Characterization of Deposits in Calcific Tendinitis of the Shoulder: Deposits Are Composed of Large Aggregates of Highly Crystalline, Rod-Like Crystals

Background: In the current literature, deposits in calcific tendinitis are described as amorphous masses of hydroxyapatite with a size in the range of 5 to 20 μm. Theoretically, these are too big to be phagocytized by macrophages and induce an inflammatory reaction. Purpose: To better characterize the deposits seen in calcific tendinitis. Study Design: Case series; Level of evidence, 4. Methods: Included in the study were 6 patients with a history of at least 1 year of shoulder pain (range, 1-14 years). Shoulder arthroscopy was performed under general anesthesia, and calcium deposits from the supraspinatus tendon and biopsies from the adjacent subacromial bursa were taken. Samples were analyzed by light microscopy and immunostained for macrophages. Scanning electron microscopy and energy-dispersive x-ray (EDX) analysis were used to assess the morphology and chemical composition of the calcific deposits. Results: Light microscopy showed round and bulky calcium deposits partially surrounded by activated CD68-positive macrophages within inflammatory tissue. Some hemosiderin positive mononuclear cells, indicative for (micro-) hemorrhage, were seen. Scanning electron microscopy revealed that the large calcific deposits (1-20 μm) were composed of rod-like structures. These highly crystalline rods had a size of approximately 100 nm in length and 20 nm in width. Chemical composition by EDX analysis showed that crystals were composed of mainly calcium, oxygen, and phosphorus, equaling the chemical composition of hydroxyapatite. Conclusion: Deposits in calcific tendinitis of the rotator cuff are not amorphous but composed of highly crystalline structures. Fragmentation of these aggregates and subsequent release of the needle-like nanocrystals might initiate the strong inflammatory reaction often seen in patients with calcifying tendinitis of the rotator cuff.

Valvular Calcific Deposits and Mortality in Peritoneal Dialysis Patients: A Propensity Score-Matched Cohort Analysis

<b><i>Objective:</i></b> This study aimed to compare mortality between peritoneal dialysis (PD) patients with and without cardiac valve calcification (CVC). <b><i>Methods:</i></b> Patients undergoing PD at the dialysis center of the Second Affiliated Hospital of Soochow University from January 1, 2009, to June 31, 2016, were included and followed through December 31, 2018. The inclusion criteria were (1) age ≥18 years and (2) PD vintage ≥1 month. The exclusion criteria were (1) a history of hemodialysis or renal transplantation before PD; (2) diagnosed congenital heart disease, rheumatic heart disease, or hyperthyroid heart disease; and (3) loss to follow-up. Differences in mortality rates were compared using a Fine-Gray proportional hazards model. <b><i>Results:</i></b> A total of 310 patient cases were included in this study, including 237 cases without CVC (non-CVC group). The CVC group included 59 cases with aortic valve calcification (AVC), 6 cases with mitral valve calcification (MVC), and 8 cases of AVC associated with MVC. After propensity score matching, 68 pairs were selected. The multivariate competing risk regression analysis revealed that age (hazard ratio [HR]: 1.06, 95% confidence interval [95% CI]: 1.03–1.10, <i>p</i> &#x3c; 0.001) and CVC group (HR: 1.83, 95% CI: 1.04–3.20, <i>p</i> &#x3c; 0.05) were independent risk factors associated with mortality. No significant difference was observed in technique survival between the 2 groups. <b><i>Conclusion:</i></b> CVC is an independent risk factor for mortality in PD patients.

Ultra-high resolution 3D MRI for chondrocalcinosis detection in the knee—a prospective diagnostic accuracy study comparing 7-tesla and 3-tesla MRI with CT

