Crystal Deposition Research Articles

Comparison of Scheimpflug Corneal Tomography and Anterior Segment Optical Coherence Tomography Measurements in Corneal Cystinosis: A Case Series.

To report the clinical course and compare the utility of Scheimpflug tomography (ST) and anterior segment optical coherence tomography (AS-OCT) for central corneal thickness (CCT) and corneal densitometry (CD) assessment in patients with corneal crystals owing to nephropathic cystinosis. A retrospective chart analysis of three patients with nephropathic cystinosis and the presence of corneal cystine crystals in both eyes was performed. All patients underwent clinical examination and anterior segment photography, ST, and AS-OCT scans. Corneal densitometry was exported from built-in proprietary software for ST and from custom-made validated software for AS-OCT. Anterior segment optical coherence tomography images were rescaled to grayscale units from 0 (maximum transparency) to 100 (minimum transparency) to match built-in ST densitometry readings. Furthermore, the mean pixel intensity, representative of CD, was calculated from the pixels corresponding to the segmented cornea. All three patients had pathognomonic cystine crystals deposits in the cornea and were treated with cysteamine medications that resulted in clinical improvement. The CCT measured using ST exhibited a range from 560 to 958 μm. Conversely, when assessed with AS-OCT, the CCT varied within the range of 548 to 610 μm. Both examinations could be performed, but in the more severe cases, AS-OCT showed far greater utility to estimate CD. In four of six eyes examined, ST showed disproportionate CCT values, compared with the AS-OCT, whereas reliable CD measurements were only available in AS-OCT. The AS-OCT could be considered a baseline ocular measurement in cystinosis and in the evaluation of disease progression and treatment efficacy.

CD8 T cell-derived perforin regulates macrophage-mediated inflammation in a murine model of gout.

Gout is characterized by hyperuricemia and recurrent inflammatory episodes caused by intra-articular crystal deposition of monosodium urate (MSU). There is a clear relationship between gout and metabolic syndrome. Recent evidence indicates that perforin plays a role in regulating glucose homeostasis and provides protection in diet-induced non-alcoholic steatohepatitis models. However, the impact of perforin on immune inflammation in gout remains unclear. We induced acute gout models in both wild-type (WT) mice and Prf1null mice by administering intra-articular injections of MSU crystals. We compared the ankle joint swelling and the histological score between the two groups. Furthermore, we investigated underlying mechanisms through in vitro co-culture experiments involving CD8 T cells and macrophages. In this study, Prf1null mice showed significantly more pronounced ankle swelling with increased inflammatory cell infiltrations compared with WT mice 24h after local MSU injection. Moreover, MSU-induced Prf1null mice exhibited increased accumulation of CD8 T cells but not NK cells. Perforin-deficient CD8 T cells displayed reduced cytotoxicity towards bone marrow-derived M0 and M1 macrophages and promoted TNF-α secretion from macrophage. Perforin from CD8 T cells limits joint inflammation in mice with acute gout by downregulating macrophage-mediated inflammation. Key Points • Perforin deficiency increased swelling in the ankle joints of mice upon MSU injection. • Perforin deficiency is associated with increased immune cell recruitment and severe joint damage in gout. • Perforin regulated CD8 T cell accumulation in gout and promoted CD8 T cell cytotoxicity towards M0 and M1 macrophages. • CD8 T cell-derived perforin regulated pro-inflammatory cytokine secretion of macrophage.

Adsorption of phosphate over a novel magnesium-loaded sludge-based biochar.

