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Translational Andrology and Urology, 2023

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5

Traction groups (17% vs. 24% at 2.5 V, 19% vs. 24% at 5 V,
23% vs. 27% at 7.5 V; α >0.05 for all). Furthermore, ratsthat underwent PTT showed comparable EF to those in the
Sham surgery group at all voltages (24% vs. 32% at 2.5 V,
24% vs. 28% at 5 V, 27% vs. 39% at 7.5 V; α >0.05 for all)(Figure 2). No voltage data was recorded for one of the
traction animals due to technical difficulties, so n=7 for thatgroup.

SPL

*

34

**

32
SPL, mm

30
28
26
24
22
20

Starting length
Sham

Day 28
Crush

Western blots

TractioneNOS
Western blot analysis was performed on corporal tissue,
which revealed significantly greater eNOS expression in
the Traction group relative to the Crush group (1.6 vs. 0.5;
α <0.05). Sample S1 had to be excluded due to apparent
contamination when creating the protein lysate. There wasno significant difference in eNOS expression between the
Sham and Traction groups (Figure 3A,3B).

Figure 1 Graph showing average SPL of the Sham, Crush, andTraction group preoperatively and at the end of traction. The
Traction group had significantly greater SPL than the Sham group.
The Traction group had significantly greater SPL than the Crushgroup. ANOVA with Tukey-Kramer post-hoc analysis: *, α <0.05;**, α <0.01. SPL, stretched penile length; ANOVA, analysis ofvariance.

Geudens et al. In vivo and ex vivo radiological assessment of COVID-19

3656

HIF-1αHIF-1αwestern blot (Figureon allCOVID-3
ARDS 3C) was performed
IPF
samples, but the blot containing animals 1–4 for the Sham,
Crush, and Traction group appeared contaminated andwas thereby excluded from analysis. Analysis of animals
5–8 from each group revealed significantly greater HIF-1α
expression in the Traction group relative to the Crush group(2.1±1.4 vs. 0.3±0.2; α <0.05). There was no significant
difference between the Sham and Traction group (1.1±0.5
vs. 2.1±1.4; α >0.05) or the Sham and Crush groups (1.1±0.5
vs. 0.3±0.2; α >0.05).

ΔICP/MAP

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A0.50

Control 1

0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.00

COVID-1

COVID-2**

Middle lobe

ΔICP/MAP
Upper lobe

*

2.5 V
Sham

5V
Crush

7.5 V
Traction

Figure 2 Graph of EF as determined by change in ΔICP/MAP.

eNOS IHC

The ΔICP/MAP in the Sham group was significantly greater than
Lower lobe

the Crush group at 2.5, 5, and 7.5 V. ANOVA with Tukey-Kramer
post-hoc analysis: *, α <0.05. EF, erectile function; ΔICP/MAP,
intracavernosal pressure/mean arterial pressure.

EF

B

Bronchiectasis

GGO

Consolidations

Slides stained with eNOS IHC are shown below (Figure 4).
IHC was performed on several slides from each group(Sham n=3, Crush n=3, Traction n=4). Compared to the
Crush group, the Traction group had noticeably increased
expression of eNOS throughout the corpora. This confirms
thatReticulations
the increased eNOS
expression observedon western
Honeycombing
Septal thickening
blot is due to increased expression in the corpora.

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Thirty days after surgery, EF was assessed by measuring
the ΔICP/MAP during cavernous nerve stimulation at 2.5,
5, and 7.5 V. Animals that received a sham operation had
Trichrome staining
significantly greater EF (ΔICP/MAP) compared to the
Crush group at all voltages (32% vs. 17% at 2.5 V, 38% vs.
Trichrome staining was used to obtain SM-to-COL ratios
19% at 5 V, 39% vs. 23% at 7.5 V; α <0.05 for all). Therefor each group (Figure 5). Smaller SM-to-COL ratios
Figure 5 CT features of COVID-19 lungs per lobe compared to control, ARDS, and IPF. (A) Density of COVID-19 lungs is increased in all
indicate less SM and more fibrosis. The Sham and Traction
was no significant difference in EF between the Crush andlobes compared to controls while deterioration is equivalent in ARDS and IPF. (B) The most prevalent and typical CT features (blue arrows)
are shown. COVID, coronavirus disease; ARDS, acute respiratory distress syndrome; IPF, idiopathic pulmonary fibrosis; GGO, ground glass
opacities; CT, computed tomography.
© Translational Andrology and Urology. All rights reserved.

