Successful reperfusion, rather than number of passes, predicts clinical outcome after mechanical thrombectomy

2019 ◽  
Vol 12 (6) ◽  
pp. 548-551 ◽  
Author(s):  
Daniel A Tonetti ◽  
Shashvat M Desai ◽  
Stephanie Casillo ◽  
Jeremy Stone ◽  
Merritt Brown ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Mechanical Thrombectomy ◽  
Multivariate Logistic Regression Analysis ◽  
Functional Independence ◽  
Study Cohort ◽  
Vessel Occlusion ◽  
Nihss Score ◽  
Group 3 ◽  
Group 2 ◽  
Number Of Passes

IntroductionFor patients undergoing mechanical thrombectomy, numerous (>3) thrombectomy passes may be harmful. However, non-recanalization leads to poor outcomes. For patients requiring multiple thrombectomy passes to achieve reperfusion, it remains unclear if the risk/benefit ratio favors recanalization.ObjectiveTo test the hypothesis that the benefits afforded by successful reperfusion outweigh the risk conveyed by the numerous passes required.MethodsWe retrospectively reviewed prospectively collected data for patients presenting to a comprehensive stroke center with anterior circulation large vessel occlusion (ACLVO) and undergoing thrombectomy requiring more than one pass over 24 months. We stratified patients into three groups: group 1 (successful reperfusion in 2–3 passes), group 2 (successful reperfusion in ≥4 passes), and group 3 (unsuccessful reperfusion).Results250 patients with ACLVO constituted the study cohort. Despite similar demographics, group 2 patients had better clinical outcomes than those in group 3 at 24 hours (National Institutes of Health Stroke Scale (NIHSS) score 13.5 vs 19.1, p<0.001) and at 90 days (modified Rankin Scale score 0–2 rates of 31.1% vs 0.0%, p=0.006) On multivariate logistic regression analysis, age (p=0.034), Alberta Stroke Program Early CT Score (p<0.01), NIHSS score (p=0.02), and parenchymal hematoma type 2 (p=0.015) were significant predictors of functional independence among those who achieved successful reperfusion, but the number of passes required did not predict outcome for these patients (p=0.74).ConclusionPatients who achieve successful reperfusion after many passes have better clinical outcomes than those who do not, despite the number of passes and procedural time required. The number of passes required to achieve successful reperfusion beyond the first pass is not a predictor of functional independence.

Abstract P488: The Impact of First Pass Effect on Acute Ischemic Stroke Clinical Outcomes: Why We Need to Continue to Improve Mechanical Thrombectomy?

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Ameer E Hassan ◽  
Mahmoud Dibas ◽  
Amr Ehab El-Qushayri ◽  
Sherief Ghozy ◽  
Adam A Dmytriw ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Clinical Outcomes ◽  
Mechanical Thrombectomy ◽  
Functional Independence ◽  
Vessel Occlusion ◽  
First Pass Effect ◽  
Improved Outcomes ◽  
First Pass ◽  
The Impact

Background: Mechanical thrombectomy (MT) has significantly improved outcomes of acute ischemic stroke (AIS) patients due to large vessel occlusion (LVO). The first-pass effect (FPE), defined as achieving complete reperfusion (mTICI3/2c) with a single pass, was reported to be associated with higher functional independence rates following EVT and has been emphasized as an important procedural target. We compared MT outcomes in patients who achieved FPE to those who did not in a real world large database. Method: A retrospective analysis of LVO pts who underwent MT from a single center prospectively collected database. Patients were stratified into those who achieved FPE and non-FPE. The primary outcome (discharge and 90 day mRS 0-2) and safety (sICH, mortality and neuro-worsening) were compared between the two groups. Results: Of 580 pts, 261 (45%) achieved FPE and 319 (55%) were non-FPE. Mean age was (70 vs 71, p=0.051) and mean initial NIHSS (16 vs 17, p=0.23) and IV tPA rates (37% bs 36%, p=0.9) were similar between the two groups. Other baseline characteristics were similar. Non-FPE pts required more stenting (15% vs 25%, p=0.003), and angioplasty (19% vs 29%, p=0.01). The FPE group had significantly more instances of discharge (33% vs 17%, p<0.001), and 90-day mRS score 0-2 (29% vs 20%, p<0.001), respectively. Additionally, the FPE group had a significant lower mean discharge NIHSS score (12 vs 17, p<0.001). FPE group had better safety outcomes with lower mortality (14.2% vs 21.6%, p=0.03), sICH (5.7% vs 13.5, p=0.004), and neurological worsening (71.3% vs 78.4%, p=0.02), compared to the non-FPE group. Conclusion: Patients with first pass complete or near complete reperfusion with MT had higher functional independence rates, reduced mortality, symptomatic hemorrhage and neurological worsening. Improvement in MT devices and techniques is vital to increase first pass effect and improve clinical outcomes.

