Ki Won Moon

The Efficacy of Diacerein in Hand Osteoarthritis: A Double-Blind, Randomized, Placebo-Controlled Study

BACKGROUND Diacerein is a drug used in osteoarthritis (OA) that elicits an inhibitory effect on interleukin-1 and metalloproteases. Although diacerein has shown modest efficacy and safety in the treatment of knee and hip OA, there have been no placebo-controlled clinical trials for hand OA. OBJECTIVE The aim of the current study was to investigate the efficacy and tolerability of diacerein in patients with hand OA. METHODS Patients fulfilling the American College of Rheumatology criteria for hand OA participated in this randomized, double-blind, placebo-controlled study. Eligible patients were >40 years of age, had at least 1 tender joint, and had a joint pain visual analog scale of >30 mm. Patients received diacerein (50 mg) or placebo BID for 12 weeks. The primary end point was the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain score at 4 weeks. Secondary end points were AUSCAN pain score at 12 weeks and AUSCAN physical function and stiffness score, patient and physician global assessment, functional index of hand OA scores, and multidimensional health assessment questionnaire results at 4 weeks and 12 weeks. RESULTS Eighty-six Korean patients were enrolled (42 diacerein, 44 placebo). The intention-to-treat and per-protocol analyses revealed no significant differences between the 2 groups in terms of change in AUSCAN pain score at 4 weeks, except for improvement in physician global assessment at 4 weeks (per-protocol analysis, P = 0.004). The safety profile of diacerein was comparable to placebo, except for frequent discoloration of the urine (88% vs 20%). CONCLUSION These results suggest that diacerein 50 mg BID may be ineffective in controlling the symptoms of hand OA. ClinicalTrials.gov identifier: NCT00685542.

Sonography of the first metatarsophalangeal joint and sonographically guided intraarticular injection of corticosteroid in acute gout attack.

The aims of this study were to identify the characteristic ultrasound (US) findings of the first metatarsophalangeal joint (MTPJ1) in acute gout attack and to evaluate the efficacy and safety of US‐guided intraarticular corticosteroid injection of the MTPJ1.

Risk factors for acute kidney injury by non-steroidal anti-inflammatory drugs in patients with hyperuricaemia

OBJECTIVE NSAIDs are commonly prescribed to control gout attacks in patients with hyperuricaemia. We investigated risk factors for NSAID-induced acute kidney injury (AKI) in patients with hyperuricaemia. METHODS We identified 328 patients with hyperuricaemia treated with NSAIDs at Seoul National University Hospital between December 1998 and January 2008 to investigate risk factors for NSAID-induced AKI. The risk factors evaluated included age, sex, BMI, comorbidity, NSAID COX-2 selectivity, baseline glomerular filtration rate (GFR), serum uric acid, serum albumin, haemoglobin level, ratio of blood urea nitrogen and serum creatinine and the use of allopurinol. After extracting possible risk factors through univariate analysis, multivariate logistic regression analysis was performed with backward selection to derive a risk model for NSAID-induced AKI in patients with hyperuricaemia. RESULTS Thirty (9.1%) NSAID users developed AKI. Univariate analysis revealed that old age (P = 0.008), low GFR (P = 0.001), low serum albumin (P < 0.001) and low haemoglobin levels (P < 0.001) were possible risk factors. Multivariate logistic regression analysis showed that low baseline GFR [odds ratio (OR) 4.86, 95% CI 1.27, 18.55, P = 0.021, for GFR 15-29 vs ≥60 ml/min/1.73 m(2)] and low serum albumin (OR 4.43, 95% CI 1.82, 10.80, P = 0.001, for albumin ≤4 vs >4 g/dl) are risk factors for NSAID-induced AKI in patients with hyperuricaemia. CONCLUSION Low GFR and low serum albumin are risk factors for AKI in hyperuricaemic patients treated with NSAIDs. Our results suggest that NSAIDs should be used with caution in patients with low serum albumin.

