Comparison of Single Intra-Articular Injection of Novel Hyaluronan (HYA-JOINT Plus) with Synvisc-One for Knee Osteoarthritis: A Randomized, Controlled, Double-Blind Trial of Efficacy and Safety.

BACKGROUND: Viscosupplementation has been widely used for the treatment of knee osteoarthritis. Because we found no well-controlled trial comparing single-injection regimens of hyaluronan for knee osteoarthritis, we compared the efficacy and safety of a single intra-articular injection of a novel cross-linked hyaluronan (HYA-JOINT Plus) with a single injection of Synvisc-One in patients with knee osteoarthritis. METHODS: In a prospective, randomized, controlled, double-blind trial with a 6-month follow-up, 132 patients with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) were randomized to receive 1 intra-articular injection of 3 mL of HYA-JOINT Plus (20 mg/mL) (n = 66) or 6 mL of Synvisc-One (8 mg/mL) (n = 66). The primary outcome was the change from baseline in the visual analog scale (VAS) (0 to 100 mm) pain score at 6 months. Secondary outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, Likert scale), Lequesne index, timed "Up & Go" (TUG) test, single-limb stance (SLS) test, use of rescue analgesics, and patient satisfaction. RESULTS: A total of 121 patients were available for the intention-to-treat analysis at 6 months. Both groups had a significant improvement in the VAS, WOMAC, and Lequesne index scores at each follow-up visit (p < 0.001). Patients who received HYA-JOINT Plus experienced a significantly greater improvement in the VAS pain score at 1, 3, and 6 months compared with those treated with Synvisc-One (adjusted mean difference: -12.0, -8.5, and -6.6; p = 0.001, 0.033, and 0.045, respectively). There were no significant between-group differences in any of the secondary outcomes except the WOMAC stiffness scores at 6 months, which favored HYA-JOINT Plus treatment (p = 0.043). The TUG time did not change significantly in either group during the study (p > 0.05), but the SLS time improved significantly in both the HYA-JOINT Plus and the Synvisc-One group (p = 0.004 and p = 0.022, respectively). No significant between-group differences were observed with respect to patient satisfaction or consumption of analgesics. No serious adverse events occurred following the injections. CONCLUSIONS: A single injection of either HYA-JOINT Plus or Synvisc-One is safe and effective for 6 months in patients with knee osteoarthritis. HYA-JOINT Plus is superior to Synvisc-One in terms of reducing the VAS pain score at 1, 3, and 6 months and the WOMAC stiffness score at 6 months, with similar safety. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Cardiopulmonary Function, Exercise Capacity, and Echocardiography Finding of Pediatric Patients With Kawasaki Disease: An Observational Study.

Coronary artery (CA) abnormalities influence exercise capacity (EC) of patients with Kawasaki disease (KD), and Z-score of CA is a well established method for detecting CA aneurysm. We studied the influence of KD on cardiopulmonary function and EC; meanwhile we analyzed echocardiographic findings of KD patients. We also assessed the correlation between CA Z-score and EC of KD patients to see if CA Z-score of KD patients could reflect EC during exercise.Sixty-three KD patients were recruited as KD group 1 from children (aged 5-18 y) who received transthoracic echocardiographic examinations and symptom-limited treadmill exercise test for regular follow-up of KD from January 2010 to October 2014 in 1 medical center. We then divided KD group 1 into KD group 2 (<5 y, n = 12) and KD group 3 (≥5 y, n = 51) according to time interval between KD onset to when patients received test. Control groups were matched by age, sex, and body mass index. Max-Z of CA was defined as the maximal Z-score of the proximal LCA or RCA by Dalliarre equation or Fuse calculator.All routine parameters measured during standard exercise test were similar between KD and control groups, except that peak rate pressure products (PRPPs) in KD group 1 to 3 were all lower than corresponding control groups significantly (P = 0.010, 0.020, and 0.049, respectively). PRPPs correlated with Max-Z of CA by both equations modest inversely (by Dallaire, P = 0.017, Spearman rho = -0.301; by Fuse, P = 0.014, Spearman rho = -0.309).Our study recruited larger number of KD patients and provided a newer data of EC of KD patients. Our finding suggests that after acute stage of KD, patients could maintain normal cardiorespiratory fitness. Therefore, we believe that it is important to promote cardiovascular health to KD patients and KD patients should exercise as normal peers. However, since KD patients might still have compromised coronary perfusion during exercise, it remains crucial to assess and monitor cardiovascular risk of KD patients. Max-Z of CA correlates with PRPP modest inversely and might be used as a follow-up indicator of CA reserve during exercise after acute stage of KD.

Tanshinone IIA Attenuates H2O2 -induced injury in human umbilical vein endothelial cells.

The injury of endothelial cell is the critical event of vascular disease. In endothelial cell, oxidative stress is regarded as critical to pathogenic factors in endothelial cell injury and apoptosis. Tanshinone IIA is the main effective component of Salvia miltiorrhiza known as "Danshen" in traditional Chinese medicine for treating cardiovascular disorders, but the mechanism by which it exerts the protective effect is not well established. The present study was designed to test the hypothesis that tanshinone IIA can inhibit hydrogen peroxide ( H(2)O(2) )-induced injury and unravel its intracellular mechanism in human umbilical vein endothelial cells (HUVECs). In this study, HUVECs were treated with tanshinone IIA in the presence/absence of H(2)O(2) . The protective effects of tanshinone IIA against H(2)O(2) were evaluated. Our results show that HUVECs incubated with 200 µM H(2)O(2) had significantly decreased the viability of endothelial cells, which was accompanied with apparent cell apoptosis, the activation of caspase-3 and the upregulation of p53 expression, which was known to play a key role in H(2)O(2) -induced cell apoptosis. However, pretreatment with tanshinone IIA (3-10 µM) resulted in a significant resistance to H(2)O(2) -induced apoptosis. In addition, pretreatment with tanshinone IIA decreased the activity of caspase-3 and p53 expression. Tanshinone IIA also induced activating transcription factor (ATF) 3 expression; while knockdown of ATF-3 with ATF-3 siRNAsignificantly reduced tanshinone IIA's protective effect. In conclusion, the present study shows that tanshinone IIA can protect endothelial cells against oxidative injury induced by H(2)O(2) , suggesting that this compound may constitute a promising intervention against cardiovascular disorders and ATF-3 may play an important role in this process.