The production of sludge-based biochar to recover phosphorus (P) from wastewater and reuse the recovered phosphorus as agricultural fertilizer is a preferred process. This article mainly studied the removal of phosphate (PO4-P) from aqueous solution by synthesizing sludge-based biochar (MgSBC-0.1) from anaerobic fermentation sludge treated with magnesium (Mg)-loading-modification, and compared it with unmodified sludge-based biochar (SBC). The physicochemical properties, adsorption efficiency, and adsorption mechanism of MgSBC-0.1 were studied. The results showed that the surface area of MgSBC-0.1 synthesized increased by 5.57 times. The material surface contained MgO, Mg(OH)2, and CaO nanoparticles. MgSBC-0.1 can effectively remove phosphate in the initial solution pH range of 3.00-7.00, with a fitted maximum phosphorus adsorption capacity of 379.52 mg·g-1. The adsorption conforms to the pseudo second-order kinetics model and Langmuir isotherm adsorption curve. The characterization of the adsorbed composite material revealed the contribution of phosphorus crystal deposition and electrostatic attraction to phosphorus absorption.

Spatiotemporal Observation of Monosodium Urate Crystals Deposition in Synovial Organoids Using Label-Free Stimulated Raman Scattering.

Gout, a common form of arthritis, is characterized by the deposition of monosodium urate (MSU) crystals in joints. MSU deposition in synovial tissues would initiate arthritis flares and recurrence, causing irreversible joint damage. However, the dynamic deposition of MSU crystals in tissues lacks experimental observation. In this study, we used chemical-specific, label-free stimulated Raman scattering (SRS) microscopy to investigate the spatiotemporal deposition and morphological characteristics of MSU crystals in human synovial organoids. Our findings revealed a critical 12-h window for MSU deposition in the lining layer of gouty synovium. Moreover, distinctive inflammatory reactions of the lining and sublining synovial layers in gout using SRS microscopy were further verified by immunofluorescence. Importantly, we identified a crucial proinflammatory role of sublining fibroblast-like synoviocytes, indicating a need for targeted medication treatment on these cells. Our work contributes to the fundamental understanding of MSU-based diseases and offers valuable insights for the future development of targeted gout therapies.

Calcium Pyrophosphate and Basic Calcium Phosphate Crystal Arthritis: 2023 in Review

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.

Determinants and impact of calcium oxalate crystal deposition on renal outcomes in acute kidney injury patients

Objectives Calcium oxalate (CaOx) crystal deposition in acute kidney injury (AKI) patients is under recognized but impacts renal outcomes. This study investigates its determinants and effects. Methods We studied 814 AKI patients with native kidney biopsies from 2011 to 2020, identifying CaOx crystal deposition severity (mild: <5, moderate: 5–10, severe: >10 crystals per section). We assessed factors like urinary oxalate, citrate, urate, electrolytes, pH, tubular calcification index, and SLC26A6 expression, comparing them with creatinine-matched AKI controls without oxalosis. We analyzed how these factors relate to CaOx severity and their impact on renal recovery (eGFR < 15 mL/min/1.73 m2 at 3-month follow-up). Results CaOx crystal deposition was found in 3.9% of the AKI cohort (32 cases), with 72% due to nephrotoxic medication-induced tubulointerstitial nephritis. Diuretic use, higher urinary oxalate-to-citrate ratio induced by hypocitraturia, and tubular calcification index were significant contributors to moderate and/or severe CaOx deposition. Poor baseline renal function, low urinary chloride, high uric acid and urea nitrogen, tubular SLC26A6 overexpression, and glomerular sclerosis were also associated with moderate-to-severe CaOx deposition. Kidney recovery was delayed, with 43.8%, 31.2%, and 18.8% of patients having eGFR < 15 mL/min/1.73 m2 at 4, 12, and 24-week post-injury. Poor outcomes were linked to high urinary α1-microglobulin-to-creatinine (α1-MG/C) ratios and active tubular injury scores. Univariate analysis showed a strong link between this ratio and poor renal outcomes, independent of oxalosis severity. Conclusions In AKI, CaOx deposition is common despite declining GFR. Factors worsening tubular injury, not just oxalate-to-citrate ratios, are key to understanding impaired renal recovery.

