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  • 1
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    Cardiac Troponin and Recurrent Major Vascular Events after Minor Stroke or Transient Ischemic Attack
    Wiley ; 2021
    In:  Annals of Neurology Vol. 90, No. 6 ( 2021-12), p. 901-912
    Details
    In: Annals of Neurology, Wiley, Vol. 90, No. 6 ( 2021-12), p. 901-912
    Abstract: This study was undertaken to investigate whether high‐sensitivity cardiac troponin T (hs‐cTnT) is associated with major adverse cardiovascular events (MACE) in patients with minor stroke or transient ischemic attack (TIA), and whether this association differs after risk stratification based on the Age, Blood Pressure, Clinical Features, Duration of Symptoms, Diabetes (ABCD 2 ) score. Methods INSPiRE‐TMS was a randomized controlled trial allocating patients with minor stroke or TIA to an intensified support program or conventional care. In this post hoc analysis, participants were categorized using hs‐cTnT levels (5th generation; Roche Diagnostics, Manheim, Germany; 99th percentile upper reference limit [URL] = 14ng/l). Vascular risk was stratified using the ABCD 2 score (lower risk = 0–5 vs higher risk = 6–7). Cox proportional hazard regression was performed using covariate adjustment and propensity score matching (PSM) for the association between hs‐cTnT and MACE (stroke/nonfatal coronary event/vascular death). Results Among 889 patients (mean age = 70 years, 37% female), MACE occurred in 153 patients (17.2%) during a mean follow‐up of 3.2 years. hs‐cTnT was associated with MACE (9.3%/yr,  〉 URL vs 4.4%/yr, ≤URL, adjusted hazard ratio [HR] = 1.63 [95% confidence interval (CI) = 1.13–2.35] , adjusted HR [Q 4 vs Q 1 ] = 2.57 [95% CI = 1.35–4.97] , adjusted HR [log‐transformed] = 2.31 [95% CI = 1.37–3.89] ). This association remained after PSM (adjusted HR = 1.76 [95% CI = 1.14–2.72]). There was a significant interaction between hs‐cTnT and ABCD 2 category for MACE occurrence ( p interaction  = 0.04). In the lower risk category, MACE rate was 9.5%/yr in patients with hs‐cTnT 〉 URL, which was higher than in those ≤URL (3.8%/yr) and similar to the overall rate in the higher risk category. Interpretation hs‐cTnT levels are associated with incident MACE within 3 years after minor stroke or TIA and may help to identify high‐risk individuals otherwise deemed at lower risk based on the ABCD 2 score. If confirmed in independent validation studies, this might warrant intensified secondary prevention measures and cardiac diagnostics in stroke patients with elevated hs‐cTnT. ANN NEUROL 2021;90:901–912
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v90.6
    DOI: 10.1002/ana.26225
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2037912-2
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  • 2
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    Frequency, clinical presentation and outcome of vigilance impairment in patients with uni- and bilateral ischemic infarction of the paramedian thalamus
    Springer Science and Business Media LLC ; 2021
    In:  Journal of Neurology Vol. 268, No. 11 ( 2021-11), p. 4340-4348
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    In: Journal of Neurology, Springer Science and Business Media LLC, Vol. 268, No. 11 ( 2021-11), p. 4340-4348
    Abstract: Ischemic stroke of the paramedian thalamus is a rare differential diagnosis in sudden altered vigilance states. While efforts to describe clinical symptomatology exist, data on the frequency of paramedian thalamic stroke as a cause of sudden impaired vigilance and on accompanying clinical signs and outcome are scarce. We retrospectively analyzed consecutive patients admitted to a tertiary stroke center between 2010 and 2019 diagnosed with paramedian thalamic stroke. We evaluated frequency of vigilance impairment (VI) due to paramedian thalamic stroke, accompanying clinical signs and short-term outcome in uni- versus bilateral paramedian lesion location. Of 3896 ischemic stroke patients, 53 showed a paramedian thalamic stroke location (1.4%). VI was seen in 29/53 patients with paramedian thalamic stroke and in 414/3896 with any stroke (10.6%). Paramedian thalamic stroke was identified as causal to VI in 3.4% of all patients with initial VI in the emergency department and in 0.7% of all ischemic stroke patients treated in our center. Accompanying clinical signs were detected in 21 of these 29 patients (72.4%) and facilitated a timely diagnosis. VI was significantly more common after bilateral than unilateral lesions (92.0% vs. 21.4%; p   〈  0.001). Patients with bilateral paramedian lesions were more severely affected, had longer hospital stays and more frequently required in-patient rehabilitation. Paramedian thalamic lesions account for about 1 in 15 stroke patients presenting with impaired vigilance. Bilateral paramedian lesion location is associated with worse stroke severity and short-term outcome. Paying attention to accompanying clinical signs is of importance as they may facilitate a timely diagnosis.
