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Aggiornamenti sull’uso
dell’ecografia in
emofilia in Italia
CONVEGNO ANNUALE AICE “ASSISTENZA DELL’EMOFILIA E DELLE MEC IN ITALIA: SCENARI IN EVOLUZIONE ”
Napoli, 30 Settembre – 2 Ottobre, 2015
Radiologia – DISSAL Università di Genova, Italy carlo.martinoli@libero.it
Carlo Martinoli, MD
Matteo Nicola Dario Di Minno, MD
Dept of Clinical and Experimental Medicine Federico II University, Naples, Italy
Gianluigi Pasta, MD
Dept of Orthopaedics. IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
Why Ultrasound?
Excellent spatial resolution
Dynamic capabilities (joint motion, muscle contraction)
Clinical examination Availability, portability (US performed at the bedside), low cost
First Line Imaging Modality Point-of-Care Imaging
quick screen system as part of the normal physical exam (not to be billed separately) extends the doctors’ vision beyond their fingertips
advent of simple to use, cheap portable machines with adequate technology to examine the MSK system with high-res
CONVEGNO ANNUALE AICE “ASSISTENZA DELL’EMOFILIA E DELLE MEC IN ITALIA: SCENARI IN EVOLUZIONE ”
Napoli, 30 Settembre – 2 Ottobre, 2015
Why Clinicians?
May radiologists have a role in the first line?
Multi-joint disease with early
changes expected to occur in joints
that are nearly asymptomatic
US performed/interpreted by the clinician
focused, decision-making strategy to answer specific clinical questions, or identify relevant biomarkers, without the need for detailed, radiological assessment
not comparable with a comprehensive MSK US examination performed by imaging specialists, but rather supporting a more time-efficient, straightforward, real-time approach to critical clinical issues that may affect patient management
CONVEGNO ANNUALE AICE “ASSISTENZA DELL’EMOFILIA E DELLE MEC IN ITALIA: SCENARI IN EVOLUZIONE ”
Napoli, 30 Settembre – 2 Ottobre, 2015
Second Opinion Need for Additional Imaging Assessment Help with Ultrasound Training
target joint
mild deficit
bleeding episodes in the past
Imaging
Department
Waiting List
no time-efficient feedback for
treatment decisions
delayed
information
Readers often unaware of haemophilia issues inadequate reporting
How many joints to
ask for imaging?
Imaging basically
underutilized
probably negative
Why Clinicians ... Workflow
CONVEGNO ANNUALE AICE “ASSISTENZA DELL’EMOFILIA E DELLE MEC IN ITALIA: SCENARI IN EVOLUZIONE ”
Napoli, 30 Settembre – 2 Ottobre, 2015
DISEASE ACTIVITY
Joint Effusion
Chronic Synovial Proliferation
OSTEOCHONDRAL DAMAGE
Chondral Abnormalities
Subchondral Bone Damage
*
4mm
Why Ultrasound in Haemophilia?
