Are patients with gout with negative dual-energy computed tomography for monosodium urate crystal deposition easy-to-treat?

OBJECTIVES: To determine the clinical associations and predictive value of two thresholds of negative dual-energy CT (DECT) for MSU crystal deposition in gout patients initiating urate lowering therapy (ULT), and identify which threshold is more clinically relevant. METHODS: Patients from the CRYSTALILLE cohort with a diagnosis of gout naive to ULT with baseline DECT scans of knees and feet were selected. Two thresholds of positivity for DECT detection of MSU crystal deposition were considered (<0.01 cm3 and <0.1 cm3). Baseline characteristics and the prediction of key outcomes after ULT initiation including reaching serum urate (SU) levels <6.0 and 5.0 mg/dl and occurrence of flares at 6, 12 and 24 months, associated with both thresholds of negative DECTs were compared with those of. PATIENT: s having positive DECT scans. RESULTS: 211 patients aged 66.2 years [57; 75.8] with a symptom duration of 3 years [0; 7.8] were included. 38/211 (18%) and 90/211 (43%) had negative DECT scans for the 0.01 and 0.1 cm3 thresholds, respectively. Factors associated with negative DECT scans were younger age, shorter symptom duration, and absence of cardiovascular disease for both volume thresholds. 9/39 (23.1%), 3/26 (11.5%), and 1/18 (5.6%) of patients with <0.1 cm3 MSU crystals had flares at 6, 12 and 24 months, respectively, compared with 18/45 (40.0%), 9/36 (25.0%) and 2/18 (11.1%) patients with ≥0.1 cm3 (p> 0.05).Overall, 95 patients (68.3%) reached SU levels <6.0 mg/dl and 68 (48.9%) <5.0 mg/dl, without any difference between positive and negative DECTs, with ULT dosages which tended to be lower in patients with negative DECT. CONCLUSION: The 0.1 cm3 threshold was better correlated to clinical presentation and evolution than 0.01 cm3. Patients with gout with negative DECTs exhibit milder disease and a lower comorbidity burden. They do not exhibit particularly easy-to-treat hyperuricemia, but may have a lower risk of flares.

Early-onset gout.

Early-onset gout (EOG) is characterized by the occurrence of the first symptoms of gout at an unusually young age, usually <40 years. The aim of this review is to provide an overview of the epidemiology, clinical presentation and prognosis, association with comorbidities and specific management of EOG. A particularly high proportion of patients with EOG come from ethnic groups with stronger genetic factors, such as populations in the Pacific and Taiwan, who therefore have the highest prevalence of gout overall. The clinical presentation and severity of gout are broadly similar between EOG and common gout, although a longer disease duration exacerbates the disease, which more often tends to become polyarticular. Patients suffering from EOG develop metabolic comorbidities commonly associated with gout earlier in life, although those tend to be less frequent at the time of diagnosis. Some international guidelines recommend early treatment of EOG patients with urate-lowering therapies.

Factors influencing the kinetics of MSU crystal depletion measured with dual-energy CT in patients with gout.

OBJECTIVE: To examine factors influencing the kinetics of monosodium urate (MSU) crystal dissolution measured with dual-energy computed tomography (DECT) during follow-up of patients with gout. METHODS: Patients with a diagnosis of gout with baseline knees and feet DECT scans exhibiting MSU crystal volumes ≥0.1 cm3 and at least one follow-up DECT were included. Spearman's correlation coefficient was used to search for association between change from baseline MSU crystal volume at 6, 12, 18 and 24 months and serum urate (SU) level. Associations between percentage change from the baseline volume of MSU crystal deposits and explanatory variables were assessed using linear mixed models. RESULTS: Sixty-two patients (age 67.3±12.8 years; 53 (85%) males) cumulating 104 follow-up DECT scans were included. Overall, SU target levels (<6.0 and <5.0 mg/dL) were achieved by 48 (77%) and 36 (58%) patients, respectively. There was a good correlation (r=0.66; p<0.0001) observed between SU level and percentage change in MSU crystal volume. The median decrease from baseline MSU crystal volume was greater in patients reaching the <5.0 mg/dL SU target than in those reaching ≥5.0 SU <6.0 mg/dL: -85% (95% CI: -94% to -72%) versus -40% (-57% to -22%; p<0.05) at 12 months. In multivariable analysis, time (in days) with a multilevel coefficient of -0.06 (95% CI: -0.08 to -0.03, p<0.001), hypertension (coefficient: 41.87, 95% CI: 16.38 to 67.18, p<0.01) and SU level <5.0 mg/dL (coefficient: -39.46, 95% CI: -70.93 to -8.34, p=0.02) were the only variables significantly associated with MSU crystal volume change. CONCLUSION: In patients with DECT-measured MSU crystal deposition, reaching the <5.0 mg/dL SU target provides more extensive and rapid crystal dissolution than reaching the <6.0 mg/dL SU target.

