Swelling Scores Research Articles

Activation of cannabinoid receptor 2 attenuates synovitis and joint distruction in collagen-induced arthritis

ObjectivesRecent studies have suggested immunomodulatory and anti-inflammatory effects of cannabinoid receptor 2 (CB2R) activation, which is devoid of psychoactivity. We have demonstrated the expression of CB2R in synovial tissue from patients with rheumatoid arthritis (RA), and its specific activation shows inhibitory effects on fibroblast-like synoviocytes. However, it is still unclear whether selective activation of CB2R inhibits joint inflammation or protects joint damage in RA. MethodsA murine model of collagen-induced arthritis (CIA) was used to evaluate the therapeutic efficacy of HU-308, a selective CB2R agonist. The disease severity was evaluated by semi-quantitative scoring of joint swelling, histological assessment of joint inflammation and structure, and radiographic assessment of joint destruction by using digital plain radiographs and micro-CT scans. The concentrations of various isotypes of anti-collagen II antibodies in sera and the levels of cytokines in culture supernatants were determined by ELISA. ResultsCompared with vehicle treatment, protective treatment with intraperitoneal injection of HU-308 (0.3–1.0mg/kg) failed to decrease the incidence of the development of CIA, but it effectively suppressed the severity of the disease. In CIA mice, treatment with HU-308 significantly decreased joint swelling, synovial inflammation, and joint destruction, as well as serum levels of anti-collagen II antibodies. In vitro, HU-308 (1–10μM) significantly suppressed the production of proinflammatory cytokines IL-6 and TNF-α from lipopolysaccharide-stimulated murine peritoneal macrophages with intact CB2R in dose-dependent manners. HU-308 failed to elicit any inhibitory effect of on lipopolysaccharide-stimulated macrophages from CB2R-knockout mice. ConclusionsActivation of CB2R by HU-308 has therapeutic potential for RA to suppress synovitis and alleviate joint destruction by inhibiting the production of autoantibodies and proinflammatory cytokines.

Thrombolysis and Iliofemoral Vein Stent Placement in Cancer Patients with Lower Extremity Swelling Attributed to Lymphedema

PurposeTo assess the effects of iliofemoral vein stent placement on symptomatic lower extremity swelling (LES), presumed to be lymphedema, in patients with cancer. Materials and MethodsDuring the period 2005–2013, 62 patients (38 female; age, 60.4 y ± 15.4) with histology-proven metastatic disease and LES resistant to standard therapies were evaluated and found to have venous outflow obstruction. Stents were placed in the iliofemoral veins or inferior vena cava, or both, and evaluated by color Doppler ultrasound or contrast-enhanced computed tomography during the follow-up period. Patient symptoms were assessed using the Venous Disability Score (VDS) and the Galway Limb Swelling score, a patient-directed, 5-question symptom scoring system. ResultsStents were successfully placed in all patients. During the follow-up period, in-stent thrombosis occurred in 13 patients, and additional stents were placed in 3 patients to treat luminal narrowing. The mean VDS improved significantly (P < .05): from 3.0 ± 0 on the day of the procedure to 2.95 ± 0.22 on day 3, 2.0 ± 0.33 on day 7, and 1.87 ± 0.34 on day 30. The mean Galway Limb Swelling score also improved significantly (P < 0.001): from 3.6 ± 0.74 on the day of the procedure to 1.96 ± 0.91 on day 3, 1.06 ± 0.78 on day 7, and 0.6 ± 0.66 on day 30. During the follow-up period, 60 patients died as a result of their underlying malignancy (mean, 230 d; range, 5–1,080 d). ConclusionsIliofemoral or iliocaval venous stent placement may have a valuable role in patients with metastatic disease and symptomatic LES associated with venous obstruction.

Suppression of skin inflammation in keratinocytes and acute/chronic disease models by caffeic acid phenethyl ester.

