The gout epidemic in French Polynesia: a modelling study of data from the Ma'i u'u epidemiological survey.

BACKGROUND: Gout is the most common cause of inflammatory arthritis worldwide, particularly in Pacific regions. We aimed to establish the prevalence of gout and hyperuricaemia in French Polynesia, their associations with dietary habits, their comorbidities, the prevalence of the HLA-B*58:01 allele, and current management of the disease. METHODS: The Ma'i u'u survey was epidemiological, prospective, cross-sectional, and gout-focused and included a random sample of adults from the general adult population of French Polynesia. It was conducted and data were collected between April 13 and Aug 16, 2021. Participants were randomly selected to represent the general adult population of French Polynesia on the basis of housing data collected during the 2017 territorial census. Each selected household was visited by a research nurse from the Ma'i u'u survey who collected data via guided, 1-h interviews with participants. In each household, the participant was the individual older than 18 years with the closest upcoming birthday. To estimate the frequency of HLA-B*58:01, we estimated HLA-B haplotypes on individuals who had whole-genome sequencing to approximately 5× average coverage (mid-pass sequencing). A subset of individuals who self-reported Polynesian ancestry and not European, Chinese, or other ancestry were used to estimate Polynesian-ancestry specific allele frequencies. Bivariate associations were reported for weighted participants; effect sizes were estimated through the odds ratio (OR) of the association calculated on the basis of a logistic model fitted with weighted observations. FINDINGS: Among the random sample of 2000 households, 896 participants were included, 140 individuals declined, and 964 households could not be contacted. 22 participants could not be weighted due to missing data, so the final weighted analysis included 874 participants (449 [51·4%] were female and 425 [48·6%] were male) representing the 196 630 adults living in French Polynesia. The estimated prevalence of gout was 14·5% (95% CI 9·9-19·2), representing 28 561 French Polynesian adults, that is 25·5% (18·2-32·8) of male individuals and 3·5% (1·0-6·0) of female individuals. The prevalence of hyperuricaemia was estimated at 71·6% (66·7-76·6), representing 128 687 French Polynesian adults. In multivariable analysis, age (OR 1·5, 95% CI 1·2-1·8 per year), male sex (10·3, 1·8-60·7), serum urate (1·6, 1·3-2·0 per 1 mg/dL), uraturia (0·8, 0·8-0·8 per 100 mg/L), type 2 diabetes (2·1, 1·4-3·1), BMI more than 30 kg/m2 (1·1, 1·0-1·2 per unit), and percentage of visceral fat (1·7, 1·1-2·7 per 1% increase) were associated with gout. There were seven heterozygous HLA-B*58:01 carriers in the full cohort of 833 individuals (seven [0·4%] of 1666 total alleles) and two heterozygous carriers in a subset of 696 individuals of Polynesian ancestry (two [0·1%]). INTERPRETATION: French Polynesia has an estimated high prevalence of gout and hyperuricaemia, with gout affecting almost 15% of adults. Territorial measures that focus on increasing access to effective urate-lowering therapies are warranted to control this major public health problem. FUNDING: Variant Bio, the French Polynesian Health Administration, Lille Catholic University Hospitals, French Society of Rheumatology, and Novartis.

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.

Prospective Monitoring of Small Intestinal Bacterial Overgrowth After Gastric Bypass: Clinical, Biological, and Gas Chromatographic Aspects.

BACKGROUND AND AIMS: Obesity is a predisposing factor for small intestinal bacterial overgrowth (SIBO). The aim of this study was to prospectively evaluate the prevalence of SIBO as well as its clinical, biological, and nutritional aspects before and up to 24 months after a Roux-en-Y gastric bypass (RYGB) surgery. PATIENTS AND METHODS: Fifty-one patients (mean BMI 46.9 kg/m2, 66.7% women) requesting RYGB were included between 2016 and 2020. Each patient underwent a glucose breath test, a standardized interrogation on functional digestive signs, a dietary survey, a blood test, a fecalogram, and anthropometric data gathering. These investigations were carried out before surgery and at 1, 3, 6, 9, 12, 18, and 24 months after RYGB. RESULTS: Before surgery, we found a prevalence of 17.6% of SIBO (95% CI = [8.9%; 31.4%]). After RYGB, at the end of 24 months of follow-up, 89.5% of patients developed SIBO. Anal incontinence appeared to be very frequent after surgery, affecting 18.8% of our population 18 months after surgery. We observed positive steatorrhea after surgery with an average of 11.1 g of lipids/24 h despite a significant limitation of dietary lipids (p = 0.0282). CONCLUSION: Our study corroborates data in the literature on the prevalence of SIBO in severe obesity patients. For the first time, we observed the sudden appearance of SIBO after RYGB, with a correlation between exhaled hydrogen on a breath test and lipid malabsorption on the fecalogram. As a result, these patients develop fatty diarrhea, with frequent fecal incontinence.

