Total knee arthroplasty and periprosthetic distal femoral fracture: looking beyond the osteoporosis to previous osteoporotic fracture.

Osteoporosis increases the risk of periprosthetic distal femoral fractures after TKA, especially in patients with a history of osteoporotic fractures. Therefore, careful assessment and proper treatment of osteoporosis need and the importance of taking osteoporotic medication needs to be recognized by the patients following primary TKA. PURPOSE: Osteoporosis is a risk factor for fractures, including those of the hip, vertebrae, and distal radius; however, the association between osteoporosis and periprosthetic fractures after total knee arthroplasty (TKA) has not been much investigated. Therefore, we aimed to investigate the association of the presence of systemic osteoporosis with periprosthetic fractures after TKA. METHODS: This study included 34 patients with periprosthetic fractures following primary TKA and 106 controls matched for age and sex. Bone mineral density was evaluated at the femoral neck, total hip, and lumbar spine using dual X-ray absorptiometry. Medical records were reviewed for age; sex; body mass index; smoking; rheumatoid arthritis, endocrine diseases, and cardiovascular diseases; history of glucocorticoid use; medication for osteoporosis; and history of previous osteoporotic fracture. In addition, anterior femoral notching after TKA was evaluated. Univariable and multivariable logistic regression analysis were used to determine factors associated with periprosthetic fracture. RESULTS: The prevalence of osteoporosis in the fracture group was higher than that in the control group (61.8% vs. 40.6%, p=0.045). The rate of medication for osteoporosis was significantly low in the fracture group (47.6 % vs 76.7%, p=0.026). History of previous osteoporotic fracture (odds ratio [OR], 9.1; p=0.015) and osteoporosis (OR, 3.6; p=0.013) were significant risk factors for periprosthetic fractures after TKA. Medication for osteoporosis could decrease the risk of periprosthetic fracture (OR 0.3; p=0.020). CONCLUSION: Osteoporosis is a major risk factor for periprosthetic distal femoral fractures after TKA. Therefore, careful assessment and proper treatment of osteoporosis need and the importance of taking osteoporotic medication needs to be recognized to the patients following primary TKA, especially in patients with a history of osteoporotic fracture. LEVEL OF EVIDENCE: Prognostic study, level III.

Clinical features and prognosis of patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.

Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) share common risk factors. They could therefore be expressed in a single patient. However, the prevalence, clinical characteristics and prognosis of individuals with comorbid IPF and COPD are not known. From 2003 to 2007, the Korean Interstitial Lung Disease Study Group created a register for idiopathic interstitial pneumonia using 2002 ATS/ERS (American Thoracic Society/European Respiratory Society) criteria. Of the 1546 IPF patients assessed, 143 had decreased lung function consistent with COPD (IPF-COPD). COPD was diagnosed based on age (≥40 years) and pulmonary function (forced expiratory volume in 1 sec [FEV1]/forced vital capacity [FVC] ratio < 0.7). The median age of the IPF-COPD group was 71.0 years (interquartile range 66.0-76.0); most patients were male (88.1%). FVC (%) was significantly higher in the IPF-COPD group; however, FEV1 (%) was significantly lower in the IPF-COPD group (P < 0.001). Diffusing capacity of the lung for carbon monoxide (DLCO) was not significantly different between the two groups. In survival analysis, age and FVC (%), but not COPD, were significantly associated with prognosis (respectively P = 0.003, 0.001 and 0.401). COPD severity was also not related to prognosis (P = 0.935). The prevalence of IPF-COPD was estimated to be ∼9.2% among all IPF patients; prognosis of patients with IPF-COPD was not worse than those with IPF alone. .

Renal outcome after kidney-transplantation in Korean patients with lupus nephritis.

