Resolution of Pulmonary Embolism on CT Pulmonary Angiography

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1 Cardiopulmonary Imaging Original Research Stein et al. PE Resolution on Follow-Up CT ngiography Cardiopulmonary Imaging Original Research Paul D. Stein bdo Y. Yaekoub 2 Fadi Matta Muhammad Janjua 2 Rushi M. Patel 3 Lawrence R. Goodman 4 Martin L. Gross 5 James E. Denier 3 Stein PD, Yaekoub Y, Matta F, et al. Keywords: CT angiography, pulmonary embolism DOI:.224/JR.9.34 Received July 3, 9; accepted after revision October 25, 9. Department of Internal Medicine, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, 445 Woodward ve., Pontiac, MI ddress correspondence to P. D. Stein (steinp@trinity-health.org). 2 Department of Internal Medicine, St. Joseph Mercy Oakland Hospital, Pontiac, MI. 3 Department of Radiology, St. Joseph Mercy Oakland Hospital, Pontiac, MI. 4 Department of Radiology, Medical College of Wisconsin, Milwaukee, WI. 5 Department of Radiology, William eaumont Hospital, Troy, MI. JR ; 94: X// merican Roentgen Ray Society Resolution of Pulmonary Embolism on CT Pulmonary ngiography OJECTIVE. The objective of our study was to retrospectively determine the rate of resolution of pulmonary emboli (PEs) in individual vessels and the rate of complete resolution of PEs on CT angiography. MTERILS ND METHODS. Follow-up CT pulmonary angiograms, obtained during the period from January 6 through May 9, of 69 patients with acute PE from two hospitals were assessed. Initial and follow-up CT angiograms were reread together by one radiologist at both of the hospitals. Images were obtained using a -, 6-, -, or 64-MDCT angiography unit with a.5-mm collimation,.25- to 2.-mm reconstruction,.3- to.5-second rotation time, and 7.5-mm/rotation table speed. ll CT angiograms were obtained using a PE protocol. RESULTS. Follow-up CT angiograms were obtained in 35 men and 34 women who ranged in age from 7 to 92 years (mean age, 58 ± 7 [SD] years). Complete CT angiographic resolution of PE was seen in six of 5 patients (%) 2 7 days after diagnostic imaging. fter day 28, complete resolution occurred in 7 of 2 patients (8%). The main pulmonary arteries showed complete PE resolution during days 2 7 in seven of nine patients (78%) and after day 28 in 34 of 36 (94%). The lobar pulmonary arteries showed complete resolution of PE during days 2 7 in 23 of 33 patients (7%) and after 28 days in 44 of 48 (92%). The segmental pulmonary arteries showed complete resolution during days 2 7 in eight of 2 patients (38%) and after day 28 in 38 of 38 (%). CONCLUSION. Most patients (8%) showed complete resolution of PE on CT angiography after 28 days. PEs resolved faster in the main and lobar pulmonary arteries than in the segmental branches. P ulmonary emboli (PEs) resolve because of natural thrombolytic processes [, 2]. Follow-up with CT pulmonary angiography of patients with acute PE gives an opportunity for detailed evaluation of the rate of resolution of PE with only anticoagulant therapy. The focus of this investigation was to retrospectively assess the rate of clearance of PE from individual vessels and the rate of complete resolution of PE on CT angiograms in a subset of patients who underwent follow-up CT pulmonary angiography. This information would be useful in determining the extent to which PE can be expected to be seen in various pulmonary vessels as time passes after an acute episode. It would also be useful in determining the rate at which a PE completely resolves on CT angiograms in patients in whom imaging is delayed or in whom additional CT angiograms are obtained for follow-up. Materials and Methods Imaging and Patients This is a retrospective collaborative study from two hospitals: St. Joseph Mercy Oakland Hospital in Pontiac, MI, and William eaumont Hospital in Troy, MI. Imaging of acute PE at William eaumont Hospital was performed using a -, 6-, -, or 64-MDCT unit. t St. Joseph Mercy Oakland Hospital, imaging was performed using a 6- or 64-detector unit. Patients with acute PE shown on CT angiograms who underwent followup CT pulmonary angiography were included if they did not receive thrombolytic therapy and if the images were of interpretable quality. Only follow-up CT pulmonary angiograms obtained with a PE protocol were evaluated. ll patients except one received anticoagulant therapy. The remaining patient underwent surgery for placement of an inferior vena cava filter and did not receive anticoagulant therapy. The reason for additional CT angiograms for follow-up, when stated, was to JR:94, May 263