Real-life practice of reflectance confocal microscopy in France: A prospective multicenter study.

BACKGROUND: Studies demonstrating the potential utility of reflectance confocal microscopy (RCM) have been performed under experimental conditions. OBJECTIVE: To provide an overview of RCM practice in real-life. METHODS: A multicenter, prospective study carried out in 10 university dermatology departments in France. RESULTS: Overall, 410 patients were enrolled. One-half of the patients (48%) were referred by private practice dermatologists. They were referred for diagnosis (84.9%) or presurgical mapping (13%). For diagnosis, the lesions were located on the face (62%), arms and legs (14.9%), and trunk (13.6%), and presurgical mapping was almost exclusively on the face (90.9%). Among those referred for diagnosis, the main indication was suspicion of a skin tumor (92.8%). Of these, 50.6% were spared biopsies after RCM. When RCM indicated surgery, histology revealed malignant lesions in 72.7% of cases. The correlation between RCM and histopathology was high, with a correlation rate of 82.76% and a kappa coefficient of 0.73 (0.63; 0.82). LIMITATIONS: This study was performed in the settings of French tertiary referral hospitals. CONCLUSION: This study shows that in real-life RCM can be integrated into the workflow of a public private network, which enables a less invasive diagnostic procedure for patients.

Retention, safety and efficacy of off-label conventional treatments and biologics for chronic calcium pyrophosphate crystal inflammatory arthritis.

OBJECTIVES: Very little is known on the efficacy and safety of drugs for the management of chronic calcium pyrophosphate (CPP) crystal inflammatory arthritis. The objectives of this work were to describe the drugs used in the management of chronic CPP crystal inflammatory arthritis in expert European centres, and to examine treatment retention. METHODS: This was a retrospective cohort study. Charts from patients with a diagnosis of persistent inflammatory and/or recurrent acute CPP crystal arthritis were reviewed in seven European centres. Baseline characteristics were collected, and visits at months 3, 6, 12 and 24 included an assessment of treatment response and safety. RESULTS: One hundred and ninety-four treatments were initiated in 129 patients. Colchicine (used first-line in n = 73/86), methotrexate (used first-line in n = 14/36), anakinra (n = 27) and tocilizumab (n = 25) were the most prescribed treatments, while long-term corticosteroids, hydroxychloroquine, canakinumab and sarilumab were used occasionally. The 24-month on-drug retention was higher for tocilizumab (40%) than anakinra (18.5%) (P < 0.05), while the difference between colchicine (29.1%) and methotrexate (44.4%) was not statistically significant (P = 0.10). Adverse events led to 14.1% of colchicine discontinuations (100% of diarrhoea), 4.3% for methotrexate, 31.8% for anakinra and 20% for tocilizumab; all other discontinuations were related to insufficient response or losses to follow-up. Efficacy outcomes did not differ significantly between treatments throughout follow-up. CONCLUSION: Daily colchicine is the first-line therapy used in chronic CPP crystal inflammatory arthritis, which is considered efficient in a third to half of cases. Second-line treatments include methotrexate and tocilizumab, which have higher retention than anakinra.

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.

Improving cognition in people with multiple sclerosis: study protocol for a multiarm, randomised, blinded trial of multidomain cognitive rehabilitation using a video-serious game (E-SEP cognition).

