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Gout Urate Cryst. Depos. Dis., Volume 2, Issue 1 (March 2024) – 8 articles

Cover Story (view full-size image): Crystal-induced arthropathies (CIA), primarily from calcium pyrophosphate and uric acid depositions, significantly impact patients' lives. Imaging, especially utilising ultrasound (US), is crucial for detecting crystal deposits in joints and periarticular tissues, which are hallmark features of these conditions. However, US requires operator expertise and a thorough understanding of the pathological mechanisms behind crystal deposition. This technical note (the first in a two-part series) aims to provide detailed guidance on using US to assess calcium pyrophosphate depositions in joints. View this paper
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9 pages, 444 KiB  
Article
Prevalence and Influence of Gout in Patients with Advanced Chronic Kidney Disease: Findings of a Large Retrospective Chart Review
by Leonard Stern, Richard J. Johnson, Payam Shakouri, Amod Athavale, Lissa Padnick-Silver, Brian LaMoreaux, Brad A. Marder and Sreedhar Mandayam
Gout Urate Cryst. Depos. Dis. 2024, 2(1), 77-85; https://doi.org/10.3390/gucdd2010008 - 21 Mar 2024
Cited by 1 | Viewed by 1674
Abstract
Gout patients have higher mortality, heavier comorbidity burden, and lower quality of life than non-gout patients, but information is sparse on how gout affects advanced CKD patients. This study examined the prevalence and potential health impacts in stage 3–5 CKD patients. Gout was [...] Read more.
Gout patients have higher mortality, heavier comorbidity burden, and lower quality of life than non-gout patients, but information is sparse on how gout affects advanced CKD patients. This study examined the prevalence and potential health impacts in stage 3–5 CKD patients. Gout was defined as being listed as a comorbidity, ULT use, and/or reported gout symptoms (tophi, >1 flare). Uncontrolled gout was defined as hyperuricemia (serum urate >6 mg/dL) with tophi, ≥2 gout flares/year, or ≥1 swollen/tender joint. This study included 746 patients (55% men, age: 56.2 ± 18.3 years, CKD-duration: 4.0 ± 4.8 years, eGFR: 32.2 ± 15.5 mL/min/1.73 m2), of which 23% met the gout criteria. Prevalence was highest in patients with stage 3b and 4 CKD. Gout patients had a significantly higher prevalence of cardiovascular comorbidities, CKD-mineral bone disorder, and back pain than non-gout patients. Uncontrolled gout patients had more hypertension, joint issues, chronic pain, febuxostat use, and colchicine use than controlled patients. Compared to those without gout, gout patients had higher rates of cardiovascular and bone diseases, with uncontrolled patients having an even higher burden. In conclusion, these data suggest that identifying and monitoring gout in CKD patients provides health benefits. However, more than one-third of gout patients did not have a formal gout diagnosis in their medical record. Full article
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7 pages, 907 KiB  
Review
Serum Urate as a Surrogate Outcome for Gout Flares: Where Do We Stand Today?
by Lisa K. Stamp, Robin Christensen and Melanie B. Morillon
Gout Urate Cryst. Depos. Dis. 2024, 2(1), 70-76; https://doi.org/10.3390/gucdd2010007 - 11 Mar 2024
Viewed by 1136
Abstract
In gout research, serum urate has been widely accepted as the primary endpoint in clinical trials of urate-lowering therapies by both the FDA and EMA for many years. However, for serum urate to be a meaningful outcome measure, it should reflect at least [...] Read more.
In gout research, serum urate has been widely accepted as the primary endpoint in clinical trials of urate-lowering therapies by both the FDA and EMA for many years. However, for serum urate to be a meaningful outcome measure, it should reflect at least one important patient-centered clinical outcome, such as gout flares. The relationship between achieving a pre-specified “target” serum urate and a corresponding improvement in patient-centered outcomes has been difficult to show due to variation in reporting of both serum urate and gout flares in clinical trials; a paradoxical rise in gout flares after starting urate-lowering therapy and a delay after achieving the pre-specified target serum urate before gout flares settle coupled with the relatively short duration of the trials. However, recent evidence from individual-level patient data from two, two-year randomized controlled trials clearly shows that achieving target urate is associated with a subsequent reduction and cessation of gout flares. In this review, we examine the evidence supporting serum urate as a surrogate outcome for gout flares, the methods, and the challenges of showing the validity of surrogacy. Full article
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10 pages, 652 KiB  
Conference Report
14th European Crystal Network (ECN) Workshop—Abstract Proceedings
by Frédéric Lioté, Fernando Perez-Ruiz, Hang-Korng Ea, Tony Merriman, Tristan Pascart and Alexander So
Gout Urate Cryst. Depos. Dis. 2024, 2(1), 60-69; https://doi.org/10.3390/gucdd2010006 - 11 Mar 2024
Cited by 1 | Viewed by 1098
Abstract
The 14th annual international European Crystal Network was held in Paris on 2 and 3 March 2023. This in-person meeting was attended by 93 participants. Over 40 research abstract submissions were received from investigators, ranging from early career investigators to senior researchers, for [...] Read more.
