What’s known on the subject? and What does the study add?
ABSTRACT ÖZET
Amaç
99mTc-dimerkaprosüksinik asit (DMSA) sintigrafisi sepere renal
fonksiyonların (SRF) hesaplanmasında altın standarttır. DMSA ve 99mTc-
Merkaptoasetilglisin-3 (MAG-3) böbrek sintigrafileri hidronefrozlu
çocukların tanısında, izleminde ve operasyon endikasyonu belirlemede
kullanılmaktadır. Her iki teknik kullanılarak SRF hesaplanabilir.
Çalışmamızda hidronefrozlu çocuklarda MAG-3 sintigrafisinin DMSA
sintigrafisine göre SRF’yi belirlemedeki etkinliği araştırıldı.
Gereç ve Yöntem
Ocak 2009 ile Ağustos 2013 tarihleri arasında çocuk ürolojisi kliniğimizde
izlenen 81 hidronefrozlu çocuk çalışmaya dahil edildi. Çocukların tanı
anındaki yaşı, cinsiyeti, renal pelvis anterior posterior (AP) çapı, parankim
kalınlığı ve DMSA ile MAG-3 sintigrafisiyle belirlenen SRF’leri kaydedildi.
Çocuklar SRF’ye göre %45, %40, %10; AP çaplarına göre 5-10 mm, 10-
20 mm, 20-30 mm ve 30-40 mm ve yaşlarına gore 24 ay altı ve üstü
olarak gruplandırıldı. Gruplar her iki nükleer görüntüleme yönteminin SRF
değerleri açısından karşılaştırıldı.
Bulgular
Seksen bir çocuğun (54 kız, 27 erkek) ortalama yaşı 25,9±39,7 aydı.
Toplam 102 hidronefrozlu böbreğin (38 sol, 22 sağ ve 21 çift taraflı) tanı
anındaki ortalama AP çapları 22,0 mm idi (min:7, max:62). AP çapa ve
yaşa göre ayrılan gruplar arası SRF değerleri her iki görüntüleme tekniği
içinde benzerdi (p>0,05). Grupların SRF %45, %40, %10’a göre aralarında
istatistiki anlamlı fark saptanmadı (p>0,05, kappa >0,7, r=0,926 Pearson).
Objective
Nuclear imaging techniques such as 99mTc-dimercaptosuccinic acid
(DMSA) and 99mTc-mercaptoacetyltriglycine (MAG-3) are widely used for
the diagnosis and follow-up of urinary tract obstructions. Both imaging
techniques provide the differential renal function (DRF) in slightly
different ways. The aim of this study was to assess the MAG-3 scan as
an adjunct or alternative to DMSA for evaluating DRF in children with
hydronephrosis.
Materials and Methods
Eighty-one patients with hydronephrosis were enrolled in this study.
Patient age, sex, anteroposterior renal pelvis diameter (RPD) at the time
of diagnosis, parenchymal thickness and the DRF percentage found by
both DMSA and MAG-3 were recorded. DMSA scintigraphy was used for
detecting renal scars and estimating DRF. MAG-3 scintigraphy was used
for evaluation of renal clearance, the collecting system’s outflow pattern
and estimating DRF.
Results
A total of 102 renal units (38 left, 22 right and 21 bilateral) were
evaluated. High correlation rates were found when we compared both
tests’ DRF values according to antero-posterior renal pelvic diameter and
patient age (p>0.05). In all groups compared in the present study, both
tests demonstrated very similar results and DRF values. Statistical analysis
of cut-offs (45%, 40%, 10%) were also similar in both methods (p>0.05,
kappa >0.7, r=0.926 Pearson).
Of all publications in the field of urology, so far no study has demonstrated that mercaptoacetyltriglycine (MAG-3) scintigraphy is as effective as
dimercaptosuccinic acid (DMSA) scintigraphy in detecting DRF. Our study demonstrates that, in the evaluation of differential renal function (DRF) in
children with hydronephrosis, MAG-3 scintigraphy provides results similar to those obtained using DMSA scintigraphy and, therefore, that it can be used
alone in determining DRF.