2 Stein et al. % of Patients With Complete n = n = 5 n = n = evaluate continuing or recurrent symptoms or to exclude a recurrence of PE. t St. Joseph Mercy Oakland Hospital, from October 6 through May 9, CT angiograms showed PE in 332 patients, among whom 38 (%) had additional CT angiograms for follow-up. t William eaumont Hospital, from January 6 through September 8, CT angiograms showed PE in 482 patients, among whom 3 (6%) had additional CT angiograms for follow-up. ll patients who, during the period of review, had additional CT angiograms for follow-up using a PE protocol were assessed. In six patients, more than one additional CT angiogram was obtained for followup. Only the first follow-up CT angiogram was included in this investigation. The attending physicians selected patients for additional CT angiography follow-up. pproval by the institutional review boards of both hospitals was obtained. Patients with acute PE were identified by a computer analysis of the hospitals records. The initial CT angiogram of each patient was reread with the follow-up CT angiogram by a local radiologist in both of the hospitals. oth radiologists had more than years experience with CT at the time of the study. They had access to the original requisition for an additional CT angiogram for followup, but no other clinical or radiologic information. The reviewers read the CT angiogram obtained at the time of acute PE diagnosis first without knowing the results of the follow-up CT angiogram. Then, the follow-up CT angiogram was brought up on a screen for a simultaneous comparison. t St. Joseph Mercy Oakland Hospital, a Centricity R workstation (GE Health Integrated IT Solutions) was used. t William eaumont Hospital, an IMPX workstation (GF) was used. Each CT pulmonary angiogram was interpreted for the presence of complete or partial occlusion of the following vessels: main pulmonary artery, right pulmonary artery, left pulmonary artery, right upper lobe pulmonary artery, right middle lobe pulmonary artery, right lower lobe pulmonary artery, left upper lobe pulmonary artery, lingular pulmonary artery, left lower lobe pulmonary artery, and segmental branches. The resolution of PEs in subsegmental branches was not assessed. We chose to exclude these cases because the positive predictive value of MDCT angiographic readings in patients in whom the largest branch showing PE was a subsegmental branch was only 25% in the Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) [3]. Complete angiographic resolution was defined as a CT pulmonary angiogram on follow-up that showed no evidence of PE in any vessel. The patient, therefore, no longer showed PE. Complete vessel resolution was defined as a CT pulmonary angiogram on follow-up that showed no PE in the vessel of interest. Other sites, however, may have continued to show PE. If the PE in the vessel of interest did not show complete resolution, there may have been no resolution or incomplete resolution. No attempt was made to characterize the degree of residual thrombi. No attempt was made to assess for the presence of webs or strictures. If the follow-up CT angiogram showed a new PE, which was defined as a PE in a larger vessel than the PE shown on the initial CT angiogram, the patient was excluded from investigation of complete angiographic resolution and the vessels in question were excluded from investigation of vessel resolution. Contralateral vessels, however, were evaluated for vessel resolution provided that no new PE was seen in a larger vessel. Contrast-enhanced CT, both for the initial and follow-up CT angiographic examinations, was performed after the injection of 9 35 ml of low-osmolar nonionic contrast material at a rate of ml/s. fter an injection-to-scan delay of 4 28 seconds, as determined by bolus-tracking software, or after a 5-mL test injection, CT angiography was performed at kvp and 3 m. The collimation was.5 mm with a.25- n = n = 2 Fig. Proportion of CT pulmonary angiograms of 69 patients showing complete angiographic resolution according to time of follow-up CT angiogram. Number of patients evaluated at each time interval is shown in each bar. to 2.