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Objectives: In the ULTIMATE study with an open label extension, we assessed the long-term effect of secukinumab at tissue level on synovitis and enthesitis, and across all psoriatic arthritis (PsA) manifestations, using both clinical evaluations and power Doppler ultrasonography (PDUS)., Methods: This randomised, placebo-controlled, Phase 3 study (ULTIMATE) included biologic-naïve patients with PsA with active PDUS synovitis and clinical enthesitis, and inadequate response to conventional synthetic disease-modifying antirheumatic drugs. The study consisted of 3 treatment periods; in the first period (baseline to week 12) patients were randomised to receive subcutaneous secukinumab (150 mg or 300 mg according to severity of skin psoriasis) or placebo every week until week 4 and once every 4 weeks up to week 12. In the second period (weeks 12-24) all patients received open-label secukinumab with placebo patients switching to secukinumab (150 mg or 300 mg). The third period (weeks 24-52) was an extended open-label treatment period. The long-term responsiveness of the Global EULAR-OMERACT Synovitis Score (GLOESS), clinical enthesitis and global PDUS-detected enthesitis score (using two candidate definitions of activity) at patient level, together with clinical efficacy across key manifestations of PsA and safety were assessed., Results: Of the 166 patients enrolled, 144 completed week 52. A significant reduction in GLOESS was demonstrated in the secukinumab group vs placebo at week 12, followed by a stable reduction of synovitis until week 52 in the secukinumab group while placebo switchers from week 12 reached a similar level of reduction at week 24 with stability thereafter. Likewise, a significant reduction in the Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index was shown in the secukinumab group vs placebo at week 12 with sustained improvement to week 52. Global OMERACT PDUS enthesitis scores were numerically lower in secukinumab vs placebo switchers in the first two treatment periods, with some stability in the third period in both groups. Improvements in clinical responses were also observed across all key domains of PsA up to week 52 in both treatment groups with no new or unexpected safety signals., Conclusions: ULTIMATE showed consistent improvements in clinically and ultrasound-assessed synovitis and enthesitis and sustained clinical efficacy through week 52 in patients with PsA treated with secukinumab and placebo switched to secukinumab., Competing Interests: Declaration of Competing Interest MAD'A reports speaker or consultant fees from Sanofi, Novartis, BMS, Janssen, Celgene, Roche, AbbVie, UCB, and Eli Lilly. PC reports research grants from UCB, MSD and Pfizer; speaker fees or consultant fees from Pfizer, MSD, Novartis, Bristol Myers Squibb, AbbVie, UCB, Eli Lilly, Gilead and Celgene Corporation. CG is a stockholder of Novartis and BMS and an employee of Novartis. PGC reports speaker fees or consultant fees from AbbVie, AstraZeneca, Eli Lilly, Galapagos, Merck, Novartis, Pfizer, Stryker and UCB. EN reports speaker fees from AbbVie, Roche, BMS, Pfizer, UCB, Lilly, Novartis, Janssen, and Celgene GmbH; honoraria for clinical trials from AbbVie, Novartis and BMS; research grants from Eli Lilly. AL reports speaker or consultant fees from Eli Lilly, Novartis, Janssen, Roche, all GSK and UCB. LS reports research grants, speaker fees, consultant fees and honoraria for clinical trials from AbbVie, Bristol-Myers Squibb, Celgene Corporation, Eli Lilly, Gilead, Merck Sharp and Dohme, Mylan, Novartis, Pfizer, Roche, Sanofi, Sandoz, Sobi, Takeda, and UCB. RB has received honoraria for speaking from Novartis. PH has nothing to disclose. IP has nothing to disclose. TC has nothing to disclose. MSS reports speaker or consultant fees or grants from AbbVie, MSD, Pfizer, Roche and UCB. MB reports speaker or consultant fees or grants from AbbVie, Amgen, BMS, Galapagos, Johnson, MSD, Novartis, Pfizer, Roche and UCB. GM reports speaker or consultant fees or grants from AbbVie, BMS, Celgene, Lilly, Novartis and Pfizer. WB and PG are employees of Novartis. MB is a consultant for Novartis, received speaker fees from Pfizer and provided expert testimony for Celltrion. GS reports speakers’ honoraria from AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, Roche and UCB., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: No clear-cut guidelines exist for the use of imaging procedures for the diagnosis of idiopathic inflammatory myopathies (IIM). The aim of the present study was to assess the diagnostic accuracy of power Doppler ultrasonography (PDUS) score in IIM patients compared with a control group and its usefulness during follow-up., Methods: All patients evaluated in the Vasculitis and Myositis Clinic, Rheumatology Unit, University of Siena were prospectively collected. All patients underwent US examination of both thighs