Evaluating the safety and short-term equivalence of colchicine versus prednisone in older patients with acute calcium pyrophosphate crystal arthritis (COLCHICORT): an open-label, multicentre, randomised trial.

BACKGROUND: Acute calcium pyrophosphate crystal arthritis causes intense joint pain mainly affecting older people. Because guidance and evidence remain scarce, management of this disease relies on expert opinion. We therefore aimed to compare the safety and short-term equivalence of low-dose colchicine with oral prednisone in older patients with acute calcium pyrophosphate crystal arthritis. METHODS: We did an open-label, multicentre, randomised, trial (COLCHICORT) at six hospitals in Paris and northern France. We enrolled patients who were admitted to hospital who were 65 years or older and who presented with acute calcium pyrophosphate crystal arthritis with a symptom duration of less than 36 h. Diagnosis of calcium pyrophosphate crystal arthritis was made by the identification of calcium pyrophosphate crystals on synovial fluid analysis or typical clinical presentation (onset of joint pain and swelling). Key exclusion criteria included absence of calcium pyrophosphate crystals on synovial fluid analysis or a history of gout. Participants were randomly allocated (1:1), using a centralised electronic treatment group allocation module, to receive either colchicine 1·5 mg on day 1 and 1 mg on day 2 (ie, the colchicine group) or oral prednisone 30 mg on days 1 and 2 (ie, the prednisone group). The primary outcome was change in joint pain (measured by visual analogue scale [VAS] from 0 mm to 100 mm) at 24 h. Equivalence was determined whether the 95% CI of the between-group difference at 24 h was within the -13 mm to +13 mm margin in the per-protocol analysis. Adverse events were recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). This trial is completed and is registered with ClinicalTrials.gov, NCT03128905. FINDINGS: Between Feb 5, 2018, and May 7, 2022, 111 patients who were admitted to hospital were randomly assigned (57 [51%] to the colchicine group and 54 [49%] to the prednisone group). 95 (86%) of 111 patients were included in the per-protocol analysis (49 [52%] in the colchicine group and 46 [48%] in the prednisone group). The median age was 88·0 years (IQR 82·0-91·0) and 69 (73%) of 95 participants were women and 26 (27%) were men. Acute calcium pyrophosphate crystal arthritis affected mainly the knee in 46 (48%) of 95 participants, the wrist in 19 (20%), and the ankle in 12 (13%). Pain VAS at baseline was 68 mm (SD 17). At 24 h, change in pain VAS was -36 mm (SD 32) in the colchicine group and -38 mm (SD 23) in the prednisone group. The between-group difference in change in pain VAS at 24 h was -1 mm (95% CI -12 to 10), showing equivalence between the two drugs. In the colchicine group, 12 (22%) of 55 patients had diarrhoea, one (2%) had hypertension, and none had hyperglycaemia. In the prednisone group, three (6%) of 54 had diarrhoea, six (11%) had hypertension, and three (6%) had hyperglycaemia. No deaths occurred in the colchicine group; two deaths occurred in the prednisone group, which were deemed unrelated to prednisone (one due to infectious valvular endocarditis leading to heart failure, and one due to a stroke). INTERPRETATION: Colchicine and prednisone exhibit equivalent short-term efficacy for the treatment of acute calcium pyrophosphate crystal arthritis, with different safety profiles in the older population. FUNDING: French Inter-regional Hospital Program of Clinical Research.

Identification and characterization of peripheral vascular color-coded DECT lesions in gout and non-gout patients: The VASCURATE study.