-mm reconstruction. The rotation time was.3.5 second and table speed, 7.5 mm/rotation. The diagnostic criteria for acute PE by CT angiography were those of PIOPED II [3]: first, failure to opacify the entire lumen due to a central filling defect (the artery may enlarge compared with its peers); second, partial filling defect surrounded by contrast material on a cross-sectional image; third, railway tracking defined as contrast material between the central filling defect and the artery wall on an in-plane longitudinal image; and, fourth, a peripheral intraluminal filling defect (i.e., the eccentric filling defect makes an acute angle with the artery wall). Statistical Methods The chi-square test was used to assess differences of proportions (InStat version 3., Graph- Pad Software). Results Follow-up CT angiograms were obtained in 69 patients (35 men, 34 women; age range, 7 92 years; mean age, 58 ± 7 years [SD]). The CT angiograms were obtained on day of follow-up in one patient, on days 2 7 in 5 patients, on days 8 4 in patients, on days 5 2 in patients, on days in, and after 28 days in 2. Complete Only one patient had a follow-up CT angiogram on day after the initial diagnostic image and no changes were observed. mong the patients who had follow-up CT angiograms on days 2 7, complete CT angiographic resolution was seen in six of 5 patients (%) (Fig. ). mong the patients who underwent CT angiograms on days 8 4, complete angiographic resolution occurred in five of (5%). etween days 5 and 2, complete resolution occurred in nine of (82%). etween days 22 and 28, complete resolution was shown in seven of (64%). fter 28 days (mean, 83 days; median, 46 days; range, days), complete angiographic resolution occurred in 7 of 2 patients (8%). Resolution in Main Pulmonary rteries Complete resolution of PE in the main, left, and right pulmonary arteries of one patient did not occur within day ( of 3 [%]) (Fig. 2). During days 2 7, seven of nine (78%) main pulmonary arteries showed complete resolution of PE. From days 8 through 28, complete resolution occurred in of 2 (83%) main pulmonary arteries and after 264 JR:94, May

3 PE Resolution on Follow-Up CT ngiography % of Vessels With Complete % of Vessels With Complete Main, right, and left n = 3 Segmental n = n = 9 n = 2 n = 2 n = n = 28 n = day 28, complete resolution occurred in 34 of 36 (94%). There was no instance in which a PE in the main pulmonary artery resolved but resulted in new emboli in either the lobar or segmental branches. n example of resolution of a PE in the main and left pulmonary arteries is shown in Figure 3. Resolution in Lobar Pulmonary rteries Complete resolution of PE in four lobar pulmonary arteries of one patient did not occur within day ( of 4 (%]) (Fig. 2). During days 2 7, 23 of 33 (7%) lobar pulmonary arteries showed complete resolution of PE. From days 8 through 28, complete resolution occurred in 44 of 56 (79%) lobar pulmonary arteries and after day 28, in 44 of 48 (92%) lobar pulmonary arteries. n example of resolution of a PE in the right descending pulmonary artery just beyond the takeoff of the pulmonary artery branch to the right upper lobe is shown in Figure 4. There was no instance in which a PE in a lobar pulmonary artery resolved but resulted in new emboli in the segmental branches. Resolution in Segmental Pulmonary rteries In patients who had follow-up studies on day, PEs in the segmental pulmonary arteries were not observed on the first CT angiogram (Fig. 2). During days 2 7, eight of 2 (38%) segmental pulmonary arteries showed complete resolution of PEs. From days 8 n = 3 n = 22 n = 36 n = 38 C % of Vessels With Complete Lobar through 28, complete resolution occurred in 67 of 96 (7%) segmental pulmonary arteries and after day 28, in 38 of 38 (%). n example of resolution of a PE in a segmental branch of the left pulmonary artery is shown in Figure 4 and of a PE in a segmental branch of the right lower lobe in Figure 5. Comparison of Vessels During days 2 7, the PEs resolved at a faster rate in the main or lobar pulmonary arteries than in the segmental branches: 3 n = 4 n = 33 n = 6 n = n = 3 n = 48 Fig. 2 Resolution of pulmonary emboli (PEs) according to vessel and number of days after initial CT angiography. Number of vessels evaluated at each time interval is shown in each bar. C, ar graphs show time of follow-up imaging revealing resolution