Jung-Soo Song

Clinical associations of anti-endothelial cell antibodies in patients with systemic lupus erythematosus

Abstract The aim of this study was to define the clinical associations of anti-endothelial cell antibody (AECA) in systemic lupus erythematosus (SLE) patients by measuring serum AECA titers to correlate with the disease activity and clinical manifestations. Forty-one SLE patients and 27 controls were studied. Serum samples were collected at the time of patient presentation with disease exacerbation and 4 weeks after the start of treatment. The disease activity was evaluated by the SLE Disease Activity Index (SLEDAI). AECA was detected by enzyme-linked immunosorbent assay (ELISA) methods with the surface antigen of the immortalized human microvascular endothelial cell line (HMEC-1). The mean immunoglobulin (Ig)G-AECA and IgM-AECA optical densities (ODs) were significantly higher in patients with SLE compared with controls [mean ± standard deviation (SD), 0.32 ± 0.15 vs 0.18 ± 0.16 and 0.29 ± 0.14 vs 0.21 ± 0.09, respectively]. There was a positive correlation between IgG-AECA and the SLEDAI scores. The positivity rate of AECA in the groups with digital vasculitis, neuropsychiatric lupus, and anti-cardiolipin antibody was significant. In conclusion, AECA may be involved in the pathogenesis of SLE and was correlated with the disease activity. It was also associated with clinical manifestations such as digital vasculitis, neuropsychiatric lupus, and anti-cardiolipin antibody positivity.

Alterations in QT Interval in Patients Undergoing Living Donor Liver Transplantation

BACKGROUND QT interval prolongation, predisposing to ventricular tachyarrhythmia, has frequently been observed in patients with liver cirrhosis. During liver transplantation (LT) surgery, electrolyte imbalance and hemodynamic instability may affect QT interval changes. We evaluated the alterations in QT parameters at each stage of LT surgery. METHODS We assessed 50 living donor LT recipients without overt heart disease for the corrected QT (QTc) and the interval from peak to the end of the T wave (T(p-e)) automatically using Bazetts formula with LabChart software. QT parameters, laboratory and hemodynamic data were simultaneously collected in the following stages of LT: before anesthetic induction (baseline), pre-anhepatic, anhepatic, 1 hour postreperfusion, and after hepatic artery anastomosis. Recipients were allocated into 2 groups according to their baseline QTc: ≥440 versus <440 msec. RESULTS QTc progressively rose from the pre-anhepatic stage remaining prolonged in each stage of LT surgery compared with the baseline. In the anhepatic stage, 54% of recipients showed marked prolongation of QTc ≥500 msec (522 ± 14), which indicated the potential for a fatal ventricular dysrhythmia: 77% and 36% in groups with QTc ≥440 and <440 msec, respectively. As opposed to changes in QTc, T(p-e) in the anhepatic stage decreased significantly; however, it returned to the baseline level in the neohepatic stage. CONCLUSION A prolonged QTc interval (≥500 msec) was frequently observed throughout the procedure of LT, even among patients with baseline QTc <440 msec, emphasizing the importance of optimizing electrolyte balance and hemodynamic status to reduce greater risk of perioperative arrhythmias.

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

Elevated Serum Homocysteine Levels Were Not Correlated with Serum Uric Acid Levels, but with Decreased Renal Function in Gouty Patients

Hyperhomocysteinemia is one of the important factors of the cardiovascular disease, and gout is well known to be associated with cardiovascular disease. There are a few reports on the serum homocysteine (Hcy) levels in patients with gout, however, the results showed discrepancies. In this study, we measured Hcy levels in patients with gout and examined factors associated with the levels of serum Hcy. Ninety-one male patients with gout and 97 age-matched healthy male controls were enrolled in the study. Serum uric acid levels were not significantly different between gout and healthy control groups. However, serum Hcy levels were significantly higher in patients with gout compared to controls (13.96±4.05 µM/L vs 12.67±3.52 µM/L, P=0.035). In gout group, patients with 1-2 stages of chronic kidney disease (CKD) had significantly lower serum Hcy than those with 3-5 stages of CKD (13.15±3.46 µM/L vs 17.45±4.68 µM/L, P<0.001). Multivariate linear analysis revealed an inverse association between serum Hcy and estimated glomerular filtration rate (eGFR) (β=-0.107, P<0.001). In conclusion, serum Hcy was elevated in male patients with gout. Hyperhomocysteinemia was not correlated with serum uric acid, but it was inversely associated with impaired renal function. Graphical Abstract

The Mid-Range of the Adjusted Level of Ferritin Can Predict the Chronic Course in Patients with Adult Onset Still’s Disease

