Predictors for thoracic aortic growth in patients with type B aortic dissection after thoracic endovascular aortic repair

Abstract

Objective

To identify independent predictors of thoracic aortic growth in patients with type B aortic dissection (TBAD) undergoing thoracic endovascular aortic repair (TEVAR).

Methods

A retrospective analysis of the patients undergoing TEVAR for TBAD or intramural hematoma (IMH) from April 2014 to April 2023 was performed. The baseline morphological data of TBAD was established through computed tomography angiography (CTA) before discharge. Patients were divided into two groups based on aortic growth: growth and no growth. Aortic growth defined as an increase ≥5 mm in thoracic maximal aortic diameter during any serial follow-up CTA measurement. Logistic regression following propensity score matching (PSM) was used to identify independent predictors for aortic growth. Receiver operating characteristic curve and cutoff value of independent predictors were calculated. Linear regression was used to establish a correlation between anatomical variables and follow-up aortic diameter.

Results

A total of 145 patients with TBAD (n = 122) or IMH (n = 23) undergoing TEVAR were included, with a male of 83.4% and a mean age of 56 ± 14.1 years. Patients in growth group and no growth group was 26 (17.9%) and 119 (80.1%), respectively. After using PSM method, matched regression analysis showed residual maximal tear diameter (OR = 0.889, 95% CI 0.830-0.952, p = 0.001) and follow-up aortic diameter (OR = 0.977, 95% CI 0.965-0.989, p < 0.001) were independent predictors for aortic growth. The cutoff value was 8.55 mm for residual tear diameter and 40.65 mm for follow-up maximal aortic diameter. The residual maximal tear diameter showed a linear correlation with follow-up aortic diameter (DW = 1.74, R2 = 6.2%, p = 0.033).

Conclusions

This study suggested that residual maximal tear diameter >8.55 mm and follow-up aortic diameter >40.65 mm could predict aortic growth in patients with TBAD undergoing TEVAR.

Keywords

Chronic type B aortic dissection thoracic endovascular aortic repair residual tear aortic growth predictor

Introduction

For the management of type B aortic dissection (TBAD), thoracic endovascular aortic repair (TEVAR) has mostly replaced open surgery repair due to lower morbidity and mortality.¹ The primary goal of TEVAR is covering the proximal entry tear, and promoting positive aortic remodeling. However, residual chronic TBAD is deteriorating the long-term results of TEVAR by increasing the rates of aortic growth, 26.1% to 49% of patients with chronic TBAD exhibited thoracic aortic growth after 2 years from TEVAR.^2–5 It’s usually considered an aortic growth when the aortic diameter enlarges by ≥ 5 mm.^6–8 Late complications, most notably the post-dissection aortic aneurysm (PDAA),⁹ often necessitate surgical, endovascular, or hybrid procedures to prevent aortic rupture.¹⁰

False lumen diameter >22 mm and patent false lumen^11–13 has proven to be predictors for late aortic growth in patients with chronic TBAD. Despite the potential benefits of TEVAR, its success has been limited by the retrograde flow through multiple distal residual tears.⁴ However, there was limited data on aortic growth outcomes from residual tears anatomy. Therefore, our study aims to identify independently predictors for aortic growth in patients with chronic TBAD after TEVAR.

Methods

Patient selection

Patients with TBAD or intramural hematoma (IMH) undergoing TEVAR at a single center were retrospectively evaluated from April 01, 2014, to April 30, 2023. Patients’ baseline characteristics and computed tomography angiography (CTA) data were collected. The baseline morphological data for the TBAD following TEVAR was established through CTA before discharge. Aortic growth defined as an increase ≥5 mm in thoracic maximal aortic diameter through follow-up CTA measurement.^8,14 Inclusion criteria included: (1) patients with TBAD or IMH; (2) patients undergoing TEVAR; (3) available DICOM-format data of CTA. The exclusion criteria included: (1) ascending aortic diseases, penetrating atherosclerotic ulcers, thoracic aortic aneurysms; (2) previous aortic replacement or TEVAR; (3) lack of pre- or post-operative CTA; (4) perioperative mortality. Patients with IMH were also included, as distinguishing this from aortic dissection was challenging.⁸ Any patients who did not meet all inclusion criteria or met any exclusion criteria were excluded.