OBJECTIVE: To characterize peripheral vascular plaques color-coded as monosodium urate (MSU) deposition by dual-energy computed tomography (DECT) and assess their association with the overall soft-tissue MSU crystal burden. METHODS: Patients with suspected crystal arthropathies were prospectively included in the CRYSTALILLE inception cohort to undergo baseline knees and ankles/feet DECT scans; treatment-naive gout patients initiating treat-to-target urate-lowering therapy (ULT) underwent repeated DECT scans with concomitant serum urate level measurements at 6 and 12 months. We determined the prevalence of DECT-based vascular MSU-coded plaques in knee arteries, and assessed their association with the overall DECT volumes of soft-tissue MSU crystal deposition and coexistence of arterial calcifications. DECT attenuation parameters of vascular MSU-coded plaques were compared with dense calcified plaques, control vessels, control soft tissues, and tophi. RESULTS: We investigated 126 gout patients and 26 controls; 17 ULT-naive gout patients were included in the follow-up study. The prevalence of DECT-based vascular MSU-coded plaques was comparable in gout patients (24.6%) and controls (23.1%; p=0.87). Vascular MSU-coded plaques were strongly associated with coexisting arterial calcifications (p<0.001), but not with soft-tissue MSU deposition. Characterization of vascular MSU-coded plaques revealed specific differences in DECT parameters compared with control vessels, control soft tissues, and tophi. During follow-up, vascular MSU-coded plaques remained stable despite effective ULT (p=0.64), which decreased both serum urate levels and soft-tissue MSU volumes (p<0.001). CONCLUSION: Our findings suggest that DECT-based MSU-coded plaques in peripheral arteries are strongly associated with calcifications and may not reflect genuine MSU crystal deposition. Such findings should therefore not be a primary target when managing gout patients.

Crystal deposition measured with dual-energy computed tomography: association with mortality and cardiovascular risks in gout.

OBJECTIVES: To determine whether the volume of monosodium urate (MSU) crystal deposition measured with dual-energy CT (DECT) is predictive of short-term mortality and development of cardiovascular comorbidities and diabetes mellitus. METHODS: Patients with a diagnosis of gout having had baseline DECT scans of their knees and feet to measure the volume of MSU crystal deposition were included to undergo a follow-up visit. Risk factors for mortality and a composite variable (onset of any cardio-metabolic event) were examined using multivariable Cox models. RESULTS: A total of 128 patients aged 66.1 (14.0) years with gout durations of 11.4 (10.4) years were included; most were naïve of urate lowering therapy (61.7%), with a follow-up visit at 24 (12, 36) months. Baseline serum urate (SU) level was 7.44 (2.29) mg/dl and DECT volume of MSU crystals was 0.2 (0, 0.9) cm3. A total of 14 patients died during follow-up, 6/14 from a cardiovascular cause, and 17 patients presented a new cardio-metabolic comorbidity. Factors associated with mortality risk were baseline DECT volume of MSU crystals [hazard ratio (HR) 1.02, 95% CI: 1.002, 1.03] and baseline SU level (HR 1.04, 95% CI: 1.003, 1.06). DECT volume of MSU crystals was the only factor associated with the onset of cardio-metabolic comorbidities with a HR of 1.014 (95% CI: 1.001, 1.03). CONCLUSIONS: Volume of MSU crystals measured with DECT is a biomarker for the risk of developing new cardio-metabolic diseases and for all-cause mortality.

Usefulness of a Visual Analog Scale for Measuring Anxiety in Hospitalized Patients Experiencing Pain: A Multicenter Cross-Sectional Study.

BACKGROUND: Anxiety is common in hospitalized patients and can worsen pain or lead to unsuccessful pain relief. AIMS: The purpose of this study was to evaluate the usefulness of measuring anxiety with a visual analog scale (VAS) in the hospitalized patient experiencing pain. DESIGN: We conducted a multiple-center cross-sectional study. PARTICIPANTS/SUBJECTS: Adult inpatients experiencing moderate to severe pain defined by a pain VAS score ≥40 of 100 were included. METHODS: Pain and anxiety data were collected using the following instruments: pain VAS, anxiety VAS, State Anxiety Scale of the Spielberger State-Trait Anxiety Inventory (STAI-YA) and Anxiety Subscale of the Hospital Anxiety and Depression Scale (HAD-A). RESULTS: Data were collected from 394 patients. Of those patients, 43.6% (171 of 392) and 36.6% (143 of 391) had significant anxiety according to STAI-Ya and HAD-A, respectively. Correlation was good between anxiety-VAS and STAI-YA (ρ = 0.67 [95% confidence interval 0.61-0.72]) and moderate between anxiety VAS and HAD-D (ρ = 0.48 [0.39-0.56]). The main factor predictive of situational anxiety was history of anxiety-depression symptoms (odds ratio = 2.95 [1.93-4.56]). For anxiety VAS score ≥ 40 of 100, the sensitivity for detecting anxiety was 81% with 70% specificity. CONCLUSION: This study confirmed the high prevalence of anxiety among inpatients experiencing pain, demonstrated the capacity of a VAS to assess this anxiety, determined an anxiety VAS cutoff level to screen for significant anxiety, and identified risk factors of anxiety in this population. Anxiety VAS has been found to be an easy-to-use method familiar to caregivers, with all the advantages needed for an effective screening instrument. An anxiety VAS score ≥40 of 100 would thus warrant particular attention to adapt care to the patient's anxiety-related pain and initiate specific therapeutic interventions.