Presence of the hyperintense acute reperfusion marker on MRI after mechanical thrombectomy for large vessel occlusion is associated with worse early neurological recovery

2016 ◽  
Vol 9 (7) ◽  
pp. 641-643 ◽  
Author(s):  
Rishi Gupta ◽  
Chung-Huan Johnny Sun ◽  
Dustin Rochestie ◽  
Kumiko Owada ◽  
Ahmad Khaldi ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Reperfusion Injury ◽  
Mechanical Thrombectomy ◽  
Binary Logistic Regression ◽  
Functional Independence ◽  
Large Vessel ◽  
Neurological Recovery ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Nihss Score

BackgroundMechanical thrombectomy has become the accepted treatment for large vessel occlusion in acute ischemic stroke. Unfortunately, a large cohort of patients do not achieve functional independence with treatment, even though the results are more robust than with medical management. The hyperintense acute reperfusion marker (HARM) on MRI is an indication of the breakdown of the blood–brain barrier and reperfusion injury.ObjectiveTo examine the hypothesis that the presence of HARM on MRI correlates with worse neurological recovery after reperfusion therapy.MethodsWe retrospectively reviewed 35 consecutive patients who between February 24, 2016 and April 23, 2016 underwent MRI to determine the presence of HARM after thrombectomy for anterior circulation large vessel occlusion. Demographic, radiographic imaging, and outcome data were collected. Univariate and binary logistic regression models were performed to assess predictors for improvement of the National Institutes of Health Stroke Scale (NIHSS) score by ≥8 points at 24 hours.ResultsThe 35 patients studied had an average age of 64±14 years of age with a median NIHSS score of 15 (IQR 9–20). Eighteen patients (51%) were found to have a HARM-positive MRI. In univariate analysis, patients with HARM were older, had lower reperfusion rates and more postprocedural hemorrhages. In binary logistic regression modeling, the absence of HARM was independently associated with a ≥8-point NIHSS score improvement at 24 hours (OR=7.14, 95% CI 1.22 to 41.67).ConclusionsThis preliminary analysis shows that the presence of HARM may be linked to worse neurological recovery 24 hours after thrombectomy. Reperfusion injury may affect the number of patients achieving functional independence after treatment.

scholarly journals Number of passes in mechanical thrombectomy: where is your limit?

2020 ◽  
Vol 33 (3) ◽  
pp. 78-82
Author(s):  
A. Filioglo ◽  
J.E. Cohen ◽  
N. Simaan ◽  
A. Honig ◽  
R.R. Leker
Keyword(s):  
Mechanical Thrombectomy ◽  
Short Review ◽  
Functional Independence ◽  
Hemorrhagic Transformation ◽  
Published Data ◽  
Vessel Occlusion ◽  
Procedural Time ◽  
Time Required ◽  
The Impact ◽  
Number Of Passes