We investigated renal outcome of kidney-transplantation in 19 Korean recipients with biopsy-proven lupus nephritis and compared it with 18 Korean age- and gender-matched recipients without lupus nephritis who were diagnosed with end-stage renal disease caused by renal diseases other than lupus nephritis in a single centre. We reviewed histological findings of kidneys and calculated cumulative dose of immunosuppressive agents. We assessed renal flare of systemic lupus erythematosus, recurrence of lupus nephritis and graft failure as prognosis. The mean age of recipients with lupus nephritis was 43.5 years and all patients were female. Six patients had class III, 10 had class IV and three had class V. There were no meaningful differences in demographic data, renal replacement modality, cumulative doses of immunosuppressants and prognosis between recipients with and without lupus nephritis. Eight patients experienced renal flare of systemic lupus erythematosus, but there were no cases of recurrence of lupus nephritis or graft failure in recipients with lupus nephritis. Kidney-recipients with class IV lupus nephritis exhibited a lower cumulative renal flare of systemic lupus erythematosus free survival rate than those with class III lupus nephritis. In conclusion, renal outcome of kidney-transplantation in patients with lupus nephritis is similar to that in those without lupus nephritis, and class IV was associated with renal flare of systemic lupus erythematosus.

Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein can reflect systemic lupus erythematosus activity.

Serum Mac-2-binding protein (M2BP) is elevated in various chronic inflammatory diseases, and evidence suggests that glycosylation of M2BP induces discrete biological effects. However, the role of serum M2BP in systemic lupus erythematosus (SLE) is still unclear. Recently, a Wisteria floribunda agglutinin-positive-M2BP (WFA+-M2BP) immunoassay has shown promise in detecting highly glycosylated M2BP. In this study, by using WFA+-M2BP immunoassay, we measured serum M2BP in 203 SLE patients and evaluated its clinical significance. Eighty patients were classified as having active SLE and 123 patients as having inactive SLE. The median serum M2BP was higher in patients with active SLE than in those with inactive SLE (2.1 vs. 0.9, p < 0.001). In multivariate linear regression analysis, serum M2BP, anti-dsDNA, C3 and erythrocyte sedimentation rate (ESR) were associated with SLEDAI-2K. Serum M2BP also strongly correlated with laboratory variables related to SLEDAI-2K, ESR and C-reactive protein. Furthermore, multivariate logistic regression analysis demonstrated that serum M2BP was useful in predicting active SLE. Finally, following immunosuppressive treatment, elevated serum M2BP significantly decreased along with improvement in disease activity. These findings suggest that serum M2BP might contribute to the inflammatory process in SLE, and measuring serum M2BP might be a useful marker to assess SLE disease activity.

Randomised controlled clinical trial of augmentation of the alveolar ridge using recombinant human bone morphogenetic protein 2 with hydroxyapatite and bovine-derived xenografts: comparison of changes in volume.

The aim of this randomised controlled clinical trial was to assess the early efficacy of bone morphogenetic protein-2 with hydroxyapatite granules (BMP-2/hydroxyapatite) on augmentation of the alveolar ridge, by comparing changes in volume with those associated with the use of an inorganic bovine-derived xenograft (BDX). We studied 20 patients who were divided into two groups using a table of random numbers, and BMP-2/hydroxyapatite and BDX were applied accordingly. Computed tomographic (CT) images and panoramic radiographs were obtained immediately after operation and four months later. CT images were reconstructed in three dimensions to measure volumetric changes, and linear measurements were made on panoramic images. The mean (SD) absorption rates for BMP-2/hydroxyapatite and BDX were 13.2 (8.8)% and 13.8 (20.5)%, respectively. While the mean value did not differ significantly between the two materials, the SD was higher in the BDX group than in the BMP-2/hydroxyapatite group. No clinically important complications occurred in either group. We conclude that both BMP-2/hydroxyapatite and BDX were effective in augmenting the alveolar ridge, but BMP-2/hydroxyapatite seemed to be more useful in complicated bone defects.

Single-stage cell-based cartilage repair in a rabbit model: cell tracking and in vivo chondrogenesis of human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel composite.

