You Jung Ha

Targeted chemo-photothermal treatments of rheumatoid arthritis using gold half-shell multifunctional nanoparticles.

We have developed RGD-attached gold (Au) half-shell nanoparticles containing methotrexate (MTX) for the treatment of rheumatoid arthritis (RA), where MTX is the most widely used disease-modifying anti-rheumatic drug (DMARD) for the treatment of RA, and RGD peptide is a targeting moiety for inflammation. Upon near-infrared (NIR) irradiation, heat is locally generated due to Au half-shells, and the drug release rate is enhanced, delivering heat and drug to the inflamed joints simultaneously. RA is a chronic inflammatory disease characterized by synovial inflammation in multiple joints within the penetration depth of NIR light. When combined with NIR irradiation, these nanoparticles containing a much smaller dosage of MTX (1/930 of MTX solution) showed greater therapeutic effects than that of a conventional treatment with MTX solution in collagen-induced arthritic mice. This novel drug delivery system is a good way to maximize therapeutic efficacy and minimize dosage-related MTX side effects in the treatment of RA. Furthermore, these multifunctional nanoparticles could be applied to other DMARDs for RA or other inflammatory diseases.

The role of 18F-fluorodeoxyglucose–positron emission tomography in the assessment of disease activity in patients with Takayasu arteritis

OBJECTIVE The assessment of disease activity in Takayasu arteritis (TA) is difficult in clinical situations because clinical symptoms and laboratory parameters do not always reflect the actual inflammation of the arterial wall. We undertook this study to comprehensively investigate the role of (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in the assessment of disease activity in patients with TA. METHODS We performed a retrospective chart review of 53 FDG-PET scans in 38 patients with TA. We measured (18) F-fluorodeoxyglucose ((18) F-FDG) accumulation in the vascular wall of the large vessel using semiquantitative (visual grade) and quantitative (standard uptake value intensity) analyses. Clinical disease activity was evaluated based on the National Institutes of Health criteria for active TA, and erythrocyte sedimentation rates (ESRs) and C-reactive protein (CRP) levels were measured. RESULTS At baseline, active vascular (18) F-FDG uptake (visual grade ≥2) was observed in 18 of 24 patients with active disease and in 5 of 14 patients with inactive disease. There was a significant association between clinical disease activity and disease activity judged by FDG-PET (P = 0.008). Visual grade, standard uptake value intensity, and the number of vascular lesions with active (18) F-FDG uptake were significantly higher in patients with active disease and correlated well with the ESR and CRP levels. In 15 followup FDG-PET scans, the changes in visual grade, areas of active vascular (18) F-FDG uptake, and standard uptake value intensity reflected changes in clinical disease activity. CONCLUSION (18) F-FDG uptake was associated with clinical disease activity and markers of inflammation, and FDG-PET reflected changes in clinical disease activity in patients with TA. FDG-PET may be a useful tool for aiding in the assessment of disease activity in patients with TA.

The role of (18) F-fluorodeoxyglucose-positron emission tomography in the assessment of disease activity in patients with takayasu arteritis.

OBJECTIVE The assessment of disease activity in Takayasu arteritis (TA) is difficult in clinical situations because clinical symptoms and laboratory parameters do not always reflect the actual inflammation of the arterial wall. We undertook this study to comprehensively investigate the role of (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in the assessment of disease activity in patients with TA. METHODS We performed a retrospective chart review of 53 FDG-PET scans in 38 patients with TA. We measured (18) F-fluorodeoxyglucose ((18) F-FDG) accumulation in the vascular wall of the large vessel using semiquantitative (visual grade) and quantitative (standard uptake value intensity) analyses. Clinical disease activity was evaluated based on the National Institutes of Health criteria for active TA, and erythrocyte sedimentation rates (ESRs) and C-reactive protein (CRP) levels were measured. RESULTS At baseline, active vascular (18) F-FDG uptake (visual grade ≥2) was observed in 18 of 24 patients with active disease and in 5 of 14 patients with inactive disease. There was a significant association between clinical disease activity and disease activity judged by FDG-PET (P = 0.008). Visual grade, standard uptake value intensity, and the number of vascular lesions with active (18) F-FDG uptake were significantly higher in patients with active disease and correlated well with the ESR and CRP levels. In 15 followup FDG-PET scans, the changes in visual grade, areas of active vascular (18) F-FDG uptake, and standard uptake value intensity reflected changes in clinical disease activity. CONCLUSION (18) F-FDG uptake was associated with clinical disease activity and markers of inflammation, and FDG-PET reflected changes in clinical disease activity in patients with TA. FDG-PET may be a useful tool for aiding in the assessment of disease activity in patients with TA.