Background and aims. Stent retriever based thrombectomy is the mainstay of treatment of acute ischemic stroke caused by large vessel occlusion. However, recanalization is sometimes not achieved even after multiple passes of the thrombectomy device. Whether revascularization becomes futile or harmful with an increasing number of passes as well as criteria for when to halt attempting recanalization remain unknown. The purpose of our work is to analyze literature data on this issue. Materials and methods. We performed a short review of the literature and summarized evidence on the impact of repeated stentriever attempts on outcome.Results. Despite some controversies, the published data indicate that up to 30 % of patients still reach favorable outcome even when ≥5 stentriever passes are performed. Probability of obtaining functional independence after multiple stentriever attempts is even higher in patients with lower baseline NIHSS score. Patients who achieve successful reperfusion after ≥5 passes have significantly higher rates of functional independence and significantly lower rates of hemorrhagic transformation compared with those who do not achieve reperfusion. Rate of target recanalization after ≥4 passes may reach 19 %. Number of passes alone is not an independent negative predictor of functional independence. The impact of multiple stentriever attempts on hemorrhagic transformation has not been well-established.Conclusions. Target vessel recanalization is an essential goal of mechanical thrombectomy, which should be pursued despite the additional number of passes and procedural time required. Number of stentriver attempts is not a game- changing factor in the decision to abort the procedure for technical futility. Treatment decisions need to be individualized for each patient based on operator’s experience and preferences, patient and clot-specific characteristics.

scholarly journals Mechanical Thrombectomy for Acute Stroke Due to Large-Vessel Occlusion Presenting With Mild Symptoms

2021 ◽  
Vol 12 ◽  
Author(s):  
Feifeng Liu ◽  
Hao Shen ◽  
Chen Chen ◽  
Huan Bao ◽  
Lian Zuo ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Acute Stroke ◽  
Mechanical Thrombectomy ◽  
Multivariate Logistic Regression Analysis ◽  
Functional Independence ◽  
Large Vessel ◽  
Large Vessel Occlusion ◽  
Multivariate Logistic Regression ◽  
Anterior Circulation ◽  
Vessel Occlusion

Purpose: To evaluate the safety and efficacy of mechanical thrombectomy (MT) for acute stroke due to large vessel occlusion (LVO), presenting with mild symptoms.Methods: A prospective cohort study of patients with mild ischemic stroke and LVO was conducted. Patients were divided into two groups: MT group or best medical management (MM) group. Propensity score matching (PSM) was conducted to reduce the confounding bias between the groups. The primary outcome was functional independence at 90 days. The safety outcome was symptomatic intracranial hemorrhage (sICH). Univariate and multivariate logistic regression analyses were used to identify the independent factors associated with outcomes.Results: Among the 105 included patients, 43 were in the MT group and 62 in the MM group. Forty-three pairs of patients were generated after PSM. There were no significant differences in sICH rates between two groups (p = 1.000). The MT group had a higher proportion of independent outcomes (83.7% MT vs. 67.4% MM; OR 2.483; 95% CI 0.886–6.959; p = 0.079) and excellent outcomes (76.7% MT vs. 51.2% MM; OR 3.150; 95% CI 1.247–7.954; p = 0.013) compared to the MM group, especially in patients with stroke of the anterior circulation (p &lt; 0.05). Multivariate logistic regression analysis showed that small infarct core volume (p = 0.015) and MT treatment (p = 0.013) were independently associated with excellent outcomes.Conclusions: Our results suggest that MT in stroke patients, presenting with mild symptoms, due to acute LVO in the anterior circulation may be associated with satisfactory clinical outcomes.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT04526756.

Abstract 1122‐000096: Transradial Results in Faster Recanalization in Left Anterior Circulation Stroke and Bovine Arch

2021 ◽  
Vol 1 (S1) ◽  
Author(s):  
Jorge H Moreno ◽  
Alberto Maud ◽  
Sheriff Faheem ◽  
Mohammad Rauf A Chaudry ◽  
Vikas Gupta ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Cerebral Circulation ◽  
Functional Outcomes ◽  
Mechanical Thrombectomy ◽  
Pass Rate ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Skin Puncture ◽  
Academic Center ◽  
Number Of Passes