1Marmara University Faculty of Medicine, Department of Urology, İstanbul, Turkey
2Marmara University Faculty of Medicine, Department of Pediatrics, İstanbul, Turkey
Cem Akbal1, Ahmet Şahan1, Asgar Garayev1, Çağrı Akın Şekerci1, Muhammed Sulukaya1,
Harika Alpay2, Tufan Tarcan1, Ferruh Şimşek1
Hidronefrozlu Çocuklarda Separe Renal Fonksiyonların DMSA ve MAG-3
Sintigrafisi ile Karşılaştırılması
Assessment of Differential Renal Function in Children with
Hydronephrosis: Comparison of DMSA and MAG-3
Doi: 10.4274/jus.366
Journal of Urological Surgery, 2015; 3: 129-134
130
Journal of Urological Surgery
2015;3: 129-134
Introduction
Hydronephrosis is a common problem in pediatric urology. There
is no absolute criterion used for determining urinary system
obstructios. The most widely accepted definition of late refers to
hydronephrosis generated by obstruction of the urinary system,
which subsequently causes progressive renal injury (1). Nuclear
imaging techniques such as 99mTc-dimercaptosuccinic acid (DMSA)
and 99mTc-mercaptoacetyltriglycine (MAG-3) are widely used for
the diagnosis and follow-up of urinary tract obstructions (2). DMSA
scan, specifically, is the reference imaging procedure for determining
renal cortical integrity and differential renal functions (DRFs) and this
feature makes it the most reliable method for detection of cortical
scarring (DRF) (3,4). DMSA scan is considered to be the most effective
method in this regard (5). However, MAG-3 scan is also good at
determining renal tubular functions such as renal uptake, excretion
and consequent drainage (6). Consequently, both methods can
calculate the contribution of each kidney to total renal function and
contribute to estimating the DRF percentage. Parenchymal features
of the kidney are best calculated with DMSA (2). Although MAG-3
allows for obtaining information about the collecting system and
the dynamics of the kidney, its percentage of DRF estimation with
sensitivity and specificity is 88-89% and 88-100%, respectively (2,7).
A difference between DRF values of more than 10% or a sole DRF
value below 45% is accepted as abnormal (8). 40% and 10% values
are often definitive for deciding on the form of treatment and on
the timing of surgical interventions (8). Particularly in such cases
described above, using both methods together is costly and leads to
more radiation exposure.
In this study, we aimed to evaluate the effectiveness of MAG-3 as
an alternative imaging method. The goal was investigate whether it
can replace DMSA imaging in evaluating DRF and to evaluate the
accuracy of decision-making for surgery indication as the stand-
alone imaging method.
Materials and Methods
The medical data of 81 patients with hydronephrosis, who attended
our pediatric urology department, were analyzed retrospectively.
Sonographically measured anteroposterior renal pelvis diameter (RPD),
parenchymal thickness and kidney dimensions were evaluated and
calculated by the radiology department at our hospital. The Society
for Fetal Urology guidelines for ultrasound grading of hydronephrosis
were used as a reference in this study (9).
Management and Follow-Up
For detailed evaluation, each patient underwent a physical
examination. A detailed medical history was obtained and urine
analysis, culture, urinary ultrasound and nuclear imaging were also
performed.
Urinary Ultrasound
Since transitory neonatal dehydration lasts about 1 week after
birth, all neonatal first urinary ultrasounds (US) are obtained after
this period. Ultrasound should assess the anteroposterior diameter
of the renal pelvis, calyceal dilatation, kidney size, thickness of the
parenchyma, cortical echogenicity, ureters, bladder wall and residual
urine volume.
Voiding Cystourethrogram
Children, who suffered from recurrent urinary tract infections (UTIs)
and had bilateral hydronephrosis, underwent voiding-cystouretrogram
(VCUG), enabling us to evaluate the uretral valves, and detect the
presence of ureteroceles, diverticula and vesicoureteral reflux.
Nuclear Imaging
DMSA and MAG-3 were performed together in all patients who were
enrolled in this study. DMSA scintigraphy was used for detecting
renal scars and estimating DRF. MAG-3 scintigraphy was used for
evaluation of renal clearance, the collecting system outflow pattern
and estimating DRF. All MAG-3 scintigraphies were performed under
standardized circumstances (hydration, transurethral catheter)
between the fourt and sixth weeks of life or after detection of
hydronephrosis by the nuclear medicine department at our hospital.
