Degenerative joint disease induced by repeated intra-articular injections of monosodium urate crystals in rats as investigated by translational imaging

The objective of this work was to assess the consequences of repeated intra-articular injection of monosodium urate (MSU) crystals with inflammasome priming by lipopolysaccharide (LPS) in order to simulate recurrent bouts of gout in rats. Translational imaging was applied to simultaneously detect and quantify injury in different areas of the knee joint. MSU/LPS induced joint swelling, synovial membrane thickening, fibrosis of the infrapatellar fat pad, tidemark breaching, and cartilage invasion by inflammatory cells. A higher sensitivity to mechanical stimulus was detected in paws of limbs receiving MSU/LPS compared to saline-injected limbs. In MSU/LPS-challenged joints, magnetic resonance imaging (MRI) revealed increased synovial fluid volume in the posterior region of the joint, alterations in the infrapatellar fat pad reflecting a progressive decrease of fat volume and fibrosis formation, and a significant increase in the relaxation time T2 in femoral cartilage, consistent with a reduction of proteoglycan content. MRI also showed cyst formation in the tibia, femur remodeling, and T2 reductions in extensor muscles consistent with fibrosis development. Repeated intra-articular MSU/LPS injections in the rat knee joint induced pathology in multiple tissues and may be a useful means to investigate the relationship between urate crystal deposition and the development of degenerative joint disease.

Upper Cervical Compression Myelopathy Caused by the Retro-Odontoid Pseudotumor With Degenerative Osteoarthritis and Calcium Pyrophosphate Dihydrate Disease: A Case Report and Literature Review

The retro-odontoid pseudotumor is often concurrent with atlantoaxial subluxation (AAS). Therefore, the pseudotumor is relatively common in rheumatoid arthritis (RA) but rare in primary osteoarthritis (OA). This is a case report of an elderly male patient suffering from neck pain and compression myelopathy caused by the craniocervical pseudotumor with OA but without atlantoaxial instability. He had long-lasting peripheral and spinal pain treated by nonsteroidal anti-inflammatory drugs. Imaging found upper cervical spondylosis without AAS or dynamic instability but with periodontoid calcifications and ossifications, suggesting calcium pyrophosphate dihydrate (CPPD) crystal deposition. Based on a comprehensive literature search and review, CPPD disease around the atlantodental joint is a possible contributor to secondary OA development and retro-odontoid pannus formation through chronic inflammation, which can be enough severe to induce compression myelopathy in non-RA patients without AAS. The global increase in the aged population advises caution regarding more prevalent upper cervical spine disorders associated with OA and CPPD.

The effect of therapy on subclinical atherosclerosis of the carotid arteries in patients with calcium pyrophosphate crystal deposition disease and osteoarthritis (pilot study)

Endothelial dysfunction associated with chronic microcrystalline inflammation plays a role in the progression of atherosclerosis in calcium pyrophosphate crystal deposition diseases (CPPD).The aim of the study was to assess the dynamics of the development of atherosclerosis based on changes in the thickness of the intima-media complex (ICIM) of the carotid arteries (CA) in patients with CPPD receiving long-term anti-inflammatory therapy (colchicine, methotrexate, hydroxychloroquine).Materials and methods. 26 patients with CPPD and 26 patients with osteoarthritis aged over 18 years old were included. Exclusion criteria: age >65 years; presence of cardiovascular diseases. The blood lipid spectrum, hs-CRP level, anthropometric parameters were determined for all, and Doppler ultrasound ultrasonography of the carotid arteries (CA) was performed. Patients were followed up for not <6 months, assessed ICIM CA at 1 visit, then patients with CPPD, at the discretion of the attending physician, were prescribed methotrexate at a dose of 15 mg per week, hydroxychloroquine 200 mg 1 time per day or colchicine 0.5 mg 2 times a day. Patients could take NSAIDs if they were in pain. The SCORE index has been calculated for everyone.Results. Initially, ICIM values did not differ in patients with CPPD and OA. Initially, ICIM>0.9 mm were detected in 11 of 22 (50%) patients with CPPD and in OA in 8 of 19 (42%) (p=0.39). In dynamics, patients with CPPD revealed a decrease in the number of patients with ICIM>0.9 mm from 42 to 18%. At the same time, in 8 patients with CPPD, ICIM>0.9 mm was combined with a CRP level >0.2 mg/l. Out of 22 patients with CPPD, 14 (64%) patients showed a decrease in the mean values of ICIM, in 2 (9%) patients - an increase, in 5 patients the mean values of ICIM did not change. After 6 months of therapy, out of 11 patients with CPPD with ICIM >0.9 mm, after 6 months of therapy, in 7 cases there was a decrease in the indicator less than the specified value, in 5 of them a decrease in serum CRP level <2 mg/l was recorded. In patients with CPPD, the serum CRP level significantly decreased; in patients with OA, it did not change. Out of 19 patients with OA, 9 (47%) patients showed an increase in the mean ICIM over time, while the rest did not change. In those treated with hydroxychloroquine, a decrease in the mean ICIM parameters was observed in 5 out of 6 (83%) patients, colchicine - in 6 out of 9 (67%) patients, methotrexate - in 4 out of 7 (57%) patients.With CPPD, the result of therapy with colchicine, methotrexate and hydroxychloroquine in relation to the development of the initial signs of atherosclerosis according to Doppler ultrasound ultrasonography of CA can be realized based on the presence of chronic inflammation.