Objectives To test the diagnostic accuracy of a 3D dual-echo steady-state (DESS) sequence at 7-T MRI regarding the detection of chondral calcific deposits of the knee in comparison to 3-T MRI, using CT as cross-sectional imaging reference standard. Methods CT and 7-T MRI (DESS) of knee joints in 42 patients with radiographically known chondrocalcinosis (13 of 42 bilateral) were prospectively acquired for all included patients (n = 55 knee joints). Additionally, 3-T MRI (DESS) was performed for 20 of these 55 knee joints. Two fellowship-trained musculoskeletal radiologists scored eight cartilage regions of each knee joint separately regarding presence of cartilage calcification, diagnostic confidence level, and sharpness of calcific deposits. In an explorative subanalysis, micro-CT of the menisci was evaluated after knee arthroplasty in one patient. Diagnostic performance metrics and nonparametric tests were used to compare between modalities. p values < 0.05 were considered to represent statistical significance. Results Sensitivity for chondrocalcinosis detection was significantly higher for 7-T MRI (100%) compared to 3-T MRI (reader 1: 95.9%, p = 0.03; reader 2: 93.2%, p = 0.002). The diagnostic confidence was significantly higher for both readers at 7 T compared to both 3-T MRI (p < 0.001) and to CT (p = 0.03). The delineation of chondral calcifications was significantly sharper for 7-T compared to both 3-T MRI and CT (p < 0.001, both readers). Micro-CT in one patient suggested that 7-T MRI may potentially outperform standard CT in diagnosing chondral calcifications. Conclusion 3D-DESS imaging at 7-T MRI offers a significantly higher sensitivity in detection of chondral calcific deposits compared to 3-T MRI. Key Points • 3D dual-echo steady-state (DESS) MRI at 7 T has a higher sensitivity in detection of chondral calcific deposits compared to 3-T MRI (p ≤ 0.03). • 3D DESS MRI at 7 T yields no false-negative cases regarding presence of chondral calcific deposits. • 3D DESS MRI at 7 T offers better delineation and higher diagnostic confidence in detection of chondral calcific deposits compared to 3-T MRI (p < 0.001).

POS0393 FIBRIN DEPOSITION IS AN ACTIVE TRIGGER OF CARTILAGE DEGENERATION IN RHEUMATOID ARTHRITIS

Background:Fibrin(ogen) maintains inflammation in various disorders but has never been linked to cartilage damage in rheumatoid arthritis (RA) or other forms of inflammatory arthritis.Objectives:To investigate the role of fibrin deposition on cartilage integrity in arthritis.Methods:Fibrin deposition on knee cartilage was analyzed by immunohistochemistry in RA patients and in murine adjuvant-induced arthritis (AIA). In chondrocytes, fibrinogen expression (Fgα, Fgβ, Fgγ) and procoagulant activity were evaluated by qRT-PCR and turbidimetry respectively. Fibrin-induced catabolic genes were assessed by qRT-PCR in chondrocytes. Fibrin-mediated chondro-synovial adhesion (CSA) with subsequent cartilage tears was studied in co-cultures of human RA cartilage with autologous synoviocytes, in the AIA model, and by MRI. The link between fibrin and calcification was examined in human RA cartilage stained for calcific deposits and in vitro in fibrinogen-stimulated chondrocytes.Results:Fibrin deposition on cartilage correlated with the severity of cartilage damage in human RA explants and in AIA wildtype (WT) mice, while fibrinogen deficient (Fg-/-) mice were protected. Accordingly, fibrin upregulated catabolic enzymes (Adamts5 and Mmp13) in chondrocytes. Secondly, CSA was present in fibrin-rich and damaged cartilage in AIA WT but not in Fg-/- mice. In line, autologous human synoviocytes, cultured on RA cartilage explants, adhered exclusively to fibrin-positive degraded areas. Gadolinium-enhanced MRI of human joints showed contrast-enhancement along cartilage surface in RA patients but not in controls. Finally, fibrin co-localized with calcification in human RA cartilage and triggered chondrocyte mineralization inducing pro-calcification genes (Anx5, Pit1, Pc1) and cytokine (IL-6). Although at a much lesser extent, we observed similar fibrin-mediated mechanisms in osteoarthritis (OA).Conclusion:Fibrin deposition directly impacts on cartilage integrity via induction of catabolism, mechanical stress, and calcification. Potentially, fibrin is a key factor of cartilage damage occurring in RA as a secondary consequence of inflammation.Disclosure of Interests:None declared

MO798ORAL CALCITRIOL USE, VERTEBRAL FRACTURES AND VASCULAR CALCIFICATION IN HEMODIALYSIS PATIENTS: RESULTS FROM VITAMIN K ITALIAN (VIKI) STUDY