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
    URL: Article
    DOI: 10.1007/s00415-021-10565-y
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    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1421299-7
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  • 3
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    HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology
    EMBO ; 2010
    In:  Molecular Systems Biology Vol. 6, No. 1 ( 2010-01)
    Details
    In: Molecular Systems Biology, EMBO, Vol. 6, No. 1 ( 2010-01)
    Abstract: We present HepatoNet1, a manually curated large‐scale metabolic network of the human hepatocyte that encompasses 〉 2500 reactions in six intracellular and two extracellular compartments. Using constraint‐based modeling techniques, the network has been validated to replicate numerous metabolic functions of hepatocytes corresponding to a reference set of diverse physiological liver functions. Taking the detoxification of ammonia and the formation of bile acids as examples, we show how these liver‐specific metabolic objectives can be achieved by the variable interplay of various metabolic pathways under varying conditions of nutrients and oxygen availability.
    Type of Medium: Online Resource
    ISSN: 1744-4292 , 1744-4292
    URL: Article
    DOI: 10.1038/msb.2010.62
    Language: English
    Publisher: EMBO
    Publication Date: 2010
    detail.hit.zdb_id: 2193510-5
    SSG: 12
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  • 4
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    Assessment of thrombus length in acute ischemic stroke by post-contrast magnetic resonance angiography
    BMJ ; 2018
    In:  Journal of NeuroInterventional Surgery Vol. 10, No. 8 ( 2018-08), p. 756-760
    Details
    In: Journal of NeuroInterventional Surgery, BMJ, Vol. 10, No. 8 ( 2018-08), p. 756-760
    Abstract: Post-contrast magnetic resonance angiography (PC-MRA) enables visualization of vessel segments distal to an intra-arterial thrombus in acute ischemic stroke. We hypothesized that PC-MRA also allows clot length measurement in different intracranial vessels. Methods Patients with MRI-confirmed ischemic stroke and intracranial artery occlusion within 24 hours of symptom onset were prospectively evaluated. PC-MRA was added to a standard stroke MRI protocol. Thrombus length was measured on thick slab maximum intensity projection images. Clinical outcome at hospital discharge was assessed by modified Rankin Scale (mRS). Results Thirty-four patients (median age 72 years) presenting with a median National Institutes of Health Stroke Scale score of 11 and a median onset to imaging time of 116 min were included. PC-MRA enabled precise depiction of proximal and distal terminus of the thrombus in 31 patients (91%), whereas in three patients (9%) PC-MRA presented a partial occlusion. Median thrombus length in patients with complete occlusion was 9.9 mm. In patients with poor outcome (mRS ≥3) median thrombus length was significantly longer than in those with good outcome (mRS ≤2;P=0.011). Conclusions PC-MRA demonstrates intra-arterial thrombus length at different vessel occlusion sites. Longer thrombus length is associated with poor clinical outcome. Clinical trial registration NCT02077582; Results.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    URL: Article
    DOI: 10.1136/neurintsurg-2017-013454
    Language: English
    Publisher: BMJ
    Publication Date: 2018
    detail.hit.zdb_id: 2506028-4
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  • 5
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    High‐Sensitivity Cardiac Troponin T and Recurrent Vascular Events After First Ischemic Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Journal of the American Heart Association Vol. 10, No. 10 ( 2021-05-18)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 10 ( 2021-05-18)