TWO MAIN DOMAINS
Often Undetected at Phys Ex Hyperlax Joints in Children
Very early, aggressive damage Symptoms appear later than expected
CONVEGNO ANNUALE AICE “ASSISTENZA DELL’EMOFILIA E DELLE MEC IN ITALIA: SCENARI IN EVOLUZIONE ”
Napoli, 30 Settembre – 2 Ottobre, 2015
Assumption #1 - synovium
HAEMOPHILIC ARTHROPATHY
excellent biomarker of previous
(recent) joint bleeds
haemosiderin - synovium
basically hypovascular at CD/PD
RHEUMATOID ARTHRITIS
excellent biomarker of inflammation
active vs. inactive disease
active disease basically hypervascular at CD/PD
Indicator of Disease
Activity
CONVEGNO ANNUALE AICE “ASSISTENZA DELL’EMOFILIA E DELLE MEC IN ITALIA: SCENARI IN EVOLUZIONE ”
Napoli, 30 Settembre – 2 Ottobre, 2015
IRON
the diffuse osteochondral damage in HA may warrant the policy of considering one surface representative of the overall status of the joint without significantly reducing the sensitivity of the method
Assumption #2 – osteochondral surfaces
CONVEGNO ANNUALE AICE “ASSISTENZA DELL’EMOFILIA E DELLE MEC IN ITALIA: SCENARI IN EVOLUZIONE ”
Napoli, 30 Settembre – 2 Ottobre, 2015
ease of learning for non-expert musculoskeletal sonologists
ease of use with conventional US machines, including portable machines
reasonably informative to assess the status of the joints in terms of disease activity and disease damage in HA
reliable and repeatable enough for being used as a marker to monitor the efficacy of treatment and the evolution of damage in longitudinal studies
time efficient to be implemented in the daily activity
AD-HOC SCANNING PROTOCOLS
ELBOW
KNEE
ANKLE
Haemophilia Early Arthropathy Detection with UltraSound
CONVEGNO ANNUALE AICE “ASSISTENZA DELL’EMOFILIA E DELLE MEC IN ITALIA: SCENARI IN EVOLUZIONE ”
Napoli, 30 Settembre – 2 Ottobre, 2015
Systematic evaluation of the joint recesses Selection of a target osteochondral surface (one per joint) DAMAGE
ACTIVITY ✔
Job for Imaging Specialists
Ligaments
Muscles
Tendons
Nerves
Vessels
✗ Is the HEAD-US system equivalent to a MSK Ultrasound Exam?
Haemophilia Early Arthropathy Detection with UltraSound
CONVEGNO ANNUALE AICE “ASSISTENZA DELL’EMOFILIA E DELLE MEC IN ITALIA: SCENARI IN EVOLUZIONE ”
Napoli, 30 Settembre – 2 Ottobre, 2015
Will HEAD-US be best utilised as an adjunct to physical examination assessment tools?
Will it compete by virtue of its shorter learning curve and more objective assessment?
Physical (complex) US (simple, confirmatory) US (first) Physical (simplified)
Haemophilia Early Arthropathy Detection with UltraSound
Physical assessment of joint status often falls below the standards of due care
The short learning curve of HEAD-US combined with "simplified" physical tests tailored to specific aspects that are “blind” at US, would offer the best potential
small/peripheral centers, where local expertise may fall short, due
to a lack of training and dedicated personnel
CONVEGNO ANNUALE AICE “ASSISTENZA DELL’EMOFILIA E DELLE MEC IN ITALIA: SCENARI IN EVOLUZIONE ”
Napoli, 30 Settembre – 2 Ottobre, 2015
US vs Clinical Examination (Gilbert & HJHS)
US vs X-ray
(Pettersson)
US vs MRI (Compatible scale)
CENTER Investigators
