Lindi Jiang

Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies.

Type 2 diabetes mellitus (T2DM) influences bone metabolism, but the relation of T2DM with bone mineral density (BMD) remains inconsistent across studies. The objective of this study was to perform a meta-analysis and meta-regression of the literature to estimate the difference in BMD (g/cm2) between diabetic and non-diabetic populations, and to investigate potential underlying mechanisms. A literature search was performed in PubMed and Ovid extracting data from articles prior to May 2010. Eligible studies were those where the association between T2DM and BMD measured by dual energy X-ray absorptiometry was evaluated using a cross-sectional, cohort or case–control design, including both healthy controls and subjects with T2DM. The analysis was done on 15 observational studies (3,437 diabetics and 19,139 controls). Meta-analysis showed that BMD in diabetics was significantly higher, with pooled mean differences of 0.04 (95% CI: 0.02, 0.05) at the femoral neck, 0.06 (95% CI: 0.04, 0.08) at the hip and 0.06 (95% CI: 0.04, 0.07) at the spine. The differences for forearm BMD were not significantly different between diabetics and non-diabetics. Sex-stratified analyses showed similar results in both genders. Substantial heterogeneity was found to originate from differences in study design and possibly diabetes definition. Also, by applying meta-regression we could establish that younger age, male gender, higher body mass index and higher HbA1C were positively associated with higher BMD levels in diabetic individuals. We conclude that individuals with T2DM from both genders have higher BMD levels, but that multiple factors influence BMD in individuals with T2DM.

Features of urate deposition in patients with gouty arthritis of the foot using dual‐energy computed tomography

To investigate features of urate deposition in gout and the association between these features and attacks of gouty arthritis using dual‐energy computed tomography (CT).

Evaluation of Clinical Measures and Different Criteria for Diagnosis of Adult-onset Still’s Disease in a Chinese Population

Objective. To determine the value of clinical measures in diagnosis of adult-onset Still’s disease (AOSD), and to identify the optimal set of proposed classification criteria, in a Chinese population. Methods. A total of 70 patients with AOSD and 140 non-AOSD inpatients with fever were retrospectively identified at Zhongshan Hospital, Shanghai, from January 2003 to December 2009. Clinical measures and 4 sets of diagnostic criteria (Yamaguchi, Calabro, Cush, and Reginato) were evaluated by sensitivity, specificity, positive/negative predictive value (PPV, NPV), and positive/negative likelihood ratio (PLR, NLR) for diagnosis of AOSD. Results. In our series, higher sensitivity included hyperpyrexia (temperature ≥ 39°C, 94.29%), arthralgia (80.0%), polymorphonuclear neutrophils (PMN) ≥ 75% (84.29%), serum ferritin ≥ 2-fold the upper normal value (90.0%), negative antinuclear antibodies (85.29%), and rheumatoid factor (84.38%); while higher specificity included transient erythema (98.57%), sore throat (85.0%), leukocytes ≥ 15,000/mm3 (87.86%), and PMN ≥ 85% (85.0%). Rash, arthralgia, and sore throat were found to have better sensitivity and specificity (PLR 3.29–4.86). Leukocytes ≥ 10,000/mm3, PMN ≥ 80%, and serum ferritin ≥ 5-fold the upper normal limit were set as critical points. The Reginato criteria set had the highest specificity, 99.29%. The Yamaguchi set had the highest sensitivity, 78.57%, with a better accuracy of 87.14%. Conclusion. The Yamaguchi diagnostic criteria had better accuracy in Chinese patients. Indicators such as rash, arthralgia, sore throat, leukocytes ≥ 10,000/mm3, PMN ≥ 80%, and serum ferritin ≥ 5-fold the upper normal limit were helpful for diagnosis of AOSD. We recommend using these indicators in combination instead of alone.

Dual-energy computed tomography for monitoring the effect of urate-lowering therapy in gouty arthritis

To investigate the relationships between changes in serum urate levels and dual‐energy computed tomography (DE‐CT) results during urate‐lowering therapy (ULT) and to investigate the effects of treatment duration and drugs on changes in DE‐CT results.