in axial and longitudinal scans, which were also performed twice (T1) or three times (T2)., Results: Forty-five patients with IIM (median [interquartile range] age 55 [45-66] years; 35 female) were enrolled. Receiver operating characteristic curves distinguished patients and controls based on ∑power Doppler (PD), ∑oedema, ∑atrophy and CRP. The best cut-off value for ∑PD was 0.5, ∑oedema 1.5, ∑atrophy 0.5 and CRP 0.22 mg/dl. In a logistic regression analysis, the variables that most influenced diagnosis of IIM were ∑PD and ∑oedema (P = 0.017 and P = 0.013, respectively). ∑Oedema was lower at T1 (P = 0.0108) and T2 (P = 0.0012) than at T0. Likewise, ∑PD was lower at T1 (P = 0.0294) and T2 (P = 0.0420) than at T0. Physician global assessment was lower at T1 (P = 0.0349) and T2 (P = 0.0035) than at baseline., Conclusion: Our findings show that PDUS is a reliable diagnostic tool in the differential diagnosis between inflammatory and non-inflammatory myopathies. Moreover, PDUS can be employed also during the follow-up of patients with IIM. A reduction in disease activity, measured by physician global assessment, led to a concomitant decrease in both oedema and PD, which was directly correlated with their rate of change. This underlines the close link between clinical assessment and PDUS findings, not only at diagnosis but also during monitoring., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Objectives : Although the ultrasound-guided technique is used in caudal epidural injections, severe complications can happen if ultrasound cannot identify the occurrence of intravascular injection. To determine intraepidural and intravascular injection during caudal epidural injections, we used power Doppler ultrasonography (PDU) when injecting medications into the epidural space. Materials and Methods : This is a retrospective study that enrolled a total of 277 patients with refractory low back pain or degenerative disc from January 2019 to December 2019. The injectate flow of caudal epidural injections was examined with the assistance of PDU and confirmed by fluoroscopy. Four flow patterns were identified by PDU in our study: the "Earthworm sign," the "Patch sign," the "Tubular sign" and the "Absent flow sign." The accuracy of PDU in identifying intraepidural and intravascular injections was determined by fluoroscopy images recorded during each injection. Results : We evaluated 277 patients (mean age, 68.6 ± 13.2 years; 106 men). The "Patch sign" showed a sensitivity of 88.76% and a specificity of 80% in predicting epidural injection without intravascular injection. The "Earthworm sign" demonstrated a sensitivity of 70% and a specificity of 100% in detecting intravascular injection. The "Tubular sign" showed a specificity of 100% and a sensitivity of 9.4% in predicting successful epidural injection. The absence of a flow signal showed a sensitivity of 1.87% and a specificity of 90% in predicting successful epidural injection. Conclusions : Ultrasound-guided caudal epidural injection can accurately determine intraepidural and intravascular injections with the assistance of PDU and is thus a good alternative technique to fluoroscopy-guided caudal epidural injection.

Background: Inflammatory bowel disease (IBD) is closely associated with spondylarthritis (SpA) and enthesitis, as an important feature of SpA, is a common extraintestinal manifestation of IBD. Enthesitis may be clinically silent in a high proportion of patients with IBD without clinical signs or a diagnosis of SpA. Objectives: The aim of this study was to compare the prevalence of ultrasound (US) verified enthesitis in IBD patients with and without SpA, with patients with irritable bowel syndrome (IBS) and healthy subjects (HC) serving as controls. Methods: IBD patients with or without SpA, patients with IBS and HC were prospectively recruited and clinically assessed. Ultrasound examination was performed at 14 entheses. The ultrasound abnormalities were scored according to the Madrid Ankylosing Spondylitis Enthesitis Index (MASEI). Results: We included 33 IBD patients without SpA, 14 IBD patients with SpA, 26 IBS patients and 18 HC. Higher MASEI scores were found in patients with IBD without SpA [median 21.0 range (8.0-53.0)] and IBD associated SpA [33.0 (8-50)] than in IBS patients [10.5 (0-42.0)- p < 0.001 for both comparison] and HC [12.0 (2.0-38.0)- p < 0.01]. PD, enthesophytes and erosions were more common in patients with IBD with or without SpA as compared to IBS patients and HC. IBD patients with SpA compared to IBD without SpA demonstrated significant higher prevalence of erosion and structural irregularity and consequently significant higher MASEI ( p < 0.05 for all comparison). Conclusions: Ultrasound verified enthesitis is more common in patients with IBD with or without SpA as compared to patients with IBS or HC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Husic, Lackner, Kump, Högenauer, Graninger and Dejaco.)