Skin inflammation plays a central role in the pathophysiology and symptoms of diverse chronic skin diseases including atopic dermatitis (AD). In this study, we examined if caffeic acid phenethyl ester (CAPE), a skin-permeable bioactive compound from propolis, was protective against skin inflammation using in vitro cell system and in vivo animal disease models. CAPE suppressed TNF-α-induced NF-κB activation and expression of inflammatory cytokines in human keratinocytes (HaCaT). The potency and efficacy of CAPE were superior to those of a non-phenethyl derivative, caffeic acid. Consistently, topical treatment of CAPE (0.5 %) attenuated 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced skin inflammation on mouse ear as CAPE reduced ear swelling and histologic inflammation scores. CAPE suppressed increased expression of pro-inflammatory molecules such as TNF-α, cyclooxygenase-2 and inducible NO synthase in TPA-stimulated skin. TPA-induced phosphorylation of IκB and ERK was blocked by CAPE suggesting that protective effects of CAPE on skin inflammation is attributed to inhibition of NF-κB activation. Most importantly, in an oxazolone-induced chronic dermatitis model, topical application of CAPE (0.5 and 1 %) was effective in alleviating AD-like symptoms such as increases of trans-epidermal water loss, skin thickening and serum IgE as well as histologic inflammation assessment. Collectively, our results propose CAPE as a promising candidate for a novel topical drug for skin inflammatory diseases.

Will sialylation change intravenous immunoglobulin therapy in the future?

Will sialylation change intravenous immunoglobulin therapy in the future?

Modeling and design of challenge tests: Inflammatory and metabolic biomarker study examples

Given the complexity of pharmacological challenge experiments, it is perhaps not surprising that design and analysis, and in turn interpretation and communication of results from a quantitative point of view, is often suboptimal. Here we report an inventory of common designs sampled from anti-inflammatory, respiratory and metabolic disease drug discovery studies, all of which are based on animal models of disease involving pharmacological and/or patho/physiological interaction challenges. The corresponding data are modeled and analyzed quantitatively, the merits of the respective approach discussed and inferences made with respect to future design improvements. Although our analysis is limited to these disease model examples, the challenge approach is generally applicable to the vast majority of pharmacological intervention studies.In the present five Case Studies results from pharmacodynamic effect models from different therapeutic areas were explored and analyzed according to five typical designs. Plasma exposures of test compounds were assayed by either liquid chromatography/mass spectrometry or ligand binding assays. To describe how drug intervention can regulate diverse processes, turnover models of test compound–challenger interaction, transduction processes, and biophase time courses were applied for biomarker response in eosinophil count, IL6 response, paw-swelling, TNFα response and glucose turnover in vivo. Case Study 1 shows results from intratracheal administration of Sephadex, which is a glucocorticoid-sensitive model of airway inflammation in rats. Eosinophils in bronchoalveolar fluid were obtained at different time points via destructive sampling and then regressed by the mixed-effects modeling. A biophase function of the Sephadex time course was inferred from the modeled eosinophil time courses. In Case Study 2, a mouse model showed that the time course of cytokine-induced IL1β challenge was altered with or without drug intervention. Anakinra reversed the IL1β induced cytokine IL6 response in a dose-dependent manner. This Case Study contained time courses of test compound (drug), challenger (IL1β) and cytokine response (IL6), which resulted in high parameter precision. Case Study 3 illustrates collagen-induced arthritis progression in the rat. Swelling scores (based on severity of hind paw swelling) were used to describe arthritis progression after the challenge and the inhibitory effect of two doses of an orally administered test compound. In Case Study 4, a cynomolgus monkey model for lipopolysaccharide LPS-induced TNFα synthesis and/or release was investigated. This model provides integrated information on pharmacokinetics and in vivo potency of the test compounds. Case Study 5 contains data from an oral glucose tolerance test in rats, where the challenger is the same as the pharmacodynamic response biomarker (glucose). It is therefore convenient to model the extra input of glucose simultaneously with baseline data and during intervention of a glucose-lowering compound at different dose levels.Typically time-series analyses of challenger- and biomarker-time data are necessary if an accurate and precise estimate of the pharmacodynamic properties of a test compound is sought. Erosion of data, resulting in the single-point assessment of drug action after a challenge test, should generally be avoided. This is particularly relevant for situations where one expects time-curve shifts, tolerance/rebound, impact of disease, or hormetic concentration–response relationships to occur.