Transl Androl Urol 2023 | https://dx.doi.org/10.21037/tau-23-53

were found. Organizing pneumonia was present in a limited
amount in COVID-2 with intra-alveolar fibroblastic plugs.
Discussion

volumes decline based on serial CT scans (28). The
reduction in lung volume is probably caused by tractionof the fibrosis on the periphery of the lung limiting the
expansion. Increased lung density as seen in ARDS and IPF,
particularly in the lower lobe, was also found in COVID-19
lungs. The rapid onset of disease is in line with previous
findings showing rapid abnormal chest CT in hospitalized
patients after onset of symptoms (11). Clinically, it is shownthat lung volume correlates with pulmonary function tests
in IPF, indicating the potential to use this parameter tomonitor disease in COVID-19 patients (29).
We showed, for the first time, that the number of visible
large and small airways increased in COVID-19, probably
caused by thickening of the airway wall and distortion of thelumen as also shown in IPF (30). Large airways were alsopresent in more distal generations in COVID-19 patientsas a result of traction bronchiectasis. This will severely
impact gas delivery and exchange, leading to aggravation of

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precisely rendered.

Translational Pediatrics, Vol 12, No 7 July 2023
80.0%
70.0%

67.3%

60.0%
50.0%

J Thorac Dis 2023;15(7):3646-3661 | https://dx.doi.org/10.21037/jtd-22-1488≥600 represent
dpi
that theLegible
patientsfor
did not express IgG against
reviewers.
CoV-2 nucleocapsid
protein. Patients with severe COV

have more humoral responses with the production o
IgG than patients with mild COVID-19 (P=0.001).

44.2%

40.0%
30.0%

Without comorbidities
With comorbidities

60.5%© Journal of Thoracic Disease. All rights reserved.

Percentage

Resolution

This study demonstrates the consequences of SARS-CoV-2
induced COVID-19-ARDS on the human lung leading
to organized fibrosis in different regions of the lung. The
study shows that the lung volume decrease can be followed
on serial CT scans with disease progression while density
increased, however, different stages of radiological patterns
are observed between and within COVID-19 patients. Thisis also the first study showing small airway pathologies in
COVID-19 lungs.
Lung volumes showed an initial rapid decrease with asubsequent gradual decrease over the course of disease,which led to a reduced volume of about 60% in explanted
lungs. Similarly, Robbie et al. demonstrated that lung

Discussion

32.7%
27.6%

In this study, we describe seroprevalence of AntiCoV-2 IgG Antibodies in children characterized w
9.6%
7.6%
10.0%
5.8%
5.9%
presence of comorbidities. Since March 2020, c
2.7%
7 million children have tested positive for SARS0.0%
IgG 1 IgG 2 IgG 3 IgG 4 IgG 5 IgG 6
in the United States (12). Levels of antibody rep
Translational Pediatrics, Vol 12, No 7 July 2023
1409
important markers of protection against severe disea
Figure 2 Percentage of patients with a positive IgG test. IgG,
Images: Although many≥300 ordpihospitalization (13), in our study, 63% have p
immunoglobulin
Effects of PGE1 on G.
pulmonary
hypertension on the heart
PGE1 maintains the ductus arteriosus
web-based images often appear
patent to augment systemic blood flow
Anti-SARS-CoV-2 IgG, this number is muchthrough the aorta in the setting of left
ventricular failure
PGE1 acts as a direct
than the reported by Mamishi et al. (14) that wa
at very low resolutions (72 dpi or
pulmonary vasodilator at
the pulmonary arteries
but they report that nearly half of the patients su
lower), readers will only benefit
7.00
from an underlying disease including cardiovascu
Patient typefrom your research if your images
Hospitalized
immunodeficiency disorders and malignancies while
Outpatientoffer hi-resolution detail.
6.00
study was the 32%.
It is important to mention a key difference be
PGE1 reduces rightventricular
the immune response of children and adults is th
5.00 afterload
Figure 3 Effects of PGE1 on pulmonary hypertension on the heart. PGE1 is administered to maintain ductal patency in congenital
heart
formershow a higher expression of pattern recog
disease allowing improved pulmonary and systemic blood flow. This approach can also be beneficial in infants with CDH who experience
receptors(the proteins that detect aberrant RNA)
Tip: Larger fonts can be readmoreright
easily.
supra-systemic
ventricular pressures. A patent PDA can reduce the afterload on the right heart by serving as a “pressure relief
valve”.
4.00
Images created with BioRender. PGE1, prostaglandin E1; CDH, congenital diaphragmatic hernia; PDA, patent ductus arteriosus. respiratory epithelium and in anti-gen-presenting
such as macrophages and dendritic cells. The incr
3.00(26). Notably, there wasregion, timing of identification of defect (early prenatal,
not, were directed to comfort care
receptors such as MDA5 and RIG-1 is, in turn,late prenatal, liveborn, etc.), and length/completenessno difference in mortality, showing that “predetermined”
of follow-up (1). Classification of high risk CDHto
is nowa more robust innate response against SARS-C
physiologic limits predicting mortality were inaccurate.
being based on prenatally identified factors, includingThis is consistent with previous evidence that an aggressive
compared to the average adult. Some pediatric patien
2.00
ultrasound and MRI derived measurements, and/or
approach, giving every isolated CDH an opportunity for
postnatal factors including birth weight, Apgar
score, symptoms also show damage to the IFN-1 re
ECLS support and attempt at diaphragm repair, optimized
severe1
2
3 severity
4 of pulmonary
5
6hypertension, arterial blood gas
survival (16). This evidence changed prenatal counselingsystem,demonstrating the importance of this sys
lgG quantification
test saturation, and/or vital signs. The presencevalues, oxygenand has warranted additional studies to be consideredof major cardiac or chromosomal anomalies, irrespectiveofby the larger CDH community (26). These changes in
the pathophysiology
the disease,
Updatedof4 August2023both in the adu
Figure3 Quantification
IgGandby typeof ofpatients
and month.
IgG,risk in CDH (30).
timingidentification,
also may alter
early resuscitation,leveraging
an aggressive approach
pediatric
population (15).
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up on
an opportunity for survival, offer many new avenues for
immunoglobulin G.
ECLS therapies or those with a greater than 50% chanceofchange and open the door for further exploration. As we
Despiteits selective advantage, the spread ofmortality (30). The survival of these infant’s hinges on earlystart to make advances in genomics and functional studies,
infectious
variants such as omicron showed that childdetection and appropriate risk stratification for appropriate
the underlying causes and pathophysiologic challenges inMedian of IgG (BAU/mL)