The 14th annual international European Crystal Network was held in Paris on 2 and 3 March 2023. This in-person meeting was attended by 93 participants. Over 40 research abstract submissions were received from investigators, ranging from early career investigators to senior researchers, for plenary oral and poster presentations. Here, we present the accepted, lightly edited abstracts from the presenters consenting to have their work published. We thank and congratulate the presenters for their work and contributions to the meeting. Full article
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8 pages, 218 KiB  
Review
A New Era for Calcium Pyrophosphate Deposition Disease Research: The First-Ever Calcium Pyrophosphate Deposition Disease Classification Criteria and Considerations for Measuring Outcomes in Calcium Pyrophosphate Deposition Disease
by Sara K. Tedeschi
Gout Urate Cryst. Depos. Dis. 2024, 2(1), 52-59; https://doi.org/10.3390/gucdd2010005 - 5 Feb 2024
Cited by 3 | Viewed by 1030
Abstract
Calcium pyrophosphate deposition (CPPD) disease is a crystalline arthritis that was described more than 60 years ago, yet our knowledge about this condition greatly lags behind other forms of arthritis. This is an exciting era for CPPD disease as a robust framework for [...] Read more.
Calcium pyrophosphate deposition (CPPD) disease is a crystalline arthritis that was described more than 60 years ago, yet our knowledge about this condition greatly lags behind other forms of arthritis. This is an exciting era for CPPD disease as a robust framework for CPPD clinical research has been established. The American College of Rheumatology (ACR) and EULAR co-sponsored the development of the first-ever classification criteria for CPPD. The Outcomes Measures in Rheumatology (OMERACT) CPPD Ultrasound Subtask Force developed and validated definitions for ultrasonographic findings of CPPD, and the OMERACT CPPD Working Group is establishing a core outcome domain set for this crystalline arthritis. This review focuses on key elements of the 2023 ACR/EULAR CPPD disease classification criteria and considerations for measuring outcomes in CPPD disease. Full article
7 pages, 1043 KiB  
Brief Report
The Prevalence of Titanium Dioxide Particles in Synovial Fluid Samples Drops after European Union Ban
by Tom Niessink, Matthijs Janssen, Tim L. Jansen and Cees Otto
Gout Urate Cryst. Depos. Dis. 2024, 2(1), 45-51; https://doi.org/10.3390/gucdd2010004 - 1 Feb 2024
Cited by 1 | Viewed by 1287
Abstract
Due to health concerns, the European Union has banned the use of titanium dioxide nanoparticles in consumables in February 2022, with a 6-month transitional period ending in August 2022. We studied the prevalence of titanium dioxide nanoparticles in synovial fluid samples during and [...] Read more.
Due to health concerns, the European Union has banned the use of titanium dioxide nanoparticles in consumables in February 2022, with a 6-month transitional period ending in August 2022. We studied the prevalence of titanium dioxide nanoparticles in synovial fluid samples during and after the transitional period. A total of 302 samples were collected as a consecutive series between 1 April 2022 and 15 June 2023 from patients visiting the department of rheumatology at VieCuri Medical Centre in Venlo, The Netherlands. The samples were primarily collected for diagnostic purposes and only clinical waste material was used for this study. From each sample, up to 40 μl of fluid was analysed with Raman spectroscopy for the presence of titanium dioxide particles. The trend in prevalence was calculated with a 3-month wide moving average. A total of 13 out of 302 samples (4.3%) contained titanium dioxide (TiO2). The prevalence of TiO2 decreased between the transitional period and the period after the ban (p = 0.0154, with a relative risk ratio of 4.9 (95% CI 1.35–17.74). There was no significant difference in patient characteristics between the TiO2 positive and the TiO2 negative group. These results are hinting towards a possible relationship between the EU-ban and the identified decrease in prevalence. Full article
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11 pages, 4905 KiB  
Review
Imaging Follow-Up of MSU Crystal Depletion
by Sébastien Ottaviani
Gout Urate Cryst. Depos. Dis. 2024, 2(1), 34-44; https://doi.org/10.3390/gucdd2010003 - 24 Jan 2024
Cited by 1 | Viewed by 1562
Abstract
Imaging modalities such as ultrasonography (US) and dual-energy computed tomography (DECT) have been recognized for their abilities to detect monosodium urate (MSU) crystals. The main described features of gout detected by DECT (tophus) or US (tophus, double contour [DC] sign and aggregates) are [...] Read more.
