scholarly journals Role of VASP Phosphorylation Assay in Monitoring the Antiplatelet Therapy

2013 ◽  
Vol 13 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Marian Fedor ◽  
R. Simonova ◽  
J. Fedorova ◽  
I. Skornova ◽  
L. Duraj ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stent Thrombosis ◽  
Cardiac Death ◽  
P2y12 Receptor ◽  
Response To Treatment ◽  
Reactivity Index ◽  
Inadequate Response ◽  
Vasp Phosphorylation ◽  
Platelet Receptor ◽  
Increased Risk

Abstract Dual antiplatelet treatment with clopidogrel and aspirin represents standard regimen in prevention of thromboembolic events in patients with ischemic heart disease undergoing percutaneous coronary intervention (PCI). One of the greatest pitfalls of clopidogrel treatment is large inter-individual variability in response. Large amount of patients does not respond adequately and therefore are not „protected“ even in spite of receiving the therapy. Poor responders are exposed to three-fold increased risk of myocardial infarction, stent thrombosis and cardiac death. Clopidogrel is an antiplatelet prodrug, whose active metabolite inhibits platelet function by irreversible binding to the (adenosine diphosphate) platelet receptor P2Y12. Receptor P2Y12 plays primal role in ADP-mediated platelet activation, and also in mechanism of action of ADP inhibitors such as clopidogrel, prasugrel etc. Reasons stated above, raised the necessity for implementing reliable laboratory test in order to identify the unprotected patients. In an ideal scenario, such test would serve to adjust the dose and guide the individual tailored treatment. Vasodilator Stimulated Phosphoprotein (VASP) is an intracellular platelet protein which is non phosphorylated at basal state. Since its relation in cascade with P2Y12 receptor, VASP phosphorylation corerlates with inhibition of P2Y12 which is the receptor of prime importance in ADP mediated activation of platelets and as is primary target of ADP inhibitors action. Outcome of the assay is represented as the value of platelet reactivity index (PRI), where PRI values above 50% are considered inadequate response to treatment and signal exposure to increased risk of myocardial infarction, post-PCI stent thrombosis and cardiac death. VASP-P flow cytometric assay is emerging into the spotlight as the promising method, mostly for its specificity for ADP inhibitors, better outlook for standardising results and lesser sample manipulation compared to multiple electrode aggregometry.

Abstract 2125: P Wave Morphology Is a Predictor of Poor Cardiac Outcome and Death in MADIT II Patients

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Fredrik Holmqvist ◽  
Pyotr G Platonov ◽  
Scott McNitt ◽  
Slava Polonsky ◽  
Jonas Carlson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Death ◽  
P Wave ◽  
Wave Duration ◽  
P Wave Duration ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Wave Morphology ◽  
Cardiac Outcome ◽  
Madit Ii

The objective of the present study was to non-invasively analyse atrial electrophysiology to identify markers associated with increased risk of mortality and deterioration of heart failure in a high-risk population with advanced CHF and a history of acute myocardial infarction. Patients included in MADIT II with sinus rhythm at baseline were studied (n=802). Unfiltered and bandpass filtered signal-averaged P waves were analyzed to determine orthogonal P wave morphology, P wave duration and RMS20. The association between P wave parameters and data on the clinical course and cardiac events during a mean follow-up of 20 months was analyzed. P wave duration was 139±23 ms and the RMS20 was 1.9±1.1 μV. None of these parameters were significantly associated with poor cardiac outcome. Differences in P wave morphology were independently predictive of non-sudden cardiac death (HR 2.66; 95% CI 1.41–5.04, P=0.0027). In addition, in univariate analyses differences in P wave morphology were found to be associated with an increased risk of all-cause mortality (HR 1.35; 95%CI 1.01–1.81, P=0.042) and cardiac death (HR 1.54; 95%CI 1.10 –2.16, P=0.011) (figure ) In the present study the value of analyzing the P wave morphology in patients with previous myocardial infarction and CHF is demonstrated. Changes in P wave morphology were shown to be independently predictive of increased risk of non-sudden cardiac death. Furthermore, statistically significant associations between P wave morphology changes and all-cause mortality, cardiac death and CHF hospitalization was demonstrated.