Association of Specific Comorbidities with Monosodium Urate Crystal Deposition in Urate-Lowering Therapy-Naive Gout Patients: A Cross-Sectional Dual-Energy Computed Tomography Study.

(1) Background: To determine which factors are associated with the volume of monosodium urate (MSU) crystal deposition quantified by dual-energy computed tomography (DECT) in urate-lowering therapy (ULT)-naive gout patients. (2) Methods: In this multicenter cross-sectional study, DECT scans of knees and feet/ankles were prospectively obtained from ULT-naive gout patients. Demographic, clinical (including gout history and comorbidities), and biological data were collected, and their association with DECT MSU crystal volume was analyzed using bivariate and multivariate analyses. A second bivariate analysis was performed by splitting the dataset depending on an arbitrary threshold of DECT MSU volume (1 cm3). (3) Results: A total of 91 patients were included. In the bivariate analysis, age (p = 0.03), gout duration (p = 0.003), subcutaneous tophi (p = 0.004), hypertension (p = 0.02), diabetes mellitus (p = 0.05), and chronic heart failure (p = 0.03) were associated with the total DECT volume of MSU crystal deposition. In the multivariate analysis, factors associated with DECT MSU volumes ≥1 cm3 were gout duration (odds ratio (OR) for each 10-year increase 3.15 (1.60; 7.63)), diabetes mellitus (OR 4.75 (1.58; 15.63)), and chronic heart failure (OR 7.82 (2.29; 31.38)). (4) Conclusion: Specific comorbidities, particularly chronic heart failure and diabetes mellitus, are more strongly associated with increased MSU crystal deposition in knees and feet/ankles than gout duration, regardless of serum urate level.

Monosodium urate burden assessed with dual-energy computed tomography predicts the risk of flares in gout: a 12-month observational study : MSU burden and risk of gout flare.

BACKGROUND: Predicting the risk of flares in patients with gout is a challenge and the link between urate burden and the risk of gout flare is unclear. The objective of this study was to determine if the extent of monosodium urate (MSU) burden measured with dual-energy computed tomography (DECT) and ultrasonography (US) is predictive of the risk of gout flares. METHODS: This prospective observational study recruited patients with gout to undergo MSU burden assessment with DECT (volume of deposits) and US (double contour sign) scans of the knees and feet. Patients attended follow-up visits at 3, 6 and 12 months. Patients having presented with at least one flare at 6 months were compared to those who did not flare. Odds ratios (ORs) (95% confidence interval) for the risk of flare were calculated. RESULTS: Overall, 64/78 patients included attended at least one follow-up visit. In bivariate analysis, the number of joints with the double contour sign was not associated with the risk of flare (p = 0.67). Multivariate analysis retained a unique variable: DECT MSU volume of the feet. For each 1 cm3 increase in DECT MSU volume in foot deposits, the risk of flare increased 2.03-fold during the first 6 months after initial assessment (OR 2.03 (1.15-4.38)). The threshold volume best discriminating patients with and without flare was 0.81 cm3 (specificity 61%, sensitivity 77%). CONCLUSIONS: This is the first study showing that the extent of MSU burden measured with DECT but not US is predictive of the risk of flares.

The lack of association between the burden of monosodium urate crystals assessed with dual-energy computed tomography or ultrasonography with cardiovascular risk in the commonly high-risk gout patient.

BACKGROUND: Gout is associated with higher cardiovascular risk that increases with disease severity. The objective of this study was to explore the relationship between the extent of monosodium urate (MSU) crystal deposition, assessed with ultrasonography (US) and dual-energy computed tomography (DECT), and cardiovascular risk. METHODS: Gout patients were included in this cross-sectional study to undergo DECT scans for the assessment of total MSU volume deposition in the knees and feet, and US to evaluate the number of joints with the double contour (DC) sign. Participants were screened for traditional cardiovascular risk factors, and levels of the American College of Cardiology (ACC)/American Heart Association (AHA) 10-year risk for heart disease or stroke were calculated. The primary endpoint was the Spearman correlation coefficient ρ between DECT MSU volume and cardiovascular risk. RESULTS: A total of 42 patients were included; they were predominantly male (40/42) and aged 63.0 ± 13.2 years. Overall, 28/42 patients presented with the metabolic syndrome and the average 10-year coronary event or stroke risk according to the ACC/AHA (n = 33) was 21 ± 15%. Correlations between DECT volumes of MSU deposits in the knees, feet, and knees + feet and cardiovascular risk according to the ACC/AHA were very poor, with ρ = 0.18, -0.01, and 0.13, respectively. The was no correlation between the number of joints with the DC sign and cardiovascular risk (ρ = -0.07). DECT MSU deposit volume was similar in patients with and without metabolic syndrome (p = 0.29). CONCLUSIONS: The extent of MSU burden does not increase the estimated risk of cardiovascular events in gout patients.