Cymbopogon proximus and Petroselinum crispum seed ethanolic extract/Gum Arabic nanogel emulsion: Preventing ethylene glycol and ammonium chloride-induced urolithiasis in rats

Urolithiasis is a prevalent urological disorder that contributes significantly to global morbidity. This study aimed to assess the anti-urolithic effects of Cymbopogon proximus (Halfa Bar) and Petroselinum crispum (parsley) seed ethanolic extract /Gum Arabic (GA) emulsion, and its nanogel form against ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. Rats were divided into four groups: group 1 served as the normal control, group 2 received EG with AC in drinking water for 14 days to induce urolithiasis, groups 3 and 4 were orally administered emulsion (600 mg/kg/day) and nanogel emulsion (600 mg/kg/day) for 7 days, followed by co-administration with EG and AC in drinking water for 14 days. Urolithiatic rats exhibited a significant decrease in urinary excreted magnesium, and non-enzymic antioxidant glutathione and catalase activity. Moreover, they showed an increase in oxalate crystal numbers and various urolithiasis promoters, including excreted calcium, oxalate, phosphate, and uric acid. Renal function parameters and lipid peroxidation were intensified. Treatment with either emulsion or nanogel emulsion significantly elevated urolithiasis inhibitors, excreted magnesium, glutathione levels, and catalase activities. Reduced oxalate crystal numbers, urolithiasis promoters’ excretion, renal function parameters, and lipid peroxidation while improving histopathological changes. Moreover, it decreased renal crystal deposition score and the expression of Tumer necrosis factor-α (TNF-α) and cleaved caspase-3. Notably, nanogel emulsion showed superior effects compared to the emulsion. Cymbopogon proximus (C. proximus) and Petroselinum crispum (P. crispum) seed ethanolic extracts/GA nanogel emulsion demonstrated protective effects against ethylene glycol induced renal stones by mitigating kidney dysfunction, oxalate crystal formation, and histological alterations.

Herbo-Mineral Medicine, Lithom Exhibits Anti-Nephrolithiasis Activity in Rat Model of Hyperoxaluria by Attenuating Calcium Oxalate Crystal Formation and Oxidative Stress.

Calcium oxalate monohydrate (COM) forms the most common type of kidney stones observed in clinics, elevated levels of urinary oxalate being the principal risk factor for such an etiology. The objective of the present study was to evaluate the anti-nephrolithiatic effect of herbo-mineral formulation, Lithom. The in vitro biochemical synthesis of COM crystals in the presence of Lithom was performed and observations were made by microscopy and Scanning Electron Microscope (SEM) based analysis for the detection of crystal size and morphology. The phytochemical composition of Lithom was evaluated by Ultra-High-Performance Liquid Chromatography (UHPLC). The in vivo model of Ethylene glycol-induced hyperoxaluria in Sprague-Dawley rats was used for the evaluation of Lithom. The animals were randomly allocated to 5 different groups namely Normal control, Disease control (ethylene glycol (EG), 0.75%, 28 days), Allopurinol (50 mg/kg, q.d.), Lithom (43 mg/kg, b.i.d.), and Lithom (129 mg/kg, b.i.d.). Analysis of crystalluria, oxalate, and citrate levels, oxidative stress parameters (malondialdehyde (MDA), catalase, myeloperoxidase (MPO)), and histopathology by hematoxylin and eosin (H&E) and Von Kossa staining was performed for evaluation of Lithom. The presence of Lithom during COM crystals synthesis significantly reduced the average crystal area, feret's diameter, and area-perimeter ratio, in a dose-dependent manner. SEM analysis revealed that COM crystals synthesized in the presence of 100 and 300 μg/mL of Lithom exhibited a veritable morphological transition from irregular polygons with sharp edges to smoothened smaller cuboid polygons. UHPLC analysis of Lithom revealed the presence of Trigonelline, Bergenin, Xanthosine, Adenosine, Bohoervinone B, Vanillic acid, and Ellagic acid as key phytoconstituents. In EG-induced SD rats, the Lithom-treated group showed a decrease in elevated urinary oxalate levels, oxidative stress, and renal inflammation. Von Kossa staining of kidney tissue also exhibited a marked reduction in crystal depositions in Lithom-treated groups. Taken together, Lithom could be a potential clinical-therapeutic alternative for management of nephrolithiasis.