OBJECTIVE: Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have gained popularity as a promising cell source for regenerative medicine, but limited in vivo studies have reported cartilage repair. In addition, the roles of MSCs in cartilage repair are not well-understood. The purpose of this study was to investigate the feasibility of transplanting hUCB-MSCs and hyaluronic acid (HA) hydrogel composite to repair articular cartilage defects in a rabbit model and determine whether the transplanted cells persisted or disappeared from the defect site. DESIGN: Osteochondral defects were created in the trochlear grooves of the knees. The hUCB-MSCs and HA composite was transplanted into the defect of experimental knees. Control knees were transplanted by HA or left untreated. Animals were sacrificed at 8 and 16 weeks post-transplantation and additionally at 2 and 4 weeks to evaluate the fate of transplanted cells. The repair tissues were evaluated by gross, histological and immunohistochemical analysis. RESULTS: Transplanting hUCB-MSCs and HA composite resulted in overall superior cartilage repair tissue with better quality than HA alone or no treatment. Cellular architecture and collagen arrangement at 16 weeks were similar to those of surrounding normal articular cartilage tissue. Histological scores also revealed that cartilage repair in experimental knees was better than that in control knees. Immunohistochemical analysis with anti-human nuclear antibody confirmed that the transplanted MSCs disappeared gradually over time. CONCLUSION: Transplanting hUCB-MSCs and HA composite promote cartilage repair and interactions between hUCB-MSCs and host cells initiated by paracrine action may play an important role in cartilage repair.

Accuracy of Xpert(®) MTB/RIF assay compared with AdvanSure™ TB/NTM real-time PCR using bronchoscopy specimens.

BACKGROUND: The performance of Xpert(®) MTB/RIF assay, an automated nucleic acid amplification test (NAAT) that was developed for the detection of tuberculosis (TB), has been evaluated in various clinical settings. However, few studies have compared Xpert with other NAATs, especially its performance using lower respiratory tract specimens (LRTS). OBJECTIVE: To compare the practical diagnostic performance of the Xpert assay with that of the AdvanSure™ TB/NTM RT-PCR kit in the detection of pulmonary TB (PTB), using LRTS obtained through bronchoscopy. RESULTS: Of 249 patients included, 105 had culture-confirmed PTB. Using culture as reference, the overall sensitivity of Xpert and AdvanSure was respectively 92.4% and 83.8%. When acid-fast bacilli smear results were taken into consideration, the sensitivity of Xpert for smear-positive and smear-negative LRTS was respectively 100% and 88.9%, while that of the AdvanSure was 100% and 76.4%. Xpert showed better results than AdvanSure in terms of sensitivity in smear-negative LRTS (P = 0.012), but no difference in smear-positive LRTS. CONCLUSIONS: Xpert may be advantageous in the detection of PTB using LRTS, particularly in low microbiological burden settings.

Effect of Lactobacillus plantarum CJLP243 on the growth performance and cytokine response of weaning pigs challenged with enterotoxigenic Escherichia coli.