Comparison of adenocarcinoma (ACA) and squamous cell carcinoma (SCC) of the uterine cervix: A population-based epidemiologic study of 60,000 women in Brazil.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1587-1587
Author(s):  
Angelica Noguelra Rodrigues ◽  
Luiz Claudio Santos Thuler ◽  
Anke Bergmann ◽  
Suzana Sales de Aguiar ◽  
Carlos Gil Moreira Ferreira
Keyword(s):  
Uterine Cervix ◽  
Epidemiologic Study ◽  
Tumor Stage ◽  
Population Based ◽  
Response To Treatment ◽  
Inadequate Response ◽  
Chi Square ◽  
Cervical Cancers ◽  
Increased Risk ◽  
Screening Strategies

1587 Background: Most cancers of the uterine cervix are SCC, but the relative and absolute incidence of ACA has risen in recent years, particularly in younger patients, and ACA now accounts for about 20% of invasive cervical cancers in screened populations worldwide. However, the developing world, with sub-optimally screened women, accounts for more than 80% of incident cervical cancers. Our objective was to compare epidemiological, clinical characteristics, and treatment outcome of ACA with those of SCC of the cervix, with respect to ethnic group, age and stage at diagnosis, and pattern of response to first treatment in a sub-optimally screened population. Methods: Data of cervical cancer patients with SCC and ACA (adenosquamous + adenocarcinoma) treated from 2000 through 2009 were obtained from the Brazilian Hospital Cancer Register databases. Summary odds ratios and chi-square tests were estimated. Results: A total of 60,883 patients were analyzed: 54,425 (89.4%) cases of SCC, and 6,458 (10.6%) of ACA. Compared to ACA, the SCC cohort were younger (49.37 x 51.83 years, p<0.001), more frequently black (58.1% x 49.2%, p<0.001), presented higher degree of illiteracy (22.7 x 16.1%, p<0.001), and alcohol (13 x 9.8%, p<0.001) and tobacco dependence (41.5 x 31%, p<0.001). Tumor stage at the time of diagnosis was also significantly different (p<0.01). Considering prognostic factors, in both subtypes, more than 60% of the patients were stage II or inferior and ACA was associated with a significantly increased risk of inadequate response after the first course of treatment (crude OR=1.14 CI95%=1.07-1.21; adjusted OR=0.94 CI95%=0.87-1.01) and of death (crude OR=1.26 CI95%=1.15-1.38; adjusted OR=1.1 CI95%=1.00-1.23). Conclusions: Differences between ACA and SCC were found in age at diagnosis, extent of disease and ethnic distribution. In spite of these differences, the inadequate response to treatment seems to be mainly the result of more advanced stage, rather than cell type. Screening strategies with higher sensitivity are necessary, and irrespectively of histological subtype, quality of treatment must be improved in developing countries.

279Clinical outcome after coronary bifurcation stenting: a systematic review and network meta-Analysis of PCI bifurcation techniques comprising 5572 patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Di Gioia ◽  
J Sonck ◽  
I Colaiori ◽  
T Mizukami ◽  
M Kodeboina ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stent Thrombosis ◽  
Cardiac Death ◽  
Meta Analysis ◽  
Evaluation Framework ◽  
Left Main ◽  
Coronary Bifurcation ◽  
Bifurcation Lesions ◽  
Provisional Stenting ◽  
Crush Technique