Is mechanical bowel preparation still necessary for gynecologic laparoscopic surgery? A meta-analysis.

A number of studies have proven that mechanical bowel preparation (MBP) has no benefits in elective colorectal surgery. However, studies specifically related to gynecologic laparoscopic surgery are scant. We undertook a meta-analysis to assess the necessity of MBP before gynecologic laparoscopic surgery. The electronic databases MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched to identify relevant randomized controlled trials. Two authors independently extracted data from each study. The primary outcome of interest was the quality of surgical field. Secondary outcomes of interest included postoperative pain, abdominal swelling, nausea/vomiting, and length of hospital stay. Three studies involving 372 participants were included in the meta-analysis. The results showed that MBP did not significantly increase the overall quality of surgical field exposure (odds ratio, 0.82; 95% confidence interval [CI], 0.46-1.49; P = 0.52). MBP also did not appear to significantly change the mean scores of postoperative pain (weighted mean difference, 0.09; 95%CI, -0.54-0.71; P = 0.79), the incidence of nausea/vomiting (odds ratio, 1.56; 95%CI, 0.80 to 3.03; P = 0.19), the mean scores of abdominal swelling (weighted mean difference, -0.26; 95%CI, -0.83-0.30; P = 0.36), and length of hospital stay (weighted mean difference, 0.05; 95%CI, -0.13-0.22; P = 0.62). Our results suggest that routine use of MBP for gynecologic laparoscopic surgery should not be recommended. However, additional randomized controlled trials using large samples are needed to confirm these findings.

Use of Xinfeng capsule to treat abarticular pathologic changes in patients with rheumatoid arthritis

ObjectiveTo observe the influence of Xinfeng-capsule (XFC) on abarticular pathologic changes (APCs) and other indices of patients with rheumatoid arthritis (RA) and explore the mechanism of action of XFC in improving such changes. MethodsThree-hundred RA patients were divided randomly into a treatment group (n=150) and control group (n=150). A normal control (NC) group (n=90) was also created. Changes in cardiac function, pulmonary function, anemia indices and platelet parameters of RA patients were measured. Curative effects of the two groups were compared, and comparison carried out with the NC group. ResultsIn 300 RA patients, late diastolic peak flow velocity (A peak) was much higher (P<0.01) and early diastolic peak flow velocity (E peak), E/A, and left ventricular fraction shortening much lower (P<0.01) than those in the NC group. Vital capacity (VC), forced vital capacity in one second, forced vital capacity (FVC), maximal voluntary ventilation (MVV), maximal expiratory flow in 50% of VC (FEF50) and FEF75 were lowered remarkably (P< 0.05 or P<0.01). Platelet count (PLT), plateletcrit (PCT) and mean platelet volume (MPV) increased markedly (P<0.05 or P<0.01), and hemoglobin (Hb) level decreased significantly (P<0.05). After XFC treatment, the A peak and PLT and PCT were much lower (P<0.05), and E/A and the number of red blood cells as well as Hb level were much higher (P< 0.05), as were FVC, MVV and FEF50 (P<0.05 or P< 0.01), in the treatment group than those in the NC group. Total score of pain and swelling in joints, uric-acid level and high-sensitivity C-reactive protein level were much lower, and superoxide dismutase level as well as the number of CD4 + CD25 + regulation T cells (Treg) and CD4 + CD25 + CD127-Treg were much higher (P<0.05 or P<0.01) in the treatment group than those in the NC group. ConclusionRA patients with pathologic changes in joints also suffer from lower cardiac and pulmonary functions and from parameters of anemia and platelet factors. XFC can improve the symptoms of RA patients, ameliorate their cardiac and pulmonary functions and reduce the parameters of anemia and platelet factors. XFC lowers the immune inflammatory reaction to improve APCs in RA patients.

Anti-IL-31 receptor antibody is shown to be a potential therapeutic option for treating itch and dermatitis in mice.