Dopamine receptor DR2 expression in B cells is negatively correlated with disease activity in rheumatoid arthritis patients

OBJECTIVE Dopamine receptor (DR) signaling is involved in the pathogenesis of autoimmune diseases. We aimed to measure the expression levels of DR1-5 on B cells from patients with rheumatoid arthritis (RA) and to analyze the relationship between DRs and clinical manifestations, inflammatory biomarkers, functional status and disease activity. METHODS A total of 29 patients with RA, 12 healthy donors and 12 patients with osteoarthritis (OA) were recruited in this study. Flow cytometry was used to measure the levels of DR1-5 expressed on B cells. The relationships between B cell DR expressions and clinical features in RA patients were analyzed using the Spearman correlation test. RESULTS The expression levels of B cell DR1-5 in both the RA and OA groups were lower than those in healthy controls. After 3 months of medication, all five receptors were elevated in RA patients, with DR2 and DR3 being significantly increased from the baseline. DR2 expression on B cells was negatively correlated with inflammatory biomarkers and disease activity. CONCLUSION RA patients had lower expression level of DR2 on B cells compared to the healthy controls, and the level of DR2 negatively correlated with the disease activity. DR2 and DR3 might be novel predictors of patient responses to disease modifying antirheumatic drug therapy.

The Risk Factors for Nosocomial Infection in Chinese Patients with Active Rheumatoid Arthritis in Shanghai

Objective. To analyse the potential risk factors of nosocomial infections in patients with active rheumatoid arthritis (RA). Methods. A total of 2452 active RA patients at Hospitals in Shanghai between January 2009 and February 2011 were analyzed. Their demographic and clinical characteristics were compared with those without infection, and the potential risk factors were determined by logistic regression analysis. Results. Multivariate analysis indicated the gender (OR = 0.70, 95% CI 0.53–0.92), duration in hospital (OR = 1.03 , 95%CI 1.01–1.05), number of organs involved (OR = 0.82, 95%CI 0.72–0.92), number of disease-modifying antirheumatic drugs ((DMARDs) (OR = 1.22, 95%CI 1.061–1.40)), corticosteroid therapy (OR = 1.02, 95%CI 1.01–1.03), peripheral white blood cell counts ((WBC) (OR = 1.04, 95%CI 1.00–1.08)), levels of serum albumin (OR = 0.98, 95%CI 0.97–0.99), and C-reactive protein ((CRP) (OR = 1.03 , 95%CI 1.01–1.04)) that were significantly associated with the risk of infections. Conclusion. The female patients, longer hospital stay, more organs involved, more DMARDs, corticosteroid usage, high counts of WBC, lower serum albumin, and higher serum CRP were independent risk factors of infections in active RA patients.

Comparing the usefulness of four imaging techniques in the same gouty arthritis patient.