Introduction : We compared technical and clinical outcomes of transradial (TRA) versus transfemoral (TFA) access for mechanical thrombectomy (MT) of acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the left anterior cerebral circulation of bovine origin. Methods : A single‐center retrospective review of a prospectively maintained neuro‐interventional database from a large volume service in a tertiary academic center. Procedural metrics, technical, and clinical outcomes data were collected and analyzed for patients who underwent MT presenting with AIS and LVO in the left anterior circulation of bovine origin. Primary outcomes included the average number of passes, single first effective pass, rate of successful recanalization (thrombolysis in cerebral infarction (TICI) score ≥ 2b), 3‐month disability modified Rankin Scale (mRS) score ≤2, time from skin puncture to microcatheter placement and recanalization. Results : Between January 2018 and January 2021, 26 patients (TRA = 13, TFA = 13) underwent MT. The TRA cohort had a significantly shorter time in minutes for skin puncture to microcatheter placement (TRA: 17.0± 5.8 vs TFA: 35.4± 20.5, P = 0.0001), shorter skin puncture to recanalization (TRA: 34.0± 15.6 vs TFA: 58.1± 34.6, P = 0.01), and shorter total fluoroscopy time (TRA: 13.8±9.4 vs TFA: 29.5±18.0, P = 0.03). The 3‐month mRS score of 0–1 was higher in the TRA group (38.5% vs 7.69%, P = 0.06). Conclusions : In patients with LVO in the left anterior cerebral circulation of bovine origin, right TRA access permits more direct navigation and provides a stable platform resulting in shorter procedure times and faster recanalization with the potential to improve functional outcomes.

scholarly journals Embotrap Extraction & Clot Evaluation & Lesion Evaluation for NeuroThrombectomy (EXCELLENT) Registry design and methods

2021 ◽  
pp. neurintsurg-2021-017671
Author(s):  
Adnan H Siddiqui ◽  
Muhammad Waqas ◽  
Waleed Brinjikji ◽  
Simon De Meyer ◽  
Karen Doyle ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Mechanical Thrombectomy ◽  
Safety Data ◽  
Functional Independence ◽  
Clinical Findings ◽  
Histopathological Analysis ◽  
Imaging Findings ◽  
Vessel Occlusion ◽  
Registration Number ◽  
Design And Methods

BackgroundRelationships between occlusive clot histopathology, baseline characteristics, imaging findings, revascularization rates, and clinical outcomes of stroke patients with large vessel occlusion (LVO) are not well understood. This study will assess the real-world experience on the efficacy and safety of using the EmboTrap device as the first approach in LVO patients and explore the associations between clot histological characteristics, imaging and clinical findings, revascularization rates, and clinical outcomes.MethodsProspective, global, multicenter, single-arm, imaging core laboratory, and clot analysis central laboratory observational registry. Adult patients (>18 years) with LVO, treated with EmboTrap as the first attempted device, will be eligible for study participation.ResultsUp to 1000 subjects at 50 international sites may be enrolled. Occlusive clots will be collected from at least 500 subjects. Independent central and imaging core laboratories will perform clot analysis and image adjudication. Statistical analysis will assess the association between imaging and clinical findings, clot characteristics, subject comorbidities, revascularization, and clinical outcomes. Study endpoints are functional independence (modified Rankin Scale score ≤2 at 90 days), expanded Thrombolysis In Cerebral Infarction (eTICI) score ≥2b50 rate, first-pass effect, number of passes, embolization into new territory, symptomatic intracranial hemorrhage, and 90-day mortality.ConclusionsThe EXCELLENT registry will provide reproducible effectiveness and safety data of EmboTrap for its use for mechanical thrombectomy. Additionally, the study will characterize the blood clots retrieved during mechanical thrombectomy with respect to their composition and histopathological analysis and potential correlations with clinical and imaging findings.Trial registration numberNCT03685578.

Revascularization and functional outcomes after mechanical thrombectomy for acute ischemic stroke in elderly patients

2020 ◽  
Vol 132 (4) ◽  
pp. 1182-1187 ◽  
Author(s):  
Carrie E. Andrews ◽  
Nikolaos Mouchtouris ◽  
Evan M. Fitchett ◽  
Fadi Al Saiegh ◽  
Michael J. Lang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Elderly Patients ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Multivariate Logistic Regression Analysis ◽  
Standard Of Care ◽  
Stroke Severity ◽  
Vessel Occlusion ◽  
Younger Patients ◽  
Success Of Treatment