Abstract Background The optimal PCI technique for bifurcation lesions remains a matter of debate. Several RCT have compared different bifurcation PCI techniques. Provisional stenting has been recommended as the default technique for most bifurcation lesions. However, emerging data suggests that double-kissing crush technique can be considered in true left main bifurcation lesions and has been endorsed by the European Society of Cardiology Guidelines. Purpose To compare the clinical outcome between different bifurcation PCI techniques. Methods We searched MEDLINE for randomized clinical trials (RCT) comparing PCI bifurcation techniques for coronary bifurcation lesions. Outcomes of interest were major adverse cardiovascular events (MACE) defined as the composite of cardiac death, myocardial infarction (MI) and target vessel or lesion revascularization (TVR/TLR), and the individual components of MACE. Stent thrombosis was assessed as defined by the ARC. Stratification based on left-main or distal bifurcations was performed. We evaluated the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We estimated summary odds ratios (ORs) using pairwise and Bayesian network meta-analysis. Results We identified 263 studies and of these included 19 RCT including 5572 patients treated with 5 bifurcation PCI techniques namely provisional stenting, systematic T-stenting, crush, culotte and double-kissing crush. Median follow-up was 12 months (IQR 8 to 36). When all bifurcation lesions were combined, double-kissing crush technique reduced the occurrence of MACE (OR 0.42; CrI 0.28 to 0.61) compared to provisional stenting. This difference was driven by a reduction in TVR/TLR (OR 0.39; CrI 0.25 to 0.65). No differences were found in cardiac death, MI or stent thrombosis among analyzed PCI techniques. No differences in MACE were observed between provisional stenting, systematic T-stenting, crush. In distal bifurcations (n=17 studies, 4634 patients), double-kissing crush also showed to reduce MACE (OR 0.48; CrI 0.29 to 0.67 vs. Provisional). In left-main bifurcations (n=3 studies, 938 patients) no differences in MACE were found between PCI techniques. Conclusions In this network meta-analysis, PCI bifurcation techniques were similar with respect to the occurrence of cardiac death, myocardial infarction and stent thrombosis. When all coronary bifurcations were combined, an advantage of double-kissing crush was observed in terms of MACE driven by lower rate of repeated revascularization. Further studies are required to define the best PCI bifurcation technique for left main coronary artery disease.

Evidence for the Cardioprotective Effects of Omega-3 Fatty Acids

2002 ◽  
Vol 36 (12) ◽  
pp. 1950-1956 ◽  
Author(s):  
Douglas N Carroll ◽  
Mary T Roth
Keyword(s):  
Myocardial Infarction ◽  
Fatty Acids ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Serum Triglyceride ◽  
Biomedical Literature ◽  
Omega 3 ◽  
Increased Risk

OBJECTIVE: To review available literature regarding the cardiovascular effects of marine-derived ω-3 fatty acids and evaluate the benefit of these fatty acids in the prevention of coronary heart disease. DATA SOURCES: Biomedical literature accessed through a MEDLINE search (1966–April 2002). Search terms included fish oil, omega-3 fatty acid, sudden death, hypertriglyceridemia, myocardial infarction, and mortality. DATA SYNTHESIS: Following an early 1970's observational investigation that ω-3 fatty acids may reduce the occurrence of myocardial infarction—related deaths in Greenland Eskimos, additional trials have been conducted that support this finding. Epidemiologic and clinical trial data suggest that ω-3 fatty acids may reduce the risk of cardiovascular-related death by 29–52%. In addition, the risk of sudden cardiac death was found to be reduced by 45–81%. Possible mechanisms for these beneficial effects include antiarrhythmic properties, improved endothelial function, antiinflammatory action, and reductions in serum triglyceride concentrations. ω-3 Fatty acids are fairly well tolerated; potential adverse effects include bloating and gastrointestinal distress, “fishy taste” in the mouth, hyperglycemia, increased risk of bleeding, and a slight increase in low-density-lipoprotein cholesterol. CONCLUSIONS: ω-3 Fatty acids may be beneficial and should be considered in patients with documented coronary heart disease. They may be particularly beneficial for patients with risk factors for sudden cardiac death.