of PEs in main, right, and left pulmonary arteries (); lobar pulmonary arteries (); and segmental pulmonary arteries (C). of 42 (7%) versus eight of 2 (38%), respectively (p <.) (Fig. 2). However, complete resolution after day 28 occurred in 92 % of these vessels regardless of the order (size) of the vessels with PE. Discussion The proportion of patients showing complete resolution of PEs on the follow-up CT angiograms increased with the time after the initial diagnostic CT angiogram. CT pulmonary angiograms showed complete resolution Fig. 3 7-year-old man with stroke, chronic obstructive pulmonary disease, deep venous thrombosis, and acute pulmonary embolism., Initial CT angiogram shows thrombus (arrow) in main and left pulmonary arteries., Follow-up CT angiogram obtained 3 days after shows complete resolution. JR:94, May 265

4 Stein et al. in % of patients on days 2 7, 5% of patients on days 8 4, and 82% of patients on days 5 2. fter 28 days, there was no meaningful increase in the proportion of patients in whom complete angiographic resolution occurred, 8%. During days 2 7, PEs resolved at a faster rate in the main and lobar pulmonary arteries than those in the segmental branches, 7% versus 38%, respectively. However, complete resolution after day 28 occurred in 92 % of the vessels regardless of the order of the vessels. We did not assess the rate of PE resolution in the subsegmental branches. Images showing the subsegmental vessels were often unclear, so interpretation was uncertain. The difficulties of diagnosing PEs in the subsegmental vessels on CT angiography and even on conventional pulmonary angiography have been well documented [3, 4]. Kappa statistics Fig year-old woman with several episodes of dyspnea on exertion., Initial CT angiogram shows acute pulmonary embolism (arrow) with thrombus in right descending pulmonary artery just beyond takeoff of pulmonary artery branch to right upper lobe. In addition, there is thrombus in segmental branch of left pulmonary artery., Follow-up CT angiogram obtained 3 months after shows complete resolution of all emboli. Fig year-old woman with several episodes of dyspnea on exertion (same patient in Fig. 4)., Initial CT angiogram shows thrombus (arrow) in segmental branch of right lower lobe pulmonary artery., Follow-up CT angiogram obtained 3 months after shows complete resolution. for the diagnosis of PE in the subsegmental vessels have been shown to be low on conventional pulmonary angiograms [4]. With this background in mind, we decided not to evaluate the subsegmental vessels for PE. The results of previous studies in the literature with regard to the complete resolution of PEs on images (CT angiograms, conventional angiograms, and perfusion lung scans) are outlined in Table. The data in Table are arranged according to the time interval between the diagnostic image and the follow-up image. We are not aware of any prior studies showing the rate of resolution according to the order of vessels. Our results related to complete resolution are similar to those of López-aret et al. [5] (i.e., complete resolution in 9% of patients within 3 days). However, our results showed a higher proportion of patients with complete resolution after 28 days than the results reported by Van Rossum et al. [6] (32%) and Remy-Jardin et al. (48%) [7]. Regarding complete resolution of PE on conventional pulmonary angiograms or CT angiograms, previous investigators, based on pooled data, showed complete resolution after 7 days in two of 44 (5%) patients [2, 8 ] (Table ). In our experience, a larger proportion of patients showed complete resolution in 7 days: six of 6 patients (38%). In 2 days, previous investigators showed complete resolution in six of 5 patients (%) [2, 8], whereas our results showed complete resolution in 4 of 2 patients (67%) in 8 2 days. fter month, the proportion of patients showing complete resolution varied widely, but on average, PEs had resolved in 85 of 36 patients (63%) [2, 5 7]. PEs showed complete resolution after 28 days in 7 of 2 patients (8%). The rate of complete resolution on perfusion lung scans is also shown in Table. The proportion of patients with complete resolution of perfusion defects within 7 days was six of 89 (7%) [2], and based on pooled data, the proportion with complete resolution at 3 6 months was 78 of 2 patients (33%) [2, 3]. fter 