Differences in Clinical Manifestations and Outcomes between Adult and Child Patients with Henoch-Schönlein Purpura

We aimed to investigate differences in clinical manifestations and outcomes between adult and child patients with Henoch-Schönlein purpura (HSP), and to analyze the factors associated with poor prognosis for HSP nephritis. This retrospective 10-yr study enrolled 160 patients with HSP who visited Severance Hospital. Purpura was mostly detected in lower extremities, but purpura in upper extremities was more frequently observed in adults than children (41.7% vs 19.3%). Children had a greater frequency of arthralgia (55.4% vs 27.1%), while adults had a greater frequency of diarrhea (20% vs 1.6%). Anemia, elevated C-reactive protein, and level of IgA were more frequently observed in adults (25% vs 7.1%, 65.6% vs 38.4%, 26.3% vs 3.5%). Renal involvement in adults was more severe than in children (79.2% vs 30.4%). Chronic renal failure showed a significant difference in outcomes of HSP between adults (10.4%) and children (1.8%) after a follow up period of an average of 27 months. Furthermore, renal insufficiency at diagnosis was significantly related to the progression to chronic renal failure. Our results showed several differences in the clinical features of HSP between adults and children. Adults with HSP had a higher frequency of renal insufficiency and worse renal outcomes than children. Renal insufficiency at diagnosis might be of predictive value for the progression to chronic renal failure in HSP patients. Graphical Abstract

Serum calprotectin as a marker for disease activity and severity in adult-onset Still's disease.

Objective. Calprotectin is a calcium-binding cytosolic protein of the neutrophil, monocyte, and macrophage, and its secretion increases during activation of these cells. Our objective was to measure serum calprotectin concentrations in patients with adult-onset Still’s disease (AOSD) and to correlate serum calprotectin with the activity and severity of AOSD. Methods. We enrolled 25 patients with AOSD and 30 age- and sex-matched healthy controls. Thirty-one serum samples were obtained from patients with AOSD during active or inactive disease and were assayed for calprotectin by ELISA. Clinical and laboratory data related to disease activity and severity were collected at the same time, and systemic scores for disease severity were calculated. Results. Mean calprotectin levels in patients with AOSD were significantly higher than in controls (57.11 ± 25.38 ng/ml vs 34.90 ± 4.85 ng/ml, respectively; p < 0.05). Patients with active AOSD had a significantly higher mean calprotectin level than those with inactive disease (61.26 ± 25.59 ng/ml vs 35.32 ± 5.90 ng/ml; p < 0.05). Calprotectin levels decreased significantly after treatment in all 6 patients with AOSD from whom followup samples were obtained (p = 0.028). Serum calprotectin showed strong correlations with serum ferritin (r = 0.686, p < 0.001), lactate dehydrogenase (r = 0.647, p < 0.001), leukocyte count (r = 0.774, p < 0.001), aspartate aminotransferase (r = 0.387, p = 0.042), and C-reactive protein (r = 0.588, p = 0.001), but not with erythrocyte sedimentation rate, arginine aminotransferase, hemoglobin, or platelet count. Serum calprotectin showed a significant correlation with AOSD systemic scores, reflecting disease severity (r = 0.803, p < 0.001). Conclusion. Serum calprotectin increased in patients with AOSD, in close correlation with disease activity and severity. These findings suggest that serum calprotectin can provide a reliable clinical marker for monitoring the disease activity and severity of AOSD.

Plasma chemerin levels in rheumatoid arthritis are correlated with disease activity rather than obesity.