Anti-gouty arthritis and anti-inflammatory effects of curcumin nanoparticles in monosodium urate crystals induced Balb/C mice.

Gout is a metabolic condition characterized by the accumulation of urate crystals in the synovial joints. These crystal depositions result in joint swelling and increased concentration of serum uric acid in blood. The commercially available drugs lower serum uric acid levels and reduce inflammation, but these standard therapies have many side effects.This study aimed to investigate anti-gout and anti-inflammatory properties of curcumin nanoparticles (CNPs). For this purpose, CNPs were prepared by dissolving curcumin into dichloromethane. Then, gout was induced by injecting monosodium urate crystals (MSU) in the ankle joint and in the intra-peritoneal cavity which caused ankle swelling and increased blood uric acid levels. CNPs in different concentrations (5, 10, and 20ppm) and allopurinol were orally administered. The MSU crystals increased the xanthine oxidase levels both in serum and the liver. Moreover, MSU crystals increased the serum levels of interleukin 1β, interleukin-6, tumor necrosis factor-alpha, liver function tests markers, renal function tests markers, and lipid profiles. However, the administration of CNPs decreased the levels of all these variables. CNPs increased the serum high-density lipoprotein and interleukin-10 levels. Moreover, CNPs also reduced ankle swelling significantly. Hence, the levels ofxanthine oxidase, uric acid and ankle swelling were reduced significantly by oral administration of CNPs. Our findingsindicate that CNPs through their anti-inflammatory properties significantly alleviate gouty arthritis. Thus, the study concluded that CNPs can be developed as an efficient anti-gout agent with minimal side effects.

Investigation of the association between the polymorphism &lt;i&gt;SLC2A9&lt;/i&gt; rs2280205 and gout in Vietnamese population

Gout, a predominant form of inflammatory arthritis, is characterized by the deposition of uric acid crystals in joints and other tissues. Genome-wide association studies (GWAS) have established the association between gout and genetic variants of solute carrier family 2 member 9 (SLC2A9). In this study, we assessed the association of the single nucleotide polymorphism SLC2A9 rs2280205 with gout susceptibility in the Vietnamese population. Genomic DNA was extracted from the peripheral blood of 477 samples (160 gout patients and 317 healthy controls). The polymorphism rs2280205 of the SLC2A9 gene was genotyped using the PCR-RFLP method. Results indicated that the allele distribution of this variant was in accordance with Hardy-Weinberg Equilibrium, and the genotype frequencies of rs2280205 GG/GA/AA were 0.65, 0.33, and 0.02, respectively. However, no relation was identified between SLC2A9 rs2280205 and gout in this studied population. This research contributed a preliminary insight into the genetic factors in the development of gout in the Vietnamese population.

N-acetylcysteine regulates oxalate induced injury of renal tubular epithelial cells through CDKN2B/TGF-β/SMAD axis.

