Journal Description
Gout, Urate, and Crystal Deposition Disease
Gout, Urate, and Crystal Deposition Disease
is an international, peer-reviewed, open access journal on gout, urate, and crystal deposition disease, published quarterly online by MDPI. The journal is owned by the Gout, Hyperuricemia and Crystal Associated Disease Network (G-CAN) and its members receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions. If you become a member of G-CAN you will benefit of 20% discount on the APC.
- Rapid Publication: first decisions in 16 days; acceptance to publication in 5.8 days (median values for MDPI journals in the second half of 2023).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
Latest Articles
Gout and Gout-Related Comorbidities: Insight and Limitations from Population-Based Registers in Sweden
Gout Urate Cryst. Depos. Dis. 2024, 2(2), 144-156; https://doi.org/10.3390/gucdd2020013 - 7 May 2024
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Population-based databases in Nordic countries offer unique opportunities for large-scale population-based epidemiological studies. The personal identity number enables researchers to link different registers at the individual level, which can be used for large-scale epidemiological population-based studies. This review outlines how these opportunities have
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Population-based databases in Nordic countries offer unique opportunities for large-scale population-based epidemiological studies. The personal identity number enables researchers to link different registers at the individual level, which can be used for large-scale epidemiological population-based studies. This review outlines how these opportunities have been used so far in the field of gout research, as well as the potential challenges and limitations. Their major advantage is that they cover the entire population, minimizing problems such as selection bias and loss to follow-up. This has enabled us to provide information on gout regarding risk factors; occurrence; association with comorbidities in relation to gout onset; treatment patterns; as well as its effect on other outcomes, such as sick leave and mortality. Validity issues, missing data, and legal issues are some of the challenges that researchers need to deal with. Choosing the most appropriate combination of databases to use for a specific question is crucial in order to maximize validity and adjust for confounders. Despite challenges and potential limitations, the Swedish registers have provided valuable epidemiological results and will continue to play an important role in the years to come.
Full article
Open AccessBrief Report
Sex-Specific Differences in Cytokine Production Capacity in Patients with Gout Compared to Controls
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Medeea Badii, Orsolya I. Gaal, Ioana Hotea, Valentin Nica, Andreea M. Mirea, Dragoş Mărginean, HINT Consortium, Cristina Pamfil, Simona Rednic, Radu A. Popp, Tania O. Crişan and Leo A. B. Joosten
Gout Urate Cryst. Depos. Dis. 2024, 2(2), 133-143; https://doi.org/10.3390/gucdd2020012 - 22 Apr 2024
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Gout, an inflammatory disease orchestrated by interleukin-1β activation and release, is more prevalent in men. The clinical profiles of patients with gout report differences by sex. This study aims to investigate sex-specific cytokine profiles in circulation and in stimulated peripheral blood mononuclear cells
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Gout, an inflammatory disease orchestrated by interleukin-1β activation and release, is more prevalent in men. The clinical profiles of patients with gout report differences by sex. This study aims to investigate sex-specific cytokine profiles in circulation and in stimulated peripheral blood mononuclear cells (PBMCs) of patients with gout and controls. Participants included in the gout group met the criteria of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR). The control group included individuals with varying levels of serum urate and absence of gout. PBMCs were stimulated in vitro for 24 h with various TLR ligands. Cytokines were determined in culture supernatants and plasma. Plasma IL-1Ra and high-sensitivity C-reactive protein (hsCRP) were higher in men with gout compared to men without gout whereas no significant differences in circulating cytokines were observed in women. PBMCs of patients with gout showed higher cytokine production of IL-1β, IL-1Ra, and TNF-α following 24 h stimulation, predominantly observed in women. We identified sex-specific cytokine production in gout in response to in vitro stimulation. While men with gout had higher levels of circulating cytokines, stimulated PBMCs of women with gout show an enhanced capacity for cytokine production. These data may suggest potentially different regulatory mechanisms of inflammation in men and women with gout.