IL-31, which is described as a pruritogenic cytokine, is linked to the itching that is associated with allergic and non-allergic eczema, but the precise pruritogenic mechanism of IL-31 and its potential as a therapeutic target for atopic dermatitis (AD) have not been determined. We investigated the effects of existing drugs on the scratching behaviour induced by an i.v. injection of IL-31 to clarify whether IL-31 induced pruritus indirectly. In addition, we studied the effects of an anti-IL-31 receptor α subunit (anti-IL-31 receptor α) neutralizing antibody on chronic pruritus-inducing dermatitis in an AD-like model to determine whether IL-31 not only induces scratching behaviour, but is also the causative factor in an AD phenotype. The scratching behaviour induced by an i.v. injection of IL-31 was inhibited by pretreatment with an anti-IL-31 receptor α-neutralizing antibody. In contrast, it was not inhibited significantly by a non-sedative antihistamine (terfenadine), immunosuppressants (dexamethasone and tacrolimus), or a μ-opioid receptor antagonist (naloxone). The anti-IL-31 receptor α-neutralizing antibody reduced the ear swelling and dermatitis score in a chronic pruritus-inducing AD-like model. Moreover, treatment with the anti-IL-31 receptor α-neutralizing antibody showed therapeutic effects on the dermatitis even if it was injected after the disease had developed. Anti-IL-31 receptor α is a potential novel therapeutic approach for escaping from the itch-scratch cycle and also a treatment for dermatitis in AD.

Effect of local continuing cold compress on postoperative nursing of patients with total knee replacement

Objective To explore the effect of local continuing cold compress on postoperative nursing of patients with total knee replacement .Methods One hundred patients with total knee replacement were chosen and divided into the control group and the observation group , each with 50 cases.The control group received the routine postoperative nursing , and the observation group received the local continuing cold compress on the basis of routine nursing .The degree of pain , the situations of the local swelling and bleeding were recorded and compared between two groups .Results The average score of pain 48 hours after the operation was （7.1 ±2.6） in the control group, and was （4.7 ±1.3） in the observation group; the score of swelling was （2.2 ±0.6） in the control group, and was （1.1 ±0.4） in the observation group;the amount of bleeding was （608.7 ±49.8） ml in the control group, and was （431.6 ±24.1） in the observation group, and the differences were statistically significant （t=6.784, 3.862, 64.852, respectively; P〈0.05）.The case of intra-articular puncture in the observation was 1 case, and was 7 cases in the control group; the average amount of draining fluid in the observation group was 8 ml, and was （13.7 ±1.9） ml in the control group .The patient satisfaction in the observation group was （99.6 ±0.2）%, and was higher than （98.7 ±0.4） %in the control group, and the difference was statistically significant （χ2 =3.076,P〈0.05）.Conclusions The local continuing cold compress in patients with total knee replacement after the operation can effectively relieve the pain , and reduce the incidence of complication , and increase the patient satisfaction . Key words: Total knee replacement; Local cold compress; Nursing; Postoperative complications; Effect

AB0127 Prophylactic and Therapeutic Administration of β-Glucan from Pleurotus Ostreatus Decreases the Development of Arthritis and Potentiates Methotrexate Treatment in Rats with Adjuvant Arthritis

BackgroundBeta-glucans are naturally occurring polysaccharides, which are integral constituents of the cell wall of bacteria, plants and yeasts. They modify biological response, have anticarcinogenic activity and enhance non-specifically the host...

AB0145 Sodium Chloride Aggravates Arthritis by TH17 Polarization

BackgroundRecent studies demonstrated that sodium chloride (NaCl) can be a risk factor for autoimmune disease through the induction of pathogenic IL-17 producing T helper (Th17) cells.ObjectivesThis study was aimed to...

THU0138 Glpg0634m1, A Major Metabolite of the Jak1-Selective Inhibitor Glpg0634, is Also Jak1-Selective and Efficient in the Rat CIA Model

BackgroundGLPG0634 is a JAK inhibitor displaying a high selectivity for JAK1 over JAK2 in human whole blood assays. It is currently being developed as an oral treatment for rheumatoid arthritis...

