Ultrasound imaging for the rheumatologist XXVI. Sonographic assessment of the knee in patients with psoriatic arthritis

Objective. To investigate the prevalence and severity of sonographic-detected abnormalities in,knee osteoarthritis (OA) and to correlate ultrasound (US) findings with clinical data. Methods. Outpatients with chronic, painful knee OA according to the ACR criteria were consecutively recruited and underwent clinical and US examinations. An expert rheumatologist recorded the presence of knee joint pain, swelling and tenderness, patient's global assessment of knee pain using visual analogue scale (VAS), and Lequesne Index of severity for knee OA. A second rheumatologist, blinded to the clinical data, performed the knee US examination using a Logiq9 machine equipped with a 12MHz linear probe and registering the presence of joint effusion, synovial proliferation, power Doppler (PD) signal, Baker's cyst, osteophytes and femoral cartilage abnormalities. Results. One hundred and sixty-four knees of 82 patients (53 women, 29 men) were studied; mean age was 63.2 +/- 8.1 SD years, mean disease duration was 4.3 +/- 5.6 SD years. All patients complained of at least one knee joint pain during physical activity. Mean patient's VAS for knee pain was 48.4 +/- 19.9 SD mm, mean Lequesne Index was 8.2 +/- 4.4 SD. Knee swelling was present in 39% of the patients and tenderness was found in 65.8%. US showed: joint effusion in 43.3% of the patients, synovial proliferation in 22.1%, PD signal in 2.9%, Baker's cysts in 6.6%, cartilage abnormalities in 79%, osteophytes in 100%. In all patients US findings were present at least at the level of one knee. Statistically significant correlations were demonstrated between a composite inflammatory score and both VAS (p=0.004) and Lequesne Index (p < 0.0001). Conclusions. This US study showed both inflammatory abnormalities and structural damage lesions in knee OA. Interestingly, statistically significant correlations were demonstrated between US inflammatory findings and the main clinical tests for OA, confirming that sonography has a relevant role in the global evaluation of patients with knee OA

Ultrasound imaging for the rheumatologist XXVII. Sonographic assessment of the knee in patients with rheumatoid arthritis

The aims of our study were to investigate the prevalence of ultrasound (US) pathologic abnormalities and to compare them with the clinical findings in the knee of rheumatoid arthritis (RA) patients. One hundred RA patients were enrolled in the study. Bilateral US examination of the knee was performed to visualise the presence of effusion, synovial proliferation, bone erosions, femoral cartilage abnormalities, quadricipital and/or patellar enthesopathy. The popliteal fossa and the calf region were also evaluated to detect popliteal cyst. We observed joint effusion in 140 out of 200 (70%) knees. Synovial hypertrophy was present in 115 out of 140 (82%) knees associated with effusion and in 22 out of 115 (19%) knees intra-articular power Doppler (PD) signal was found. Hyperechoic spots within the cartilage layer, suggestive of pyrophosphate crystals deposit, were detected in the knees of 3 patients. US signs of quadricipital and/or patellar enthesopathy were detected in 53 out 200 (26%) knees. Bone erosions were visualised in 16 out 200 (8%) knees. Popliteal cyst was found in 66 out of 200 (33%) joints. US examination of the knee is more sensitive than clinical examination in the detection of joint inflammation and allows for the identification of different patterns of pathologic changes at knee level, including morphostructural changes at both cartilage and tendon level

Ultrasound Effectiveness of Steroid Injection for hand Psoriatic Dactylitis: Results from a Longitudinal Observational Study

Introduction: To assess clinical and ultrasound effectiveness&nbsp;of&nbsp;steroid injection (local treatment, LT) into the digital&nbsp;flexor tendon sheath for the treatment of psoriatic dactylitis compared to systemic treatment (ST) alone. Methods: In this observational, multicentre, prospective study, 88 cases of symptomatic hand dactylitis were evaluated clinically and sonographically by high-frequency ultrasound (US) probe in both greyscale (GS) and power Doppler (PD). The presence of flexor tenosynovitis (FT), soft tissue oedema (STO), peritendon extensor inflammation and synovitis was assessed (including DACtylitis glObal Sonographic—DACTOS—score) before treatment, at 1-month (T1) and 3-months (T3) follow-up. LT was proposed to all patients. Patients refusing LT were treated with oral NSAIDs. Patients continued the same baseline csDMARDs and/or corticosteroid therapy during the whole follow-up period. US response was defined for DACTOS score &lt; 3 and US remission for DACTOS score = 0. Results: At T3 evaluation the ST group showed a significantly higher persistence (grade &gt; 1) of FT and STO (p &lt; 0.001 for all) and MCP synovitis (p = 0.001). US remission was achieved&nbsp;only in the LT group (at T3 31% vs. 0, p &lt; 0.001). The percentage of patients with DACTOS &lt; 3 was significantly greater in the LT group compared with ST group, at both T1 (49% vs. 5%, p &lt; 0.001) and T3 evaluation (76% vs. 7%, p &lt; 0.001). In multiple conditional logistic regression analysis, the only factor associated with US remission was LT (T3 odds ratio = 41.21, p &lt; 0.001). Conclusions: US confirmed the effectiveness of steroid injection for dactylitis by demonstrating that it involves the resolution of extra-articular inflammation, in particular FT and STO