This study was aimed to investigate the preventive effects of N-acetyl-L-cysteine (NAC) against renal tubular cell injury induced by oxalate and stone formation and further explore the related mechanism. Transcriptome sequencing combined with bioinformatics analysis were performed to identify differentially expressed gene (DEG) and related pathways. HK-2 cells were pretreated with or without antioxidant NAC/with or silencing DEG before exposed to sodium oxalate. Then, the cell viability, oxidative biomarkers of superoxidase dismutase (SOD) and malondialdehyde (MDA), apoptosis and cell cycle were measured through CCK8, ELISA and flow cytometry assay, respectively. Male SD rats were separated into control group, hyperoxaluria (HOx) group, NAC intervention group, and TGF-β/SMAD pathway inhibitor group. After treatment, the structure changes and oxidative stress and CaOx crystals deposition were evaluated in renal tissues by H&E staining, immunohistochemical and Pizzolato method. The expression of TGF-β/SMAD pathway related proteins (TGF-β1, SMAD3 and SMAD7) were determined by Western blot in vivo and in vitro. CDKN2B is a DEG screened by transcriptome sequencing combined with bioinformatics analysis, and verified by qRT-PCR. Sodium oxalate induced declined HK-2 cell viability, in parallel with inhibited cellular oxidative stress and apoptosis. The changes induced by oxalate in HK-2 cells were significantly reversed by NAC treatment or the silencing of CDKN2B. The cell structure damage and CaOx crystals deposition were observed in kidney tissues of HOx group. Meanwhile, the expression levels of SOD and 8-OHdG were detected in kidney tissues of HOx group. The changes induced by oxalate in kidney tissues were significantly reversed by NAC treatment. Besides, expression of SMAD7 was significantly down-regulated, while TGF-β1 and SMAD3 were accumulated induced by oxalate in vitro and in vivo. The expression levels of TGF-β/SMAD pathway related proteins induced by oxalate were reversed by NAC. In conclusion, we found that NAC could play an anti-calculus role by mediating CDKN2B/TGF-β/SMAD axis.

CT imaging features of calcium pyrophosphate dihydrate crystal deposition involving spine

PurposeTo explore the computed tomography (CT) imaging features of the spine involved by calcium pyrophosphate dihydrate crystal deposition disease (CPPD-CDD) in order to improve the understanding of this disease. Materials and methodsAmong 79 patients diagnosed with CPPD-CDD in our hospital, 51 patients with spinal involvement were selected, 9 patients without CT examination were excluded, and 42 patients were finally included as research objects. The CT images of the 42 patients were retrospectively analyzed. The analysis contents mainly included the distribution of lesions and the characteristic imaging findings of intervertebral disc, posterior ligament complex, sacroiliac joint and atlantoaxial joint. ResultsIn this paper, 42 patients with 11 males and 31 females were studied. The onset age ranged from 62 to 95 years. There were 264 lesions in 42 patients with spinal involvement, including 177 lumbar vertebrae, 43 cervical vertebrae, 27 thoracic vertebrae and 17 sacroiliac joints (14 bilateral and 3 unilateral). Characteristic imaging findings include: disc calcification (129 cases), posterior ligament complex calcification (107 cases), sacroiliac articular cartilage calcification (17 cases), and ligaments around the odontoid process calcification (11 cases). ConclusionsThe characteristic images of CPPD-CDD involving the spine are calcification of intervertebral disc, posterior ligament complex, sacroiliac joint surface and ligaments around odontoid process, and the lesions are frequent and coexisting, so it should be differentiated from gout, rheumatoid arthritis, ankylosing spondylitis, ossification of ligamentum flavum, basic calcium phosphate and infectious spondylodiscitis.

Gout: physical activity in therapy and prevention of the disease

Gout is a systemic chronic inflammatory disease associated with purine metabolism disorders. Risk factors for gout are a combination of genetic and environmental factors. Taking into account such features of the pathogenesis of gout as hyperuricemia and the deposition of monosodium urate crystals in tissues and joints, the development of the inflammatory, researchers studied the effect of physical activity on its main links. The intensity of the load and the type of physical exercise were taken into account due to their possible effect on metabolic processes. There is currently no reliable evidence on the importance of physical activity in reducing serum uric acid levels. Research has shown that physical activity has a positive effect on inflammation between gout attacks. The use of physical exercise can indirectly affect uric acid levels by reducing body weight in comorbid pathologies. EULAR emphasizes physical activity to prevent cardiovascular risks, which is also important for gout. Conclusions. Physical activity as one of the components of lifestyle is important for gout due to its effect on the inflammatory process and the prevention of relapses, a general strengthening effect on the body, an effect on hyperuricemia due to the positive effect associated with comorbid pathology, and a decrease in cardiovascular risk and associated him premature death. Physical activity of low and moderate intensity is effective for gout. Preference is given to aerobic exercise, taking into account the nature of metabolism and the possible impact on the occurrence of gout attacks. Further study and development of the characteristics of physical activity in gout are necessary to improve the prevention and treatment of the disease, and the development of individual recommendations for patients (for the management of gout).