The purpose of the present study was to evaluate the effect of diets containing Lactobacillus plantarum CJLP243 on the growth and cytokine response of weaning pigs (Sus scrofa) challenged with enterotoxigenic Escherichia coli (ETEC). In a 28-d experiment (14 d before and 14 d after challenge), a total of 108 pigs at 20 ± 1 d of age were allotted to 1 of 6 diets. These were a control diet without ETEC challenge (CON) and 5 treatment diets with ETEC challenge, including a control diet with ETEC challenge (negative control, NC); a positive control diet containing antibiotics (PC); control diet plus (10(8), 10(9), or 10(10)) cfu/kg L. plantarum CJLP243 (T1, T2, and T3, respectively). After challenge, NC showed the least ADFI, whereas PC and T3 had the greatest ADFI (P = 0.002). The ADG of PC, T2, and T3 were greater (P = 0.001) than that of CON, NC, and T1 during wk 1 to wk 2. During wk 3 to wk 4, a marked decline was seen in NC (P = 0.001) compared with CON, whereas PC and T3 showed increased ADG (P = 0.001). The overall ADG of PC and T3 were greater (P < 0.001) than the remaining groups. The PC and T3 had the greatest G:F during the second 2 wk (P = 0.002), and the overall 4-wk experimental period (P = 0.003). At 3 h after challenge, all groups except CON had greater rectal temperatures (RT; P < 0.05). The RT decreased to prechallenge temperatures at 9 h (PC and T3), 24 h (T1 and T2), and remained increased until d 7 in NC. At 7 and 14 d postinfection, the number of animals detected positive for ETEC by PCR assay was the greatest in NC; however, the PC group had the fewest ETEC-positive animals (P < 0.05), which was similar to T3. All challenged pigs, except T2, had greater concentrations of serum haptoglobin compared with CON, with the greatest concentration observed in NC (P < 0.001). Challenged pigs had increased serum concentrations of tumor necrosis factor alpha (TNF-α) 3 to 48 h postinfection, with the greatest concentration of TNF-α at 48 h observed in NC (P < 0.05). Similarly, greater (P < 0.05) serum concentrations of interferon-γ were observed for 9 h (T1 and T3), 24 h (T2 and PC), and 48 h (NC) postinfection. The serum concentration of IL-6 increased (P < 0.05) for 3 h in T3 and 24 h in NC. In conclusion, our findings suggest that L. plantarum CJLP243, at a concentration of 10(10) cfu/kg, may serve as a potential alternative to antibiotic supplementation to improve the growth and health performance of weaning pigs, especially during acute inflammation of the gut after bacterial infections.

Long-term clinical outcomes and risk factors for the occurrence of post-operative complications after cardiovascular surgery in patients with Behçet's disease.

OBJECTIVES: Cardiovascular surgery in patients with Behçet's disease (BD) frequently leads to postoperative complications such as anastomotic leakage, occlusion or pseudoaneurysm. We evaluated the clinical outcomes and related risk factors of postoperative complications in BD patients undergoing cardiovascular surgeries, as well as the long-term efficiency of postoperative immunosuppressive treatment. METHODS: Forty-one patients with BD who had undergone cardiovascular surgery between 1990 and 2009 were studied. We evaluated the patients' clinical data, postoperative complications, and survival rate. Risk factors related to the occurrence of postoperative complications were identified by univariate analysis using the Kaplan-Meier method with the log-rank test and multivariate analysis using the Cox proportional hazards regression model. RESULTS: Fifty-nine operations were performed in 41 patients. During the mean follow-up period of 65.3±48.1 months, complications such as paravalvular leakage, dehiscence, fistula, graft occlusion, or pseudoaneurysm occurred in 29 operations (49.2%). The cumulative occurrence rate of postoperative complication was 10.2% at three months, 32.8% at 12 months, and 43.8% at 24 months. Upon univariate analysis, young age, high Creactive protein levels, lack of postoperative immunosuppression, and short disease duration were identified as significant factors responsible for the occurrence of postoperative complications. In multivariate analysis, postoperative immunosuppression was found to independently lower the risk of complications. The 5-year survival rate was significantly higher in patients with postoperative immunosup immunosuppression than in those without (84.5% vs. 45.0%, p=0.011). CONCLUSIONS: The present study suggests that postoperative immunosuppressive therapy after cardiovascular surgeries in BD patients is important for reducing the development of serious postoperative complications.

Effect of alendronate on healing of extraction sockets and healing around implants.

OBJECTIVES: The purpose of this study was to evaluate the effect of alendronates on healing of extraction sockets and healing around implants in the maxilla of rats. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were used. The rats in bisphosphonate group were subcutaneously injected with alendronate (5.0 mg kg(--1)) three times a week for 4 weeks. Both sides of the maxillary first molars were extracted, and customized titanium implants (Ø1.5 × 2.0 mm) were placed immediately into one side. Rats were killed at 3, 7, 14, or 28 days following surgery. RESULTS: New bone formation in extraction sockets, bone area around the implant site, and bone-implant contact were not delayed in the bisphosphonate group. The tartrate-resistant acid phosphatase positive cell count did not differ between bisphosphonate and control groups; however, empty lacunae were observed significantly more in bisphosphonate group. The differences in empty lacunae were shown at different time points between the implant sites and extraction sites: at 7 days after extraction, and at 14 and 28 days after implantation. CONCLUSIONS: Alendronates seemed to decrease bone resorption but not to decrease bone formation. Empty lacunae were observed significantly more at later time points in implant sites compared to extraction sockets.