Variables and definition

Variables included demographic data (age, gender), type of diagnosis (TBAD, IMH), history (smoker, alcohol use), comorbidities (hypertension, diabetes mellitus, coronary heart disease, renal insufficiency, Marfan’s syndrome), and the origin of renal or visceral arteries including arising from the true lumen (TL), false lumen (FL) or from a combination of both lumen (CL), measurements from preoperative CTA (preoperative maximal aortic diameter, patency status of false lumen including patent, partial thrombosis, and complete thrombosis), measurements from postoperative CTA (patency status of false lumen, number and size of residual tears, length of patent false lumen), and measurements from follow-up CTA (follow-up maximal aortic diameter). We only collected residual tear data from the CTA of patients with a residual false lumen following TEVAR.

As shown in the Figure 1, Symbol 1 was the distance of the residual tear from the main stent graft. Symbol 2 was the length of patent false lumen of residual aortic dissection. The length of coverage was the mean coverage length on aorta by stent grafts. The residual tears, which linked the false lumen to the true lumen, were located at a distance from the main stent graft. These residual tears included distal stent-induced new entry (dSINE). The diameter of all residual tears was measured, but only the first tear diameter and the maximal residual tear diameter were calculated in the study. According to STORAGE guidelines,¹⁵ residual tear diameter (Figure 2(a)) and aortic diameter (Figure 2(b)) measurements were taken from planes perpendicular to the aortic centerline using Endosize software (Therenva, Rennes, France). The length of the patent false lumen was measured along the aortic centerline (Figure 2(c)).

Figure 1.

The diagram of residual aortic dissection after thoracic endovascular aortic repair. Symbol 1 was the distance of the residual tear from the main stent graft. Symbol 2 was the length of patent false lumen of residual aortic dissection.

Figure 2.

(a) Measurement of the residual tear diameter was taken from planes perpendicular to the aortic centerline. (b) Measurement of the thoracic aortic diameter was taken from planes perpendicular to the aortic centerline. (c) The length of the patent false lumen was measured along the aortic centerline.

For patients with uncomplicated TBAD, initial management strategy was the best medical treatment. TEVAR was performed in the subacute phase (after 2 weeks). Conversely, for complicated TBAD, such as rupture or malperfusion, or uncomplicated TBAD with high-risk features, TEVAR was performed immediately.

Statistical analysis

Data was analyzed using IBM SPSS Statistics 26. Continuous variables were analyzed by t test, while dichotomous variables were analyzed by the chi-squared test. Potential predictors (p < 0.1) were analyzed using univariate and multivariate binary logistic regression. To analyze the anatomical variables of chronic TBAD, propensity score matching (PSM) was implemented to overcome other potential confounding bias. Receiver operating characteristic (ROC) curves, area under the curve (AUC), and cutoff values of independent predictors were obtained. Linear regression was used to establish a correlation between anatomical data of TBAD and follow-up maximal aortic diameter. Kaplan-Meier analysis was used to establish the event-free survival rate. Significance difference was defined as p < 0.05.

Results

Patient’s characteristics

A total of 145 patients were included, 122 diagnosed with TBAD and 23 with IMH. The mean age was 56 ± 14.1 years and 83.4% were male. The patient’s characteristics and postoperative morphological data of residual aortic dissection were shown in Table 1.

Table 1.

Potential predictor identifying on patients’ baseline characteristics and postoperative morphological data of residual aortic dissection.