Introduction: Multiple sclerosis (MS) is a prevalent neurological disease characterised by disseminated areas of demyelination and atrophy within the central nervous system, inducing cognitive disorders in 45%-65% of persons with MS (PwMS). Neuropsychology and neuroimaging studies provide evidence of the effectiveness of cognitive rehabilitation interventions, including memory and attention. Recently, serious game therapy (SGT) has been used in rehabilitation to improve cognitive processing speed. The aim of this study is to describe the protocol of a randomised controlled trial (RCT) to test the efficacy of a tablet-based cognitive home intervention among ambulatory PwMS, in comparison to a standardised neuropsychological rehabilitation. Methods and analysis: This will be a parallel-assignment, double-blinded, RCT. One hundred and fifty (75 per arm) PwMS will be randomly assigned to receive cognitive rehabilitation session over 4 months (four 20-min sessions/week) of either: (1) tablet-based SGT or (2) conventional cognitive exercises. The same assessor will evaluate outcome measures at three points: at baseline (T0), after the 16 therapy sessions weeks (T1), and 6 months after the end of treatment (T2). The primary outcomes were the scores from the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Data analysis will be performed to compare the efficacy of the two treatments. We expect superior efficiency of tablet-based SGT in contrast to conventional cognitive exercises, based on BICAMS measures of speed processing information and episodic memory. Ethics and dissemination: The trial protocol is registered on ClinicalTrials.Gov (NCT04694534) and benefits from a favourable opinion from an ethics committee (RC-P0066-2018-A00411-54).

Prediction of renal and cardiometabolic outcomes in gout during urate-lowering therapy by sonography.

OBJECTIVES: To assess whether the extent of monosodium urate (MSU) crystal deposition estimated by ultrasound could predict renal and cardiometabolic events during urate-lowering therapy (ULT). METHODS: A prospective study on gout patients from two referral centers initiating ULT who underwent baseline ultrasound and were followed for 1 year. Ultrasound scans assessed six joints for double-contour (DC) signs and tophi. A five-point change (mL/min/1.73 m2 ) in the glomerular filtration rate at month 12 (M12) was considered significant. Outcomes of interest were renal function degraded versus improved and a composite cardiometabolic outcome (new hypertension, diabetes, atherosclerotic disease, and cardiovascular death). Homogeneity analyses and Cox regression models were performed. RESULTS: One hundred sixty patients were recruited. At baseline, 81.1% of patients (n = 129) showed sonographic tophi with a mean number of 1.4 joints (±1.3) with a DC sign. At M12, 18 patients (11.3%) were lost to follow-up. The serum urate (SU) target (<6.0 mg/dL) was reached in 86 patients (69.9%). Regarding renal function, 15.9% of patients showed improvement, while in 31.0% it degraded. Fourteen new cardiometabolic events occurred in 12 patients. Neither the DC sign nor tophi showed any significant impact on the outcomes of interest. Baseline SU level was higher in those with renal improvement but not with renal decline, while achieving the SU target protected against new cardiometabolic events (HR = 0.2; 95% CI: 0.05-0.81). CONCLUSIONS: Sonographic MSU crystal burden was unhelpful in predicting renal and cardiometabolic events during the first year of ULT. Reaching the SU target prevented cardiometabolic events, while its benefit in preserving/improving renal function is unclear.

New horizons in the analysis of hospital readmissions of older adults.

This short communication highlights analytical methods that can be usefully applied to the problem of hospital readmissions of older adults. The limitations of the models currently used in studies of hospital readmissions are described. In summary, analyses of hospital readmissions face two important methodological and statistical problems not accounted for by these currently used statistical models: the potential recurrence of readmissions, and death, a terminal event which absorbs the readmission process. Not addressing the issue raised by recurrent events and terminal event generates biased estimates. We discuss an approach for the analysis of hospital readmission risk and death in the same framework. Understanding the features of this kind of approaches is essential at a time when high-quality data on hospital readmission in older patients are becoming available to a large number of researchers. Models adapted for the analysis of recurrent and terminal events are presented, and their application to studies of hospital readmission are explained, with reference to two cohorts of several thousand older individuals.

Associations of Changes in Knee Hyaline Cartilage Composition Measured With Dual-Energy Computed Tomography in Gout, Aging and Osteoarthritis.