Purpose and Hypothesis: Mid-portion Achilles tendinopathy is characterized by a proliferation of small vessels, called neovascularization, which can be demonstrated by power Doppler sonography (PD). Neovascularization can be correlated with diagnosis and consequent therapies focused on vascular supply. Published data regarding the relationship between neovascularisation and symptoms, such as pain and disability, are contradictory. The hypothesis that contrast-enhanced ultrasound (CEUS) could detect with more sensibility than PD the new vessel ingrowth in human degenerated Achilles tendons and therefore the correlation of neovascularization with pain and disability, was evaluated., Methods: Thirty consecutive patients of recalcitrant Achilles tendinopathy were studied with ultrasound greyscale (US), PD, CEUS and magnetic resonance imaging. Neovascularization was recorded as percentage on the whole extension of examined area. The vascularization time was recorded as venous and arterial type. Imaging data were classified both concurrently with the examination and in a secondary blinded assessment; any difference in the subjective assessment was discussed and a consensus view formed. Pain and disability were assessed by Western Ontario McMaster Universities Arthritis Index (WOMAC) and EuroQuality of life 5-dimension-5-level questionnaire and visual analogue scale (EQ-VAS). All results were analysed with suitable statistical methods., Results: 76.7% of cases were degenerated; 23.3% had also partial discontinuity of the fibres. PD detected vascularization in 54% of cases, whereas CEUS in 83% of cases: in 13 cases, PD did not detect vascularization. The vascularization time was rapid (< 20 s, arterial type) in 60% of cases. WOMAC pain mean value is 6.4 and SD 3.4; WOMAC total score mean value is 21.6 and SD 12.8. EQ-VAS mean value is 56 and SD 18.3. No statistically significant correlation emerged between vascularization and pain/disability., Conclusions: CEUS showed a greater ability to detect neovessels than PD in chronic Achilles tendinopathies. Nevertheless in 30 consecutive tendinopathies, no correlation between pain/disability and neovascularization was found: the role of multiple neovessels continue to be unclear. The possibility to discriminate arterial from venous vessels ('vascularization time') could be useful to understand the pathophysiology of tendinopathies and its healing process., Study Type: Diagnostic study., Level of Evidence: II.

The sensitivity of lymph node core-needle biopsy under imaging guidance requires validation. We employed power Doppler ultrasonography (PDUS) to select the lymph node most suspected of malignancy and to histologically characterize it through the use of large cutting needle. Institutional review board approval and informed consent were obtained for this randomized clinical trial. In a single center between 1 January 2009 and 31 December 2015, patients with lymph node enlargement suspected for lymphoma were randomly assigned (1:1) to biopsy with either standard surgery or PDUS-guided 16-gauge modified Menghini needle. The primary endpoint was the superiority of sensitivity for the diagnosis of malignancy for core-needle cutting biopsy (CNCB). Secondary endpoints were times to biopsy, complications, and costs. A total of 376 patients were randomized into the two arms and received allocated biopsy. However, four patients undergoing CNCB were excluded for inadequate samples; thus, 372 patients were analyzed. Sensitivity for the detection of malignancy was significantly better for PDUS-guided CNCB [98.8%; 95% confidence interval (CI), 95.9-99.9] than standard biopsy (88.7%; 95% CI, 82.9-93; P < 0.001). For all secondary endpoints, the comparison was significantly disadvantageous for conventional approach. In particular, estimated cost per biopsy performed with standard surgery was 24-fold higher compared with that performed with CNCB. The presence of satellite enlarged reactive and/or necrotic lymph nodes may impair the success of an open surgical biopsy (OSB). PDUS and CNCB with adequate gauge are diagnostic tools that enable effective, safe, fast, and low-cost routine biopsy for patients with suspected lymphoma, avoiding psychological and physical pain of an unnecessary surgical intervention.