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Open AccessReview
Circadian Rhythms in NLRP3 Inflammasome Regulation: Possible Implications for the Nighttime Risk of Gout Flares
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Raewyn C. Poulsen and Nicola Dalbeth
Gout Urate Cryst. Depos. Dis. 2024, 2(2), 108-132; https://doi.org/10.3390/gucdd2020011 - 15 Apr 2024
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Gout flares more frequently start late at night or in the early morning compared to during the day. The reasons for this are unknown. Activation of the NLRP3 inflammasome in monocytes/macrophages is central to initiation of gout flares. Here, we review the mechanisms
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Gout flares more frequently start late at night or in the early morning compared to during the day. The reasons for this are unknown. Activation of the NLRP3 inflammasome in monocytes/macrophages is central to initiation of gout flares. Here, we review the mechanisms by which circadian clocks control the NLRP3 inflammasome and the implications of this for the nighttime pattern of gout flares. Several hormones involved in inflammation regulation, e.g., glucocorticoids, melatonin and melanocortins, are under circadian control, with both circulating hormone levels as well as the expression of their receptors on target tissues showing time-of day differences. In addition, the NLRP3 inflammasome is also under the control of the macrophage circadian clock, leading to time-of-day differences in expression of NLRP3 inflammasome components and susceptibility to inflammasome-activating stimuli. MSU crystal exposure leads to altered expression of circadian clock components in macrophages, leading to time-of-day-specific loss of repression of NLRP3 inflammasome activity. Taken together, there is clear evidence that circadian clocks regulate the NLRP3 inflammasome and that this regulation may be compromised by MSU crystal exposure in gout. Circadian control of the inflammasome may be one of the factors contributing to nighttime susceptibility to gout flares.
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Open AccessReview
Calcium Pyrophosphate and Basic Calcium Phosphate Crystal Arthritis: 2023 in Review
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Augustin Latourte, Hang-Korng Ea and Pascal Richette
Gout Urate Cryst. Depos. Dis. 2024, 2(2), 101-107; https://doi.org/10.3390/gucdd2020010 - 5 Apr 2024
Abstract
Calcium-containing crystal deposition diseases are extremely common in rheumatology. However, they are under-explored compared to gout or other inflammatory rheumatic diseases. Major advances have been made in 2023 that will undoubtedly stimulate and facilitate research in the field of calcium pyrophosphate (CPP) deposition
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Calcium-containing crystal deposition diseases are extremely common in rheumatology. However, they are under-explored compared to gout or other inflammatory rheumatic diseases. Major advances have been made in 2023 that will undoubtedly stimulate and facilitate research in the field of calcium pyrophosphate (CPP) deposition disease (CPPD): the ACR/EULAR classification criteria for CPPD and a semi-quantitative OMERACT score for ultrasound assessment of the extent of CPP deposition have been validated and published. A large randomized controlled trial compared the efficacy and safety of colchicine and prednisone in acute CPP arthritis. Preclinical studies have elucidated the pro-inflammatory and anti-catabolic effects of basic calcium phosphate (BCP) crystals on mononuclear cells and chondrocytes. The association between osteoarthritis (OA) and IA calcifications has been the subject of several epidemiological publications, suggesting that calcium crystals are associated with a greater risk of progression of knee OA. Research in the field of calcium crystal deposition diseases is active: the areas of investigation for the coming years are broad and promising.
Full article
Open AccessReview
Optimising the Use of Ultrasound in Gout: A Review from the Ground Up
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Emilio Filippucci, Edoardo Cipolletta, Silvia Sirotti and Georgios Filippou
Gout Urate Cryst. Depos. Dis. 2024, 2(2), 86-100; https://doi.org/10.3390/gucdd2020009 - 4 Apr 2024
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The use of ultrasonography (US) has considerable potential for the diagnosis and monitoring of gout due to its capacity to detect monosodium urate deposits. In the last decade, a critical amount of scientific data has become available. Consensus-based definitions for ultrasonographic elementary lesions
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The use of ultrasonography (US) has considerable potential for the diagnosis and monitoring of gout due to its capacity to detect monosodium urate deposits. In the last decade, a critical amount of scientific data has become available. Consensus-based definitions for ultrasonographic elementary lesions in gout have been developed, tested, and validated, as well as a semiquantitative scoring system for their quantification. Many scanning protocols have been proposed in different clinical scenarios. In this review, we formulate a set of practical suggestions for the use of the US in daily practice. We discuss the current knowledge to indicate which joints and structures are to be scanned and which elementary findings are to be evaluated according to the clinical scenario. While for some clinical settings, a quite definite scanning protocol can be indicated, others still need to be further investigated, and how to obtain the best out of the US is still entrusted to the individual experience.