OBJECTIVE: To characterize dual-energy computed tomography (DECT) changes depicting hyaline cartilage changes in gout patients with and without osteoarthritis (OA) and in comparators without gout. DESIGN: Patients with suspected crystal-associated arthropathy were enrolled and underwent bilateral DECT scans of the knees. Standardized regions of interest were defined in the femorotibial hyaline cartilage. Five DECT parameters were obtained: CT numbers in Hounsfield units (HU) at 80 and 140 kV, the electron density (Rho), the effective atomic number (Zeff), and the dual-energy index (DEI). Zones were compared between patients with gout, with and without knee OA, and between patients with gout and comparators without gout, after adjustment for confounders. RESULTS: A total of 113 patients with gout (mean age 63.5 ± 14.3 years) and 15 comparators without gout (mean age 75.8 ± 11.5 years) were included, n = 65 (51%) had knee OA, and 466 zones of hyaline cartilage were analyzed. Older age was associated with lower attenuations at 80 kV (P < 0.01) and 140 kV (P < 0.01), and with Rho (P < 0.01). OA was characterized by lower attenuation at 140 kV (P = 0.03), but the lower Rho was nonsignificant after adjustment for confounders. In gout, hyaline cartilage exhibited lower Rho values (adjusted P = 0.04). Multivariable coefficients of association with Rho were -0.21 [-0.38;-0.04] (P = 0.014) for age, -4.15 [-9.0;0.7] (P = 0.093) for OA and 0.73 [-0.1;1.56] (P = 0.085) for monosodium urate volume. CONCLUSION: Gout was associated with DECT-detected changes in cartilage composition, similar to those observed in older patients, with some similarities and some differences to those seen in OA. These results suggest the possibility of potential DECT biomarkers of OA.

Satisfaction and feasibility of videoconsultation (VC) in orthopaedic and trauma surgery in the context of the COVID-19 pandemic: Prospective study of 783 patients.

BACKGROUND: The COVID-19 pandemic has required that specialists use videoconsultation (VC) to maintain continuity of care. As in-person consultations (IPCs) and surgical procedures were cancelled, VC became the tool of choice. No recent French study has assessed VC as the main consultation modality. The objective of this prospective study was to evaluate: 1) patient satisfaction, 2) access to and the future of VC, 3) and the reasons for VC refusal in the setting of the pandemic. HYPOTHESIS: Patients responded favourably to VC. PATIENTS AND METHOD: We conducted a prospective, single-centre, observational study of consecutive patients who were invited to switch from IPC to VC during the lockdown of March 16 to May 11, 2020, when IPCs were not available. All patients were included in the study, regardless of whether they accepted the VC. The reasons for refusal were recorded at the time of the invitation. The surgeons sent the patients who accepted an emailed satisfaction questionnaire after the VC. RESULTS: Of the 783 patients with scheduled IPCs, 291 (37.2%) accepted a VC instead, 408 (52.1%) refused the VC, and 84 (10.7%) could not be contacted by telephone and were therefore excluded. The VC acceptance rate was 37% (291/783). Of the 291 VC patients, 233 (80.1%) returned the satisfaction questionnaire, although 2 questionnaires had too many missing data to be included, leaving 231 patients for the analysis. The VC was the first consultation with the surgeon for 66 (28.6%) patients. Of the 165 (71.4%) other patients, 51.6% (85/165) were receiving post-operative follow-up. On a 0-5 scale, the global VC experience was scored 4.3±0.8. Of the 231 VC patients, 161 (69.7%) felt that the VC was equivalent to an IPC, 18 (7.8%) that it was poorer, and 7 (3%) that it was better than an IPC; 45 (19.5%) had no opinion on this point. If choosing between a VC or an IPC had been possible during this first lockdown, 168/231 (72.7%) patients would have chosen an IPC. In contrast, 198/231 (85.7%) patients said they would choose an IPC after the lockdown. The group that refused the VC had a significantly older mean age (57.8±16.4 years vs. 48.0±14.4 years, p<0.0001) and lived closer to the institution (p<0.0001), whereas the sex distribution was comparable, with 42.9% of males (175/408) refusing and 46.8% (108/231) accepting the VC (p=0.39). The main reason for refusal was a wish for an in-person encounter with the surgeon (268/408, 65.7%). Patients aged ≥65 years were more likely to refuse due to technical considerations (access to electronic equipment and to the Internet), whereas patients ≤35 years were more likely to wait for an IPC. CONCLUSION: The rate of satisfaction with the VC was high. Satisfaction was not significantly associated with the reason for the consultation (joint involved, degenerative or post-traumatic condition, first VC, first consultation, or follow-up before or after surgery). Although most patients who accepted the VC felt that this modality was equivalent to an IPC, many remained desirous of an in-person encounter with the surgeon, notably among the youngest individuals. Outside the setting of a pandemic, the IPC remains the consultation modality of choice for most of our patients. LEVEL OF EVIDENCE: V, prospective study without a control group.