OBJECTIVEMechanical thrombectomy (MT) is now the standard of care for acute ischemic stroke (AIS) secondary to large-vessel occlusion, but there remains a question of whether elderly patients benefit from this procedure to the same degree as the younger populations enrolled in the seminal trials on MT. The authors compared outcomes after MT of patients 80–89 and ≥ 90 years old with AIS to those of younger patients.METHODSThe authors retrospectively analyzed records of patients undergoing MT at their institution to examine stroke severity, comorbid conditions, medical management, recanalization results, and clinical outcomes. Univariate and multivariate logistic regression analysis were used to compare patients < 80 years, 80–89 years, and ≥ 90 years old.RESULTSAll groups had similar rates of comorbid disease and tissue plasminogen activator (tPA) administration, and stroke severity did not differ significantly between groups. Elderly patients had equivalent recanalization outcomes, with similar rates of readmission, 30-day mortality, and hospital-associated complications. These patients were more likely to have poor clinical outcome on discharge, as defined by a modified Rankin Scale (mRS) score of 3–6, but this difference was not significant when controlled for stroke severity, tPA administration, and recanalization results.CONCLUSIONSOctogenarians, nonagenarians, and centenarians with AIS have similar rates of mortality, hospital readmission, and hospital-associated complications as younger patients after MT. Elderly patients also have the capacity to achieve good functional outcome after MT, but this potential is moderated by stroke severity and success of treatment.

SOFIA catheter for direct aspiration of large vessel occlusion stroke: A single-center cohort and meta-analysis

2021 ◽  
pp. 159101992110053
Author(s):  
Federico Bolognini ◽  
Pablo A Lebedinsky ◽  
Mariano Musacchio ◽  
Mariette Delaitre ◽  
Abdoulaye M Traoré ◽  
...  
Keyword(s):  
Rescue Therapy ◽  
Meta Analysis ◽  
Functional Independence ◽  
Large Vessel ◽  
Study Cohort ◽  
Large Vessel Occlusion ◽  
First Line ◽  
Vessel Occlusion ◽  
Global Rate ◽  
Symptomatic Intracranial Hemorrhage

Background and Purpose Direct aspiration (DA) using large-bore distal aspiration catheters is an established strategy for the endovascular thrombectomy (EVT) of large-vessel occlusion stroke (LVOS). However, the performance of individual catheters like SOFIA has yet to be examined. Methods We present a cohort of 144 consecutive patients treated with first-line DA and SOFIA 6 F Plus catheter for LVOS. We also conducted a systematic review of the literature searching multiple databases for reports on thrombectomy with DA and SOFIA catheters and performed a meta-analysis of recanalization, safety, and clinical outcomes. Results In the study cohort a successful recanalization (mTICI 2b-3) rate of 75.7% was achieved with DA alone, the global rate for functional independence (90-day mRS 0-2) was 40.3%. For the metanalysis we selected nine articles that included a total of 758 patients treated with first-line thrombectomy with the SOFIA catheters. The mTICI 2b-3 rate was 71.6% (95%CI, 66.3-76.5%) while a rescue stent-retriever was used in 24.1% (95%CI, 17.7-31.9%) of cases. The overall mTICI2b-3 rate after DA and rescue therapy was 88.9% (95%CI, 82.6-93.1%). We found a pooled estimate of 45.6% (95%CI, 38.6-52.8%) for functional independence, a mortality within 90 days of 19% (95%CI, 14.1-25.0%) and a rate of 5.8% (95%CI, 4.2-8.0%) of symptomatic intracranial hemorrhage. Conclusion The DA approach for LVOS with the SOFIA catheters is highly effective with an efficacy and safety profile comparable to those found in contemporary thrombectomy trials and observational studies that use other devices or approaches.