Ultrasonography and dual-energy computed tomography provide different quantification of urate burden in gout: results from a cross-sectional study.

BACKGROUND: Ultrasonography (US) and dual-energy computed tomography (DECT) can assess urate burden in gout. The objective of this study was to compare the quantification of urate deposition provided by US to the one provided by DECT. METHODS: Patients with a diagnosis of gout were prospectively recruited to undergo quantification of urate deposition using US and DECT. US examination for tophi and the double contour (DC) sign was performed on the knees and feet and corresponding DECT scans provided volumes of tophi and of overall urate deposition. The primary endpoint was the intra-class correlation coefficient (ICC) of the volume of the index tophus measured by US and DECT and its 95% confidence interval (CI 95%). RESULTS: Of the 64 patients included, 34 presented with at least one tophus on US. DECT inter-reader agreement for urate deposition was perfect with an ICC of 1 (1-1) and good for the measurement of the index tophus with an ICC of 0.69 (0.47-0.83). The ICC for the measurement of the index tophus between the two techniques was poor with a value of 0.45 (0.1-0.71). The average ratio between the index tophi volume as assessed by DECT and US was 0.65. The number of DC-positive joints did not correlate with DECT volume of overall deposits (Spearman correlation coefficient of 0.23). CONCLUSIONS: DECT measurements of tophi give smaller volumes to the same tophi measured with US, and US signs of urate deposition in joints do not correlate with overall DECT volumes of extra-articular deposition.

Long-term results of infliximab therapy in rheumatoid arthritis: experience acquired by the North-Pas-de-Calais hospital network.

OBJECTIVE: Infliximab is effective in patients with rheumatoid arthritis (RA). Add-on infliximab therapy in patients on methotrexate results in a rapid gain in effectiveness, which lasts at least 1 year. The objective of this study was to evaluate the effectiveness and continuation rate of infliximab in patients with RA after the first year of treatment. METHODS: The first 50 patients with RA who were given infliximab in the North-Pas-de-Calais region of France were included in a multicenter open-label study. The patients had severe RA or failed to respond to conventional medications. Infliximab was given in a dosage of 3 mg/kg every 8 weeks in combination with methotrexate. Effectiveness was evaluated using the DAS28-3 score and EULAR response criteria. The dates and reasons of infliximab discontinuations were recorded. RESULTS: The 2-year infliximab continuation rate was 70%. Serious adverse events requiring infliximab discontinuation occurred in 7 patients. Mean DAS28-3 scores in the 35 patients who took infliximab for at least 2 years were 6.42 at baseline, 4.33 after 30 weeks, 4.31 after 54 weeks, and 3.86 after 102 weeks. According to EULAR criteria after 102 weeks, there were 12 good responders, 18 moderate responders, and 5 nonresponders. CONCLUSION: Experience acquired in the North-Pas-de-Calais district of France suggests that infliximab is continued for more than 2 years in more than two-thirds of patients and remains effective over this period.

Primary amyloidoma of the axis and acute spinal cord compression: a case report.

BACKGROUND: Localized primary amyloidosis is a disease characterized by a single tumor and localized amyloid deposit (amyloidoma) with no evidence of generalized amyloidosis. The occurrence of an amyloidoma in the spine is rare and only three cases affecting the axis have been previously reported. We describe the case of a 79-year-old woman presenting with a mass involving the odontoid process, responsible for an acute tetraparesia. Diagnosis of local primary amyloidosis was made after surgical excision. RESULTS: Despite the critical presentation, outcome was excellent after total excision of the mass. This case can be classified as a primary localized amyloidoma. The patient did not exhibit any infection, tumor or inflammatory disease, and continued investigations failed to demonstrate other amyloid deposit after one-year follow-up. CONCLUSIONS: Amyloidoma must be discussed in presence of a tumor-like mass of the odontoid process and may be responsible, as in our case, for spinal cord compression.