Peripheral blood stem cell mobilisation by granulocyte-colony stimulating factor in patients with acute and old myocardial infarction for intracoronary cell infusion.

BACKGROUND/AIMS: Peripheral blood stem cells (PBSC) are one of the most promising stem cell sources for treatment of ischaemic heart disease. However, the experience of mobilisation and collection of PBSC using granulocyte-colony stimulating factor (G-CSF) in patients with myocardial infarction (MI) is still limited. We report our experiences with the feasibility and safety of collection of mobilised PBSC with G-CSF in MI patients, and the influence of acute ischaemia on efficacy of PBSC collection. METHODS: 74 patients with acute or old myocardial infarction (AMI vs OMI, n = 46 and n = 28) underwent PBSC collection after administration of G-CSF twice a day at a dose of 5 microg/kg for 3 days. Flow cytometric analysis of cell surface markers was performed. RESULTS: No evidence of inflammation or ischaemia was observed during G-CSF mobilisation and PBSC collection. The yield of CD34(+) cells was 12.9 (SD 15.92) x10(9)/l (5.04% (5.30%) of total cells) with a product volume of 37.9 (8.4) ml after 5650 (987) ml of blood were processed during PBSC collection. Stem cell mobilisation and collection by G-CSF is more efficient in AMI than in OMI, and proportions of cells positive for VE-cadherin or KDR/CD34 are significantly greater in AMI than in OMI (p<0.01). CONCLUSION: We could obtain sufficient numbers of PBSC for intracoronary infusion with the G-CSF-based mobilisation strategy without complications even in patients with MI. PBSC collection after mobilisation with G-CSF is a safe and feasible method of stem cell collection for therapeutic purpose in patients with MI.

Bortezomib attenuates murine collagen-induced arthritis.

OBJECTIVES: Nuclear factor kappa B (NF-kappaB) is a major regulator of pivotal proinflammatory cytokines in the pathogenesis of rheumatoid arthritis (RA). Bortezomib inhibits NF-kappaB activation by blocking the degradation of the NF-kappaB inhibitor, I-kappaB. In this study, the efficacy of bortezomib on murine collagen-induced arthritis (CIA) was investigated. METHODS: Thirty-five male DBA/1 mice were divided into five groups. All mice except controls were injected with type II collagen. Mice in the bortezomib-treated groups were injected intraperitoneally with 0.01, 0.1 and 1 mg/kg bortezomib twice a week for 2 weeks. Controls and mice in the untreated group were also injected intraperitoneally with phosphate-buffered saline in the same manner. Arthritis score and paw thickness were measured and histopathological assessment of joint sections was performed. The expression of proinflammatory cytokines and enzymes was evaluated by immunohistochemical staining. Joint destruction was confirmed using three-dimensional micro-computerised tomography (CT). Blood cells were counted and liver and kidney functions were monitored. RESULTS: Bortezomib significantly attenuated the severity of arthritis and histopathological findings in CIA mice. The expression of tumour necrosis factor alpha, IL-1beta, IL-6, matrix metalloproteinase 3, cyclooxygenase 2 and inducible nitric oxide synthase decreased in bortezomib-treated mice compared with untreated mice. In addition, micro-CT confirmed that bortezomib reduced joint destruction. No adverse effects in blood cells, liver or kidneys were observed with bortezomib treatment. CONCLUSIONS: These data suggest that bortezomib may play an anti-inflammatory role in the pathophysiology of RA and serve as a new therapeutic modality for RA.

Relationship of angiogenic factors to disease activity and radiographic damage in rheumatoid arthritis.