Objective: This study aimed to determine the prevalence of subclinical enthesopathy in patients with psoriasis using power Doppler ultrasonography (PDUS) and its association with other disease parameters., Material and Methods: A total of 50 patients with psoriasis (31 females) aged 19-70 years underwent a thorough clinical examination that included assessment of body mass index (BMI) and psoriasis area and severity index (PASI) score. Measurements of inflammatory markers, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum uric acid, and plain radiography of the heels, knees, and sacroiliac joints were performed for all patients. Patients without clinical evidence of arthritis or enthesitis underwent an ultrasonographic (US) examination. According to the US examination, patients were classified into group I (patients with enthesitis) and group II (patients without enthesitis)., Results: In group I, Achilles enthesis was the most common site of US enthesitis (33.3%), followed by distal patellar enthesis (22.2%), proximal patellar enthesis (16.7%), quadriceps enthesis (16.7%), and plantar aponeurosis enthesis (11.1%). There was a statistically significant positive correlation between the occurrence of enthesitis and the patient's age, disease duration, PASI score, BMI, and hyperuricemia (p<0.05 for each). In contrast, there was no significant correlation between enthesitis and sex or radiographic sacroiliitis (p>0.05 for each)., Conclusion: In addition to the importance of PDUS as a complimentary tool for examining enthesis in patients with psoriasis, the presence of high PASI score, increased BMI and hyperuricemia, and a long disease duration can be considered as predictive parameters for the presence of psoriatic enthesitis., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

The aim of this study was to investigate the compatibility of the visual evaluation result of the blood flow characteristics and the blood flow measurements of the CL and the predictability of the responses given by corpora lutea with varying levels of blood flow to an induction of luteolysis by a PGF 2α injection and to determine the possibility of increase in serum estrogen and progesterone concentrations in parallel with increased luteal blood flow (LBF). The cows, bearing a CL (n = 60; postpartum 35 days), were injected with PGF 2α and were monitored for signs of estrous following the first injection. The cows, which did not show estrous signs, were examined for the presence of a CL on Day 14, whereas those that showed signs of estrous were examined on Day 10 following the onset of estrous. The level of LBF was visually graded as + (low; GI), ++ (medium; GII), +++ (high; GIII), and ++++ (very high; GIV). Immediately after the examination of LBFs, a second intramuscular injection of PGF 2α was injected. In the cows, which were determined to be in estrous, the diameter of the Graafian follicles was measured by B-mode ultrasonography. Subsequently, these animals were artificially inseminated. The animals, which did not show estrous after the second injection, were examined as previously described and monitored for signs of estrous. A strong correlation (r = 0.654; P < 0.001) was determined to exist between the results of the visual examination of the images and the results obtained for the LBF area with the use of the Pixel Flux software. GIII (0.83 ± 0.15 cm 2 ) and GIV (1.03 ± 0.48 cm 2 ) were found to differ from GI (0.47 ± 0.23 cm 2 ) and GII (0.51 ± 0.12 cm 2 ) for the size of the LBF (P < 0.001). Serum progesterone levels in groups (GI, GII, GIII, and GIV) were determined to be 4.44 ± 2.42 ng/mL, 6.03 ± 2.37 ng/mL, 7.01 ± 2.94 ng/mL, and 7.17 ± 1.69 ng/mL, respectively. The comparative evaluation of the study groups showed that the groups did not statistically differ for the period between PGF 2α injection and the onset of estrous, mean Graafian follicle size and estrogen levels. No direct correlation existed between these reproductive parameters and LBF., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Following Achilles tendon rupture, running is often allowed after 6 months. However, tendon healing is slow and the metabolic status of the tendon at this point is unknown. The purpose of this study was to investigate tendon metabolism (glucose uptake) and vascularization at 3, 6 and 12 months after Achilles tendon rupture as measured using PET and power Doppler ultrasonography (PDUS)., Methods: The study group comprised 23 patients with surgically repaired Achilles tendon rupture who were investigated at 3 months (n = 7), 6 months (n = 7) and 12 months (n = 9) after surgery. The triceps surae complex was loaded over 20 min of slow treadmill walking while a radioactive tracer ((18)F-FDG) was administered prior to PET. Vascularization was measured in terms of PDUS flow activity, and patient-reported outcomes were scored using the Achilles tendon rupture score (ATRS) and sports assessment (VISA-A) questionnaire., Results: Relative glucose uptake ((18)F-FDG) was higher in repaired tendons than in intact tendons at all time-points (6, 3 and 1.6 times higher at 3, 6 and 12 months, respectively; P ≤ 0.001), and was also higher in the tendon core than in the periphery at 3 and 6 months (P ≤ 0.02), but lower at 12 months (P = 0.06). Relative glucose uptake was negatively related to ATRS at 6 months after repair (r = -0.89, P ≤ 0.01). PDUS flow activity was higher in repaired tendons than in intact tendons at 3 and 6 months (P < 0.05 for both), but had normalized by 12 months., Conclusion: These data demonstrate that the healing process as determined by metabolic activity and vascularization continues for 6 months after injury when large loads are typically allowed on the tendon. Indeed, metabolic activity remained elevated for more than 1 year after injury despite normalized vascularization. The robust negative correlation between tendon metabolism and patient-reported outcome suggests that a high metabolic activity 6 months after the injury may be related to a poor clinical healing outcome.