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Open AccessArticle
Prevalence and Influence of Gout in Patients with Advanced Chronic Kidney Disease: Findings of a Large Retrospective Chart Review
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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
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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
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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.
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Open AccessReview
Serum Urate as a Surrogate Outcome for Gout Flares: Where Do We Stand Today?
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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
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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
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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.
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Open AccessConference Report
14th European Crystal Network (ECN) Workshop—Abstract Proceedings
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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
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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
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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.
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Open AccessReview
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
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Sara K. Tedeschi
Gout Urate Cryst. Depos. Dis. 2024, 2(1), 52-59; https://doi.org/10.3390/gucdd2010005 - 5 Feb 2024
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
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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
Open AccessBrief Report
The Prevalence of Titanium Dioxide Particles in Synovial Fluid Samples Drops after European Union Ban
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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
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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
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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.
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Open AccessReview
Imaging Follow-Up of MSU Crystal Depletion
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Sébastien Ottaviani
Gout Urate Cryst. Depos. Dis. 2024, 2(1), 34-44; https://doi.org/10.3390/gucdd2010003 - 24 Jan 2024
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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
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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.
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Open AccessTechnical Note
Optimizing the Use of Ultrasound in Calcium Pyrophosphate Deposition (CPPD): A Review from the Ground Up
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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 1
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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,
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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.
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Open AccessReview
The Evolving Landscape of Gout in the Female: A Narrative Review
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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
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
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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
Open AccessReview
Calcium Pyrophosphate and Basic Calcium Phosphate Deposition Diseases: The Year in Review 2022
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Geraldine Mary McCarthy
Gout Urate Cryst. Depos. Dis. 2023, 1(4), 234-242; https://doi.org/10.3390/gucdd1040019 - 12 Oct 2023
Abstract
Calcium-containing crystal deposition diseases are a common cause of pain and disability but remain relatively under-investigated. No drug has been identified that can prevent deposition or effect dissolution of either calcium pyrophosphate (CPP) or basic calcium phosphate (BCP) crystals. In comparison to the
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Calcium-containing crystal deposition diseases are a common cause of pain and disability but remain relatively under-investigated. No drug has been identified that can prevent deposition or effect dissolution of either calcium pyrophosphate (CPP) or basic calcium phosphate (BCP) crystals. In comparison to the field of gout and urate biology, published research in relation to calcium crystal deposition diseases in 2022 was relatively modest in quantity. In CPP deposition (CPPD) disease, progress was made mainly in epidemiology, imaging, surgical management and Gitelman’s syndrome. In relation to BCP crystals, the effect on tenocytes in vitro was explored and results indicate that BCP crystals likely reduce tendon matrix integrity via their interaction with tenocytes. The involvement of calcification in the progression of osteoarthritis (OA) was elegantly demonstrated contributing to further discovery of the process of OA progression. There was a paucity of mechanistic and genetic studies in calcium crystal deposition diseases published in 2022, nor any breakthrough in therapy, showing that there is abundant scope for investigation under these themes in the future.
Full article
Open AccessReview
Gout in Paleopathology: A Review with Some Etiological Considerations
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Nellissa Y. Ling, Siân E. Halcrow and Hallie R. Buckley
Gout Urate Cryst. Depos. Dis. 2023, 1(4), 217-233; https://doi.org/10.3390/gucdd1040018 - 28 Sep 2023
Cited by 2
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Gout has been part of human history for thousands of years. Skeletal evidence of the disease among past people in Europe is often associated with high-status individuals whose lifestyles comprised risk factors for gout, including increased sedentism and greater access to rich, high-caloric,
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Gout has been part of human history for thousands of years. Skeletal evidence of the disease among past people in Europe is often associated with high-status individuals whose lifestyles comprised risk factors for gout, including increased sedentism and greater access to rich, high-caloric, food. A growing body of evidence, however, has shown that multiple factors other than lifestyle also contribute to gout development. In 2011, Buckley presented a review of modern and pre-modern gout cases in which she proposed that selective pressures may partly underlie the high prevalence of gout in the population history of the Pacific region. In this paper, we provide an update on Buckley’s 2011 review of gout in human history. We also review early life stress as a potential underlying factor to consider for gout development, particularly among small prehistoric communities where opulent lifestyles traditionally associated with gout were unlikely to have occurred.