20.0%

15.7%

17.3%

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Translational Pediatrics, Vol 12, No 7 July 2023

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80.0%
70.0%
60.0%

67.3%

With comorbidities

60.5%

50.0%

Percentage

Without comorbidities

44.2%

40.0%

32.7%
27.6%

30.0%
20.0%

15.7%

10.0%

17.3%
7.6%

9.6%
5.9%

IgG 4

IgG 5

5.8%
2.7%

0.0%
IgG 1

IgG 2

IgG 3

IgG 6

• EPSrepresent that theAny
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type.
protein. Patients with severe COV• JPG
have more humoral
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IgG than patients• withmild COVID-19 (P=0.001).
TIF/TIFF• PNG
Discussion • DOC• PPT
In this study, we describe seroprevalence of Anti• PSD in children characterized w
CoV-2 IgG Antibodies• AI
presence of comorbidities.
Since March 2020, c
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1409
important markers of protection against severe disea
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or
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immunoglobulin
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Effects of PGE1 on pulmonary
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through the aorta in the setting of left
ventricular failure
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Patient
type
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immunodeficiency disorders and malignancies while
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6.00
study was the 32%.
It is important to mention a key difference be
PGE1 reduces rightthe immune response of children and adults is th
5.00 afterload
ventricular
Figure 3 Effects of PGE1 on pulmonary hypertension on the heart. PGE1 is administered to maintain ductal patency in congenital
heart
formershow a higher expression of pattern recog
disease allowing improved pulmonary and systemic blood flow. This approach can also be beneficial in infants with CDH who experience
receptors (the proteins that detect aberrant RNA)
Tip: If a figure includes bothline art
images,linetheart
guidelines.
supra-systemicrightandventricularpressures.
patent PDAthe
can reduce
afterloadon the right heart by serving as a “pressure relief valve”.
4.00 Afollow
Images created with BioRender. PGE1, prostaglandin E1; CDH, congenital diaphragmatic hernia; PDA, patent ductus arteriosus. respiratory epithelium and in anti-gen-presenting
File Sizesuch as macrophages and dendritic cells. The incr
3.00(26). Notably, there wasregion, timing of identification of defect (early prenatal,
not, were directed to comfort care
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liveborn,system.
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but noagainst SARS-Ca morerobustinnateresponseof follow-up (1). Classification of high risk CDHto
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Vol 13, No 7 July 2023
4643
Quantitative Imagingand
inhas
Medicine
andSurgery,
Vol
13,
No
7
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lgG quantification
test saturation, and/or vital signs. The presence
warranted additional studies to be considered
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yourImages, please provide both textvalues,
andoxygenno text
versions
the pathophysiologyof the disease, both in the adu
of major cardiac or chromosomal anomalies, irrespectiveofby the larger CDH community (26). These changes in
Figure3 Quantification
IgGandby typeof ofpatients
and month.
IgG,risk in CDH (30).
timingidentification,
also may alter
early resuscitation,leveraging
an aggressive approach
pediatric population (15).
High risk infants are those that are more likely to end up on
opportunity forsurvival, offer manyG.
new avenues for
immunoglobulin
CaudalAanchange
Despiteits selective advantage, the spread of
ECLS therapies or those with a greater than 50% chanceofand open the door for further exploration. As wemortality (30). The survival of these infant’s hinges on earlystart to make advances in genomics and functional studies,
infectious
variants
such as omicron showed that childdetection and appropriate risk stratification for appropriate
the underlying causes and pathophysiologic challenges in
deployment of critical therapeutic interventions,familyCDH are becoming more apparent. By understanding thealsosusceptible