MILANO Elena Santagostino,
Gianluigi Pasta
PARMA Annarita Tagliaferri
Franca Rivolta
GENOVA Carlo Martinoli
Claudio Molinari
FIRENZE Massimo Morfini
NAPOLI Giovanni Di Minno
Dario Di Minno
Participating Centers
Procedure Totali = 646
Characteristics of the study population
Hemophilia A Hemophilia B
Number of patients 49 12
Severe hemophilia 36(73.5%) 9 (75%)
Mild/moderate 13(26.5%) 3 (25%)
Age 30 31
History of inhibitory antibodies 12 (24.5%) 0
High-titer inhibitors (>5BU) 8 (16.3%) 0
Treatment
Prophylaxis 37 (75.5%) 8 (66.7%)
On-demand 12 (24.5%) 4 (33.3%)
Number of joints studied
Hemophilia A
Overall 145
Ankles 68
Knees 39
Elbows 38
WFH 136
HJHS 2.0 91
HJHS 2.1 81
HEAD-US 145
Pettersson 131
MRI 62
Results of the examinations
Mean Median IQR
Gilbert 2.14 1 0-3
HJHS 2.0 5.18 3 0-8
HJHS 2.1 5.41 4 0-9
X-ray 3.18 1 0-6
US 3.3 3 1-6
Assessment of early arthropathic changes
Gilbert HJHS 2.0 HJHS 2.1 X-ray US
0 44.8% 29.7% 27.2% 45% 22.1%
1 16.2% 13.2% 14.8% 9.9% 9%
2 7.35% 5.5% 4.9% 4.6% 10.3%
3 7.35% 3.3% 2.5% 3.8% 10. 3%
4 3.7% 4.4% 6.2% 4.6% 9%
5 4.4% 4.4% 7.4% 3.8% 13.1%
6 3.7% 7.7% 4.9% 4.6% 17.2%
7 4.4% 6.6% 3.7% 3.0% 8.3%
8 2.9% 2.2% 2.5% 7% 0.7%
9 3.7% 2.2% 2.5% 3% -
10 1.5% 2.2% 2.5% 3.8% -
>10 - 18.6% 20.9% 6.9% -
Results of the examinations
Gilbert vs HEAD-US Total joints Ankles Knees Elbows
ICC 0.725
(0.614-0.804)
0.647
(0.423-0.784)
0.812
(0.629-0.905)
0.801
(0.606-0.900)
r 0.574,
P < 0.001
0.478,
P < 0.001
0.767,
P < 0.001
0.670,
P < 0.001
Gilbert = 0 61 joints
US = 0 23 joints (37.7%)
US ≥ 1 38 joints
Synovium: 15 joints (8 grade 1 and 7 grade 2), Cartilage: 34 joints (9 grade 1; 8 grade 2; 11 grade 3 and 6 grade 4) Bone: 8 joints (5 grade 1 and 3 grade 2).
HJHS 2.0 vs HEAD-US Total joints Ankles Knees Elbows
ICC 0.714
(0.566-0.811)
0.701
(0.469-0.831)
0.805
(0.508-0.923)
0.677
(0.223-0.866)
r 0.744,
P < 0.001
0.713,
P < 0.001
0.972,
P < 0.001
0.642,
P = 0.001
HJHS 2.0 = 0 27 joints
US = 0 18 joints (66.7%)
US ≥ 1 9 joints
Synovium: 3 joints (2 grade 1 and 1 grade 2), Cartilage: 7 joints (3 grade 1; 3 grade 2; 1 grade 3) Bone: 1 joints (grade 1).
HJHS 2.1 vs HEAD-US Total joints Ankles Knees Elbows
ICC 0.700
(0.534-0.807)
0.702
(0.464-0.834)
0.813
(0.465-0.935)
0.641
(0.009-0.870)
r 0.720,
P < 0.001
0.695,
P < 0.001
0.980,
P < 0.001
0.632,
P = 0.007
HJHS 2.1 = 0 22 joints
US = 0 16 joints (72.7%)
US ≥ 1 6 joints
Synovium: 3 joints (2 grade 1 and 1 grade 2), Cartilage: 5 joints (2 grade 1; 1 grade 2; 2 grade 3) Bone: 1 joints (grade 1).
Pettersson (X-ray) vs HEAD-US Total joints Ankles Knees Elbows
ICC 0.805
(0.725-0.862)
0.802
(0.666-0.883)
0.778
(0.569-0.886)
0.822
(0.652-0.909)
r 0.759,
P < 0.001
0.759,
P < 0.001
0.724,
P < 0.001
0.773,
P < 0.001
X-ray = 0 59 joints
US = 0 21 joints (35.5%)
US ≥ 1 38 joints
Synovium: 13 joints (8 grade 1 and 5 grade 2), Cartilage: 33 joints (9 grade 1; 11 grade 2; 12 grade 3, 1 grade 4) Bone: 4 joints (grade 1).
… ongoing …
- Stratification for age (pediatric patients)
- Assessment of joints with HEAD-US = 0
- Identification of cut-off points for disease
- Comparison with MRI
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