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 cm <sup>3</sup> ). (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 cm <sup>3</sup> 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

Interrogation of the perturbed gut microbiota in gouty arthritis patients through in silico metabolic modeling

Recent studies have shown perturbed gut microbiota associated with gouty arthritis, a metabolic disease characterized by an imbalance between uric acid production and excretion. To mechanistically investigate altered microbiota metabolism associated with gout disease, 16S rRNA gene amplicon sequence data from stool samples of gout patients and healthy controls were computationally analyzed through bacterial community metabolic models. Patient-specific community models constructed with the metagenomics modeling pipeline, mgPipe, were used to perform k-means clustering of samples according to their metabolic capabilities. The clustering analysis generated statistically significant partitioning of samples into a Bacteroides-dominated, high gout cluster and a Faecalibacterium-elevated, low gout cluster. The high gout cluster was predicted to allow elevated synthesis of the amino acids D-alanine and L-alanine and byproducts of branched-chain amino acid catabolism, while the low gout cluster allowed higher production of butyrate, the sulfur-containing amino acids L-cysteine and L-methionine, and the L-cysteine catabolic product H2S. By expanding the capabilities of mgPipe to provide taxa-level resolution of metabolite exchange rates, acetate, D-lactate and succinate exchanged from Bacteroides to Faecalibacterium were predicted to enhance butyrate production in the low gout cluster. Model predictions suggested that sulfur-containing amino acid metabolism generally and H2S more specifically could be novel gout disease markers

Dual-energy computed tomography vs ultrasound, alone or combined, for the diagnosis of gout: a prospective study of accuracy.

To examine the accuracy of dual-energy CT (DECT) vs ultrasound or their combination for the diagnosis of gout. Using prospectively collected data from an outpatient rheumatology clinic at a tertiary-care hospital, we examined the diagnostic accuracy of either modality alone or their combination, by anatomical site (feet/ankles and/or knees), for the diagnosis of gout. We used two standards: (i) demonstration of monosodium urate crystals in synovial fluid (gold), and (ii) modified (excluding DECT and ultrasound) 2015 ACR-EULAR gout classification criteria (silver). Of the 147 patients who provided data, 48 (33%) had synovial fluid analysis performed (38 were monosodium urate-crystal positive) and mean symptom duration was 9.2 years. One hundred (68%) patients met the silver standard. Compared with the gold standard, diagnostic accuracy statistics for feet/ankles DECT, feet/ankles ultrasound, knees DECT and knees ultrasound were, respectively: sensitivity: 87%, 84%, 91% and 58%; specificity: 100%, 60%, 87% and 80%; positive predictive value: 100%, 89%, 97% and 92%; negative predictive value: 67%, 50%, 70% and 33%; area under the receiver operating characteristic curve: 0.93, 0.72, 0.89 and 0.66. Combining feet/ankles DECT with ultrasound or knees DECT with ultrasound led to a numerically higher sensitivity compared with DECT alone, but overall accuracy was lower. Similarly, combining imaging knees to feet/ankles also yielded a numerically higher sensitivity and negative predictive values compared with feet/ankles DECT alone, without differences in overall accuracy. Findings were replicated compared with the silver standard, but with lower numbers. Feet/ankles or knees DECT alone had the best overall accuracy for gout diagnosis. The DECT-US combination or multiple joint imaging offered no additional increase in overall diagnostic accuracy

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

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. 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 <sub>eff</sub> ). 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 <sub>eff</sub> . 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/cm <sup>3</sup> : 0.037 ± 0 versus 0.034 ± 0, p = 0.008) and Z <sub>eff</sub> (200 mg /cm <sup>3</sup> : 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 <sub>eff</sub> (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. 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

Dual-energy computed tomography in calcium pyrophosphate deposition: initial clinical experience.

To determine the dual-energy computed tomography (DECT) attenuation properties of meniscal calcifications in calcium pyrophosphate deposition (CPPD) in vivo, and assess whether DECT was able to discriminate meniscal CPP deposits from calcium hydroxyapatite (HA) in subchondral and trabecular bone. Patients with clinical suspicion of crystal-related arthropathy (gout and/or CPPD) and knee DECT scans were retrospectively assigned to CPPD (n = 19) or control (n = 21) groups depending on the presence/absence of chondrocalcinosis on DECT. Two observers drew standardized regions of interest (ROI) in meniscal calcifications, non-calcified menisci, as well as subchondral and trabecular bone. Five DECT parameters were obtained: CT numbers (HU) at 80 and 140 kV, dual-energy index (DEI), electron density (ρ <sub>e</sub> ), and effective atomic number (Z <sub>eff</sub> ). The four different knee structures were compared within/between patients and controls using linear mixed models, adjusting for confounders. Meniscal calcifications (n = 89) in CPPD patients had mean ± SD CT numbers at 80 and 140 kV of 257 ± 64 and 201 ± 48 HU, respectively; with a DEI of 0.023 ± 0.007, and ρ <sub>e</sub> and Z <sub>eff</sub> of 140 ± 35 and 8.8 ± 0.3, respectively. Meniscal CPP deposits were readily distinguished from calcium HA in subchondral and trabecular bone (p ≤ 0.001), except at 80 kV separately (p = 0.74). Z <sub>eff</sub> and ρ <sub>e</sub> both significantly differed between CPP deposits and calcium HA in subchondral and trabecular bone (p < 0.0001). This proof-of-concept study shows that DECT has the potential to discriminate meniscal CPP deposits from calcium HA in subchondral and trabecular bone in vivo, paving the way for the non-invasive biochemical signature assessment of intra- and juxta-articular calcium crystal deposits