    Abstract: Recent evidence suggests cardiac troponin levels to be a marker of increased vascular risk. We aimed to assess whether levels of high‐sensitivity cardiac troponin T (hs‐cTnT) are associated with recurrent vascular events and death in patients with first‐ever, mild to moderate ischemic stroke. Methods and Results We used data from the PROSCIS‐B (Prospective Cohort With Incident Stroke Berlin) study. We computed Cox proportional hazards regression analyses to assess the association between hs‐cTnT levels upon study entry (Roche Elecsys, upper reference limit, 14 ng/L) and the primary outcome (composite of recurrent stroke, myocardial infarction, and all‐cause death). A total of 562 patients were analyzed (mean age, 67 years [SD 13]; 38.6% women; median National Institutes of Health Stroke Scale=2; hs‐cTnT above upper reference limit, 39.2%). During a mean follow‐up of 3 years, the primary outcome occurred in 89 patients (15.8%), including 40 (7.1%) recurrent strokes, 4 (0.7%) myocardial infarctions, and 51 (9.1%) events of all‐cause death. The primary outcome occurred more often in patients with hs‐cTnT above the upper reference limit (27.3% versus 10.2%; adjusted haza rd ratio, 2.0; 95% CI, 1.3–3.3), with a dose‐response relationship when the highest and lowest hs‐cTnT quartiles were compared (15.2 versus 1.8 events per 100 person‐years; adjusted hazard ratio, 4.8; 95% CI, 1.9–11.8). This association remained consistent in sensitivity analyses, which included age matching and stratification for sex. Conclusions Hs‐cTnT is dose‐dependently associated with an increased risk of recurrent vascular events and death within 3 years after first‐ever, mild to moderate ischemic stroke. These findings support further studies of the utility of hs‐cTnT for individualized risk stratification after stroke. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01363856.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.120.018326
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2653953-6
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  • 6
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    Abstract TMP65: Sex Differences in Outcomes of Acute Myocardial Injury After Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2024
    In:  Stroke Vol. 55, No. Suppl_1 ( 2024-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Abstract: Introduction: Sex differences in presentation, treatment, and prognosis of cardiovascular disorders are well recognized. Although an association between acute myocardial injury and mortality after ischemic stroke has been demonstrated, it is unclear whether prevalence and outcome of post-stroke acute myocardial injury differ between women and men. Methods: We prospectively screened consecutive patients with acute ischemic stroke and serial high-sensitivity cardiac troponin T (hs-cTnT) measurements admitted to our center (January 2019-December 2020). Acute myocardial injury was defined as at least one hs-cTnT value above the upper reference limit (URL=14 ng/L) with a rise/fall of 〉 20%. Additionally, rates of acute myocardial injury were calculated with sex-specific hs-cTnT cut-offs (women URL=9ng/L; men URL=16ng/L). Results: Of 1,067 patients included, 494 were women (46%). Women were older, had higher rate of known atrial fibrillation, were more likely to be functional dependent before admission, and had higher stroke severity (all p-values 〈 0.05). The prevalence of acute myocardial injury differed by sex (29% women vs 23% men, P =0.024). In multivariate analysis, statistically significant associations between acute myocardial injury and outcomes were observed in women (7-day mortality: aOR=3.2 [1.07-9.3]; in-hospital mortality: aOR=3.3 [1.4-7.6] ; mRS at discharge: aOR=1.6 [1.1-2.4]), but not in men (Fig.1). The implementation of sex-specific cut-offs did not increase the prognostic value of acute myocardial injury for unfavorable outcomes. The ROC-derived optimal cut-offs of hs-cTnT peak values for predicting of early mortality was higher than current URLs and sex-specific (women=29.5 ng/L vs men=66 ng/L; negative predictive value: 98.46% and 99.23%) (Fig.2). Conclusions: The prevalence of acute myocardial injury after ischemic stroke and its association with mortality and unfavorable functional outcome might be sex-dependent.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.55.suppl_1.TMP65
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 1467823-8
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  • 7
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    Can intracranial time-of-flight-MR angiography predict extracranial carotid artery stenosis?