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Open AccessReview
Does Monosodium Urate Crystal Vascular Deposition Exist? Review of the Evidence
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Tristan Pascart and Jean-François Budzik
Gout Urate Cryst. Depos. Dis. 2023, 1(3), 208-216; https://doi.org/10.3390/gucdd1030017 - 11 Sep 2023
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Cardiovascular disease in gout is a central issue, but the underlying mechanisms linking the two are unclear. The existence of monosodium (MSU) crystal deposition directly inflaming vessel walls has been recurrently suggested and challenged since the 1950s and is again a matter of
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Cardiovascular disease in gout is a central issue, but the underlying mechanisms linking the two are unclear. The existence of monosodium (MSU) crystal deposition directly inflaming vessel walls has been recurrently suggested and challenged since the 1950s and is again a matter of active debate since recent studies using dual-energy computed tomography (DECT) suggested a higher prevalence of plaques considered to be containing MSU crystals in patients with gout. The objective of this review is to critically cover the evidence gathered on MSU crystal deposition in the cardiovascular system. In patients affected with gout, histological evidence of MSU crystals in arteries lacks a biochemical characterization supporting the observation in polarized light microscopy, while current knowledge on vascular lesions identified in DECT as containing MSU crystals suggests that they may be only artifacts, including in cadaveric and phantom studies. In individuals without gout, MSU crystal deposition in vessel walls have not been demonstrated, despite higher urate local plaque concentrations and increased xanthine oxidase activity. Gout is associated with increased arterial calcification and atherosclerosis, both being potential confounders of suspected MSU crystal deposition for the analysis of DECT scans and histopathology, respectively. In summary, the reality of the presence of MSU crystals in vascular plaques has not been demonstrated so far, and needs further investigation as it represents a potential outcome for cardiovascular complications of gout.
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Open AccessArticle
Atherogenic Activation of Human Vascular Smooth Muscle Cells by Monosodium Urate Crystals
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Ru Liu-Bryan, Tracy Guo, Jennifer Lee and Robert Terkeltaub
Gout Urate Cryst. Depos. Dis. 2023, 1(3), 192-207; https://doi.org/10.3390/gucdd1030016 - 14 Aug 2023
Cited by 1
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Gout is strongly associated with atherosclerosis and other cardiovascular comorbidities. Furthermore, sites of extra-articular monosodium urate (MSU) crystal deposits in gout can include heart valves and atherosclerotic artery plaques, but with unclear effects therein. Hence, we seminally explored cultured vascular smooth muscle cell
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Gout is strongly associated with atherosclerosis and other cardiovascular comorbidities. Furthermore, sites of extra-articular monosodium urate (MSU) crystal deposits in gout can include heart valves and atherosclerotic artery plaques, but with unclear effects therein. Hence, we seminally explored cultured vascular smooth muscle cell (VSMC) responsiveness to MSU crystals. To limit confounding effects, we cultured human aortic VSMCs under serum-free conditions to assess MSU crystal effects on VSMC differentiation and function, differentially expressed genes (DEGs) via RNA sequencing, and selected atherogenic changes in cytokines and the lipidome. MSU crystals induced p38 phosphorylation, IL-6, and VSMC vacuolization with dysregulated autophagy. MSU-crystal-induced DEGs included decreased late-stage autophagosome maturation mediator GABARAPL1, decreased physiologic VSMC differentiation regulators (LMOD1 and SYNPO2), increased ATF4, CHOP, and the intrinsic apoptosis signaling pathway in response to ER stress, and neointimal atherogenic nuclear receptors (NR4A1 and NR4A3). MSU crystals alone increased the levels of cholesterol biosynthetic intermediates 14-demethyl-lanosterol (14-DML), desmosterol, and zymosterol. Adding MSU crystals increased oxidized LDL’s capacity to increase intracellular 27-OH cholesterol, and MSU crystals and oxidized LDL synergistically induced a marked release of arachidonate. In conclusion, MSU crystals deposited in arterial media and neointima have the potential to dysregulate VSMC differentiation and proteostasis, and to induce further atherogenic effects, which include enhanced VSMC loading of oxidized cholesterol intermediates and release of IL-6 and arachidonic acid (AA).