OBJECTIVE: To determine the association between angiogenic factor mRNA expression and disease activity and radiographic damage in patients with rheumatoid arthritis (RA). METHODS: We enrolled 42 RA patients and assessed their disease activity (DAS28) and Larsen scores. We used a semi-quantitative reverse transcriptase-polymerase chain reaction to measure levels of angiogenin, endoglin, survivin and angiomotin mRNA in peripheral blood mononuclear cells (PBMCs) from 42 patients and in fibroblasts-like synoviocytes (FLS) from 14 RA patients. Then, we compared the angiogenic factor mRNA expression levels and parameters for disease activity and radiographic damage between RA patients and 42 healthy controls. We also compared the mRNA levels from FLS between 14 RA patients and 12 osteoarthritis (OA) patients. RESULTS: PBMCs from RA patients showed increased expression of survivin and angiomotin mRNA compared to controls, while rheumatoid FLS showed increased expression for all genes tested compared to OA FLS. Angiogenin, endoglin, and angiomotin mRNA levels of PBMCs did not show any significant correlation with DAS28, but the survivin mRNA level in PBMCs showed a significant positive correlation with DAS28 (p=0.003) and Larsen scores (p=0.012). Survivin was the only angiogenic factor that showed a significant association with the Larsen score. CONCLUSION: The systemic and local production of angiogenic factors are increased in patients with RA and, of the genes tested in this study, survivin gene expression correlated well with disease activity and radiographic damage in patients with RA.

Osteopontin might be involved in bone remodelling rather than in inflammation in ankylosing spondylitis.

OBJECTIVES: To determine whether osteopontin (OPN) is increased in patients with AS and to investigate its relationship to inflammatory disease activity and bone remodelling process. METHODS: This cross-sectional study included 30 patients with AS and 23 age- and sex-matched healthy controls. We assessed clinical characteristics and laboratory parameters including the ESR, CRP, lipid profiles, the Bath AS disease activity index (BASDAI) and the Bath AS radiographic index (BASRI). To evaluate bone metabolism, we tested ALP, OCN and C-telopeptide of type I collagen (CTX-I). Plasma levels of OPN, TNF-alpha and IL-6 were measured by ELISA, and mRNA expression in peripheral blood mononuclear cells (PBMCs) was performed by RT-PCR. Changes in OPN level were also evaluated in eight patients after the treatment with a TNF-alpha blocker. RESULTS: Patients with AS had significantly higher plasma OPN, TNF-alpha and IL-6 levels and more mRNA expression than healthy controls. Plasma OPN levels were correlated with serum ALP, OCN and CTX-I levels, but not with ESR, CRP, lipid profiles, BASDAI or BASRI. Treatment with a TNF-alpha blocker did not alter OPN levels, although it reduced the disease activity. CONCLUSIONS: Patients with AS had higher levels of OPN compared with controls. The plasma OPN level was correlated with serum ALP, OCN and CTX-I levels, but not with disease activity in AS. OPN might be involved in bone remodelling rather than in inflammation in AS.

Adiponectin mitigates the severity of arthritis in mice with collagen-induced arthritis.

OBJECTIVE: Adiponectin (AD) is considered an inflammation modulator. In this study, we investigated the effect of AD on rheumatoid arthritis (RA) using a collagen-induced arthritis (CIA) mouse model and RA synovial fibroblasts (RASF). METHODS: Fifteen DBA/1 mice were divided into three groups. All mice, except the control group, were injected with type II collagen. AD was intra-articularly injected in the left hind legs after arthritis development (the AD-treated group). The severity of the arthritis was measured using an arthritis score and paw thickness. A histopathological assessment of joint sections was performed by haematoxylin/eosin (H&E) staining. Tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and matrix metalloproteinase (MMP)-3 expression was evaluated by immunohistochemical staining in the CIA mice. Synovial tissue was obtained from four RA patients during total joint replacement. RASF cultures were established from this tissue. RASF were pretreated with AD and stimulated by TNFalpha or IL-1beta. TNFalpha, IL-1beta, IL-6, and MMP-3 production was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). RASF proliferation was evaluated using the MTT assay. RESULTS: AD significantly mitigated the severity of the arthritis and histopathological findings indicative of RA in CIA mice. TNFalpha, IL-1beta, and MMP-3 expression decreased, but IL-6 expression in AD-treated joint tissues increased. Moreover, AD reduced TNFalpha, IL-1beta, and MMP-3 expression in stimulated RASF and increased IL-6 expression in IL-1beta-stimulated RASF. AD significantly inhibited IL-1beta-induced RASF proliferation, despite increased IL-6 expression. CONCLUSION: These data suggest that AD may play an anti-inflammatory role in the pathophysiology of RA.