Acute Polyarticular Gout due to Chronic Kidney Disease

Gout is a crystal deposition disorder that typically presents as an acute flare of the first metatarso-phalangeal joint of the great toe. Rarely gout can present as an acute poly-articular disease with involvement of multiple joints. Evaluation of patients with poly-articular arthropathy with appropriate investigations like uric acid levels, renal function tests and synovial fluid analysis helps in the early diagnosis of poly-articular gout. Immediate treatment with urate lowering agents during the acute flare provides immediate pain relief and prevents progression of disease & bone destruction.

Effect of colchicine, methotrexate, and hydroxychloroquine therapy on cardiovascular outcomes in patients with calcium pyrophosphate crystal deposition disease

Anti-inflammatory therapy, such as colchicine (COL), has been suggested to affect the incidence of cardiovascular events in patients with calcium pyrophosphate crystal deposition disease (CPPD).Objective: to study the effect of anti-inflammatory therapy with COL, hydroxychloroquine (HC), and methotrexate (MT) on cardiovascular outcomes in patients with CPPD.Patients and methods. The study included 305 patients with CPPD, the majority (62.30%) were women. The average follow-up period was 3.9±2.7 years. Among factors influencing cardiovascular outcome were considered: gender; age; smoking; alcohol intake >20 conventional doses per week; arterial hypertension; a history of cardiovascular diseases (CVD), in particular ischemic heart disease, acute myocardial infarction, acute cerebrovascular accident, chronic heart failure >III stage according to NYHA, as well as type 2 diabetes mellitus (DM); body mass index >25 kg/m2 and >30 kg/m2; cholesterol level (CHOL) >5.1 mmol/l; glomerular filtration rate (GFR) < 60 ml/min/1.73 m2; serum uric acid level >360 μmol/l; hypercalcemia (serum calcium level >2.62 mmol/L); CRP level >2 mg/l; the presence of hyperparathyroidism (parathyroid hormone level >65 pg/ml); CPPD phenotypes (asymptomatic, osteoarthritis with calcium pyrophosphate crystals, chronic arthritis, acute arthritis); intake of COL, HC, MT, glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs).Results and discussion. 264 patients were under dynamic observation. Any of the studied cardiovascular events were registered in 79 (29.9%) patients. During the observation period, 46 (17.4%) patients died, in 76.1% of cases the cause of death was CVD. Death from other causes was diagnosed in 11 (23.9%) patients. Non-fatal cardiovascular events were reported in 44 (16.7%) cases. The risk of cardiovascular events was higher in patients over 65 years of age (odds ratio, OR 5.97; 95% confidence interval, CI 3.33–10.71), with serum cholesterol levels ≥5.1 mmol/L (OR 1,95; 95% CI 1.04–3.65), GFR <60 ml/min/1.73 m2 (OR 2.78; 95% CI 1.32–5.56), history of CVD (OR 2,32; 95% CI 1.22–4.44). COL therapy reduced the risk of cardiovascular events (OR 0.20; 95% CI 0.11–0.39).Conclusion. Poor CVD outcomes in CPPD are associated with age, hypercholesterolemia, chronic kidney disease, and a history of CVD. The use of COL, in contrast to MT and HC, was accompanied by a decrease in cardiovascular risk.

Prevalence and Outcomes Associated with Hyperuricemia in Hospitalized Patients with COVID-19

<b><i>Introduction:</i></b> Coronavirus 2019 (COVID-19) can increase catabolism and result in hyperuricemia. Uric acid (UA) potentially causes kidney damage by alteration of renal autoregulation, inhibition of endothelial cell proliferation, cell apoptosis, activation of the pro-inflammatory cascade, and crystal deposition. Hyperuricemia in patients with COVID-19 may contribute to acute kidney injury (AKI) and poor outcomes. <b><i>Methods:</i></b> We included 834 patients with COVID-19 who were &#x3e;18 years old and hospitalized for &#x3e;24 h in the Mount Sinai Health System and had at least 1 measurement of serum UA. We examined the association between the first serum UA level and development of acute kidney injury (AKI, defined by KDIGO criteria), major adverse kidney events (MAKE, defined by a composite of all-cause in-hospital mortality or dialysis or 100% increase in serum creatinine from baseline), as well as markers of inflammation and cardiac injury. <b><i>Results:</i></b> Among the 834 patients, the median age was 66 years, 42% were women, and the median first serum UA was 5.9 mg/dL (interquartile range 4.5–8.8). Overall, 60% experienced AKI, 52% experienced MAKE, and 32% died during hospitalization. After adjusting for demographics, comorbidities, and laboratory values, a doubling in serum UA was associated with increased AKI (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.9–4.1), MAKE (OR 2.5, 95% CI 1.7–3.5), and in-hospital mortality (OR 1.7, 95% CI 1.3–2.3). Higher serum UA levels were independently associated with a higher level of procalcitonin (β, 0.6; SE 0.2) and troponin I (β, 1.2; SE 0.2) but were not associated with serum ferritin, C-reactive protein, and interleukin-6. <b><i>Conclusion:</i></b> In patients admitted to the hospital for COVID-19, higher serum UA levels were independently associated with AKI, MAKE, and in-hospital mortality in a dose-dependent manner. In addition, hyperuricemia was associated with higher procalcitonin and troponin I levels.