Anti-arthritic activity of Xanthium strumarium L. extract on complete Freund׳s adjuvant induced arthritis in rats

Ethnopharmacological relevanceXanthium strumarium L. fruit (Xanthiu fruit) has been traditionally used as a medicinal herb in China for the treatment of many ailments including rheumatoid arthritis. However, the anti-arthritic activity of Xanthium strumarium fruit has still not been demonstrated. In the present study, we confirmed that the extract of Xanthium strumarium (EXS) prevents rheumatoid arthritis induced by Complete Freund׳s Adjuvant (CFA) in rats. Materials and methodsMale Wistar rats (160±10g) were immunized by intradermal injection of 0.1mL of CFA into the left hind metatarsal footpad. EXS was administered orally at a dose of 300 and 75mg/kg once a day after the induction of adjuvant arthritis. Methotrexate (3mg/kg, twice a week) was used as a positive control. Paw swelling, arthritic score, body weight loss, spleen index, thymus index, serum cytokines, inflammatory mediators and histological change were measured. The chemical profile of EXS was analyzed by HPLC-DAD. ResultsWe found that the EXS significantly suppressed paw swelling and arthritic score, increased body weight loss and decreased the thymus index. The overproduction of TNF-α and IL-1β were remarkably suppressed in the serum of all EXS-treated rats, and in contrast IL-10 was markedly increased. The level of COX-2 and 5-LOX was also decreased with EXS treatment. Ten phenolic acid derivatives were identified from 14 detected peaks by HPLC-DAD with the reference substances and verified by LC–MS. ConclusionsThese results suggest the potential effect of EXS as an anti-arthritis agent towards CFA-induced arthritis in rats. Xanthium strumarium has the potential to be regarded as a candidate for use in general therapeutics and as an immune-modulatory medicine in rheumatoid arthritis.

Interleukin-21 receptor deficiency increases the initial toll-like receptor 2 response but protects against joint pathology by reducing Th1 and Th17 cells during streptococcal cell wall arthritis.

The cytokine interleukin-21 (IL-21) can have both proinflammatory and immunosuppressive effects. The purpose of this study was to investigate the potential dual role of IL-21 in experimental arthritis in relation to Th17 cells. Antigen-induced arthritis (AIA) and chronic streptococcal cell wall (SCW) arthritis were induced in IL-21 receptor-deficient (IL-21R(-/-) ) and wild-type mice. Knee joints, synovial tissue, and serum were analyzed for arthritis pathology and inflammatory markers. During AIA and chronic SCW arthritis, IL-21R deficiency protected against severe inflammation and joint destruction. This was accompanied by suppressed serum IgG1 levels and antigen-specific T cell responses. Levels of IL-17 were reduced during AIA, and synovial lymphocytes isolated during SCW arthritis for flow cytometry demonstrated that mainly IL-17+ interferon-γ (IFNγ)-positive T cells were reduced in IL-21R(-/-) mice. However, during the acute phases of SCW arthritis, significantly higher joint swelling scores were observed, consistent with enhanced tumor necrosis factor and IL-6 expression. Interestingly, IL-21R(-/-) mice were significantly less capable of up-regulating suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 messenger RNA. IL-21 stimulation also affected the Toll-like receptor 2 (TLR-2)/caspase recruitment domain 15 response to SCW fragments in vitro, indicating that impaired SOCS regulation in the absence of IL-21 signaling might contribute to the increased local activation during SCW arthritis. In contrast to the proinflammatory role of IL-21 in adaptive immunity, which drives IL-17+IFN+ cells and joint pathology during chronic experimental arthritis, IL-21 also has an important immunosuppressive role, presumably by inhibiting TLR signaling via SOCS-1 and SOCS-3. If this dual role of IL-21 in various immune processes is present in human disease, it could make IL-21 a difficult therapeutic target in rheumatoid arthritis.