tosevereclinical symptoms.
percentage of positive expressioncounseling,is higher
in the group withresource allocation, and establishment of caremolecular mechanisms and pathways that are most frequently
Innateimmunity also recruits and coordinates s
EOtargets,
includingappropriate
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In
disrupted, medical
teams
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to
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infants’comorbidities. The percentage of decrease in the positivity
many cases, prenatal imaging detects and appropriately
care based on their needs, using a “personalized medicine”
T riskand B leukocytes via chemokines. These cells,of theis similarin Despite
both groups,
forthethefirstpriormonth,
they
stratifies
patient’s
to birth,
but risk is not static
approach, outcomes
will test
continue
to improve.
Semilunar-linewithRAin these patients and variables like gestational age of birth,natural killer cells, are part of acquired immun
advances, discovering each mutation
the phenotypic
start withIO60%andand
67% for thegroup with comorbidities
the transition from fetal circulation, and iatrogenicshort,factors this process generates neutralizing antibodies
variability associated with the myriad of variables remains aafter birth allwhile
affect thepatient’s
challenge and oneandthat requires
furtherrespective
exploration (29). comorbidities,
withoutforthe outcomes
sixth and alter theirprotein S, thus preventing the virus from entering
evolving “risk profile” (9).
month it is 5.8%
(Figure2). measurements bestAnother
Prenatally,
image derived
predict
TA and 2.7% respectively
key difference between young and adult pat
Defining and identifying current survival in high-riskEnterocoelia
high risk CDH. The most frequently obtained andOf the 237 included in the study,
110 patients requiredCDH
theamount of virgin leukocytes, since the latter gro
investigated imaging findings include LHR, O/E LHR, O/E
lungthevolume(FLV),
Currently, the overallmortality
in CDH remains In
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Figure TFLV,
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arePPLV, percentage
a smaller reservoir and, therefore, cannot generate mMedialof liver herniation, and stomach herniation. O/E-LHR is the
65% and 80%, largely dependingLateralon the institution,higher in the patients that require hospital management due
antibodies in the appropriate proportion to avoid aC(Text Version)to moderate COVID-19 (P<0.001). In Table 3, we present(No Text
Version)seriousclinical picture.
EO
EO© Translational Pediatrics. All rights reserved.
Transl Pediatr 2023;12(7):1403-1415 | https://dx.doi.org/10.21037/tp-23-240
Méndez-Echevarría et al. (9) report that pediatric p
the differences between the severity of COVID-19, the zeroseTranslational Pediatrics, Vol 12, No 7 July 2023

N

N

ee

ee

dl

dl

e

e

Median of IgG (BAU/mL)

Figure 2 Percentage of patients with a positive IgG test. IgG,

IO

RA

Semilunar-line

IO© Translational Pediatrics. All rights reserved.
Local anesthetics

cs

Transl Pediatr 2023;12(7):1319-1326 | https://dx.doi.org/10.21037/tp-

Midclavicular lineTA

TA
Anterior axillary line

LateralMedialLateralUpdated 4 August 2023

milunaris approach for
TAP block(A) Diagramof ultrasoundprobe placement;
Figure1 Thetechnique.
details of umbilicalparamediansemilunaris
approach for TAP block technique. (A) Diagram of ultrasound probe placement;h for abdominal fascial
block; images(C) afterof theblock LA
medially(B)planeultrasoundofcompletion
semilunar line
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Figure legends
Figure legends must be typed on a separate page. Legends should be concise but comprehensive. The figure and its legend must be
understandable without reference to the text. Please include definitions of any symbols used and define / explain all abbreviations
and units of measurement.
1. If it is a “(A)(B)(C)(D).....” combined picture, the beginning of the Figure Legend needs an overview.
2. Cell map must describe magnification in the Figure Legend (or there is “Scale bar” on the image).
3. Cell staining diagrams need to describe the staining method in the Figure Legend.

Updated 4 August 2023