Indications for surgical intervention are an impaired DRF due to
obstruction or a decrease in DRF in subsequent studies and increased
anteroposterior diameter on ultrasound, and kidney detoriaration-
grade IV dilatation as defined by the Society for Fetal Urology. %10,
40%, 45% are important cut-off values to make surgical decisions.
More than 10% difference between the two renal units (<45% DRF) is
considered abnormal (8,10,11). In the case of serial renogram results,
less than 40% is the cut-off value to make the surgical decision for
pyeloplasty and 10% is the cut-off value to make the surgical decision
for a simple nephrectomy. The DMSA and MAG-3 DRF results of the
patients were categorized according to cut-off values (10%, 40%,
45%) and were later compared.
Since the kidneys complete their development during the first years of
postnatal life and reach their full functional maturity in adolescence,
the postnatal age criteria became important when DRF are compared
Akbal et al.
Comparison of DMSA and MAG-3 in Children with Hydronephrosis
ABSTRACT ÖZET
Sonuç
MAG-3 sintigrafisi SRF değerlendirmesinde DMSA sintigrafisi kadar
etkili bir testtir. Hidronefroz ile takip edilen çocukların SRF acısından
değerlendirilmesinde ve izleminde tek test olarak kullanılabilir.
Anahtar Kelimeler
Böbrek, hidronefroz, MAG-3, DMSA, separe fonksiyon, çocuk
hastalar
Conclusion
DMSA and MAG-3 are tests that are of assistance in the evaluation of
hydronephrosis. Compared to DMSA, MAG-3 also provides valuable
information to evaluate DRF values in hydronephrotic renal unit (RU).
Avoiding unnecessary DMSA imaging will save time and cost and prevent
over-radiation of the pediatric population.
Key Words
Kidney, hydronephrosis, MAG-3, DMSA, differential function, children
131
Journal of Urological Surgery
2015;3: 129-134
regarding to DMSA and MAG-3 results. Thus, both tests predictive
for DRF according to age were also compared. Patients with urinary
system anatomical abnormalities (solitary and horse shoe kidneys,
duplicated system, agenetic or nephrectomize) were excluded from
the study.
Statistical Analysis
Statistical analysis was performed using original SPSS software,
version 20.0 (IBM Corp, NY, USA). Each test was classified as <10%,
<40% and <45% according to DRF values. Inter-method analyses
were carried out by means of Kappa statistics. The McNemar and
Mann-Whitney U tests were also applied in the statistical analysis of
the study where necessary. A p value of less than 0.05 was considered
statistically significant.
Results
A total of 183 patients with hydronephrosis attended our pediatric
urology outpatient clinic. Data of 81 of these patients were available.
Fifty-four patients were male (66.7%) and 27 were female (33.3%).
A total of 102-38 left, 22 right and 21 bilateral-hydronephrotic renal
units were detected. The mean age of the patients at the time of
diagnosis was 25.9±39.7 months. Estimated mean anteroposterior
RPD was 22 mm (min:7, max:62). Thirty-six ureteropelvic junction-
plasty (UPJ-plasty), 3 ureteroneocystostomy (UNC), 3 posterior
ureteral valve (PUV) ablation and 5 diagnostic cystoscopy operations
were performed. Thirty-four of the patients included in this study
were diagnosed with transient hydronephrosis and did not require
any surgical intervention. These patients were followed using periodic
ultrasound screening (Table 1). Comparison of anteroposterior RPD
values measured during the follow-up by DMSA and MAG-3 RF is also
presented in Table 1. In all groups compared in the present study, both
tests demonstrated very similar results and DRF values. No statistically
significant difference was determined between the results.
The present study also analyzed DRF within 3 groups (≤45%, ≤40%
and ≤10%) for more accurate timing of surgical intervention or
follow-up. From those patients who were evaluated using DMSA, 20
renal units were detected at ≤45%, 14 renal units at ≤40% and 2 renal
units at ≤10%. MAG-3 also showed similar results: 27 renal units were
detected at ≤45%, 12 renal units at ≤40% and 3 renal unit ≤10%. The
results in each group were compared using the McNemar test and no
significant differences were found. A close correlation was determined
between the DRF values obtained by these two tests (Kappa values:
0.673, 0.725 and 0.794, respectively (substantial agreement)) (Table 2).