Background and Aims In patients with Chronic Kidney Disease (CKD) mineral, bone, and calcific cardiovascular abnormalities are associated to adverse clinical outcomes, including fractures, cardiovascular events and mortality. Vitamin D hormonal system along with alteration levels that occur in calcium, phosphate, PTH, FGF23/Klotho are the main responsible of the bone and vascular metabolism changes, particularly in hemodialysis (HD) patients that experienced the very negative clinical consequences (decreased bone mass, increased fragility fractures and vascular calcification). In the setting of a comparative effectiveness study, we investigated the effect of oral calcitriol on fractures in HD patients taking into account a series of potential confounders. Method We conducted a secondary analysis of the VIKI database, a cross-sectional study involving 387 HD patients from 18 Italian dialysis centers. Routine biochemistry and bone biochemical markers such as vitamin K levels, VKDPs, vitamin 25(OH)D, ALP, PTH, Ca, P, osteocalcin (BGP), Matrix Gla Protein (MGP) were assessed. The presence of Vertebral Fractures (VF) and Vascular Calcification (VC) was determined through spine radiograph. Reduction of &gt;20% of vertebral body height was considered a VF. The severity of the vertebral fractures was estimated as mild, moderate and severe (reduction: 20-25%, 25-40% or &gt;40%, respectively). VC were quantified by measuring the length of calcific deposits along the arteries (mild 0,1-5 cm, moderate 5,1-10 cm and severe &gt;10 cm). Results 177 out 387 patients (45.7%) were treated with oral calcitriol. Oral calcitriol-treated and untreated patients did not differ as for Ca, P, PTH, Albumin, BGP, MGP, and ALP. The prevalence of VF was significantly lower in patients receiving oral calcitriol than in those untreated (48.6% vs 61%, P=0.015), whereas the presence of aortic and iliac calcifications was similar between the two groups (aortic: 81.9% vs 79.5% respectively, P=0.552; iliac: 52.0% and 59.5%, P=0.167). No significant between-groups differences were observed in terms of calcification severity. In a multivariable logistic regression analysis, after adjustment for all potential confounders, oral calcitriol was associated with a marked reduction (-40.2%) of the odds of fractures (OR: 0.598, 95% CI: 0.363-0.985, P=0.043) (see Table). Conclusion A significant association was found between oral calcitriol and lower VF rate in HD patients. Such an effect remained significant also after data adjustment for a large series of potential confounders. Further prospective and interventional studies are needed to confirm these findings.

Efficacy of Adjuvant Application of Platelet-Rich Plasma After Needle Aspiration of Calcific Deposits for the Treatment of Rotator Cuff Calcific Tendinitis: A Double-Blinded, Randomized Controlled Trial With 2-Year Follow-up

Background: Needle aspiration of calcific deposits (NACD) is a frequently used treatment for rotator cuff calcific tendinitis (RCCT). However, a substantial number of patients experience recurrent or persisting shoulder symptoms after NACD. Purpose: To compare the effects of adjuvant application of platelet-rich plasma (PRP) after NACD (NACP+PRP) with those of conventional NACD with corticosteroids (NACD+corticosteroids) on pain, shoulder function, and quality of life (QoL). Study Design: Randomized controlled trial; Level of evidence, 1. Methods: In a single-center, double-blinded, randomized controlled trial, 80 adults with symptomatic RCCT were randomly allocated to receive NACD+corticosteroids or NACD+PRP. Pain, shoulder function, and QoL were assessed at baseline; 6 weeks; and 3, 6, 12, and 24 months after treatment using a numeric rating scale for pain (NRS); the Constant-Murley score (CMS); the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH); the Oxford Shoulder Score (OSS); and the EuroQol 5-dimension scale (EQ-5D). Additionally, resorption of calcific deposits and the integrity of rotator cuff tendons were assessed by using standard radiographs and ultrasound examination, respectively. The results were analyzed using noninferiority analysis for NRS scores and a mixed model for repeated measures. Results: Eighty patients were included (48 female; mean age, 49 ± 6 years; 41 patients in the NACD+PRP group). Both groups showed improvement of clinical scores at the 2-year follow-up ( P < .001 for all clinical scores). NACD+PRP was found to be noninferior to NACD+corticosteroids with regard to the mean decrease of NRS scores (4.34 vs 3.56; P = .003). Mixed-model analysis showed a significant difference in favor of NACD+PRP (CMS, P < .001; DASH, P = .002; OSS, P = .010; EQ-5D, P < .001). However, clinically relevant differences in favor of NACD+PRP were only seen at the 6-month follow-up for NRS and CMS scores, whereas at the 6-week follow-up a clinically relevant difference in favor of NACD+corticosteroids was found for all clinical scores except for the NRS. Full resorption of calcific deposits was present in 84% of the NACD+PRP group compared with 66% in the NACD+corticosteroids group ( P = .081). In the NACD+PRP group, 10 (24%) patients required a second NACD procedure compared with 19 (49%) patients in the NACD+corticosteroids group ( P = .036). Six complications, of which 5 were frozen shoulders, occurred in the NACD+PRP group compared with 1 complication in the NACD+corticosteroids group ( P = .11). Conclusion: NACD+PRP resulted in worse clinical scores at the 6-week follow-up but better clinical scores at the 6-month follow-up compared with NACD+corticosteroids. At the 1- and 2-year follow-ups, the results were comparable between groups. Furthermore, PRP seemed to reduce the need for additional treatments but was associated with more complications. In conclusion, NACD+corticosteroids had a favorable early effect on pain and function combined with low comorbidity. Thus, it remains the treatment of choice for patients with RCCT. Registration: NCT02173743 (ClinicalTrials.gov identifier).