Objective. To find a measure that can predict the disease course in patients with adult onset Still’s disease (AOSD). Methods. We retrospectively investigated the medical records of 71 hospitalized patients with AOSD. Patients were divided according to chronic and nonchronic disease course. The initial laboratory results were defined as those at the time of admission, the extremely deviated laboratory results as the highest or the lowest results, and the adjusted laboratory results as area under the curve divided by the days of hospitalization. All measures were compared and the odds ratio (OR) for the chronic disease pattern was assessed. Results. The mean age was 39.7 ± 13.5 years and women accounted for 63 of the total 71 (88.7%). Thirty patients (42.3%) had self-limited disease, 9 (12.7%) intermittent disease, and 23 (32.4%) the chronic disease pattern (32.4%). Nine patients (12.7%) died. The initial levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and ferritin, the highest levels of lactate dehydrogenase (LDH) and ferritin, and the adjusted level of ferritin in patients with chronic disease were significantly higher than those with nonchronic disease. Among them, only the middle range of the adjusted ferritin level (784.1~4120.0 ng/ml) was found to have a significant predictive value for the chronic disease pattern (OR 81.7, p = 0.007). Conclusion. A novel measure, the adjusted level of ferritin during the first hospitalization, might be useful to predict progression to chronic disease in patients with AOSD.

Usefulness of Serum Leucine-Rich Alpha-2 Glycoprotein as a Disease Activity Biomarker in Patients with Rheumatoid Arthritis

Our study aimed to investigate whether serum leucine-rich alpha-2-glycoprotein (LRG) levels are elevated in patients with rheumatoid arthritis (RA). In addition, we assessed their correlation with disease activity parameters and pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α). Our study included 69 patients with RA and 48 age- and sex-matched healthy controls. Serum concentrations of TNF-α and LRG were determined by enzyme-linked immunosorbent assay. Serum LRG concentrations were significantly elevated in patients with RA compared with those in healthy controls (30.8±14.4 vs. 22.2±6.1 ng/mL; P<0.001). In patients with RA, serum LRG levels were found to be correlated with disease activity score 28 (DAS28), erythrocyte sedimentation rate, and C-reactive protein levels (γ=0.671; γ=0.612; and γ=0.601, P<0.001, respectively), but not with serum TNF-α levels. Serum LRG levels in patients with an active disease status (DAS28≥2.6) were significantly higher than those in remission (DAS28<2.6) (36.45±14.36 vs. 24.63±8.81 ng/mL; P<0.001). Our findings suggest that serum LRG could contribute to the inflammatory process independent of TNF-α and it may be a novel biomarker for assessing inflammatory activity in patients with RA. Graphical Abstract

Levels of Plasma-soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) Are Correlated with Disease Activity in Rheumatoid Arthritis

Objective. To determine whether levels of plasma-soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) are elevated in patients with rheumatoid arthritis (RA) and whether levels are correlated with disease activity and other variables. Methods. Our study included 71 patients with RA and 50 age- and sex-matched healthy controls. Clinical characteristics and laboratory measures, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and 28-joint Disease Activity Score (DAS28) were assessed. Plasma levels of sTREM-1 and tumor necrosis factor-α (TNF-α) were measured by ELISA. Results. Patients with RA had significantly higher plasma sTREM-1 levels than healthy controls (170.10 ± 84.71 pg/ml vs 97.41 ± 40.64 pg/ml; p < 0.001). In patients with RA, plasma sTREM-1 levels were found to be correlated with DAS28, ESR, CRP, white blood cell counts, neutrophil counts, and plasma TNF-α levels (r = 0.329, p = 0.005; r = 0.241, p = 0.043; r = 0.314, p < 0.001; r = 0.261, p = 0.028; r = 0.278, p = 0.019; and r = 0.313, p = 0.009, respectively). Plasma sTREM-1 levels in patients with active disease status (DAS28 > 3.2) were significantly higher than in those with low disease status (DAS28 ≤ 3.2; 208.89 ± 100.14 pg/ml vs 150.29 ± 68.70 pg/ml; p = 0.005). Conclusion. Patients with RA had higher plasma sTREM-1 levels than healthy controls, and plasma sTREM-1 levels were correlated with disease activity measures, suggesting that plasma sTREM-1 could play a role in the inflammatory process associated with TNF-α, and that it may be a useful disease activity marker in RA.