Abstract 572: Hyperglycemia and Poor Outcomes in Patients without Diabetes Mellitus in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS): A Propensity Matched Analysis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Prakash C Deedwania ◽  
Bertram Pitt ◽  
Enrique V Carbajal ◽  
Ali Ahmed
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Propensity Scores ◽  
Cox Regression ◽  
Baseline Serum ◽  
Increased Risk

Background: The effect of hyperglycemia on outcomes in patients with acute MI (AMI) and low LVEF without diabetes mellitus is not well known. Methods: In the EPHESUS trial, of the 4411 non-DM patients, 554 had baseline hyperglycemia (≥140 mg/dL). Propensity scores for hyperglycemia were calculated for each of the 4411 patients based on 63 baseline covariates, and a greedy 1:8 matching protocol was used to match 400 and 2542 patients respectively with and without hyperglycemia. Matched Cox regression models were used to estimate associations between hyperglycemia and outcomes during 16 months of follow up. Results: Patients with hyperglycemia were more likely to be older, have higher heart rate, lower LVEF, and receive nitrates, statins, digoxin, loop diuretics, and PTCA during index admission. Unadjusted hazard ratios {HR} and 95% confidence intervals {CI} for hyperglycemia were: all-cause death (1.51; 1.22–1.87; P<0.001), cardiovascular (CV) death (1.52; 1.21–1.90; P<0.001), heart failure (HF) death (2.19, 1.46–3.29; P<0.001), all-cause hospitalization (1.23; 1.08–1.40; P=0.002), CV hospitalization (1.51, 1.24–1.84; P<0.001) and HF hospitalization (1.75; 1.37–2.25; P<0.001). In the matched cohort, hyperglycemia was significantly associated with CV death (HR=1.25, 95%CI=1.01–1.54; P=0.039), sudden cardiac death (HR=1.33; 95%CI=1.02–1.73, P=0.035) and fatal/nonfatal AMI (HR=1.53, 95%CI=1.07–2.19; P=0.04; Figure ). Conclusions: In non-diabetic post-AMI HF patients, hyperglycemia is a poor prognosticator and is associated with increased risk of fatal and non-fatal AMI, CV death, HF deaths, sudden cardiac death, and CV hospitalization. Figure Fatal or non fatal acute myocardial infarction (AMI) by baseline serum glucose in post-AMI patients with no known history of diabetes mellitus

Early Stent Thrombosis after Percutaneous Coronary Intervention for Acute Myocardial Infarction

2012 ◽  
Vol 7 (1) ◽  
pp. 33 ◽  
Author(s):  
Georgios J Vlachojannis ◽  
Bimmer E Claessen ◽  
George D Dangas ◽  
◽  
◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Percutaneous Coronary Intervention ◽  
Stent Thrombosis ◽  
Coronary Intervention ◽  
Treatment Modalities ◽  
Related Factors ◽  
Ongoing Research ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
St Elevation

Stent thrombosis (ST) is the most feared complication of coronary stent treatment because of its morbidity and mortality. Ongoing research is focusing on the frequency and the timing in various patient subsets as well as the factors associated with the occurrence of ST. The mechanism of ST is multifactorial, hence various procedure-, lesion- and patient-related factors have been associated with its occurrence. Beside these factors the role of adjunctive antithrombotic therapy remains unchallenged. Emerging data suggest that primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI) can be a predictor of subsequent ST. As patients presenting with STEMI are at increased risk of ST, employment of the optimal pharmacological, procedure- and device-related prevention and treatment modalities are imperative.

scholarly journals Head-to-Head Comparison of Consensus-Recommended Platelet Function Tests to Assess P2Y12 Inhibition—Insights for Multi-Center Trials