More detailed anteroposterior (AP) RPD statistics are summarized in
Table 3. We used 5 cut-offs and assessed DRF values within 5 groups:
5-10 mm: 11 patients, 10-20 mm: 31 patients, 20-30 mm: 21 patients,
30-40 mm: 13 patients and ≤40 mm: 5 patients. After classification of AP
RPD based on the cut offs, DRF values were assessed and DMSA-MAG-3
results were found N to be not statistically different (p≥0.05) (Table 3).
Sixty-six of the 81 patients were younger than 24 months at the
time of diagnosis (mean: 40.4±34.2 SD). The remaining 15 patients
were older than 24 months (mean: 407.2±184.4 SD weeks). MAG-3
demonstrated similar results to those of DMSA and no statistically
significant difference was found (Table 4). The scintigraphic results
as obtained by MAG-3 scan were very close to those by DMSA with
statistically significant correlations of DRF values (r=0.926) (Figure 1).
Akbal et al.
Comparison of DMSA and MAG-3 in Children with Hydronephrosis
Table 1. Comparison between 99mTc-DMSA and 99mTc-MAG-3 DRF results according to hydronephrosis etiology
n Right kidney DRF (%) Left kidney DRF (%) Hydronephrotic kidney
APD (mm) p value
Follow-up
DMSA 34 49.1 (±11.4) 50.8 (±11.4) 16.2 (±9.2) <0.408
MAG-3 34 48.5 (±12.8) 51.4 (±12.8)
UPJ-plasty
DMSA 36 52.6 (±12.0) 47.6 (±12.7) 28.6 (±12.5) <0.216
MAG-3 36 50.8 (±14.3) 49.2 (±12.6)
UNC
DMSA 3 61.6 (±11.5) 38.3 (±11.5) 14.5 (±2.1) <0.260
MAG-3 3 56.6 (±6.0) 43.3 (±6.0)
PUV ablation
DMSA 3 20.3 (±24.8) 79.6 (±24.8) 22.0 (±9.8) <0.697
MAG-3 3 21.6 (±22.5) 78.3 (±22.5)
Diagnostic cystoscopy
DMSA 5 41.6 (±27.0) 58.4 (±27.0) 17.0 (±9.1) <0.794
MAG-3 5 41.2 (±26.1) 58.8 (±26.1)
Total DMSA 81 49.6 (±14.7) 50.5 (±15.0) 22.0 (±12.2) <0.316
MAG-3 81 49.2 (±15.5) 50.8 (±15.0)
MAG-3: Mercaptoacetyltriglycine, DMSA: Dimercaptosuccinic acid, UNC: Ureteroneocystostomy, PUV: Posterior ureteral valve, UPJ-plasty: Ureteropelvic junction-plasty,
APD: Anterior-posterior diameter, DRF: Differential renal function
Table 2. DMSA and MAG-3 comparison with regard to specific DRF results (≤45%, ≤40% and ≤10%)
DRF/Total DMSA DRF % MAG-3 DRF % p value (McNemar test) Kappa value
<45% / Total 20/81 (24.6%) 27/81 (33.3%) p=0.065 0.673 (very good)
<40% / Total 14/81 (17.3%) 12/81 (14.8%) p=0.687 0.725 (very good)
<10% / Total 2/81 (2.4%) 3/81 (3.7%) p>0.05 0.794 (very good)
MAG-3: Mercaptoacetyltriglycine, DMSA: Dimercaptosuccinic acid, DRF: Differential renal function, RPD: Renal pelvis diameter
132
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2015;3: 129-134
Discussion
DMSA and MAG-3 are tests that are of assistance in the evaluation
of hydronephrosis and that are often employed together during the
clinical decision making process (8). Although the pharmacokinetic
properties of the nuclear agents employed in the two tests differ,
both tests predict the separated renal functions (12,13). In the present
study, it was concluded that in the case of patients for which DMSA
and MAG-3 are utilized regardless of the etiology of hydronephrosis,
considering separated renal functions and variables such as patient
age, the degree of hydronephrosis and etiology is believed to separate
the two tests; in the clinical setting, MAG-3 can be employed in place of
DMSA. A statistically significant difference was not detected between
the two tests when they were compared based on hydronephrosis
degree and etiology and patient age. The two tests were also found to
be highly similar and compatible when compared in terms of clinical
applicability.
