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To Reviewer 1
1. Some grammatical corrections were made by a professional English edit
service.
2.
As you suggested, recurring bacteraemia with the same micro-organism
often due to intravascular focus (infected vascular prosthesis).
Then, it was
possible that graft infection had already existed when lumbar pyogenic
spondylitis was found out (which probably came from oral infection).
addition, the graft infection might had cured by through antibiotics.
In
However, 1st and 2nd
18F-FDG-PET/CT
demonstrated that almost same
SUVmax values (6.45 vs 6.43) and distribution patterns of FDG-uptake
around the aortic graft.
been negative.
not.
We believe it suggested that the graft infection had
Actually, we never know whether it was graft infection or
The point what we would like to stress is that regardless its diagnosis
(graft infection or not), FDG-PET/CT contributes to find remote organ
infection and determining following treatment policy.
So, we added following sentences (blue with underline);

In Case Report, Case1, Page 5.
< Eighteen months after the diagnosis, a second
resolution of the abnormal accumulation of
18F-FDG-PET/CT
18F-FDG
SUVmax (6.43) and the distribution pattern of
showed
in L5, while both
18F-FDG
around the aortic
graft were unchanged (Fig. 3) >

In Discussion, Page 9.
<18F-FDG-PET/CT enabled us to find an infectious nidus remote from the
graft in Case 1 and to diagnose aortic graft infection in Case 2. Graft
infection could have preceded and, in fact, caused the lumbar pyogenic
spondylitis in Case 1, as recurrent bacteremia with the same microorganism
suggested an intravascular focus. But we speculate that it was an extraaortic
source due to the lack of change in the appearance of the graft between the
first and second
18F-FDG-PET/CT
studies. Regardless,
18F-FDG-PET/CT
enabled the diagnosis of an infectious focus, which could then be addressed.
>
3.
Regarding to life long antibiotics in Case 2
Even though conjunctive omentopexy was added with repeat ascending
aorta replacement, the aortic valve prosthesis and aortic root graft
prosthesis were left in place.
selected.
Then, a long term antibiotics therapy was
We will attempt discontinue antibiotics in near future.
So, we added following sentences (blue with underline);

<
In Case Report, Case 2, Page 6
Minomycin hydrochloride 200 mg/day was begun on POD 8 as other
intravenous antibiotics were discontinued, and he remains on that dose as
an outpatient, because the old aortic valve prosthesis and aortic root graft
prosthesis were left in place.
4.
>
PET/CT-images: in clinical practice the images with only one color are
used.
That setting improves interpretation of the images. (I am very sorry,
but I could not understand your suggestion’s meaning.
The figures we
evaluated FDG-PET/CT were color.).
5.
Regarding to Echocardiography in Case 1.
No sign which suspecting graft infection, for example effusion around
vascular graft was detected.
We added following sentences (blue with
underline);

<
In Case Report, Case 1, Page 4
Echocardiography did not show any infectious signs, such as
intravascular vegetations or effusion around the graft. >
To Reviewer 2
1.
Fig1 and Fig 5 were removed, as followed your suggestion.
Then, figure
number was changed.
2. Regarding to Fig 4 (New Fig 3, 2nd FDG-PET/CT), this clearly
demonstrated
that
healed
spondylodiscitis,
while
a
substantial
physiological FDG accumulation around the vascular graft had not been
changed compared with the initial FDG-PET/CT. In addition, FDG
accumulation pattern and SUVmax were almost same compare with
those of 1st FDG-PET/CT.
important.
We believe these information was very
So, we think Fig 4 (New Fig 3) should not be removed.
We added following sentences (blue with underline);

In Case Report, Case 1, Page 5
< Eighteen months after the diagnosis, a second
resolution of the abnormal accumulation of
18F-FDG-PET/CT
18F-FDG
SUVmax (6.43) and the distribution pattern of
showed
in L5, while both
18F-FDG
around the aortic
graft were unchanged (Fig. 3). >

In Legends, Fig 3, Page 14
< It showed resolution of the abnormal accumulation of 18F-FDG in L5, while
both SUVmax (6.43) and the distribution pattern of
18F-FDG
around the
aortic graft were unchanged. >
3. Thank you for introducing the report which SUVmax value may help a
making diagnosis of graft infection.

We add following sentences.
In Discussion, Page 8
< According to Tokuda et al [12], an SUVmax value of greater than 8 in
perigraft tissue is suspicious for graft infection. This cut-off value must be
further assessed, as its experience was limited to only nine cases(thoracic
graft infections; 4 positive vs 5 negative cases). Actually in our Case 2, a
definite graft infection, SUVmax around the graft was lower than 8. >

In References, Page 13
(12) Tokuda Y, Oshima H, Araki Y, Narita Y, Mutsuga M, Kato K, Usui A.
Detection
of
thoracic
18F-fluorodeoxyglucose
tomography.
aortic
positron
prosthetic
emission
graft
infection
with
tomography/computed
Eur J Cardio-Thorac Surg 2013, 43:1183-7
Reviewer 3
Thank you very much for reviewing this manuscript.
We made various changes following other reviewer’s advices.
Reviewer 4
1.
Regarding how
do we
distinguish physiological
accumulation. It was very important and not easy.
or abnormal
As, we had described
in Discussion, Page 9, ; “ Extensive linear FDG uptake of mild-to-moderate
intensity along vascular grafts that have no evidence of infection has been
previously described [1, 4]”.
In addition, SUVmax may be felpful.
We add
following sentences.

In Discussion, Page 8
< According to Tokuda et al [12], an SUVmax value of greater than 8 in
perigraft tissue is suspicious for graft infection. This cut-off value must be
further assessed, as its experience was limited to only nine cases(thoracic
graft infections; 4 positive vs 5 negative cases). Actually in our Case 2, a
definite graft infection, SUVmax around the graft was lower than 8. >
2.
Regarding to relationship between CRP and FDG accumulation.
Generally, inflammatory cell increase glucose metabolism. Then, usually
there may be a positive correlation between CRP and FDG accumulation, on
the aspect.
But, FDG accumulation does not always means existing
inflammation.
In addition, even in low grade inflammation with low level of CRP,
FDG-PET may enable to detect its inflammatory focus because its sensitivity
is high.
But SUVmax should be relatively low.
Actually, when
FDG-PET/CT demonstrated sign of graft infection in Case 2, CRP level had
been as low as 3mg/dl.
(You can see time course of CRP in “original”
manuscript Fig 1 and Fig 5.
Unfortunately, these figures were removed in
revised manuscript because following other reviewer’s advice. )
3.
Of course, any cancer have never been pointed out in Case 2.
The
patient underwent repeated blood examinations, and whole body CT in many
times.