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.

Can Dual-Energy Computed Tomography Be Used to Identify Early Calcium Crystal Deposition in the Knees of Patients With Calcium Pyrophosphate Deposition?

OBJECTIVE: To assess the ability of dual-energy computed tomography (DECT) in identifying early calcium crystal deposition in menisci and articular cartilage of the knee, depending on the presence/absence of chondrocalcinosis seen on conventional CT. METHODS: One hundred thirty-two knee DECT scans from patients with suspected crystal-associated arthropathy were reviewed and assigned to a calcium pyrophosphate deposition (CPPD) group (n = 50) or a control group (n = 82). Five DECT attenuation parameters were measured in preset regions of interest (ROIs) in menisci and articular cartilage and compared between groups using linear mixed models with adjustment for confounders. Subgroup analysis, excluding ROIs with chondrocalcinosis seen on conventional CT, was performed. RESULTS: In both menisci and articular cartilage, and for all 5 DECT attenuation parameters, calcified ROIs in CPPD patients showed significantly higher values than ROIs in controls (P ≤ 0.036). Conversely, noncalcified ROIs in CPPD patients were comparable with those in controls (P ≥ 0.09). While specific DECT parameters yielded good accuracy (area under the curve [AUC] 0.87-0.88) in differentiating calcified ROIs in CPPD patients from ROIs in controls, DECT failed to distinguish between noncalcified ROIs in CPPD patients and controls (AUC 0.58-0.59). CONCLUSION: While DECT has the potential to characterize knee intraarticular mineralization, this technique cannot yet accurately identify early calcium crystal deposition that is not visible as chondrocalcinosis on conventional CT.

BONE PERFUSION AND ADIPOSITY BEYOND THE NECROTIC ZONE IN FEMORAL HEAD OSTEONECROSIS: A QUANTITATIVE MRI STUDY.

PURPOSE: To describe bone perfusion and adiposity beyond the necrotic zone with quantitative MRI techniques in osteonecrosis of the femoral head (ONFH). METHOD: In this cross-sectional multicentre study, we recruited patients suffering from late-stage ONFH or hip osteoarthritis. Hip MRI included quantitative MRI sequences: chemical-shift imaging and dynamic contrast-enhanced MRI. We drew regions of interest inside the necrotic zone (inner necrosis and its border) and outside (femoral head, neck and greater trochanter) in ONFH. In the control group, regions of interest were drawn in the femoral head, femoral neck and the greater trochanter. For each region of interest, we measured fat fraction, and calculated semi-quantitative (area under the curve, initial slope) and pharmacokinetic perfusion parameters (Ktrans and Kep). RESULTS: Thirty-two male adults (mean age 58 ±â€¯9 years, range 38-74 years) were included. Sixteen patients formed the ONFH group and fifteen the control group; one was excluded. In the normal-appearing non-necrotic part of the femoral head, fat fraction was not significantly different in comparison with controls (p = 1), but Ktrans was significantly lower than in controls (0.012 ±â€¯0.018 vs. 0.027 ±â€¯0.045; p = 0.05). This perfusion parameter reflects exchanges between blood microvessels and bone marrow. CONCLUSIONS: Our results question the concept of adipose toxicity on the macroscopic scale, and bring up the concept of regional ischemic penumbra that goes beyond the visible necrotic zone. Further studies are required to test these hypotheses in larger populations and earlier disease states.