Is there a role for sulphasalazine in axial spondyloarthritis in the era of TNF inhibition? Data from the NOR-DMARD longitudinal observational study

The objectives of this study were to characterize patients with predominantly axial SpA who received SSZ as their first DMARD, compare the response to treatment in patients with and without peripheral disease and identify predictors of discontinuation of SSZ. We also investigated response to TNF inhibitor (TNFi) after SSZ failure. We included DMARD-naive patients with predominantly axial SpA starting SSZ or TNFi treatment from a Norwegian, multicentre longitudinal observational study (NOR-DMARD). In patients starting SSZ, we compared the 3-month responses between patients with and without swollen joints and identified predictors of discontinuation by Cox regression analysis. Sixty-six SSZ-treated patients later switched to a TNFi, and we compared their 3-month responses and drug survival to patients starting a TNFi as their first DMARD. Patients receiving SSZ (n = 181) as their first DMARD had shorter disease duration, were more frequently female and had more swollen joints than those starting TNFi (n = 543). There was a trend toward better 3-month responses to SSZ in patients with peripheral joint swelling, and they had significantly better 3-year drug survival than patients without swollen joints at baseline. Predictors of SSZ discontinuation were no peripheral joint swelling, higher CRP and higher BASDAI back pain score. TNFi response was similar in patients previously treated with SSZ, as in DMARD-naive patients. Our findings support current recommendations of SSZ as an optional treatment in SpA patients with peripheral disease, although overall responses were modest. Initial treatment with SSZ does not seem to impair later TNFi response.

The influence of immediate knee flexion on blood loss and other parameters following total knee replacement

In an initial randomised controlled trial (RCT) we segregated 180 patients to one of two knee positions following total knee replacement (TKR): six hours of knee flexion using either a jig or knee extension. Outcome measures included post-operative blood loss, fall in haemoglobin, blood transfusion requirements, knee range of movement, limb swelling and functional scores. A second RCT consisted of 420 TKR patients randomised to one of three post-operative knee positions: flexion for three or six hours post-operatively, or knee extension. Positioning of the knee in flexion for six hours immediately after surgery significantly reduced blood loss (p = 0.002). There were no significant differences in post-operative range of movement, swelling, pain or outcome scores between the various knee positions in either study. Post-operative knee flexion may offer a simple and cost-effective way to reduce blood loss and transfusion requirements following TKR. We also report a cautionary note regarding the potential risks of prolonged knee flexion for more than six hours observed during clinical practice in the intervening period between the two trials, with 14 of 289 patients (4.7%) reporting lower limb sensory neuropathy at their three-month review.

A1.24 Cilengitide reduces pannus formation and bone erosions in collagen induced arthritis

Background and ObjectivesRheumatoid arthritis (RA) is a chronic inflammatory disease characterised by synovial inflammation and osteoclast (OC) mediated bone erosions. AlphaVbeta3 integrin (αvβ3) is highly expressed in OCs and αvβ3...

Attenuation of the progression of adjuvant-induced arthritis by 3-aminobenzamide treatment

Rheumatoid arthritis (RA) is a disease that is still insufficiently controlled by current treatments. Poly(ADP-ribose) polymerase (PARP) inhibitors ameliorate immune-mediated diseases in several experimental models, including RA, colitis, experimental autoimmune encephalomyelitis and allergy. Together these findings showed that ADP-ribosylating enzymes, in particular PARP-1, play a pivotal role in the regulation of immune responses and may represent a noble target for new therapeutic approaches in immune-mediated diseases. The effect of 3-aminobenzamide (3-AB), an inhibitor of poly(ADP-ribose) synthetase activity, was evaluated in a mouse model of adjuvant-induced arthritis (AIA) on pro-inflammatory cytokines, adhesion molecules, inflammatory mediators and chemokine production/expression in serum and knee joint. Histopathological examination was also done on joint section. Our data demonstrates that 3-AB, 10mg/kg, intraperitoneally (i.p.) significantly reduces pro-inflammatory cytokine (IL-17, TNF-α and IL-2) and chemokine (MCP-1 and MIP-2) production/expression, accompanied by amelioration of the disease as indicated by reduced paw swelling and arthritic scores and was associated with a significant reduction of VCAM-1 and ICAM-1 expression in the knee joint. Moreover, the expression of inflammatory mediators (iNOS, COX-2, MMP-2, MMP-9) and joint histological inflammatory damage was also markedly decreased. The results of this study suggest that PARP-1 inhibitor may play a role in the inflammatory arthritic process after administration of 3-AB may be a beneficial therapeutic approach.