Baseline characteristics	Total (n = 145)	Growth (n = 26)	No growth (n = 119)	p
Male, n (%)	121 (83.4)	23 (88.5)	96 (80.7)	0.077
Age, years	56 ± 14.1	56 ± 14.1	52.9 ± 13.3	0.222
Diagnosis				0.767
Type B aortic dissection, n (%)	122 (84.1)	23 (88.5)	99 (83.2)
Intramural hematoma, n (%)	23 (15.9)	3 (11.5)	20 (16.8)
Smoker, n (%)	72 (49.7)	19 (73.1)	53 (44.5)	0.01
Drinker, n (%)	69 (46.2)	18 (69.2)	49 (75.6)	0.016
Hypertension, n (%)	130 (89.7)	23 (88.5)	107 (89.9)	0.733
Diabetes mellitus, n (%)	10 (6.9)	2 (7.7)	8 (6.7)	1
Coronary artery disease, n (%)	14 (9.7)	2 (7.7)	12 (10.1)	1
Renal insufficiency, n (%)	15 (10.3)	2 (7.7)	13 (10.9)	1
Marfan’s syndrome, n (%)	1 (0.7)	0	1 (0.8)	1
Left ventricular ejection fraction, %	62.5 ± 4.7	62 ± 5.5	62.6 ± 4.5	0.624
Preoperative CTA	n = 145	n = 26	n = 119
Celiac artery arising
True lumen, n (%)	113 (77.9)	24 (92.3)	89 (74.8)	0.067
False lumen, n (%)	21 (14.5)	1 (3.8)	20 (16.8)
Combination of both, n (%)	11 (7.6)	1 (3.8)	10 (8.4)
Superior mesenteric artery arising				1
True lumen, n (%)	134 (92.4)	25 (96.2)	109 (91.6)
False lumen, n (%)	2 (1.4)	0	2 (1.7)
Combination of both, n (%)	9 (6.2)	1 (3.8)	8 (6.7)
Left renal artery arising				0.609
True lumen, n (%)	112 (77.2)	19 (73.1)	93 (78.2)
False lumen, n (%)	33 (22.8)	7 (26.9)	26 (21.8)
Combination of both, n (%)	0	0	0
Right renal artery arising				0.101
True lumen, n (%)	113 (77.9)	17 (65.4)	96 (80.7)
False lumen, n (%)	25 (17.2)	6 (23.1)	19 (16)
Combination of both, n (%)	7 (4.8)	3 (11.5)	4 (3.4)	0.532
Preoperative aortic diameter, mm	37.9 ± 7.3	39.6 ± 11	37.6 ± 7	0.397
Postoperative CTA	n = 123	n = 23	n = 100
No. of residual tears, n (%)	3.4 ± 1.6	4 ± 1.9	3.2 ± 1.4	0.051
First tear away from stent graft, mm	73.8 ± 50.5	75.3 ± 60.6	73.4 ± 47.6	0.891
First residual tear diameter, mm	5.2 ± 3.1	5.7 ± 4	5.1 ± 2.9	0.496
Maximal residual tear away from stent graft, mm	105.7 ± 57.3	113.4 ± 53.6	103 ± 58.6	0.532
Maximal residual tear diameter, mm	7.2 ± 2.9	8.7 ± 3.4	6.8 ± 2.6	0.013

Note. The bold values represent variables identified as potential predictors (p < 0.1).

For preoperative CTA, the maximal aortic diameter was 37.9 ± 7.3 mm. Among the celiac arteries, 77.9% originated from the TL, 14.5% from the FL, and 7.6% from the CL; Among the superior mesenteric artery (SMA), 92.4% originated from the TL, 1.4% from the FL, and 6.2% from the CL; Among the left renal artery, 77.2% originated from the TL, 22.8% from the FL; Among right renal artery, 77.9% originated from the TL, 17.2% from the FL, and 4.8% from the CL.

For the postoperative CTA before discharge, the No. of residual tears was 3.4 ± 1.6. The first residual tear diameter was 5.2 ± 3.1 mm, and the first tear was 73.8 ± 50.4 mm away from the stent graft. The maximal residual tear diameter was 7.2 ± 2.9 mm, and the maximal residual tear was 105.7 ± 57.3 mm away from the stent graft.

For the follow-up CTA (Table 2), the reduction, stabilization, and growth of thoracic aortic diameter was 22.1%, 60%, and 17.9%, respectively. The patent, partial or complete thrombosis in the false lumen were 44.4%, 42.2%, and 13.1%, respectively. The length of patent false lumen was 181.5 ± 74.8 mm. The follow-up maximal aortic diameter was 40.2 ± 8.3 mm.

Table 2.

Follow-up morphological data of residual aortic dissection through follow-up computed tomography angiography imaging.