The subject of the present study arose from a desire to minimize
radionuclide evaluation in the pediatric patient population. In this
study, the aim was to compare the results obtained using DMSA
and MAG-3 and contrast management in the different conditions
of hydronephroticrenal units such as transient hydronephrosis,
ureteropelvic junction obstruction (UPJO), vesicoureteric reflux (VUR),
posterior urethral valve (PUV), ectopic ureter based on DRF values.
DMSA is a radionuclide molecule that enters the proximal and distal
tubules of the kidney. For this reason, it is a method of choice for
cortical assessment. MAG-3 is mostly excreted by the proximal
tubules; it enters the collecting systems and leaves the kidneys very
fast. DMSA scan is usually performed 2-3 hours after the DMSA
injection. But MAG-3 images are obtained immediately after the
injection of MAG-3. Both techniques, therefore, estimate the kidneys`
contribution to total renal function in slightly different ways.
In the evaluation of hydronephrosis, assessment of DRF is essential
to provide a prognosis or to determine whether to perform surgery.
Although DMSA scan is the most reliable method in measuring
DRF (4), the long residence time in the renal cortex results in over-
radiation of the children who have to attend nuclear medicine clinic
twice for later scanning. In addition, evaluation by means of DMSA is
limited to only cortical assessment, not the collecting system outflow
pattern (3,4,14). Other agents, such as MAG-3, also measure DRF and
are employed in the evaluation of renal clearance. MAG-3 is cleared
from the blood by the renal tubules and excreted into the collecting
system (15,16). Therefore, it is possible to evaluate renal perfusion,
tubular function, tubular secretion to the collecting system and the
urodynamics of the collecting system by means of MAG-3. Thity
minutes after injection, most tracer activity leaves the kidney, which
is an important advantage of this technique as it makes the radiation
dose received by the patient less than that received by a patient
undergoing a DMSA scan. It should also be noted that MAG-3 takes
less time and requires less follow-up visits. The radiation exposure for
a DMSA study is approximately ten times higher than that for a MAG-
3 study, thus, eliminating the need for the DMSA study will reduce
radiation exposure. This change in practice would, therefore, result in
considerable savings in time, cost and radiation burden (13).
When previously published studies on this topic are reviewed, one
comes to see that there have been many studies comparing the
correlation between these two techniques. However, to our knowledge,
all such similar studies have been published in nuclear medicine or
radiology journals. None of them include clinical prognosis of the
disease (13,17,18,19). In addition, worldwide, no such article has been
published by a pediatric urology clinic.
Akbal et al.
Comparison of DMSA and MAG-3 in Children with Hydronephrosis
Tablo 3. Comparison DMSA and MAG-3 according to AP RPD and
DRF
Anteroposterior RPD
(mean)
n
DRF (%)
p value (right kidney) (left kidney)
5-10 mm
DMSA
11
48.5 51.5
0.929
MAG-3 48.6 51.4
10-20 mm
DMSA
31
50.1 50.1
0.752
MAG-3 50.3 49.6
20-30 mm
DMSA
21
51.3 49.6
0.050
MAG-3 53.5 48.3
30-40 mm
DMSA
13
49.6 50.3
0.399
MAG-3 48.3 51.6
40 mm
DMSA
5
52.4 47.6
0.522
MAG-3 56.2 43.8
MAG-3: Mercaptoacetyltriglycine, DMSA: Dimercaptosuccinic acid,
DRF: Differential renal function, RPD: Renal pelvis diameter, AP: Anteroposterior
Table 4. Patients age at the time of diagnosis and comparison of
results
Age Mean n
Std.
deviation p value
<24 month
DMSA 47.6 66 34
MAG-3 47.5 66 34 0.923
>24 month
DMSA 53.3 15 184
MAG-3 51.4 15 184 0.193
MAG-3: Mercaptoacetyltriglycine, DMSA: Dimercaptosuccinic acid
Figure 1. Kaplan meier analyses of cancer spesific survival between the groups
100.00
80.00
60.00
40.00
20.00
.00
.00 20.00 40.00 60.00 80.00 100.00
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Journal of Urological Surgery
2015;3: 129-134
The first published articles comparing the two techniques, DMSA and
MAG-3, included only a few patients. Piepszet et al.(12) performed
and evaluated both test on healthy volunteers. As a result, they found
similar results.
