birdcage head coil. Sodium signal intensity within the lesion and homologous contralateral side was measured and compared. RESULTS: With an acquisition time of the complete magnetic resonance imaging protocol of 22 min, a nonlinear sodium signal intensity increase within the lesion over time after stroke onset was acknowledged. Onset time within six-hours showed an increase of only 8% or less, whereas onset time beyond 8·5 h demonstrated increases of 36% or more reaching a maximum of 170% > 120 h. In addition, some patients showed a difference in sodium signal intensity compared with diffusion weighted imaging lesion. CONCLUSIONS: The use of a double-tuned (1) H/(23) Na birdcage head coil in a clinical setting 'allowed sodium intensity measurements' in a justifiable time also for acute stroke patients, and heterogenous sodium signal intensity in the diffusion weighted imaging lesion might represent differences in tissue damage or repair.

Scan time reduction in ²³Na-Magnetic Resonance Imaging using the chemical shift imaging sequence: Evaluation of an iterative reconstruction method.

AIM: To evaluate potential scan time reduction in (23)Na-Magnetic Resonance Imaging with the chemical shift imaging sequence (CSI) using undersampled data of high-quality datasets, reconstructed with an iterative constrained reconstruction, compared to reduced resolution or reduced signal-to-noise ratio. MATERIALS AND METHODS: CSI (23)Na-images were retrospectively undersampled and reconstructed with a constrained reconstruction scheme. The results were compared to conventional methods of scan time reduction. The constrained reconstruction scheme used a phase constraint and a finite object support, which was extracted from a spatially registered (1)H-image acquired with a double-tuned coil. The methods were evaluated using numerical simulations, phantom images and in-vivo images of a healthy volunteer and a patient who suffered from cerebral ischemic stroke. RESULTS: The constrained reconstruction scheme showed improved image quality compared to a decreased number of averages, images with decreased resolution or circular undersampling with weighted averaging for any undersampling factor. Brain images of a stroke patient, which were reconstructed from three-fold undersampled k-space data, resulted in only minor differences from the original image (normalized root means square error < 12%) and an almost identical delineation of the stroke region (mismatch < 6%). CONCLUSION: The acquisition of undersampled (23)Na-CSI images enables up to three-fold scan time reduction with improved image quality compared to conventional methods of scan time saving.

Dose-response relationship of locally applied nimodipine in an ex vivo model of cerebral vasospasm.

INTRODUCTION: Cerebral vasospasm is a severe complication of subarachnoid hemorrhage (SAH). The calcium channel inhibitor nimodipine has been used for treatment of cerebral vasospasm. No evidence-based recommendations for local nimodipine administration at the site of vasospasm exist. The purpose of this study was to quantify nimodipine's local vasodilatory effect in an ex vivo model of SAH-induced vasospasm. METHODS: SAH-induced vasospasm was modeled by contracting isolated segments of rat superior cerebellar arteries with a combination of serotonin and a synthetic analog of prostaglandin A(2). A pressure myograph system was used to determine vessel reactivity of spastic as well as non-spastic arteries. RESULTS: Compared to the initial vessel diameter, a combination of serotonin and prostaglandin induced considerable vasospasm (55 ± 2.5 % contraction; n = 12; p < 0.001). Locally applied nimodipine dilated the arteries in a concentration-dependent manner starting at concentrations as low as 1 nM (n = 12; p < 0.05). Concentrations higher than 100 nM did not relevantly increase the vasodilatory effect. Nimodipine's vasodilatory effect was smaller in spastic than in non-spastic vessels (n = 12; p < 0.05), which we assume to be due to structural changes in the vessel wall. CONCLUSION: The described ex vivo model allows to investigate the dose-dependent efficacy of spasmolytic drugs prior to in vivo experiments. Low concentrations of locally applied nimodipine have a strong vasodilatory effect, which is of relevance when considering the local application of nimodipine in cerebral vasospasm.

Compatibility of studies and family: approaches at the Medical Faculty Mannheim.

The compatibility of studies or a career with children is becoming increasingly important. This is partly attributable to the fact that it is important for people of either gender to spend time with their families, their children. Not too long ago, raising children was almost exclusively the domain of the mother. On the other hand, more and more women study medicine. More than half of first year students are now female. Many of these young women, like their male counterparts, would like to start families. The possibility to both study and have children is particularly important during the "training" life phase. The Medical Faculty Mannheim realises the need for action and wants to actively tackle the associated challenges in terms of advice, study design and infrastructure. This article represents the steps which the faculty - in close cooperation with the Equality Office, the Dean of Studies and the University Hospital - has taken so far or is currently putting in place to enable students to successfully combine the challenge of studying with that of having children. These include individual advice services on study organisation, information about support services, changes to the infrastructure and more intensive cooperation between the various departments.

Abciximab does not prevent ischemic lesions related to cerebral angiography: a randomized placebo-controlled trial.

BACKGROUND: To assess the efficiency of IIb/IIIa platelet receptor inhibition by abciximab in the prevention of silent embolism during digital subtraction angiography. METHODS: In this randomized, double-blind, prospective study, pre- and postangiographic diffusion-weighted magnetic resonance imaging (DWI) of 184 participants was evaluated for the occurrence of silent embolism. RESULTS: No significant relationship was found between the patients receiving abciximab before digital subtraction angiography (15 of 90; 16.7%) and patients in the placebo group (16 of 94; 17.0%) regarding postangiographic appearance of silent emboli (p = 0.9). CONCLUSIONS: IIb/IIIa receptor inhibition by abciximab does not diminish the occurrence of silent embolism during digital subtraction angiography. Our findings indicate that solid blood clots are not the origin of hyperintense lesions observed on DWI and enhance the role of alternative mechanisms.