    Springer Science and Business Media LLC ; 2022
    In:  Journal of Neurology Vol. 269, No. 5 ( 2022-05), p. 2743-2749
    Details
    In: Journal of Neurology, Springer Science and Business Media LLC, Vol. 269, No. 5 ( 2022-05), p. 2743-2749
    Abstract: Extracranial stenosis of the internal carotid artery (ICA) is an important cause of ischemic stroke and transient ischemic attack (TIA). It can be diagnosed using contrast-enhanced CT or MR angiography (MRA) as well as Doppler ultrasound. In this study, we assessed the diagnostic value of intracranial time-of-flight (TOF) MRA to predict extracranial ICA stenosis (ICAS). Methods We retrospectively analyzed consecutive patients with acute ischemic stroke or TIA and middle- (50–69%) or high-grade (70–99%) unilateral extracranial ICAS according to NASCET criteria assessed by ultrasound between January 2016 and August 2018. The control group consisted of patients without extracranial ICAS. Intraluminal signal intensities (SI) of the intracranial ICA on the side of the extracranial stenosis were compared to the contralesional side on TOF-MRA source images. SI ratios (SIR) of contralesional:lesional side were compared between groups. Results In total, 151 patients were included in the main analysis. Contralesional:lesional SIR in the intracranial C4-segment was significantly higher in patients with ipsilateral extracranial ICA stenosis ( n  = 51, median 74 years, 57% male) compared to the control group ( n  = 100, median 68 years, 48% male). Mean SIR was 1.463 vs. 1.035 ( p   〈  0.001) for right-sided stenosis and 1.362 vs. 1.000 ( p   〈  0.001) for left-sided stenosis. Receiver-operating characteristic curve demonstrated a cut-off value of 1.086 for right-sided [sensitivity/specificity 75%/81%; area under the curve (AUC) 0.81] and 1.104 for left-sided stenosis (sensitivity/specificity 70%/84%; AUC 0.80) in C4 as a good predictor for high-grade extracranial ICAS. Conclusions SIR on TOF-MRA can be a marker of extracranial ICAS.
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
    URL: Article
    DOI: 10.1007/s00415-021-10876-0
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 8
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    Relationship Between Changes in the Temporal Dynamics of the Blood-Oxygen-Level-Dependent Signal and Hypoperfusion in Acute Ischemic Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Stroke Vol. 48, No. 4 ( 2017-04), p. 925-931
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 48, No. 4 ( 2017-04), p. 925-931
    Abstract: Changes in the blood-oxygen-level-dependent (BOLD) signal provide a noninvasive measure of blood flow, but a detailed comparison with established perfusion parameters in acute stroke is lacking. We investigated the relationship between BOLD signal temporal delay and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) in stroke patients. Methods— In 30 patients with acute ( 〈 24 hours) ischemic stroke, we performed Pearson correlation and multiple linear regression between DSC-MRI parameters (time to maximum [Tmax], mean transit time, cerebral blood flow, and cerebral blood volume) and BOLD-based parameters (BOLD delay and coefficient of BOLD variation). Prediction of severe hypoperfusion (Tmax 〉 6 seconds) was assessed using receiver–operator characteristic (ROC) analysis. Results— Correlation was highest between Tmax and BOLD delay (venous sinus reference; time shift range 7; median r =0.60; interquartile range=0.49–0.71). Coefficient of BOLD variation correlated with cerebral blood volume (median r = 0.37; interquartile range=0.24–0.51). Mean R 2 for predicting BOLD delay by DSC-MRI was 0.54 (SD=0.2) and for predicting coefficient of BOLD variation was 0.37 (SD=0.17). BOLD delay (whole-brain reference, time shift range 3) had an area under the curve of 0.76 for predicting severe hypoperfusion (sensitivity=69.2%; specificity=80%), whereas BOLD delay (venous sinus reference, time shift range 3) had an area under the curve of 0.76 (sensitivity=67.3%; specificity=83.5%). Conclusions— BOLD delay is related to macrovascular delay and microvascular hypoperfusion, can identify severely hypoperfused tissue in acute stroke, and is a promising alternative to gadolinium contrast agent–based perfusion assessment in acute stroke. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00715533 and NCT02077582.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.116.015566