Aktaş et al. (17) compared MAG-3 and DMSA RRF estimations and
assessed the reproducibility of these estimations in children with
unilateral hydronephrosis. Their results showed that DMSA and MAG
3 were correlated for both time intervals and for observers. DRF
estimation can be a problem in infants and in patients with higher
grades of hydronephrotic kidney. Only comparison with 45% was
slightly different in each test (17). Consequently, it is determined that
both screening techniques gave us similar results for follow-up and
for timing of operations. Therefore, we support that both techniques
can be used alone for further evaluations.
Ritchie et al. (13) compared DRF values calculated using 99mTc-DMSA
and those calculated using 99mTc-MAG-3 in pediatric patients and
again found good correlation between DMSA and MAG-3.
In the present study, the mean DRF of the left unit with 99mTc-
DMSA was 48.9% (SD 16.4) and was 49.6% (SD 15.6%) using 99mTc-
MAG-3. Thus, both tests showed a significant correlation with each
other. There was a lack of consistency between DRF estimations or
supranormal functions only in a limited number of cases (Tables 1, 4).
The measurement of DRF can be overestimated by 99mTc-MAG-3 in
the affected kidneys (5).
Although many decisions regarding surgery are based on the
functional changes detected by serial diuretic renography evaluations,
the ability of MAG-3 in estimating DRF has been questioned. In
follow-up, DRF values of 10%, 40%, 45% are important cut-off values
to make surgical decisions. More than 10% difference between the
two renal units (<45% DRF) is considered an abnormal test result
(8,10,11). According to serial renogram, less than 40% is the cut-off
value to make a surgical decision for ureteroplasty and 10% is the
cut-off value to make a surgical decision for simple nephrectomy. In
the present study, there were no statistically significant differences
in prognosis and management based on the values presented by the
two nuclear imaging methods. Only 2 patients presented dissimilar
results according to DRF 40% (DMSA: 39% and 39% vs MAG-3: 43%
and 45%, respectively) and 1 patient according to 10% (DMSA: 4%
vs MAG-3: 15%). Renal cortical thickness, pelvic anterior-posterior
diameter (APD), urine and blood tests do not contribute to follow-up
results.
In the calculation of clearance adjusted according to the body mass
index during childhood, those kidneys that demonstrated progressive
maturation until the third week, drew a plateau until year 1, appeared
to grow 1.5 times in size by year 2 and later appeared to become
fixed (20). In the present study, values obtained in 24 months were
compared and there were similar test results in each test. Regardless
of whether the kidney completes maturation or not, their power is
unchanging in determining separated renal functions.
Study Limitations
Our study included a small number of patients with low renal function
(at ≤40% and at ≤10%).
Conclusion
The results suggest that in routine clinical management and follow
up, MAG-3 scan will provide accurate DRF, similar to that with
DMSA. MAG-3 provides additional information on the urodynamics
of the urinary tract avoiding unnecessary radiation exposure besides
being timesaving. The results of MAG-3 do not change the clinical
decision on the management of the condiditon and patient follow-
up. Therefore, it is possible to regard the 99mTc-MAG-3 as adequate
in evaluating DRF as an initial screening test in children with various
renal disorders. The 99mTc DMSA scan is the only suitable in doubtful
cases such as those involving small cortical focal defects.
Ethics Committee Approval: The study were approved by the
Marmara University of Local Ethics Committee, Informed Consent:
Consent form was filled out by all participants, Concept: Cem Akbal,
Tufan Tarcan, Ferruh Şimşek, Design: Cem Akbal, Tufan Tarcan, Ferruh
Şimşek, Data Collection or Processing: Ahmet Şahan, Asgar Garayev,
Çağrı Akın Şekerci, Harika Alpay, Analysis or Interpretation: Ahmet
Sahan, Cem Akbal, Literature Search: Ahmet Sahan, Asgar Garayev,
Writing: Cem Akbal, Ahmet Şahan, Peer-review: Internal peer-
reviewed, Conflict of Interest: No conflict of interest was declared
by the authors, Financial Disclosure: The authors declared that this
study has received no financial support.
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