Effect of pulsed electromagnetic field therapy in patients undergoing total knee arthroplasty: a randomised controlled trial

PurposeIt has been reported that even one year after total knee arthroplasty (TKA), a relevant percentage of patients does not attain complete recovery and indicate unfavourable long-term pain outcome. We compared the clinical outcome of 33 patients undergoing TKA randomly assigned to the control or the pulsed electromagnetic field group (I-ONE therapy).MethodsI-ONE therapy was administered postoperatively four hours per day for 60 days. Patients were assessed before surgery and then at one, two and six months postoperatively using international scores.ResultsOne month after TKA, pain, knee swelling and functional score were significantly better in the treated compared with the control group. Pain was still significantly lower in the treated group at the six month follow-up. Three years after surgery, severe pain and occasional walking limitations were reported in a significantly lower number of patients in the treated group.ConclusionsAdvantages deriving from early control of joint inflammation may explain the maintenance of results at follow-up. I-ONE therapy should be considered an effective completion of the TKA procedure.

Abstract P6-08-04: Prognostic significance of quality-of-life scores in early stage and relapsed breast cancer: Results from seven randomized trials of the International breast cancer study group

Abstract We performed an individual patient meta-analysis to investigate the prognostic value of patient self-reported quality-of-life (QL) scores at baseline, and at several times prior to and following disease relapse on subsequent overall survival (OS) in seven randomized trials of the International Breast Cancer Study Group. Patients with early stage breast cancer who participated in randomized trials that compared adjuvant therapies, and who had subsequent disease relapse, completed QL assessments for physical well-being, mood, appetite, nausea and vomiting, arm swelling, flushing, coping effort, and utility at study entry, prior to and after disease relapse. We tested the relationships between baseline QL scores and OS using Cox regression analyses. We performed landmark analyses to assess the relationships between pre-relapse QL scores with OS using QL assessments at 1, 2 and 3 months prior to disease relapse, at the time of relapse and at two subsequent QL assessments where these were available. All Cox models were stratified by trial and included other factors related to QL and/or outcome. Among 8,024 patients, 3,834 (48%) had disease relapse after a median follow-up time of 12 years. Amongst these patients, QL score at baseline, and at 1, 2, and 3 months prior disease relapse were not significantly prognostic for OS. At disease relapse, scores for physical well-being (hazards ratio [HR] per 10 unit increase of QL score for death, 1.05; P = 0.003), mood (HR 1.05; P = 0.007), appetite (HR 1.08; P&amp;lt;0.001), and utility (HR 1.13; P = 0.008) were prognostic for subsequent OS. Nausea and vomiting (HR 1.05; P = 0.11), arm swelling (HR 1.00; P = 0.20), flushing (HR 1.01; P = 0.73), and coping effort (HR 1.02; P = 0.29) were not prognostic for subsequent OS. At post-relapse assessments at median times of 1 (HR 1.07; P&amp;lt;0.001), 6 (HR 1.08; P&amp;lt;0.001) and 10 months (HR 1.13; P&amp;lt;0.001) after disease relapse, scores for physical well-being showed increasing prognostic significance. Scores for mood, nausea and vomiting, appetite, coping effort and utility showed patterns similar to those for physical wellbeing, but scores for arm swelling and flushing were not prognostic for subsequent OS. These findings confirm and extend those of Coates et al. (J Clin Oncol 2000;18:3768 - 3774) based on two of the trials included in the present analysis. At baseline and prior to relapse, QL scores did not have any prognostic significance for subsequent OS. At and after disease relapse, QL scores substantially predicted for subsequent OS, with stronger association for QL scores later in the course of relapsed disease. Patient perception of the severity of underlying illness after relapse might be a potential reason that determines the reported QL scores and thus contributes to their prognostic significance. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-08-04.