Graft Contrast–Induced Nephropathy Caused by Prerenal Transplant Computed Tomography: A Case Report

BACKGROUND We report a case of posttransplant contrast-induced nephropathy (CIN) that occurred after performing computed tomography (CT) scanning for pretransplant cardiac and vascular evaluation. CASE PRESENTATION The patient had an 8-year history of hemodialysis and was admitted to the hospital for a kidney transplant from a deceased donor. Cardiac CT imaging and 3-dimensional low-extremity CT angiography were performed to confirm the patients cardiac and iliac artery function. After successful transplantation surgery, the patient had a urine output of 250 mL and a reduced creatinine level from 8.8 to 2.3 mg/dL on postoperative day 4. However, urine output suddenly decreased to 30 mL and the creatinine level suddenly increased to 7.6 md/dL without any symptoms such as fever or graft tenderness. The patient tested negative for panel-reactive antibodies and donor-specific antibodies, and he was discharged 1 week later with an improvement in symptoms. Results of a graft biopsy indicated CIN, and the contrast-enhanced kidney was observed on noncontrast CT imaging that was performed immediately after transplantation to rule out vascular problems as well as other complications. CONCLUSIONS There may be residual contrast present from pretransplant CT imaging, which could affect the functional kidney grafts after transplantation and can lead to CIN. This scenario could potentially lead to loss of graft function, suggesting that caution should be observed when ordering CT imaging in this patient population.

Efficacy and Safety of Induction Therapy in Kidney Transplantation: A Network Meta-Analysis

BACKGROUND Rejection and infection can occur after kidney transplantation and are important factors in preserving graft kidney function. The use of immunosuppressant agents in transplantation is therefore important, and the question of which induction therapy should be used as an immunosuppressant is controversial. OBJECTIVE The goal of this study was to assess the comparative benefits and harms of various maintenance immunosuppressive induction agents in adults undergoing kidney transplantation by using a network meta-analysis and to generate rankings of the different immunosuppressive regimens according to their safety and efficacy. METHODS CENTRAL, MEDLINE, EMBASE, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trial registers were searched until May 2017 to identify randomized controlled trials on immunosuppression for kidney transplantation. RESULTS Twenty-seven studies involving 4484 participants were eligible for analysis. Induction and maintenance treatments were administered for 12 months. There was no evidence of differences in outcomes between therapies on all-cause mortality, graft loss, cytomegalovirus, BK virus, neutropenia, thrombocytopenia, and biopsy-proven acute rejection. However, compared with intravenous basiliximab (an interleukin-2 receptor antagonist [IL-2RA]), the most effective treatments to decrease biopsy-proven acute rejection were intravenous alemtuzumab and rabbit antithymocyte globulin (rATG). The odds ratios were 0.45 (95% confidence interval [CI], 0.29-40.78) and 0.63 (95% CI, 0.42-0.95), respectively. As a side effect, rATG was accompanied by more bacterial infection than the IL-2RA (OR, 1.8 [95% CI, 1.01-2.8]). CONCLUSIONS The determination of induction in kidney transplantation is important for future prognosis of the graft kidney. Alemtuzumab and rATG exhibited lower biopsy-proven acute rejection than the IL-2RA. As a side effect, rATG produced frequent bacterial infections.

Efficacy of Ultralow-Dose Valganciclovir Chemoprophylaxis for Cytomegalovirus Infection in ABO-Incompatible Kidney Transplantation Recipients

BACKGROUND Cytomegalovirus (CMV) infection can increase morbidity and mortality in kidney transplant (KT) patients. Chemoprophylaxis with valganciclovir (VGCV) is recommended for ABO-incompatible (ABOi) KT patients as it significantly reduces CMV disease and infection. The recommended dose of VGCV for prevention of CMV in a KT recipient is 900 mg once daily, and the treatment duration is 6 months. However, because it is expensive, sufficient amounts might not be administered. METHODS We investigated whether ultralow-dose VGCV (450 mg every other day) and short dosing period (3 months) was sufficient to prevent CMV infection after ABOi KT. We retrospectively evaluated 74 adult CMV-seropositive donor/CMV-seropositive recipient (D+/R+) ABOi KT recipients from June 2009 to July 2016 who received ultralow-dose VGCV prophylaxis for 3 months. The primary outcome was occurrence of CMV infection. Secondary outcomes were leukopenia and thrombocytopenia. RESULT All patients received intravenous rituximab 200 mg once and plasmapheresis for reduction of anti-A/B antibodies and interleukin-2 antibodies before undergoing ABOi KT. Mean prophylaxis and follow-up durations were 3 and 52 months, respectively. One patient died of bacterial pneumonia. Four patients lost graft function and were undergoing hemodialysis; 3 cases were caused by antibody-mediated rejection, and 1 was due to mechanical complication after surgery. Fortunately, CMV infection did not occur in any patient. CONCLUSION Ultralow-dose VGCV is an effective prophylaxis for D+/R+ ABOi KT recipients. Especially, ultralow-dose VGCV CMV infection prevention protocol in Asian populations reduced the side effects and cost.