This study was undertaken to evaluate the usefulness of vascular pattern analysis on microvascular ultrasonography in distinguishing metastatic lymphadenopathy from tuberculous lymphadenitis, compared with conventional power Doppler ultrasonography, and to evaluate inter-observer agreement for microvascular ultrasonography. Thirty-four patients with metastatic lymphadenopathy and 27 patients with tuberculous lymphadenitis were included. The level of inter-observer agreement was excellent or good for all aspects of vascular pattern analysis on both ultrasonographic examinations. Vascular distribution, internal vascularity and internal vascular features of lymph nodes on microvascular ultrasonography differed significantly different (p ≤ 0.002) between metastatic lymphadenopathy and tuberculous lymphadenitis. A central vascular pattern with displacement was prevalent in metastasis, and an avascular pattern was more frequent in tuberculosis. Internal vascularity of metastasis was higher than that of tuberculosis. Vascular patterns on power Doppler ultrasonography did not differ significantly. Vascular pattern analysis using microvascular ultrasonography can be helpful in differentiating metastatic lymphadenopathy from tuberculous lymphadenitis with good inter-observer agreement., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Purpose: Power Doppler ultrasonography (PD-US) is a motion-sensitive modality that can display flow characteristics regardless of the direction. This increased motion sensitivity can be used as a parameter to show the tissue motion on artificially generated fremitus images. This study aimed to confirm any signs of incarceration in abdominal wall hernias proven by herniorrhaphy by examination with dynamic PD-US (during manual compression-decompression maneuvers)., Methods: Twenty-seven patients with anterior abdominal wall hernia with a narrow neck (<1 cm in diameter) were examined firstly with gray-scale ultrasonography (GS-US), and then with dynamic PD-US. Two independent radiologists, who were blinded to the real-time images showing the orientation and motion of the hernia neck, completed the examinations. These images were evaluated for any signs of incarceration, as well as the orientation of the hernia neck., Results: Orientations of the hernia neck were not described on GS-US images in 13 lesions and on dynamic PD-US images in 3 lesions. While the GS-US examination revealed incarcerated hernia in four of the patients, the dynamic PD-US examination revealed an additional seven patients with symptoms associated with incarceration., Conclusion: Dynamic PD-US may show the orientation of the hernia neck and any sign of incarceration more accurately and clearly than conventional GS-US. Being informed about these features preoperatively is of utmost importance. Thus, anterior abdominal wall hernias should be examined by dynamic PD-US.

Introduction: The aim of this study was to evaluate the role of bedside ultrasonography (US) in early diagnosis of musculoskeletal complications (MSC) of acquired brain injuries, to describe its incidence and US features in a neurorehabilitation setting., Materials and Methods: All 163 patients admitted in tertiary-level neurorehabilitation unit with diagnosis of stroke or severe brain injury (SBI), with symptoms or signs of musculoskeletal pathology, underwent bedside US., Results: MSC were diagnosed in 51.5%. In 86.9% US clarified diagnosis and/or modified therapeutic approach. Shoulder pain was observed in 27.6%. US showed a shoulder subluxation in 73.3% and a frozen shoulder in 8.8% of painful shoulders. In all the cases rotator cuff abnormalities were noted. Wrist-hand syndrome was observed in 29.4%. US showed mild effusion in wrist joints and tendon sheaths and subcutaneous edema without significant vascularity. Neurogenic heterotopic ossification was observed in 1.8%. US demonstrated the "zone phenomenon" or heterogeneously hypoechoic mass with low resistance vessels within the lesions. Contractures and spasticity were observed in 18.4%. US allowed reliable guidance for Botulinum toxin A injection. Relapsing osteoarthritis and acute arthritis were diagnosed in 15.3% and 7.3% respectively. Patients with MSC had lower Functional Independence Measurement (FIM) and Katz index scores in discharge (p < 0.04 and p < 0.0294 respectively) and more length of hospital stay (p = 0.0024)., Discussion: Musculoskeletal pathology frequently complicates the course of acquired brain injuries and it delays functional recovery. Bedside US is a cheap and sensitive diagnostic tool and it can aid clinicians to define diagnosis and to choose therapeutic approach.