2020 ◽  
Vol 9 (2) ◽  
pp. 332
Author(s):  
Jean-Christophe Bélanger ◽  
Fabio Luiz Bandeira Ferreira ◽  
Mélanie Welman ◽  
Rahma Boulahya ◽  
Jean-François Tanguay ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Receptor Activation ◽  
P2y12 Receptor ◽  
Reactivity Index ◽  
Specific Method ◽  
Vasp Phosphorylation ◽  
Receptor Inhibitor

The vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation level is a highly specific method to assess P2Y12 receptor inhibition. Traditionally, VASP phosphorylation is analyzed by flow cytometry, which is laborious and restricted to specialized laboratories. Recently, a simple ELISA kit has been commercialized. The primary objective of this study was to compare the performance of VASP assessment by ELISA and flow cytometry in relation to functional platelet aggregation testing by Multiplate® whole-blood aggregometry. Blood from 24 healthy volunteers was incubated with increasing concentration of a P2Y12 receptor inhibitor (AR-C 66096). Platelet function testing was carried out simultaneously by Multiplate® aggregometry and by VASP assessment through ELISA and flow cytometry. As expected, increasing concentrations of the P2Y12 receptor inhibitor induced a proportional inhibition of platelet aggregation and P2Y12 receptor activation across the modalities. Platelet reactivity index values of both ELISA- and flow cytometry-based VASP assessment methods correlated strongly (r = 0.87, p < 0.0001) and showed minimal bias (1.05%). Correlation with Multiplate® was slightly higher for the flow cytometry-based VASP assay (r = 0.79, p < 0.0001) than for the ELISA-based assay (r = 0.69, p < 0.0001). Intraclass correlation (ICC) was moderate for all the assays tested (ICC between 0.62 and 0.84). However, categorization into low, optimal, or high platelet reactivity based on these assays was strongly concordant (κ between 0.86 and 0.92). In conclusion, the consensus-recommended assays with their standardized cut-offs should not be used interchangeably in multi-center clinical studies but, rather, they should be standardized throughout sites.

scholarly journals RR Variability in Acute Coronary Syndromes

2020 ◽  
Vol 70 (12) ◽  
pp. 4436-4441
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cardiac Death ◽  
Independent Predictor ◽  
Autonomic Modulation ◽  
Frequency Range ◽  
Increased Risk ◽  
Coronary Syndromes ◽  
The Time Domain ◽  
Rr Variability

Heart rate variability (HRV) is a simple measure that estimates cardiac autonomic modulation. Analysis in the time domain and frequency range of RR variability suggests that the negative prognosis of patients with acute myocardial infarction is related to the overall neuro-vegetative imbalance. The alteration of RR variability reflects the dysfunction of the autonomic nervous system and especially the reduction of parasympathetic tone. The results of this study confirm the association between the reduction of RR variability and the increased risk of adverse events and mortality after acute myocardial infarction. Moreover, it appears that RR variability is an independent predictor for atrial fibrillation. Keywords: RR variability, myocardial infarction, HRV, sudden cardiac death

scholarly journals Association Between Silent Myocardial Infarction and Long‐Term Risk of Sudden Cardiac Death

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Yun‐Jiu Cheng ◽  
Yu‐He Jia ◽  
Feng‐Juan Yao ◽  
Wei‐Yi Mei ◽  
Yuan‐Sheng Zhai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Population Attributable Fraction ◽  
Cardiovascular Health Study ◽  
Primary Study ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Silent Myocardial Infarction