Follow-up computed tomography angiography	Total (n = 123)	Growth (n = 23)	No growth (n = 100)	p
False lumen patency status				0.103
Patent, n (%)	40 (44.4)	11 (61.1)	29 (40.3)
Partial thrombosis, n (%)	38 (42.2)	6 (33.3)	32 (44.4)
Complete thrombosis, n (%)	12 (13.1)	1 (5.6)	11 (15.2)
Patent false lumen length, mm	181.5 ± 74.8	200.3 ± 64.3	175.8 ± 77.3	0.238
Follow-up maximal aortic diameter, mm	40.2 ± 8.3	46.6 ± 10.9	38.7 ± 6.9	0.001

Note. The bold values represent variables identified as potential predictors (p < 0.1).

Potential predictor identifying

Of the 145 patients, 119 in growth group, 26 in no growth group. The baseline characteristics of the patients and the factor screening results were presented in Table 1. The potential predictors (p < 0.1) included male (80.7% vs 88.5%, p = 0.077), smoker (44.5% vs 73.1%, p = 0.010), alcohol use (75.6% vs 69.2%, p = 0.016), celiac artery originating from TL (74.8 vs 92.3, p = 0.067), residual No. of tears (3.2 ± 1.4 vs 4 ± 1.9, p = 0.051), maximal residual tear diameter (6.8 ± 2.6 vs 8.7 ± 3.4, p = 0.013), and maximal aortic diameter (46.6 ± 10.9 vs 38.7 ± 6.9, p = 0.001).

Logistic regression analysis

As shown in Table 3, univariate logistic regression analysis showed that male (OR = 5.99, 95% CI 0.771 - 46.523, p = 0.087), smoker (OR = 0.296, 95% CI 0.116 - 0.757, p = 0.011), alcohol use (OR = 0.311, 95% CI 0.125 - 0.772, p = 0.012), celiac artery originating from TL (OR = 0.247, 95% CI 0.055 - 1.109, p = 0.068), maximal residual tear diameter (OR = 1.184, 95% CI 0.984 - 1.425, p = 0.073) and follow-up maximal aortic diameter (OR = 1.110, 95% CI 1.409 - 1.174, p < 0.001) might be potential predictors for aortic growth (p < 0.1). Furtherly multivariate analysis indicated that celiac artery originating from TL (OR = 0.089, 95% CI 0.010 - 0.789, p = 0.030), maximal residual tear diameter (OR = 1.249, 95% CI 1.003 - 1.554, p = 0.047) and follow-up maximal aortic diameter (OR = 1.164, 95% CI 1.076 - 1.125, p < 0.001) were predictors for aortic growth.

Table 3.

Binary logistic regression analysis to identify risk factors for distal aortic instability in TBAD patients undergoing TEVAR.

Variables	Univariate analysis		Multivariate analysis
Variables	p	OR (95% CI)	p	OR (95% CI)
Male	0.087	5.99 (0.771–46.523)	0.750	1.575 (0.096–25.807)
Smoker	0.011	0.296 (0.116–0.757)	0.394	0.500 (0.102–2.463)
Drinker	0.012	0.311 (0.125–0.772)	0.970	1.029 (0.224–4.730)
Celiac artery arising	0.068	0.247 (0.055–1.109)	0.030	0.089 (0.010–0.789)
No. of residual tears	0.161	1.279 (0.907–1.805)	ND	ND
Maximal tear diameter	0.073	1.184 (0.984 - 1.425)	0.047	1.249 (1.003–1.554)
Postoperative maximal aortic diameter	<0.001	1.110 (1.049–1.174)	< 0.001	1.164 (1.076–1.259)

TBAD: type B aortic dissection; TEVAR: thoracic endovascular aortic repair; OR = odds ratio; ND = not done. Note. The bold values showed a significant difference (p < 0.05) in predictors of aortic growth.

Propensity score matching

PSM was employed to control variables that were unrelated to the anatomy of chronic TBAD, including smoker and alcohol use. A total of 37 pairs completed the matching. There was no difference in smoker (growth group 29.4% vs no growth group 30.1%, p = 0.176) and alcohol use (growth group 36.3% vs no growth group 50.6%, p = 0.273) between the two groups, indicating a good matching effect.

As shown in Table 4. The maximal residual tear diameter (growth group 8.73 ± 3.37 mm vs no growth group 6.74 ± 2.57 mm, p = 0.011) and follow-up maximal aortic diameter (growth group 48.78 ± 12.03 mm vs no growth group 38.85 ± 6.87 mm, p < 0.001) showed significant differences. Further regression analysis showed that the maximal residual tear diameter (OR = 0.889, 95% CI 0.830-0.952, p = 0.001) and follow-up maximal aortic diameter (OR = 0.977, 95% CI 0.965-0.989, p < 0.001) were independent predictors for aortic growth in patients with TBAD after TEVAR.