Upadacitinib effectiveness and factors associated with minimal disease activity achievement in patients with psoriatic arthritis: preliminary data of a real-life multicenter study

Background: Upadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24&nbsp;weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA. Methods: One hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12&nbsp;weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis. Results: At baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs.&nbsp; At 24&nbsp;weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 ± 13.5 (p &lt; 0.001) for DAPSA and 1.21 ± 0.97 (p &lt; 0.001) for ASDAS-CRP. Thirteen patients (10%) discontinued UPA due to a lack of efficacy or non-serious adverse events. No serious adverse events were observed. Male gender (OR 2.54, 95% CI 1.03-6.25 p = 0.043), being naïve to biological DMARDs (OR 4.13, 95% CI 1.34-12.71, p = 0.013) and elevated baseline CRP (OR 2.49, 95% CI 1.02-6.12, p = 0.046) were associated with MDA response at week 24. Conclusions: This is one of the first real-life studies supporting the effectiveness of UPA and its safety profile in PsA patients. Furthermore, the study identifies predictors of MDA response to UPA treatment at 6&nbsp;months

Psoriatic Dactylitis: Current Perspectives and New Insights in Ultrasonography and Magnetic Resonance Imaging

Dactylitis, one of the most typical features of psoriatic arthritis (PsA), is the diffuse swelling of the digits and is determined by the involvement of different anatomic structures, including: the subcutaneous fibrous tissue “accessory pulley” system; flexor tendons, with their related structures; the articular synovium; the small enthesis of the hands. Dactylitis is currently considered both a marker of disease activity and severe prognosis and its importance in PsA is emphasized by the inclusion in the classification criteria of PsA. This review focuses on the role of imaging in the management of PsA patients with dactylitis in clinical practice and in a research setting. Furthermore, imaging could be a valuable tool to assist in unravelling some of the underlying mechanisms of the onset and chronicization of dactylitis in PsA patients

MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors

There is increasing evidence that oncogenic transformation modifies the metabolic program of cells. A common alteration is the upregulation of glycolysis, and efforts to target glycolytic enzymes for anticancer therapy are under way. Here, we performed a genome-wide haploid genetic screen to identify resistance mechanisms to 3-bromopyruvate (3-BrPA), a drug candidate that inhibits glycolysis in a poorly understood fashion. We identified the SLC16A1 gene product, MCT1, as the main determinant of 3-BrPA sensitivity. MCT1 is necessary and sufficient for 3-BrPA uptake by cancer cells. Additionally, SLC16A1 mRNA levels are the best predictor of 3-BrPA sensitivity and are most elevated in glycolytic cancer cells. Furthermore, forced MCT1 expression in 3-BrPA–resistant cancer cells sensitizes tumor xenografts to 3-BrPA treatment in vivo. Our results identify a potential biomarker for 3-BrPA sensitivity and provide proof of concept that the selectivity of cancer-expressed transporters can be exploited for delivering toxic molecules to tumors.National Institutes of Health (U.S.) (NIH CA103866)Jane Coffin Childs Memorial Fund for Medical Research (Fellowship)National Science Foundation (U.S.) (Fellowship)Howard Hughes Medical Institute (Investigator

Targeting cancer metabolism: a therapeutic window opens

Genetic events in cancer activate signalling pathways that alter cell metabolism. Clinical evidence has linked cell metabolism with cancer outcomes. Together, these observations have raised interest in targeting metabolic enzymes for cancer therapy, but they have also raised concerns that these therapies would have unacceptable effects on normal cells. However, some of the first cancer therapies that were developed target the specific metabolic needs of cancer cells and remain effective agents in the clinic today. Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy.Burroughs Wellcome FundSmith Family FoundationStarr Cancer ConsortiumDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.