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1467823-8
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  • 9
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    Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Stroke Vol. 51, No. 1 ( 2020-01), p. 209-215
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 1 ( 2020-01), p. 209-215
    Abstract: Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods— FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results— FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 ( P =0.169) and shift analysis ( P =0.086) but reached significance for mRS score of 0 to 2 ( P =0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions— In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.119.027390
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 10
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    Adapting the Computed Tomography Criteria of Hemorrhagic Transformation to Stroke Magnetic Resonance Imaging
    S. Karger AG ; 2013
    In:  Cerebrovascular Diseases Extra Vol. 3, No. 1 ( 2013-8-27), p. 103-110
    Details
    In: Cerebrovascular Diseases Extra, S. Karger AG, Vol. 3, No. 1 ( 2013-8-27), p. 103-110
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 The main safety aspect in the use of stroke thrombolysis and in clinical trials of new pharmaceutical or interventional stroke therapies is the incidence of hemorrhagic transformation (HT) after treatment. The computed tomography (CT)-based classification of the European Cooperative Acute Stroke Study (ECASS) distinguishes four categories of HTs. An HT can range from a harmless spot of blood accumulation to a symptomatic space-occupying parenchymal bleeding associated with a massive deterioration of symptoms and clinical prognosis. In magnetic resonance imaging (MRI) HTs are often categorized using the ECASS criteria although this classification has not been validated in MRI. We developed MRI-specific criteria for the categorization of HT and sought to assess its diagnostic reliability in a retrospective study. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Consecutive acute ischemic stroke patients, who had received a 3-tesla MRI before and 12-36 h after thrombolysis, were screened retrospectively for an HT of any kind in post-treatment MRI. Intravenous tissue plasminogen activator was given to all patients within 4.5 h. HT categorization was based on a simultaneous read of 3 different MRI sequences (fluid-attenuated inversion recovery, diffusion-weighted imaging and T2* gradient-recalled echo). Categorization of HT in MRI accounted for the various aspects of the imaging pattern as the shape of the bleeding area and signal intensity on each sequence. All data sets were independently categorized in a blinded fashion by 3 expert and 3 resident observers. Interobserver reliability of this classification was determined for all observers together and for each group separately by calculating Kendall's coefficient of concordance 〈 i 〉 (W) 〈 /i 〉 . 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Of the 186 patients screened, 39 patients (21%) had an HT in post-treatment MRI and were included for the categorization of HT by experts and residents. The overall agreement of HT categorization according to the modified classification was substantial for all observers ( 〈 i 〉 W 〈 /i 〉 = 0.79). The degrees of agreement between experts ( 〈 i 〉 W 〈 /i 〉 = 0.81) and between residents ( 〈 i 〉 W 〈 /i 〉 = 0.87) were almost perfect. For the distinction between parenchymal hematoma and hemorrhagic infarction, the interobserver agreement was almost perfect for all observers taken together ( 〈 i 〉 W 〈 /i 〉 = 0.82) as well as when experts ( 〈 i 〉 W 〈 /i 〉 = 0.82) and residents ( 〈 i 〉 W 〈 /i 〉 = 0.91) were analyzed separately. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 The ECASS CT classification of HT was successfully adapted for usage in MRI. It leads to a substantial to almost perfect interobserver agreement and can be used for safety assessment in clinical trials.
    Type of Medium: Online Resource
    ISSN: 1664-5456
    URL: Article
    DOI: 10.1159/000354371
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2013
    detail.hit.zdb_id: 2651613-5
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