4 years, complete resolution of perfusion scan defects, based on pooled data, was shown in 26 of 382 patients (68%) [, 4 6] (Table ). Wartski and Collignon [3] showed that 35 of 77 patients (46%) showed complete PE resolution on perfusion scans at 3 months if the initial pulmonary vascular obstruction was < 5% [3]. If the initial pulmonary vascular obstruction was 5%, only 7 of patients (2%) showed complete resolution on the perfusion scan. Menéndez et al. [2] showed that the size of residual defects at 6 months depended mainly on the size of defects at 7 days. lthough the size of the perfusion defect affected the proportion of patients with residual defects [3], our data showed that the size of individual vessels with PE did not affect the proportion of vessels that showed complete resolution after 28 days. This finding suggests that the total number of occluded end-arteries and not the size of the vessels or order of the vessels affect the proportion of patients with residual defects. strength of our investigation is the number of patients investigated, which is high in comparison with previous investigations. nother strength is that we evaluated the rate or resolution according to the order of the vessel involved, which has not been done previously 266 JR:94, May

5 PE Resolution on Follow-Up CT ngiography TLE : Resolution of Pulmonary Emboli Shown on Pulmonary ngiograms ccording to Duration of Follow-Up mong Patients Treated With nticoagulants, an Inferior Vena Cava Filter, or oth First uthor, Year of Publication [Reference No.] to our knowledge. There were several limitations of this investigation. The investigation was retrospective. Only a small proportion of the patients with PE had follow-up CT angiograms. Therefore, there may have been bias in the selection of patients for follow-up imaging. patient who is referred for follow-up CT pulmonary angiography may be at higher risk for residual and recurrent PEs than one who is not, and this bias may have impacted the results in favor of a higher prevalence of residual thrombi. ecause the study was retrospective, we were not always able to obtain some clinical information, such as the reason for the follow-up CT angiogram. Only one radiologist interpreted each CT angiogram. We did not look for sequelae of chronic PE (webs, strictures, mosaic perfusion, enlarged central pulmonary arteries, or pruning of the peripheral pulmonary arteries). need for additional follow-up studies to more accurately define the rate of resolution after documented PE has been identified [7]. Published rates of resolution differ, and the proportion of patients with residual thrombi Imaging Method Time Interval etween Diagnostic and Follow-Up Imaging also differs. Routine imaging with perfusion scans after cessation of anticoagulant therapy in patients with acute PE to establish a new baseline has been recommended [3]. In patients with persisting thromboembolic obstruction or with persisting cardiopulmonary complaints, one should be alert for the development of chronic thromboembolic hypertension [7]. It had been thought that chronic thromboembolic pulmonary hypertension occurs in only..5% of patients with acute PE [8]; however, more recent data indicate an incidence of 3.8% [9]. Recognition that PEs resolve at a faster rate in the main and lobar pulmonary arteries than in the segmental branches assists in recognizing the difficulties in diagnosing PE if the CT angiogram is delayed several days after the onset of symptoms. This information is also important for interpreting the significance of continuing thromboembolic obstruction when obtaining follow-up studies. In conclusion, after 28 days, 8% of our patients who underwent follow-up CT angiography showed complete resolution of PE on CT No. of Patients With Complete Resolution / Total No. of Patients (%) Dalla-Volta, 992 [] Conventional pulmonary angiography d /6 () Hirsh, 97 [9] Conventional pulmonary angiography d / () McDonald, 97 [] Conventional pulmonary angiography 2 d /9 () Dalen, 969 [2] Conventional pulmonary angiography 7 d /7 () Present study CT pulmonary angiography 7 d 6/6 (38) Fred, 966 [8] Conventional pulmonary angiography 7 d 2/2 () Present study CT pulmonary angiography 8 2 d 4/2 (67) Dalen, 969 [2] Conventional pulmonary angiography 2 d 2/ () Fred, 966 [8] Conventional pulmonary angiography 3 9 d 4/5 () López-eret, [5] CT pulmonary angiography 3 d 48/53 (9) Dalen, 969 [2] Conventional pulmonary angiography 34 d /2 (5) Van Rossum, 998 [6] CT pulmonary angiography 42 d 6/9 (32) Present study CT pulmonary angiography mo 7/2 (8) Remy-Jardin, 997 [7] CT pulmonary angiography mo 3/62 (48) Menéndez, 998 [2] Perfusion lung scanning 7 d 6/89 (7) Wartski, [3] Perfusion lung scanning 3 mo 52/57 (33) Menéndez 998 [2] Perfusion lung scanning 6 mo 26/83 (3) UKPET, 973 [] Perfusion lung scanning y 42/5 (84) a Miniati, 6 [5] Perfusion lung scanning y 53/235 (65) Paraskos, 973 [4] Perfusion lung scanning 2.4 y 28/43 (65) ellanova, 983 [6] Perfusion lung scanning 3 4 y 38/54 (7) Note UKPET = Urokinase Pulmonary Embolism Trial. a Residual perfusion defect < %. pulmonary angiograms. Emboli resolved at a faster rate in the main and lobar pulmonary arteries than in the segmental branches. However, complete resolution occurred in more than 9% of the PEs in the main, lobar, and segmental pulmonary arteries after 28 days regardless of the order of the vessels. References. [No authors listed]. The Urokinase Pulmonary Embolism Trial: a national cooperative study. Circulation 973; 47[suppl 2]:II II8 2. Dalen JE, anas JS Jr, rooks HL, Evans GL, Paraskos J, Dexter L. Resolution rate of acute pulmonary embolism in man. N Engl J Med 969; 2: Stein PD, Fowler SE, Goodman LR, et al. for the PIOPED II Investigators. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med 6; 354: Quinn MF, Lundell CJ, Klotz T, et al. Reliability of selective pulmonary arteriography in the diagnosis of pulmonary embolism. JR 987; 49: López-eret P, Pinto JM, Romero, Orgaz, JR:94, May 267

6 Stein et al. Fontcuberta J, Oblas M. Systematic study of occult pulmonary thromboembolism in patients with deep venous thrombosis. J Vasc Surg ; 33: Van Rossum, Pattynama PM, Tjin, Ton E, Kieft GJ. Spiral CT appearance of resolving clots at 6-week follow-up after acute pulmonary embolism. J Comput ssist Tomogr 998; 22: Remy-Jardin M, Louvegny S, Remy J, et al. cute central thromboembolic disease: posttherapeutic follow-up with spiral CT angiography. Radiology 997; 3:73 8. Fred HL, xelrad M, Lewis JM, lexander JK. Rapid resolution of pulmonary thromboemboli in man: an angiographic study. JM 966; 96: Hirsh J, McDonald IG, Hale G, O Sullivan EF, Jelinek VM. Comparison of the effects of streptokinase and heparin on the early rate of resolution of major pulmonary embolism. Can Med ssoc J 97; 4: FOR YOUR INFORMTION. McDonald IG, Hirsh J, Hale GS. The rate of resolution of pulmonary embolism and its effects on early survival. ustralas nn Med 97; 9[suppl ]: Dalla-Volta S, Palla, Santolicandro, et al. PIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism plasminogen activator Italian multicenter study 2. J m Coll Cardiol 992; : Menéndez R, Nauffal D, Cremades MJ. Prognostic factors in restoration of pulmonary flow after submassive pulmonary embolism: a multiple regression analysis. Eur Respir J 998; : Wartski M, Collignon M. Incomplete recovery of lung perfusion after 3 months in patients with acute pulmonary embolism treated with antithrombotic agents. J Nucl Med ; 4: Paraskos J, delstein SJ, Smith RE, et al. Late prognosis of acute pulmonary embolism. N Engl J Med 973; 289: Miniati M, Monti S, ottai M, et al. Survival and restoration of pulmonary perfusion in a long-term follow-up of patients after acute pulmonary embolism. Medicine 6; 85: ellanova, Cavalli F, ombi C, Capecchi V, Pavlica P, Viglietta G. Long-term outcome in nonmassive pulmonary embolism: radiologic, scintigraphic and functional correlation [in Italian]. Radiol Med 983; 69: Nijkeuter M, Hovens MM, Davidson L, Huisman MV. Resolution of thromboemboli in patients with acute pulmonary embolism: a systematic review. Chest 6; 29: Fedullo PF, uger WR, Kerr KM, Rubin LJ. Chronic thromboembolic pulmonary hypertension. N Engl J Med ; 345: Pengo V, Lensing W, Prins MH, et al.; Thromboembolic Pulmonary Hypertension Study Group. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 4; 35: The JR has made getting the articles you really want really easy with an online tool, Really Simple Syndication, available at It s simple. Click the yellow RSS button located in the menu on the left of the page. You ll be on your way to syndicating your JR content in no time. 268 JR:94, May

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