Table 4.

Adjusted analysis of potential predictors of thoracic aortic growth in patients with TBAD after TEVAR.

Variables	One-way ANOVA analysis			Logistic regression analysis
Variables	No growth	Growth	p	OR (95% CI)	p
Smoker, n (%)	29 (30.1)	12 (29.4)	0.176	–	–
Alcohol use, n (%)	27 (50.6)	11 (36.3)	0.273	–	–
Celiac artery originating from true lumen, n (%)	49 (86.0)	16 (94.1)	0.675	–	–
Maximal tear diameter, mm	6.74 ± 2.57	8.73 ± 3.37	0.011	0.889 (0.830–0.952)	0.001
Follow-up maximal aortic diameter, mm	38.85 ± 6.87	48.78 ± 12.03	<0.001	0.977 (0.965–0.989)	<0.001

TBAD: type B aortic dissection; TEVAR: thoracic endovascular aortic repair. Note. p < 0.05 represents a significance difference.

ROC, AUC, and cutoff value

The maximal residual tear diameter had an AUC of 0.67 (p = 0.034, 95% CI 0.513 - 0.828) for predicting aortic growth (Figure 3, red curve). The cutoff value was 8.55 mm which predicted aortic growth with a sensitivity of 82.1% and specificity of 58.8% (Figure 3). Patients with a residual tear diameter ≥8.55 mm showed a higher proportion of aortic growth (50% vs 13.2%, p = 0.001).

Figure 3.

Receiver operating characteristic curves. Red curve: the residual maximal tear diameter had an AUC of 0.67 for predicting aortic instability. Blue curve: The follow-up thoracic aortic diameter had an AUC of 0.79 for predicting aortic instability. AUC: area under curve.

The follow-up maximal aortic diameter demonstrated an AUC of 0.79 (p < 0.001, 95% CI 0.694 - 0.895) for predicting aortic growth (Figure 3, blue curve). The cutoff value was 40.65 mm, which predicted aortic growth with a sensitivity of 88.5% and specificity of 68.1%. Follow-up maximal aortic diameter ≥40.65 mm was associated with a higher proportion of aortic growth (32.8% vs 7.1%, p < 0.001) than those with an aortic diameter <40.65 mm.

The follow-up time was 46.32 ± 6.49 months (ranging from 1 to 116 months). Linear regression showed both residual tear diameter (DW = 1.74, R² = 6.2%, p = 0.033) and preoperative aortic diameter (DW = 1.72, R² = 65.1%, p = 0.015) showed a linear correlation with postoperative descending aortic diameter (Figure 4(a)). Patients with a tear diameter ≥8.55 mm also showed a significantly larger follow-up maximal aortic diameter (45.69 ± 12.39 vs 39.46 ± 7.28 mm, p = 0.010) than those with a tear diameter <8.55 mm. For adverse events, pSINE was 3, type I endoleak was 2, no ruptures, post-dissection aortic aneurysms (≥6 cm) were 6, and relevant death was 6. In analyzing the event-free survival rates across different groups, no significant differences were observed in patients with a maximal residual tear diameter of <8.55 mm versus ≥8.55 mm (log-rank = 0.13, p = 0.715) (Figure 4(b)), the follow-up maximal aortic diameter of <40.65 mm versus ≥40.65 mm (log-rank = 0.72, p = 0.190) (Figure 4(c)), the no growth versus the growth group (log-rank = 2.35, p = 0.126) (Figure 4(d)), or between patients with patent false lumen and those with false lumen thrombosis (log-rank = 0.02, p = 0.880).

Figure 4.

(a) Both residual tear diameter (p = 0.033) (Red line) and preoperative aortic diameter (p = 0.015) (Blue line) showed a linear correlation with follow-up descending aortic diameter. (b) No differences were observed in patients with a maximal residual tear diameter of < 8.55 mm versus ≥ 8.55 mm (p = 0.715). (c) No differences were observed in patients with follow-up maximal aortic diameter of < 40.65 mm versus ≥ 40.65 mm (p = 0.190). (d) No differences were observed in patients with the no growth group versus the growth group (p = 0.126).