CD99 inhibits CD98-mediated β1 integrin signaling through SHP2-mediated FAK dephosphorylation

The human CD99 protein is a 32-kDa type I transmembrane glycoprotein, while CD98 is a disulfide-linked 125-kDa heterodimeric type II transmembrane glycoprotein. It has been previously shown that CD99 and CD98 oppositely regulate β1 integrin signaling, though the mechanisms by which this regulation occurs are not known. Our results revealed that antibody-mediated crosslinking of CD98 induced FAK phosphorylation at Y397 and facilitated the formation of the protein kinase Cα (PKCα)-syntenin-focal adhesion kinase (FAK), focal adhesions (FAs), and IPP-Akt1-syntenin complex, which mediates β1 integrin signaling. In contrast, crosslinking of CD99 disrupted the formation of the PKCα-syntenin-FAK complex as well as FA via FAK dephosphorylation. The CD99-induced dephosphorylation of FAK was apparently mediated by the recruitment of Src homology region 2 domain-containing phosphatase-2 (SHP2) to the plasma membrane and subsequent activation of its phosphatase activity. Further consequences of the activation of SHP2 included the disruption of FAK-talin and talin-β1 integrin interactions and attenuation in the formation of the IPP-Akt1-syntenin complex at the plasma membrane, which resulted in reduced cell-ECM adhesion. This report uncovers the molecular mechanisms underlying the inverse regulation of β1 integrin signaling by CD99 and CD98 and may provide a novel therapeutic approach to treat inflammation and cancer.

Clinical and Laboratory Characteristics and Mortality in Korean Patients with Systemic Sclerosis: A Nationwide Multicenter Retrospective Cohort Study

Objective. We aimed to investigate demographic and clinical features and predictors of mortality in Korean patients with systemic sclerosis (SSc). Methods. We performed a retrospective multicenter medical chart review in Korean patients diagnosed with SSc from 1986 to 2016 at 11 university hospitals representing each geographic area of Korea. SSc patients were defined according to the American College of Rheumatology preliminary classification criteria and subtyped as limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc. Results. We enrolled 751 patients (female, 86.7%; mean age at diagnosis, 48.9 yrs). The most common organ involvement was interstitial lung disease (52.7%), followed by gastroesophageal reflux disease (32.9%) and pulmonary arterial hypertension (13.6%). Patients with lcSSc were more common than those with dcSSc (64.8 vs 35.2%), whereas anti-Scl-70 and anticentromere antibody positivity were identified in 302 (42.5%) and 175 (25.5%) patients, respectively. In the 46 (6.1%) patients who developed a malignancy, lung cancer (23.9%) was the most common diagnosis, followed by gastric (13%) and breast cancer (13%). During the study period, 57 (7.6%) patients died, and the 5- and 10-year survival rates were 94% and 87%, respectively. Increased age at diagnosis, cardiovascular involvement, and anti-Scl-70 antibody positivity were significant predictors of death. Conclusion. Clinical manifestations and survival rates in Korean SSc patients are similar to those of other populations. However, the prevalence of anti-Scl-70 antibody is higher in Korean SSc patients compared with whites, while the prevalence of anticentromere antibody is lower.

Primary antiphospholipid syndrome presenting with homonymous quadrantanopsia

Purpose To report a case of primary antiphospholipid syndrome presenting with isolated homonymous superior quadrantanopsia. Observations A 50-year-old Korean man presented with subjective visual disturbance for 1 month. Visual field testing showed a right homonymous superior quadrantanopsia. Brain magnetic resonance imaging (MRI) revealed an old infarct in his left occipital lobe and multiple lesions in other areas of the brain. Laboratory tests showed a marked increase in serum anti-β2 glycoprotein I antibody, which remained elevated after 12 weeks. He was diagnosed with primary antiphospholipid syndrome and started anticoagulation therapy. Conclusions and importance This is the first case report of primary antiphospholipid syndrome presenting with isolated homonymous quadrantanopsia. Antiphospholipid syndrome should be considered as a differential diagnosis in patients with homonymous visual field defects accompanying multiple cerebral infarcts.