Pentraxin 3 is a marker of early joint inflammation in patients with juvenile idiopathic arthritis

Pentraxin 3 (PTX3) is an acute phase protein produced in different body tissues. The aims of this study were to characterize PTX3 secretion in synovial fluid (SF) of juvenile idiopathic arthritis (JIA) patients and to analyze the correlation of PTX3 levels in SF with clinical characteristics and the course of the disease. SF-PTX3 levels were measured in a cohort of 75 consecutive JIA patients followed in a single center. Patients’ clinical characteristics, disease course, and therapies were analyzed for their correlation with SF-PTX3 levels. A synovial cell line was used to study the kinetics of PTX3 secretion by synoviocytes. SF-PTX3 levels varied over a wide range. Elevated SF-PTX3 levels were detected in patients who subsequently required treatment with disease-modifying antirheumatic drugs during the follow-up period. SF-PTX3 levels were found to be inversely correlated with the length of time from onset of joint swelling. No correlation was found between synovial and serum PTX3 or C-reactive protein (CRP). Following in vitro stimulation of synovial cell line with TNFa or IL1, the secretion of PTX3 increases transiently in the first 48–72 h. A similar increase was obtained in patients’ synovial fluids but not with IL6. Higher SF-PTX3 levels were found when tested closer to arthritis exacerbation and 48–72 h after in vitro stimulation of cells from a synovial cell line, implying that PTX3 plays a role in early stages of inflammation. Higher SF-PTX3 levels were associated with several clinical features reflecting disease severity and prognostic data. Measuring SF-PTX3 levels may help in providing a more focused and patient-adjusted treatment.     

Targeting oncogenic interleukin‐7 receptor signalling with N‐acetylcysteine in T cell acute lymphoblastic leukaemia

Activating mutations of the interleukin‐7 receptor (IL7R) occur in approximately 10% of patients with T cell acute lymphoblastic leukaemia (T‐ALL). Most mutations generate a cysteine at the transmembrane domain leading to receptor homodimerization through disulfide bond formation and ligand‐independent activation of STAT5. We hypothesized that the reducing agent N‐acetylcysteine (NAC), a well‐tolerated drug used widely in clinical practice to treat acetaminophen overdose, would reduce disulfide bond formation, and inhibit mutant IL7R‐mediated oncogenic signalling. We found that treatment with NAC disrupted IL7R homodimerization in IL7R‐mutant DND‐41 cells as assessed by non‐reducing Western blot, as well as in a luciferase complementation assay. NAC led to STAT5 dephosphorylation and cell apoptosis at clinically achievable concentrations in DND‐41 cells, and Ba/F3 cells transformed by an IL7R‐mutant construct containing a cysteine insertion. The apoptotic effects of NAC could be rescued in part by a constitutively active allele of STAT5. Despite using doses lower than those tolerated in humans, NAC treatment significantly inhibited the progression of human DND‐41 cells engrafted in immunodeficient mice. Thus, targeting leukaemogenic IL7R homodimerization with NAC offers a potentially effective and feasible therapeutic strategy that warrants testing in patients with T‐ALL.     

A Novel Non-Invasive Adjuvant Biomechanical Treatment for Patients with Altered Rehabilitation after Total Knee Arthroplasty: Results of a Pilot Investigation

Background

Many factors contribute to suboptimal results after total knee arthroplasty (TKA) but little is known regarding the value of postsurgical rehabilitation after TKA. We examined the effects of an enhanced closed kinematic chain exercises program (AposTherapy) on gait patterns and clinical outcomes among patients with a lack of progress in their postsurgical rehabilitation.

Methods

Twenty-two patients were prospectively followed during the study. Gait spatiotemporal parameters were measured at the initial evaluation, after 15 minutes of therapy, and after 3 months of therapy. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the short form (SF) 36 health survey were completed by patients before treatment and after 3 months of treatment.

Results

The WOMAC and SF-36 scores improved significantly after 3 months of treatment. Gait velocity, single limb support, and step length of the operated leg improved significantly even after a single 15 minutes treatment. Normal gait velocity was observed in 36% of patients after 3 months of treatment.

Conclusions

A physiotherapy program that included enhanced closed kinematic chain biomechanical therapy was beneficial for patients who experienced a suboptimal rehabilitation course after TKA.     

Percutaneous coronary interventions in diabetic patients: is complete revascularization important?

BACKGROUND: The long-term prognosis of diabetic patients with multivessel coronary artery disease (CAD) treated by surgical or percutaneous coronary revascularization is significantly worse as compared to non-diabetics. Lower rates of complete revascularization may be one factor that influences the poor long-term outcome in the diabetic population. Our study assessed the impact of complete revascularization on the long-term prognosis in diabetic patients with CAD treated by percutaneous coronary intervention (PCI). The study included 658 consecutive diabetic patients (mean age, 60.9+/-10.1 years) who underwent PCI. Multivessel disease was present in 352 patients (53.5%). Revascularization was complete in 94 (26.7%) and incomplete in 258 (73.3%) patients with multivessel disease. Reasons for incomplete revascularization included angioplasty of only the culprit lesion (43.4%); small vessel size (22.8%); moderate lesion, defined as diameter stenosis 50-69% (18.6%); chronic total occlusion of the non-intervened vessel (6.6%); and others (8.5%). Overall survival rate at 5 years was 87.4%. Patients who underwent complete revascularization had a 94.5% survival rate, compared to 83.0% for those with incomplete revascularization (p<0.001). Similarly, the rates of myocardial infarction-free survival were significantly higher in patients with complete versus incomplete revascularization (92.9% versus 79.9%, respectively). Incomplete revascularization was the most powerful independent predictor of mortality at follow-up (relative risk 95% confidence interval, 1.54-7.69; p=0.003). Our data suggest that complete myocardial revascularization may improve the long-term prognosis after PCI of diabetic patients with multivessel CAD.     

Staged versus one-step approach for multivessel percutaneous coronary interventions

Background Percutaneous coronary interventions (PCIs) in patients with multivessel coronary artery disease (CAD) may be staged or performed in a single session. No data exist about the relative safety and efficacy of these 2 strategies. Our aim was to compare short-term and long-term outcomes of patients with multivessel CAD who underwent PCI in 1 versus 2 sessions. Methods and Results The study included 264 consecutive patients who underwent treatment in our center during 1997 and 1998. PCI was conducted in a single session in 129 patients and was staged in 135 patients. The mean interval between the sessions in the staged group was 45.6 ± 22.3 days. The rates of major adverse cardiac events (MACEs) during in-hospital stay did not differ significantly between the staged (combined for both stages) and nonstaged groups (2.2% vs 4.6%; P = .28). A trend for lower event rates at 30-day (2.9% vs 6.9%; P = .13) and 1-year follow-up (26.1 vs 35.9; P = .08) favored the staged arm. Diameter stenosis ≥50% was found in 17% of patients in the staged group in the second session and was successfully retreated in most of them. No MACE occurred between the sessions. Multivariate analysis identified staging of the procedure as a single independent predictor of MACE at 1-year follow-up (P = .05). Conclusion Our results suggest that a practical staging strategy within 4 to 8 weeks is safe and allows for identification and treatment of potential excessive proliferative response in the previously intervened lesions during the second procedure. (Am Heart J 2002;143:1017-26.)