Mechanism of Porphyra Yezoensis Polysaccharides in Inhibiting Hyperoxalate-Induced Renal Injury and Crystal Deposition.

Oxidative damage to the kidneys is a primary factor in the occurrence of kidney stones. This study explores the inhibitory effect of Porphyra yezoensis polysaccharides (PYP) on oxalate-induced renal injury by detecting levels of oxidative damage, expression of adhesion molecules, and damage to intracellular organelles and revealed the molecular mechanism by molecular biology methods. Additionally, we validated the role of PYP in vivo using a crystallization model of hyperoxalate-induced rats. PYP effectively scavenged the overproduction of reactive oxygen species (ROS) in HK-2 cells, inhibited the adhesion of calcium oxalate (CaOx) crystals on the cell surface, unblocked the cell cycle, restored the depolarization of the mitochondrial membrane potential, and inhibited cell death. PYP upregulated the expression of antioxidant proteins, including Nrf2, HO-1, SOD, and CAT, while decreasing the expression of Keap-1, thereby activating the Keap1/Nrf2 signaling pathway. PYP inhibited CaOx deposition in renal tubules in the rat crystallization model, significantly reduced high oxalate-induced renal injury, decreased the levels of the cell surface adhesion proteins, improved renal function in rats, and ultimately inhibited the formation of kidney stones. Therefore, PYP, which has crystallization inhibition and antioxidant properties, may be a therapeutic option for the treatment of kidney stones.

The Prevalence of Nephrolithiasis and Associated Risk Factors Among the Population of the Riyadh Province, Saudi Arabia.

Background and objective Kidney stones, also referred to as nephrolithiasis or renal calculi, is a condition where crystal depositions are formed within the kidney and ideally excreted from the body via the urethra with no pain; however, larger calculi may cause significant pain and require further medical assistance. The vast majority of patients who develop renal calculi form calcium stones, which are either a composition of calcium oxalate or calcium phosphate. Other types include uric acid, struvite, and cysteine. While kidney stones are one of the most significant diseases among the Saudi population, which require an acute emergency intervention to prevent serious long-term complications,there are limited studies published regarding this condition inSaudi communities. In light of this, we performed this study to assess the prevalence, incidence, and risk factors of kidney stones among the population of Riyadh, Saudi Arabia. Methods This was a cross-sectional studyconducted in Riyadh, Saudi Arabia between Augustand October 2023, aiming to estimate the prevalence and risk factors of nephrolithiasis among residents of the Riyadh province. Data were collected through an electronic questionnairein both Arabic and Englishand distributed via social media in addition to barcode handouts in various selected venues in Riyadh. The questionnaire involved 12 questions categorized into three sections. The first section obtained demographical information while the second sectioncollected data about the past medical history of the participants. Lastly, the third section aimedto assess the prevalence of nephrolithiasis among participants or any history of the condition among their families. Results Atotal of 1,043 participants were surveyed, of whom 533 were males (51.1%). The prevalence of kidney stones was reported in 98 individuals (9.4%) overall. Individuals in the age groups of 36-50, 51-60, and >60 years showed significantly more renal stone prevalence than those in younger age groups (p<0.001). The prevalencewas found to be higher in participants who were smokers, diabetic, hypertensive, and those who suffered from inflammatory bowel disease (IBD), gout, chronic kidney disease (CKD), hyperthyroidism, and hyperparathyroidism. Participants who took calcium supplements or had a positive family history of renal stones were found to have a higher prevalence of renal stones as well. However, only hypertension, gout, and family history showed any statistical significance (p<0.05). Conclusions A direct correlation was observed between hypertension, gout, positive family history, and aging and an increased prevalence of kidney stones among theinhabitants of the Riyadh province. Therefore, we encourage the local authorities to raise awareness of kidney stones and their related risk factors among the general public. Moreover, further local studies need to be conducted to gain deeper insights into kidney stone prevalence, especially pertaining to associated comorbiditiesand the pattern of the disease itself.