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Open AccessConference Report
Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) Conference 2022: Early-Career Investigators’ Abstracts
by
Gout, Hyperuricemia and Crystal-Associated Disease Network
Gout Urate Cryst. Depos. Dis. 2023, 1(3), 167-191; https://doi.org/10.3390/gucdd1030015 - 3 Aug 2023
Cited by 1
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The eighth annual international G-CAN research symposium was held in Alexandria, VA on 21st and 22nd October 2022. This hybrid meeting, live face-to-face and virtual live symposium, was attended by over 150 participants. Over 20 research abstract submissions were received from early-career investigators,
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The eighth annual international G-CAN research symposium was held in Alexandria, VA on 21st and 22nd October 2022. This hybrid meeting, live face-to-face and virtual live symposium, was attended by over 150 participants. Over 20 research abstract submissions were received from early-career investigators, for plenary oral and poster presentations. Here, we present the accepted, lightly-edited abstracts from the presenters consenting to have their materials published. We thank and congratulate the presenters for their work and contributions to the meeting.
Full article
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Open AccessReview
Gout and Cardiovascular Disease: Mechanisms, Risk Estimations, and the Impact of Therapies
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Mariano Andrés
Gout Urate Cryst. Depos. Dis. 2023, 1(3), 152-166; https://doi.org/10.3390/gucdd1030014 - 1 Aug 2023
Cited by 5
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Gout is intimately associated with cardiovascular disease—especially in cases of an atherosclerosis origin, but also with others such as heart failure, atrial fibrillation, or aortic valve stenosis. Besides the common presence of vascular comorbidities in gout sufferers, the disease is—in itself—an independent cardiovascular
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Gout is intimately associated with cardiovascular disease—especially in cases of an atherosclerosis origin, but also with others such as heart failure, atrial fibrillation, or aortic valve stenosis. Besides the common presence of vascular comorbidities in gout sufferers, the disease is—in itself—an independent cardiovascular risk factor, with disease events and mortality attributable to having this condition. This review aims to update the current knowledge regarding several grey areas of the gout–cardiovascular disease spectrum—particularly in terms of risk variations across sex or ancestries, potential monosodium urate crystal deposition in the artery tree as a pathogenic pathway, the efforts undertaken to assess risk estimations in the gout population, and recent controversies surrounding the effects of gout therapies on cardiovascular disease.
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Open AccessReview
Epigenetic and Metabolic Regulation of Macrophages during Gout
by
Isidoro Cobo, Jessica Murillo-Saich, Mohnish Alishala and Monica Guma
Gout Urate Cryst. Depos. Dis. 2023, 1(3), 137-151; https://doi.org/10.3390/gucdd1030013 - 12 Jul 2023
Abstract
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The analysis of metabolite mediators has allowed a broader understanding of disease mechanisms. Experimental evidence indicates that metabolic rewiring is a key feature of inflammatory cells to restore tissue homeostasis upon damage. Over the last two decades, next-generation sequencing techniques have offered the
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The analysis of metabolite mediators has allowed a broader understanding of disease mechanisms. Experimental evidence indicates that metabolic rewiring is a key feature of inflammatory cells to restore tissue homeostasis upon damage. Over the last two decades, next-generation sequencing techniques have offered the possibility of looking at the genome-wide effect of the exposure of inflammatory cells to external stimuli. During gout flares, monosodium urate crystals activate a distinct metabolic profile and inflammatory transcriptional program in inflammatory cells. The extracellular signals are transduced through distinct signalling pathways, which are regulated by non-coding RNA and DNA sequences, and modification of histones. During response to inflammatory stimuli, changes in the abundance of metabolic mediators can regulate the activation of histones and of chromatin remodellers. The interplay between metabolic changes by MSUc, the regulation of epigenetic changes and the activation of transcription factor networks in inflammatory cells remains unknown. A better understanding of the interplay between metabolites and how it alters inflammatory response may provide novel insights into disease mechanisms during gout. In this review, we aim to provide a deeper understanding of the current view of how metabolic deregulation could alter the epigenetic landscape of inflammatory cells during gout.
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