Relationship of serum TWEAK level to cytokine level, disease activity, and response to anti-TNF treatment in patients with rheumatoid arthritis.

OBJECTIVES: To determine the serum concentration of tumour necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) in patients with rheumatoid arthritis (RA) and to investigate the relationship between TWEAK level and disease activity, proinflammatory cytokine levels, and response to anti-TNF treatment. METHODS: Serum samples from 40 patients with RA, 40 patients with ankylosing spondylitis (AS), and 40 healthy subjects were collected. Serum samples from 26 patients with RA who received etanercept treatment were also collected in the 12th week of etanercept therapy. Serum TWEAK, TNFalpha, and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay (ELISA), and disease activity of RA was assessed according to the 28-joint count Disease Activity Score (DAS28). RESULTS: Patients with RA had significantly higher serum levels of TWEAK, TNFalpha, and IL-6 compared with controls (p<0.05). Patients with AS also had significantly higher serum levels of TNFalpha and IL-6 (p<0.05), but their serum TWEAK levels were not different from those of the controls. In patients with RA, serum TWEAK levels correlated with DAS28 (r(2) = 0.452, p = 0.012) and TNFalpha levels (r(2) = 0.653, p<0.001) but not with IL-6 levels. Among RA patients who were treated with etanercept, responders showed a significant decrease in serum TWEAK levels at the 12th week of treatment, whereas TWEAK levels in nonresponders were not different from their baseline levels. CONCLUSIONS: Serum levels of TWEAK were significantly elevated in patients with RA, and reflected disease activity and short-term response to etanercept treatment.

Restoration of left ventricular synchronous contraction after acute myocardial infarction by stem cell therapy: new insights into the therapeutic implication of stem cell therapy for acute myocardial infarction.

OBJECTIVE: To evaluate the effects of stem cell therapy on restoration of the left ventricular (LV) synchronous contraction in patients with acute myocardial infarction (AMI). METHODS: 40 patients with AMI who underwent successful coronary revascularisation were randomly allocated to the cell infusion or the control group. Evaluations were performed with echocardiographic tissue synchronisation imaging to determine LV dyssynchrony and with cardiac magnetic resonance imaging to estimate LV ejection fraction (LVEF) at baseline and at 6 months. To quantify the severity of systolic LV dyssynchrony, the standard deviations of time to peak systolic velocity of the 12 LV segments (Ts-SD) were calculated. RESULTS: At 6 months, greater improvements of Ts-SD (DeltaTs-SD: -45.0 (40.2) vs 5.0 (39.9) ms, p<0.001) and LVEF (DeltaLVEF: 6.8% (9.1%) vs -0.2% (6.9%), p = 0.015) relative to the corresponding baseline values were observed in the cell infusion group than in the control group. By multivariate analysis, DeltaTs-SD and baseline LVEF emerged as the independent determinants of LVEF improvement and cell infusion, and baseline Ts-SD as the determinant of DeltaTs-SD improvement. Maximal exercise capacity measured by symptom-limited treadmill testing correlated well with Ts-SD but not with LVEF at 6 months of follow-up. CONCLUSION: Stem cell therapy had a favourable effect on the restoration of LV synchronous contraction in patients with AMI.

Effects of stem cell therapy with G-CSF on coronary artery after drug-eluting stent implantation in patients with acute myocardial infarction.