Periprocedural, early, and long-term risks of pacemaker implantation after atrioventricular nodal re-entry tachycardia ablation: a French nationwide cohort.

AIMS: Pacemaker implantation (PI) after atrioventricular nodal re-entry tachycardia (AVNRT) ablation is a dreadful complication. We aimed to assess periprocedural, early, and late risks for PI. METHODS AND RESULTS: All 27 022 patients who underwent latest AVNRT ablation in France from 2009 to 2017, were identified in the nationwide medicalization database. A control group of 305 152 patients hospitalized for arm, leg, or skin injuries with no history of AVNRT or supraventricular tachycardia were selected. After propensity score matching, both groups had mean age of 53 ± 18 years and were predominantly female (64%). During this 9-year period, 822 of 27 022 (3.0%) AVNRT patients underwent PI, with significant higher risk in propensity-matched AVNRT patients compared to propensity-matched controls [2.9% vs. 0.9%; hazard ratio 3.4 (2.9-3.9), P < 0.0001]. This excess risk was significant during all follow-up, including periprocedural (1st month), early (1-6 months), and late (>6 months) risk periods. Annualized late risk per 100 AVNRT patients was 0.2%. In comparison to controls, excess risk was 0.2% in <30-year-old AVNRT patients; 0.7% in 30-50-year-old; 1.1% in 50-70-year-old and 6.5% over 70-year-olds. Risk for PI was also significantly different according to three procedural factors: centres, experience, and ablation date, with a 30% decrease since 2015. CONCLUSION: Periprocedural, early, and late risks for PI were higher after AVNRT ablation compared to propensity-matched controls. Longer follow-up is needed as the excess risk seems to persist late after AVNRT ablation.

Dual-energy computed-tomography-based discrimination between basic calcium phosphate and calcium pyrophosphate crystal deposition in vivo.

BACKGROUND: Dual-energy computed tomography (DECT) is being considered as a non-invasive diagnostic and characterization tool in calcium crystal-associated arthropathies. Our objective was to assess the potential of DECT in distinguishing between basic calcium phosphate (BCP) and calcium pyrophosphate (CPP) crystal deposition in and around joints in vivo. METHODS: A total of 13 patients with calcific periarthritis and 11 patients with crystal-proven CPPD were recruited prospectively to undergo DECT scans. Samples harvested from BCP and CPP calcification types were analyzed using Raman spectroscopy and validated against synthetic crystals. Regions of interest were placed in BCP and CPP calcifications, and the following DECT attenuation parameters were obtained: CT numbers (HU) at 80 and 140 kV, dual-energy index (DEI), electron density (Rho), and effective atomic number (Z eff). These DECT attenuation parameters were compared and validated against crystal calibration phantoms at two known equal concentrations. Receiver operating characteristic (ROC) curves were plotted to determine the highest accuracy thresholds for DEI and Z eff. RESULTS: Raman spectroscopy enabled chemical fingerprinting of BCP and CPP crystals both in vitro and in vivo. DECT was able to distinguish between HA and CPP in crystal calibration phantoms at two known equal concentrations, most notably by DEI (200 mg/cm3: 0.037 ± 0 versus 0.034 ± 0, p = 0.008) and Z eff (200 mg /cm3: 9.4 ± 0 versus 9.3 ± 0, p = 0.01) analysis. Likewise, BCP calcifications had significantly higher DEI (0.041 ± 0.005 versus 0.034 ± 0.005, p = 0.008) and Z eff (9.5 ± 0.2 versus 9.3 ± 0.2, p = 0.03) than CPP crystal deposits with comparable CT numbers in patients. With an area under the ROC curve of 0.83 [best threshold value = 0.0 39, sensitivity = 90. 9% (81.8, 97. 7%), specificity = 64.6% (50.0, 64. 6%)], DEI was the best parameter in distinguishing between BCP and CPP crystal depositions. CONCLUSION: DECT can help distinguish between crystal-proven BCP and CPP calcification types in vivo and, thus, aid in the diagnosis of challenging clinical cases, and in the characterization of CPP and BCP crystal deposition occurring in osteoarthritis.

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.