Imaging modalities such as ultrasonography (US) and dual-energy computed tomography (DECT) have been recognized for their abilities to detect monosodium urate (MSU) crystals. The main described features of gout detected by DECT (tophus) or US (tophus, double contour [DC] sign and aggregates) are very specific for the diagnosis of gout, but the impact of imaging on the follow-up of MSU deposits is not well known. US and DECT allow for visualization of the disappearance of MSU crystals under adequate urate-lowering therapy (ULT). An OMERACT US score and a DECT urate score have been described. The dissolution of the DC sign is detectable on US after 3 months, whereas a decreased size or volume in tophus can be observed on US or DECT after 6 months of ULT. Serum urate level decrease is associated with a reduction in MSU crystal deposition. Finally, the risk of gout flare is associated with the baseline MSU burden and with the degree of dissolution of crystal deposition. All these data confirm that imaging could be useful in managing gout, even if its exact place in routine practice remains unclear. Full article
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17 pages, 3275 KiB  
Technical Note
Optimizing the Use of Ultrasound in Calcium Pyrophosphate Deposition (CPPD): A Review from the Ground Up
by Georgios Filippou, Silvia Sirotti, Edoardo Cipolletta and Emilio Filippucci
Gout Urate Cryst. Depos. Dis. 2024, 2(1), 17-33; https://doi.org/10.3390/gucdd2010002 - 24 Jan 2024
Cited by 5 | Viewed by 2717
Abstract
Ultrasound is a pivotal exam in calcium pyrophosphate deposition (CPPD) identification. It has been demonstrated to be feasible, accurate, and reliable for CPPD diagnosis. Even if standardized definitions and a scoring system for CPPD have been established by the OMERACT ultrasound working group, [...] Read more.
Ultrasound is a pivotal exam in calcium pyrophosphate deposition (CPPD) identification. It has been demonstrated to be feasible, accurate, and reliable for CPPD diagnosis. Even if standardized definitions and a scoring system for CPPD have been established by the OMERACT ultrasound working group, ultrasound is still considered one of the most operator-dependent techniques. This is because in ultrasound, both the acquisition and the interpretation phases of the diagnostic process are in the hands of one operator and are performed simultaneously, in contrast to what happens with other imaging exams, where the acquisition process is standardized and independent from the interpretation process. Therefore, the scanning technique and machine setting acquire a central role, almost as important as the interpretation of the images, as erroneous scanning may lead to interpretative mistakes. In this review, we will delve into the appearance of CPPD on ultrasound, based on the latest research findings, passing through its pathogenesis, and focusing on machine settings and ultrasound scanning techniques, providing some tips and tricks to facilitate accurate CPPD recognition in the most frequently affected sites. Full article
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16 pages, 378 KiB  
Review
The Evolving Landscape of Gout in the Female: A Narrative Review
by Jennifer Lee, Nicholas Sumpter, Tony R. Merriman, Ru Liu-Bryan and Robert Terkeltaub
Gout Urate Cryst. Depos. Dis. 2024, 2(1), 1-16; https://doi.org/10.3390/gucdd2010001 - 30 Dec 2023
Viewed by 1632
Abstract
Gout is at least three times more prevalent in males than in females. However, concurrent with rising total gout prevalence, complex factors, including comorbidities, diet, lifestyle, and aging, have promoted higher gout prevalence in females. This narrative review focuses on summarizing recent developments [...] Read more.
Gout is at least three times more prevalent in males than in females. However, concurrent with rising total gout prevalence, complex factors, including comorbidities, diet, lifestyle, and aging, have promoted higher gout prevalence in females. This narrative review focuses on summarizing recent developments in the landscape of gout in females and the mechanisms involved. New knowledge on sex hormone effects on both urate-excreting and urate-reabsorbing transporters and higher hypertension and chronic kidney disease prevalence in females compared to males may help explain why gout incidence rises robustly after menopause in females, to approach that in males. Racial and ethnic factors, risk profiles based on heritable genetic polymorphisms of urate transporters, diet, body mass index, and lifestyle factors differ according to sex. In addition, sex differences in clinical phenotypes, outcomes of gout, and non-gout illnesses include more frequent comorbidities, more pain and disability during gout flares, different perceptions of disease burden, and more frequent severe cutaneous hypersensitivity reaction to allopurinol in females. Collectively, such findings support the potential clinical benefits of tailoring gout and hyperuricemia treatment according to sex. Full article
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