Joint Bone Spine - In Press.Proof corrected by the author Available online since jeudi 8 aout 2013

Delta neutrophil index as a marker for differential diagnosis between flare and infection in febrile systemic lupus erythematosus patients

* These authors contributed equally to this work. Fever is a common symptom of systemic lupus erythematosus (SLE), and because of this it is difficult to discriminate between SLE flare and infection. The delta neutrophil index (DNI), automatically determined by the ADVIA 2120 electronic cell analyzer, has been reported to reflect the fraction of circulating immature granulocytes and to be associated with the presence of infection. In this study, we investigated the utility of DNI in discriminating infections from SLE flares in febrile SLE patients. In total, 111 episodes in 92 febrile SLE patients were reviewed. The infection group showed significantly higher white blood cell counts, neutrophil counts, C-reactive protein and procalcitonin than the SLE flare group. Complement (C)3 and C4 levels were decreased significantly in the SLE flare group. Patients in the SLE flare group had significantly lower DNI than those in both infection groups, with or without bacteremia. In a multivariate logistic regression analysis, only DNI was a significant independent factor for the presence of infection (odds ratio (OR): 18.9). When we selected a DNI value of 2.8% as the cutoff for infection, SLE patients with DNI ≥ 2.8% were found to be at higher risk for infection than those with DNI < 2.8% (relative risk 8.48-fold). Our data suggest that DNI may be a marker to differentiate infections from SLE flares in febrile SLE patients.

Inflammatory Polyarthritis in a Patient with Psoriasis: Is It Psoriatic Arthritis or Rheumatoid Arthrirtis?

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. There are no generally accepted diagnostic criteria for PsA. Indeed, the diagnosis of this inflammatory arthritis is made by exclusion of other possible diseases and based upon immunologic, radiologic, and clinical features which are consistent with the diagnosis. Inflammatory arthritis in a patient with psoriasis can be an important clue for the diagnosis of PsA, but the possibility for diagnosis of other inflammatory arthritides ever remains. Herein we report a case of a female patient who was not diagnosed with PsA, but with rheumatoid arthritis, even though she had psoriasis.

Patients with early arthritis who fulfil the 1987 ACR classification criteria for rheumatoid arthritis but not the 2010 ACR/EULAR criteria

Recently, a joint working group of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) was formed to develop new classification criteria for rheumatoid arthritis (RA),1 2 and announced the 2010 ACR/EULAR classification criteria for identifying patients with early RA.3 The present study was performed in order to determine whether the newly developed 2010 ACR/EULAR criteria would include patients who were previously diagnosed with early RA according to the 1987 ACR criteria.4 We studied 170 patients with early RA patients, who had been classified as having RA according to the 1987 ACR criteria. Early RA was defined by less than 12 months of symptoms. The 2010 ACR/EULAR criteria were applied to patients at the exact time point when they were identified as fulfilling the 1987 ACR criteria. The clinical characteristics and laboratory findings …

Delta neutrophil index as an early marker for differential diagnosis of adult-onset Still's disease and sepsis.

Purpose To investigate clinical implications of delta neutrophil index (DNI) to discriminate adult onset Stills disease (AOSD) from sepsis. Materials and Methods We reviewed the medical records of 13 patients with AOSD and 33 gender and age-matched patients with sepsis. In all subjects, microbial tests were performed to exclude or confirm sepsis. All laboratory data were measured two or three times during the first 3 days and represented by their mean levels. DNI was measured automatically by ADVIA 2120 for the first 3 days. Results There were no significant differences in white blood cell counts, neutrophil proportion, erythrocyte sedimentation rate and C-reactive protein between two groups. AOSD patients had notably lower DNI than sepsis patients regardless of the presence of bacteremia or not. However, both DNI and ferritin were not significant independent factors for predicting sepsis in the multivariate logistic regression analysis. Meanwhile, the area under the receiver operating characteristic curve (AUROC) of DNI was slightly higher than that of ferritin. When we set DNI of 2.75% as the cut-off value for predicting sepsis, 11 (84.6%) of AOSD patients had a DNI value below 2.75% and 2 (15.4%) of them had a DNI over 2.75% (relative risk for sepsis 176). Conclusion We suggest that DNI may be a useful marker for differential diagnosis of AOSD from sepsis in the early phase as supplementary to ferritin.