Global Hypertrophic Calcification of Shoulder Joint Capsule

Background: Calcification around the shoulder joint usually occur inside or around the tendons of the rotator cuff. We herein report on a case of global hypertrophic calcification of shoulder joint capsule in a patient with Rheumatoid arthritis. Case Report: An 86 years-old male with a long-standing history of seropositive Rheumatoid arthritis. The treatment for his Rheumatoid arthritis included Methotrexate and Hydroxychloroquine initially, but due lack of control, adalimumab was added with excellent control of his arthritis. He has progressively experienced an increasing pain and stiffness in his shoulders, in addition to an increasing limitation of shoulder movement. Magnetic Resonance Imaging revealed severe arthritis with remoulding deformity with extensive capsular calcification, intra-articular loose-bodies. Discussion: This phenomenon of calcification of shoulder capsule has not been reported before. The pathophysiology of calcific tendinopathy of the shoulder remains controversial. The calcific deposits consist of poorly-crystallized hydroxyapatite. Conclusion: Global hypertrophic calcification of shoulder joint capsule is unique and unreported in the literature. We can postulate that the long-standing inflammation of the synovial lining of the capsules had a major part. Moreover, Diabetes Mellitus, smoking, and repetitive manoeuvres are recognized contributing factors as well for similar conditions. Genetic predisposition seems to play a role as well. We think all those have played part in the development of this unprecedented presentation. Management should be tailored to target specific symptoms for pain, rigidity, and decreasing calcification size. Several options are available, including Kinesiotherapy, electrotherapy modalities, iontophoresis, electroshock wave therapy, and finally surgical approaches for progressive and refractory cases.

Diagnosis and treatment of calcific tendinitis of the shoulder

Calcific tendinitis is the leading cause of shoulder pain. Among patients with calcific tendinitis, 2.7%–20% are asymptomatic, and 35%–45% of patients whose calcific deposits are inadvertently discovered develop shoulder pain. If symptoms are present, complications such as decreased range of motion of the shoulder joint should be minimized while managing pain. Patients with acute calcific tendinitis respond well to conservative treatment and rarely require surgery. In contrast, patients with chronic calcific tendinitis often do not respond to conservative treatment and do require surgery. Clinical improvement takes time, even after surgical treatment. This review article summarizes the processes related to the diagnosis and treatment of calcific tendinitis with the aim of helping clinicians choose appropriate treatment options for their patients.

Treatment of Calcific Tendinitis around the Elbow

Purpose: This study was performed to evaluate surgical outcomes in calcific tendinitis around the elbow due to persistent pain despite conservative treatment.Methods: The study retrospectively reviewed seven consecutive patients who visited Jeju National University Hospital due to pain around the elbow and underwent operative treatment due to persisting calcific lesion evidenced by radiographs and ultrasonography. The patients’ mean age was 40 years, and the average follow-up was 5 years and 10 months. Surgical procedures were performed under brachial plexus block anesthesia to remove calcific deposits at the common extensor tendon with incision around the lesion along with repair of partially ruptured tendons during the removal using nonabsorbable sutures. The patients were immobilized with a long-arm splint in a neutral position for 2 weeks after operation, followed by rehabilitation involving continuous passive motion and physical therapy for elbow joint range of motion and muscle strengthening, respectively. Intraoperative biopsy revealed inflammatory cells and microcalcification indicative of calcific tendinitis in all patients. Surgical outcome was evaluated based on patient’s subjective satisfaction under five-point grading scale, Mayo Elbow Performance Index (MEPI) score, and the Disabilities of the Arm, Shoulder and Hand (DASH) score.Results: The patient’s subjective satisfaction scale revealed “very satisfactory” in three cases and “satisfactory” in four cases. The median MEPI and DASH score were preoperatively 45 and 88.8, which improved to 85 and 36.2 at final follow-up, respectively.Conclusion: In patients with persistent pain despite aggressive conservative treatment in calcific tendinitis, direct surgical removal of calcific deposit is an effective way to resolve symptom and prevent recurrence.