Chances and challenges of photon-counting CT in musculoskeletal imaging.

In musculoskeletal imaging, CT is used in a wide range of indications, either alone or in a synergistic approach with MRI. While MRI is the preferred modality for the assessment of soft tissues and bone marrow, CT excels in the imaging of high-contrast structures, such as mineralized tissue. Additionally, the introduction of dual-energy CT in clinical practice two decades ago opened the door for spectral imaging applications. Recently, the advent of photon-counting detectors (PCDs) has further advanced the potential of CT, at least in theory. Compared to conventional energy-integrating detectors (EIDs), PCDs providesuperior spatial resolution, reduced noise, and intrinsic spectral imaging capabilities. This review briefly describes the technical advantages of PCDs. For each technical feature, the corresponding applications in musculoskeletal imaging will be discussed, including high-spatial resolution imaging for the assessment of bone and crystal deposits, low-dose applications such as whole-body CT, as well as spectral imaging applications including the characterization of crystal deposits and imaging of metal hardware. Finally, we will highlight the potential of PCD-CT in emerging applications, underscoring the need for further preclinical and clinical validation to unleash its full clinical potential.

Crystal induced arthropathies-a comparative study of 40 patients with apatite rheumatism, chondrocalcinosis and primary synovial chondromatosis.

Introduction: Apatite rheumatism (AR), chondrocalcinosis (Ch-C), and primary synovial chondromatosis (prSynCh) are regarded as distinct clinical entities. The introduction of the non-staining technique by Bély and Apáthy (2013) opened a new era in the microscopic diagnosis of crystal induced diseases, allowing the analysis of MSU (monosodium urate monohydrate) HA (calcium hydroxyapatite), CPPD (calcium pyrophosphate dihydrate) crystals, cholesterol, crystalline liquid lipid droplets, and other crystals in unstained sections of conventionally proceeded (aqueous formaldehyde fixed, paraffin-embedded) tissue samples. The aim of this study was to describe the characteristic histology of crystal deposits in AR, Ch-C, and prSynCh with traditional stains and histochemical reactions comparing with unstained tissue sections according to Bély and Apáthy (2013). Patients and methods: Tissue samples of 4 with apatite rheumatism (Milwaukee syndrome), 16 with chondrocalcinosis, and 20 with clinically diagnosed primary synovial chondromatosis were analyzed. Results and conclusion: Apatite rheumatism, chondrocalcinosis, and primary synovial chondromatosis are related metabolic disorders with HA and CPPD depositions. The authors assume that AR and Ch-C are different stages of the same metabolic disorder, which differ from prSynCh in amorphous mineral production, furthermore in the production of chondroid, osteoid and/or bone. prSynCh is a defective variant of HA and CPPD induced metabolic disorders with reduced mineralization capabilities, where the deficient mineralization is replaced by chondroid and/or bone formation. The non-staining technique of Bély and Apáthy proved to be a much more effective method for the demonstration of crystals in metabolic diseases than conventional stains and histochemical reactions.