OBJECTIVE: The effects of stem cell therapy on the coronary vasculature were investigated in patients with acute myocardial infarction who underwent peripheral blood stem cell (PBSC) therapy in the MAGIC Cell-3-DES study. METHODS: Among 50 patients with acute myocardial infarction who underwent either sirolimus-eluting stent or paclitaxel-eluting stent implantation for the culprit lesion, intravascular ultrasound was analysed in 36 patients (cell infusion: n = 19 and control: n = 17). In the cell infusion group, PBSCs mobilised by granulocyte-colony stimulating factor were delivered via intracoronary infusion into infarcted myocardium. Proximal and distal reference segments, and stented segments, were evaluated with intravascular ultrasound at immediate post-intervention and 6-month follow-up, respectively. RESULTS: In the proximal and distal reference segments, the serial changes of lumen area, vessel area, and plaque plus media area were not significantly different between the cell infusion and the control groups. Within stented segments, mean neointimal area was similar in the two groups (cell infusion: 0.2 (SD 0.5) mm(2) vs control: 0.3 (SD 0.4) mm(2), p>0.05). However, there was a significant increase in mean peri-stent area of stented segment in the cell infusion group compared with the control group (0.7 (SD 1.4) mm(2) vs -0.1 (SD 1.2) mm(2), p<0.05). This difference mainly came from paclitaxel-eluting stent-implanted patients. CONCLUSION: Intracoronary infusion of PBSCs mobilised with G-CSF does not aggravate de novo atherosclerotic lesion and neointimal hyperplasia with DES implantation. However, it may induce peri-stent tissue growth at the stented segment, especially in patients receiving PES. Its clinical significance needs to be evaluated with long-term follow-up.

Dermatopathic lymphadenopathy in a patient with adult onset Still's disease.

Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown cause characterized by high fever accompanied by systemic manifestations. Since AOSD consists of heterogeneous symptoms and has no definite diagnostic tool, the diagnosis is based upon exclusive criteria. Dermatopathic lymphadenopathy (DL) is characterized by a localized paracortical proliferation of histiocytes and deposition of melanin in the lymph nodes. DL is not only a reactive hyperplasia of the lymph nodes, but has also been reported to be associated with hematological malignancies such as cutaneous T cell lymphoma (CTCL) and Hodgkin's lymphoma. It is therefore important to evaluate CTCL or Hodgkin's lymphoma in a patient with DL, in order to both rule out hematological malignancy and diagnose AOSD. In this report, we first describe a 37-year-old patient with AOSD whose biopsy of lymph node was proved to be DL.

Serum leptin levels correlate with interleukin-6 levels and disease activity in patients with ankylosing spondylitis.

OBJECTIVE: To determine whether serum leptin levels are elevated in men with ankylosing spondylitis (AS) and whether the levels correlate with serum cytokine profiles and disease activity of AS. METHODS: Forty-two male patients with newly diagnosed AS were enrolled. Their Bath AS Disease Activity Index (BASDAI), body mass index (BMI), and acute phase reactants, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, were assessed. Serum leptin levels were determined using radioimmunoassay (RIA) and serum cytokine profiles, including tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, and interferon (IFN)-gamma, were determined using enzyme-linked immunosorbent assay (ELISA). These results were compared with those from 42 age-matched healthy men. After a follow-up period of 31.0+/-20.1 months, clinical and biochemical variables were reassessed in the men with AS. RESULTS: At baseline, patients with AS had significantly elevated serum levels of leptin, leptin adjusted for BMI (leptin/BMI), TNFalpha, and IL-6, but not IFN-gamma, as compared to the controls. Serum leptin/BMI levels correlated well with IL-6 levels, and both leptin/BMI and IL-6 levels correlated well with BASDAI and CRP levels in patients with AS. The changes in leptin/BMI and IL-6 levels between the baseline and follow-up measurements correlated well with one another (p<0.05) and both correlated well with the changes in BASDAI (p<0.05). CONCLUSION: Serum leptin/BMI levels were increased and significantly associated with IL-6 levels and disease activity in men with AS, suggesting a possible role for leptin in the inflammatory reactions of AS.