Dear Editor, Gout is a paradoxical disease in that arthritis attacks are only intermittent, whereas the arthritis-causing uric acid is persistently in excess in the form of tophi. For each patient, the ultimate therapeutic ideal should be to completely eliminate all tophi. So far, clinicians have relied on physical examination and plain radiographs to assess the locations and sizes of gouty tophi.1 Published reports suggest that dual energy computed tomography (DECT), magnetic resonance imaging (MRI) and 2-fluoro-deoxy-d-glucose (FDG) positron emission tomography (PET) each offer a different perspective of gouty tophi.2 DECT is capable of discriminating urate from non-urate compounds.3,4 MRI is capable of delimiting the sizes of the tophi and their relationship to adjacent tissues.5 PET is capable of assessing the degree of inflammation.6 Because no study had used all four techniques concomitantly, no guidelines are available concerning their applications. In this paper, we used these four techniques to examine the same feet and knees of a patient with chronic tophaceous in gout. The results indicate two huge tophi that would have eluded detection and assessment by physical examination and plain radiographs alone in this patient. The patient is a 62-year-old man with intermittent gouty arthritis attacks of the joints of the lower extremities for 20 years. Physical examination showed tophi-like swelling at the left big toe, and minor joint swelling of both knees. Serum uric acid was 8.6 mg/L. The diagnosis of gout was confirmed by crystal examination. Plain radiographs and 3.0T MRI followed conventional methods. DECT and FDG-PET utilized the Siemens Somatom Definition Syngo 2010A and the Siemens Biograph 16 (Knoxville, TN, USA), respectively. Unsuspected from physical examination and plain radiographs, DECT shows a large urate tophus at the supra-patella region of the left knee, the length exceeding that of the patella (Fig. 1a), and having intense FDG signal in PET (Fig. 1c). X-ray shows only a small erosion to which the tophus is attached (Fig. 2c). The conventional MRI view shows only the inferior part of the tophus (Fig. 2a). The T2 sequences show that it is extra-articular (not shown). Equally surprising, although the posterior view of the DECT shows only scattered urate signals, MRI and PET reveal that they are part of another massive tophus (Figs 1b and ​and2b).2b). These features are not seen in the corresponding images of the right knee (not shown). Figure 1 Images of the left knee. Panels (a and b) are three-dimensional reconstructed dual energy computed tomography anterior and posterior views. Green color represents urate compound. Note large compact tophus above patella in (a) and scattered green patches ... Figure 2 Images of left knee. Panels (a and b) are T1-weighted magnetic resonance sagittal images. Arrow in panel (a) shows bone erosion and tophus. Arrow in panel (b) shows a homongenous mass compatible with the tophus in the positron emission tomography/computed ... For the tophus in the first big toe, this is visualized as soft tissue swelling and bone erosion on X-ray (Fig. 3a, left foot panel), and urate as well as fibrous mass on DECT (Fig. 3b left foot panel), and a heterogeneous mass on MRI (Fig. 3c). PET again shows high FDG signal (Fig. 3d). For comparison, Fig. 3a,b shows that there is no significant tophus on the right foot. Figure 3 Images of the feet. Panel (a) are plain radiographs. Arrows indicate soft tissue swelling corresponding to the tophi in the three-dimensional reconstruction of the dual energy computed tomography (DECT) image shown in panel (b). In panel (b), gouty tophi ... There are several surprising discoveries in this study. The first is that DECT shows a huge tophus attached superiorly to the left patella, the size of the tophus exceeding that of the patella. This is completely unsuspected by physical examination and plain radiograph alone. The extent of this tophus extends beyond the MRI field. This is because conventional MRI covers only the areas of the knee joint which are required in assessment of other knee pathologies. Hence, our MRI is able to visualize only the inferior half of this particular tophus. Our MRI does show that this supra-patella mass has intensity in T1 and T2 sequences compatible with those of urate tophi. Although less spectacular, the images around the left big toe also confirm that physical examination and plain radiography have greatly under-assessed the size of the tophus at that location. The second interesting finding in this study is that when we compare DECT to MRI, we notice that DECT does not necessarily provide all the information about the sizes of the tophi. MRI of the left knee reveals a large tophus situated in a posterior location. However, DECT in the same location reveals only mildly scattered urate compounds. Apparently, this tophus consists of more cellular or fibrous structures than urate crystals. The third and final contribution in this paper is that, similar to two other papers, PET does show that gout tophi reveal significant inflammation. This is compatible with the histology of recently reported tophi.7 How inflammation prevents the crystals from being solubilized remains an enigma. Since urate solubility is highly dependent on the pH of the environment, perhaps the inflammation and associated fibrosis creates a pH of the surrounding tissues high enough to protect the crystals from being rapidly dissolved. New techniques of visualizing pH in vivo would be a useful direction in future research.8

Treatment of Takayasu arteritis with the IL-6R antibody tocilizumab vs. cyclophosphamide