Monosodium urate crystal depletion and bone erosion remodeling during pegloticase treatment in patients with uncontrolled gout: Exploratory dual-energy computed tomography findings from MIRROR RCT

ObjectiveMonosodium-urate (MSU) crystal deposits can be visualized and quantified with dual-energy CT (DECT). Pegloticase lowers serum urate (SU) in uncontrolled gout patients, with methotrexate (MTX) co-therapy recommended to increase SU-lowering response rate and decrease infusion reaction risk. The literature on serial DECT-imaging during pegloticase+MTX co-therapy is sparse, with only 2 prior cases of rapid MSU deposition depletion with subsequent bone-erosion remodeling reported from a small open-label trial. Here, we report DECT findings during pegloticase treatment in a larger number of patients from a randomized controlled trial to confirm bone-erosion remodeling that follows MSU depletion with pegloticase. The influence of length-of-therapy is also explored. MethodsPatients received pegloticase (8mg every 2weeks)+MTX (15mg/week orally) or pegloticase+placebo (PBO) during the MIRROR RCT trial. A subset underwent DECT-imaging on Day1 (first pegloticase infusion) and at Weeks 14, 24, and 52. Patients with paired baseline-Week 52 images were included. Imaged regions with baseline MSU-crystal volume (VMSU)<0.5cm3 were excluded to minimize artifact contributions. VMSU and bone-erosion remodeling were assessed. ResultsEight patients (6 MTX, 2 PBO) were included. Included patients had received 52weeks (5 MTX), 42weeks (1 PBO), and 6weeks (1 MTX, 1 PBO) of pegloticase therapy. Patients who prematurely discontinued pegloticase maintained SU<6mg/dL on allopurinol (n=2)/febuxostat (n=1). At Week 52, VMSU had markedly decreased in both the pegloticase+MTX and pegloticase+PBO treatment groups, with faster depletion during pegloticase therapy. Bone-erosion remodeling was observed in 29/42 (69%) evaluated erosions: 29 (69%) size decrease, 4 (9.5%) recortication, 3 (7.1%) new bone formation. ConclusionRapid VMSU depletion during pegloticase therapy was observed with concomitant bone remodeling within 1year. Following pegloticase discontinuation, VMSU reduction slowed or stopped even when SU was maintained<6mg/dL with oral ULT. Clinical trial registrationNCT03994731.

Hydroxyapatite Crystal Deposition Disease with Multiple Joint Involvement Resulting in Severe Lumbar Spinal Canal Stenosis: A Case Report

Objectives: To describe a rare complication of hydroxyapatite (HA) crystal deposition disease (HADD) – spinal canal stenosis. To discuss clinical features and surgical management of this entity.

Osteostatin Mitigates Gouty Arthritis through the Inhibition of Caspase-1 Activation and Upregulation of Nrf2 Expression.

Gouty arthritis results from monosodium urate (MSU) crystal deposition in joints, initiating (pro)-interleukin (IL)-1β maturation, inflammatory mediator release, and neutrophil infiltration, leading to joint swelling and pain. Parathyroid hormone-related protein (107-111) C-terminal peptide (osteostatin) has shown anti-inflammatory properties in osteoblasts and collagen-induced arthritis in mice, but its impact in gouty arthritis models remains unexplored. We investigated the effect of osteostatin on pyroptosis, inflammation, and oxidation in macrophages, as well as its role in the formation of calcium pyrophosphate dihydrate crystals and MSU-induced gouty arthritis in mice models. Osteostatin ameliorated pyroptosis induced by lipopolysaccharide and adenosine 5'-triphosphate (LPS + ATP) in mice peritoneal macrophages by reducing the expression of caspase-1, lactate dehydrogenase release, and IL-1β and IL-18 secretion. Additionally, IL-6 and tumor necrosis factor-α (TNF-α) were also decreased due to the reduced activation of the NF-κB pathway. Furthermore, osteostatin displayed antioxidant properties in LPS + ATP-stimulated macrophages, resulting in reduced production of mitochondrial and extracellular reactive oxygen species and enhanced Nrf2 translocation to the nuclei. In both models of gouty arthritis, osteostatin administration resulted in reduced pro-inflammatory cytokine production, decreased leukocyte migration, and reduced caspase-1 and NF-κB activation. These results highlight the potential of osteostatin as a therapeutic option for gouty arthritis.