Discussions

This study found that residual tear diameter >8.55 mm and follow-up maximal aortic diameter >40.65 mm were independent predictors of distal aortic growth after TEVAR. In the study, results from univariate and multivariate regression analysis indicated that different predictors were associated with aortic growth, and factors unrelated to anatomical variables such as alcohol use and smoking were also identified. To address these confounding factors, PSM method was employed. The final matched binary logistic regression analysis revealed that residual tear diameter and follow-up maximal aortic diameter could independently predict distal aortic growth.

The 2022 ACC/AHA guidelines for aortic dissection recommended that an proximal entry tear >10 mm was a high-risk feature of TBAD.¹ And Evangelista et al.¹⁶ found that the proximal location of the primary entry tear could predict aortic growth, adverse events, and mortality. However, the residual tears were rarely analyzed. To our knowledge, our study was the first to find that residual tear diameter could independently predict aortic growth after TEVAR, and the residual tear diameter cut-off value was >8.55 mm to predict aortic growth. An ex-vivo study of chronic TBAD found that the larger the tear, the greater the false lumen pressure, resulting in aortic growth.¹⁷ Thus, it may be advisable to perform an additional graft implantation following a large residual tear during TEVAR.

Our study also found the residual tear diameter could predict both maximal aortic diameter and aortic growth. While preoperative aortic diameter did not pose a predictor for aortic growth, a linear relationship between preoperative and follow-up aortic diameter was found. Unfortunately, no significant correlations were identified between residual tear diameter or maximal aortic diameter and adverse events or mortality. Evidence from previous studies consistently found maximal aortic diameter could predict aortic growth, with the cutoff values ranging from 35–45 mm.^18–20 We found that patients with an aortic diameter exceeding 40.65 mm were at risk of aortic growth, the cut-off value supported by many previous studies^21–23 and guidelines.^1,8 Fortunately, the aortic growth did not show any significant correlation with mid-term reintervention or mortality in the study, but closer follow-up was recommended for patients with aortic diameter >40.65 mm owing to the risk of PDAA. Long-term results was needed.

Interestingly, it was also be found that the celiac artery originating from true lumen might predict distal aortic growth. A similar result was found by Sailer et al.²⁴ who found that branch vessel involvement in estimating flow from the false lumen was protective against aortic growth. As the first primary outflow in the descending aorta, the celiac artery played a critical role in the lumen shunt. However, adjusted logistic regression based PSM indicated that there was no correlation between celiac artery originating from true lumen and distal aortic growth.

In the study, no significant correlation was found between the No. of residual tears and aortic growth. Kotelis et al.²⁵ found presence of more than two entry tears was associated with faster overall diameter expansion and decrease of the cross-sectional surface of the true lumen over time. However, the results were controversial, because a multicenter study found increased No. of entry tears were associated with a decreased aortic growth rate.¹⁹

Limitation

There were some limitations in the study. This was a single-center retrospective analysis, and the sample was small, resulting in low-quality evidence. It should be noted that the dissected flap may be mobile, potentially causing measurement errors in the tear diameter readings.

Conclusion

To our knowledge, we firstly found that maximal residual tear diameter >8.55 mm was an independent predictor of thoracic aortic growth after TEVAR, it was reasonable to deal with large residual tears in the initial TEVAR Additionally, follow-up thoracic aortic diameter >40.65 mm also was a predictor of aortic growth. A closer follow-up was mandatory for those patients.

Footnotes

Acknowledgments

The authors thank Hao Liang (Department of Vascular Surgery, Tianjin Medical University General Hospital) for drawing Figure 1 in the paper.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Natural Science Foundation of China projects (No. 82241207 and No. 82070489); Tianjin Key Medical Discipline (Specialty) Construction Project; Tianjin Natural Science Foundation Youth Program (19JCQNJC09900), Tianjin Binhai New Area Health Commission Technology Project (2019BWKQ037), Tianjin Medical University General Hospital Youth Incubation Fund Project (ZYYFY2019014), and Tianjin Health Technology Project (ZC20189).

ORCID iDs

Yonghui Chen

Jiaxue Bi

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21.

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