OBJECTIVE To evaluate the treatment effects of the IL-6R antibody tocilizumab and cyclophosphamide (CTX) in patients with Takayasu arteritis (TA) and explore the mechanism by analyzing their effects on various cytokines. METHODS AND MATERIALS This study included 9 TA patients treated with tocilizumab, 15 TA patients treated with CTX and 24 healthy controls. Treatment effects were evaluated based on: (1) Kerr score and Indian Takayasu Clinical Activity Score (ITAS2010), (2) improvement of previous lesions and occurrence of new vascular lesions on magnetic resonance angiography (MRA), (3) changes in various cytokine levels, (4) glucocorticoid sparing, and (5) adverse effects. ELISA was used to analyze the cytokine levels. RESULTS Before treatment, all the patients had active disease accompanied with elevated C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-6 and pentraxin-3 (PTX3). Moreover, an imbalance in the MMP-TIMP system was also observed in these patients. Among them, IL-6 and MMP-9 levels were significantly associated with vascular enhancement scores and stenosis scores, respectively. At 6months after treatment, improved clinical manifestations and glucocorticoids sparing were observed in both groups without any severe side effects. Although no significant improvement occurred in the vascular stenosis, thickness and enhancement scores in both groups, a more degree of decrease of ESR, CRP level, significantly decreased MMP-9 level and increased MMP-2 level were found in the tocilizumab group than in the CTX group. CONCLUSIONS The IL-6R antibody may be more effective in mitigating vascular inflammation and remodeling than CTX via inhibition of IL-6 and MMP-9.

Comparison of bi-exponential and mono-exponential models of diffusion-weighted imaging for detecting active sacroiliitis in ankylosing spondylitis

Background There has been a growing need for a sensitive and effective imaging method for the differentiation of the activity of ankylosing spondylitis (AS). Purpose To compare the performances of intravoxel incoherent motion (IVIM)-derived parameters and the apparent diffusion coefficient (ADC) for distinguishing AS-activity. Material and Methods One hundred patients with AS were divided into active (n = 51) and non-active groups (n = 49) and 21 healthy volunteers were included as control. The ADC, diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were calculated for all groups. Kruskal–Wallis tests and receiver operator characteristic (ROC) curve analysis were performed for all parameters. Results There was good reproducibility of ADC/D and relatively poor reproducibility of D*/f. ADC, D, and f were significantly higher in the active group than in the non-active and control groups (all P < 0.0001, respectively). D* was slightly but significant lower in the active group than in the non-active and control group (P = 0.0064, 0.0215). There was no significant difference in any parameter between the non-active group and the control group (all P > 0.050). In the ROC analysis, ADC had the largest AUC for distinguishing between the active group and the non-active group (0.988) and between the active and control groups (0.990). Multivariate logistic regression analysis models showed no diagnostic improvement. Conclusion ADC provided better diagnostic performance than IVIM-derived parameters in differentiating AS activity. Therefore, a straightforward and effective mono-exponential model of diffusion-weighted imaging may be sufficient for differentiating AS activity in the clinic.

The effects of dopamine receptor 2 expression on B cells on bone metabolism and TNF-α levels in rheumatoid arthritis

BackgroundDopamine receptor 2 (DR2) expressions on B cells from Rheumatoid arthritis (RA) patients has been found to be negatively correlated with disease activity and can potentially predict the response to treatment. This study aimed to investigate the role of B cell DR2 expression on bone remodeling in RA.MethodsPatients with RA (n = 14) or osteoarthritis (OA; n = 12), and healthy controls (n = 12) were recruited for this study. Dopamine receptor (DR) 2 expression was assessed using flow cytometry. Pro-inflammatory cytokines, including interleuin(IL)-1β, IL-6, IL-17, and tumor necrosis factor(TNF)-α, and bone turnovers, including osteocalcin (OC),serum procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (β-CTX), collagen type I cross-linked telopeptide (ICTP), as well as matrix metalloproteinase-3 (MMP-3) and osteoprotegerin (OPG) were measured by electrochemiluminescence, chemiluminescence, or enzyme-linked immunosorbent assay. DR2 expression on synovial B cells from 4 RA patients and 3 OA patients was detected by immunofluorescence.ResultsThere were more DR2+CD19+ B cells in synovial tissues from RA patients than in those from OA patients. The frequency of peripheral B cells that expressed DR2 was positively correlated with plasma TNF-α level. Levels of ICTP and MMP-3 were significantly higher, and OPG were lower in RA patients compared to those in the OA group and healthy controls (all P < 0.05).ConclusionThe frequency of B cells that expressed DR2 showed a correlation with levels of the pro-inflammatory cytokine TNF-α. DR2+CD19+ B cells in synovial tissues might have a role in bone metabolism and TNF-α production.