Background Although silent myocardial infarction (SMI) is prognostically important, the risk of sudden cardiac death (SCD) among patients with incident SMI is not well established. Methods and Results We examined 2 community‐based cohorts: the ARIC (Atherosclerosis Risk in Communities) study (n=13 725) and the CHS (Cardiovascular Health Study) (n=5207). Incident SMI was defined as electrocardiographic evidence of new myocardial infarction during follow‐up visits that was not present at the baseline. The primary study end point was physician‐adjudicated SCD. In the ARIC study, 513 SMIs, 441 clinically recognized myocardial infarctions (CMIs), and 527 SCD events occurred during a median follow‐up of 25.4 years. The multivariable hazard ratios of SMI and CMI for SCD were 5.20 (95% CI, 3.81–7.10) and 3.80 (95% CI, 2.76–5.23), respectively. In the CHS, 1070 SMIs, 632 CMIs, and 526 SCD events occurred during a median follow‐up of 12.1 years. The multivariable hazard ratios of SMI and CMI for SCD were 1.70 (95% CI, 1.32–2.19) and 4.08 (95% CI, 3.29–5.06), respectively. The pooled hazard ratios of SMI and CMI for SCD were 2.65 (2.18–3.23) and 3.99 (3.34–4.77), respectively. The risk of SCD associated with SMI is stronger with White individuals, men, and younger age. The population‐attributable fraction of SCD was 11.1% for SMI, and SMI was associated with an absolute risk increase of 8.9 SCDs per 1000 person‐years. Addition of SMI significantly improved the predictive power for both SCD and non‐SCD. Conclusions Incident SMI is independently associated with an increased risk of SCD in the general population. Additional research should address screening for SMI and the role of standard post–myocardial infarction therapy.

Abstract 20675: Longest Available Follow-Up of Drug-Eluting Stents in Real World Practice - Outcomes up to 12 Years From the DESIRE Registry

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ricardo A Costa ◽  
Amanda Sousa ◽  
Adriana Moreira ◽  
Adriana Moreira ◽  
J. Ribamar Costa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stent Thrombosis ◽  
Cardiac Death ◽  
Cardiac Events ◽  
Residual Stenosis ◽  
Adverse Cardiac Events ◽  
Drug Eluting ◽  
Event Rates

Background: Despite the marked efficacy demonstrated by drug-eluting stents (DES) in reducing neointimal proliferation, and therefore, the need for target lesion revascularization (TLR), persistent concerns regarding long-term safety and efficacy, especially in more complex subset, are still. Methods: The DESIRE Registry is a large, prospective, non-randomized, single center study assessing the late outcomes of unselected pts treated with DES. Overall, 5,541 pts were consecutively enrolled from May/02-Jun/14. Clinical follow-up (FU) (97%) was performed yearly up to 12 yrs (median 4.9 yrs). Stent thrombosis (ST) was defined according to the ARC. Results: Mean age was 65 yrs, 31% had diabetes, 29% current smokers, 42% presented with ACS (17% recent myocardial infarction, MI), and the majority of lesions were highly complex (67% type B2/C). Overall, there were 8,919 lesions treated with 9,537 DES, and angiographic success was 99%. During the FU period, cumulative event rates were major adverse cardiac events (cardiac death, myocardial infarction, or TLR) 32%, myocardial infarction 8%, TLR 21%, and cardiac death 6%. As for stent thrombosis, overal rate was 2.4%, given that 95% of patients were free from this event up to 12 years. In the multivariate model, independent predictors of major adverse cardiac events were: prior revascularization by percutaneous intervention (HR 1.21, p=0.03) or surgery (HR 1.53, p<0.001), dyslipidemia (HR 1.20, p=0.03), renal insufficiency (HR 1.41, p<0.001), peripheral vascular disease (HR 2.06, p<0.001), long lesions (HR 1.38, p<0.001), acute coronary syndrome (HR 1.39, p<0.001), and residual stenosis (HR 1.02, p<0.001). As for stent thrombosis, predictors were: recent myocardial infarction (HR 2.66, p=0.001), multiple stents implanted (HR 1.89, p=0.002), saphenous vein graft (HR 2.21, p=0.004), and residual stenosis (HR 1.03, p=0.03). Conclusions: At very long-term follow-up (up to 12 years) in a large cohort of patients from the real world practice, cumulative event rates included TLR in 21% and stent thrombosis in 2.4%. Overall, there were no safety concers, given that 95% of patients were free from stent thrombosis up to 12 years.

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