Etiology of Cartilage Lesions Does Not Affect Clinical Outcomes of Patellofemoral Autologous Chondrocyte Implantation

Cartilage ◽  
2021 ◽  
pp. 194760352110309
Author(s):  
Alexandre Barbieri Mestriner ◽  
Jakob Ackermann ◽  
Gergo Merkely ◽  
Pedro Henrique Schmidt Alves Ferreira Galvão ◽  
Luiz Felipe Morlin Ambra ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Autologous Chondrocyte Implantation ◽  
Second Generation ◽  
Cartilage Lesion ◽  
Chondrocyte Implantation ◽  
Group 3 ◽  
Group 2 ◽  
Autologous Chondrocyte ◽  
Group 1

Objective To determine the relationship between cartilage lesion etiology and clinical outcomes after second-generation autologous chondrocyte implantation (ACI) in the patellofemoral joint (PFJ) with a minimum of 2 years’ follow-up. Methods A retrospective review of all patients that underwent ACI in the PFJ by a single surgeon was performed. Seventy-two patients with a mean follow-up of 4.2 ± 2.0 years were enrolled in this study and were stratified into 3 groups based on the etiology of PFJ cartilage lesions: patellar dislocation (group 1; n = 23); nontraumatic lesions, including chondromalacia, osteochondritis dissecans, and degenerative defects (group 2; n = 28); and other posttraumatic lesions besides patellar dislocations (group 3; n = 21). Patient’s mean age was 29.6 ± 8.7 years. Patients in group 1 were significantly younger (25.4 ± 7.9 years) than group 2 (31.7 ± 9.6 years; P = 0.025) and group 3 (31.5 ± 6.6 years; P = 0.05). Body mass index averaged 26.2 ± 4.3 kg/m2, with a significant difference between group 1 (24.4 ± 3.2 kg/m2) and group 3 (28.7 ± 4.5 kg/m2; P = 0.005). A clinical comparison was established between groups based on patient-reported outcome measures (PROMs) and failure rates. Results Neither pre- nor postoperative PROMs differed between groups ( P > 0.05). No difference was seen in survivorship between groups (95.7% vs. 82.2% vs. 90.5%, P > 0.05). Conclusion Cartilage lesion etiology did not influence clinical outcome in this retrospective study after second generation ACI in the PFJ. Level of Evidence Level III, retrospective comparative study.

scholarly journals Acute and Chronic Kidney Dysfunction and Outcome After Stroke Thrombectomy

2021 ◽  
Author(s):  
Simon Fandler-Höfler ◽  
Balazs Odler ◽  
Markus Kneihsl ◽  
Gerit Wünsch ◽  
Melanie Haidegger ◽  
...  
Keyword(s):  
Hospital Stay ◽  
Mechanical Thrombectomy ◽  
Multivariable Analysis ◽  
Unfavorable Outcome ◽  
Large Vessel ◽  
Study Cohort ◽  
Large Vessel Occlusion ◽  
Kidney Dysfunction ◽  
Vessel Occlusion ◽  
The Impact

AbstractData on the impact of kidney dysfunction on outcome in patients with stroke due to large vessel occlusion are scarce. The few available studies are limited by only considering single kidney parameters measured at one time point. We thus investigated the influence of both chronic kidney disease (CKD) and acute kidney injury (AKI) on outcome after mechanical thrombectomy. We included consecutive patients with anterior circulation large vessel occlusion stroke receiving mechanical thrombectomy at our center over an 8-year period. We extracted clinical data from a prospective registry and investigated kidney serum parameters at admission, the following day and throughout hospital stay. CKD and AKI were defined according to established nephrological criteria. Unfavorable outcome was defined as scores of 3–6 on the modified Rankin Scale 3 months post-stroke. Among 465 patients, 31.8% had an impaired estimated glomerular filtration rate (eGFR) at admission (< 60 ml/min/1.73 m2). Impaired admission eGFR was related to unfavorable outcome in univariable analysis (p = 0.003), but not after multivariable adjustment (p = 0.96). Patients frequently met AKI criteria at admission (24.5%), which was associated with unfavorable outcome in a multivariable model (OR 3.03, 95% CI 1.73–5.30, p < 0.001). Moreover, patients who developed AKI during hospital stay also had a worse outcome (p = 0.002 in multivariable analysis). While CKD was not associated with 3-month outcome, we identified AKI either at admission or throughout the hospital stay as an independent predictor of unfavorable prognosis in this study cohort. This finding warrants further investigation of kidney–brain crosstalk in the setting of acute stroke.

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