Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

OBJECTIVE: Axial spondyloarthritis (axSpA) is often accompanied by cardiac manifestations, such as valvular heart disease. In this prospective cohort study, we evaluated the incidence of cardiac abnormalities in Korean axSpA patients by echocardiography. METHODS: AxSpA patients were prospectively recruited from a single tertiary hospital. Baseline demographic, clinical, radiographic, and echocardiographic data were collected at the time of enrollment. Echocardiography evaluations were performed with a focus on valvular heart disease and systolic and diastolic function. Logistic regression analyses were used to identify factors associated with diastolic dysfunction in axSpA. RESULTS: A total of 357 axSpA patients were included in the analyses, of whom 78 (21.8%) exhibited diastolic dysfunction, with no reports of systolic dysfunction. Thirteen patients (3.6%) had valvular heart disease, and aortic valve regurgitation (n=5) and mitral valve regurgitation (n=6) were most common. Multivariable logistic regression analyses indicated that older age and higher body mass index (BMI) were positively associated with diastolic dysfunction, whereas human leukocyte antigen (HLA)-B27 positivity was negatively associated with diastolic dysfunction. CONCLUSION Valvular heart disease is infrequent in Korean axSpA patients. However, diastolic dysfunction is common in axSpA patients, and is significantly associated with older age, higher BMI, and HLA-B27.

Novel biologics that redirect cytotoxic T lymphocytes (CTLs) to kill tumor cells bearing a tumor associated antigen hold great promise in the clinic. However, the ability to safely and potently target CD3 on CTL toward tumor associated antigens (TAA) expressed on tumor cells remains a challenge of both technology and biology. Herein we describe the use of a Half DVD-Ig format that can redirect CTL to kill tumor cells. Notably, Half DVD-Ig molecules that are monovalent for each specificity demonstrated reduced non-specific CTL activation and conditional CTL activation upon binding to TAA compared to intact tetravalent DVD-Ig molecules that are bivalent for each specificity, while maintaining good drug like properties and appropriate PK properties.
Animals ; Antibodies, Bispecific ; immunology ; Antibodies, Monoclonal ; immunology ; pharmacokinetics ; CD3 Complex ; metabolism ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; ErbB Receptors ; metabolism ; Female ; Humans ; Lymphocyte Activation ; immunology ; Mice, SCID ; Neoplasms ; immunology ; pathology ; Rats, Sprague-Dawley ; T-Lymphocytes, Cytotoxic ; immunology

BACKGROUND: Although intravenous (i.v.) lidocaine is used as a perioperative analgesic in abdominal surgery, evidence of efficacy is limited. The infusion dose and duration remain unclear. This study aimed to investigate the effect of a longer low-dose 48-hour infusion regimen on these outcomes. METHODS: Fifty-eight adults undergoing elective open colorectal surgery were randomized into the lidocaine group (1.5 mg/kg bolus followed by 1 mg/kg/h infusion for 48 hours) and control group. After surgery, patients were given a fentanyl patient-controlled analgesia machine and time to first bowel movement (primary outcome) and flatus were recorded. Postoperative pain scores and fentanyl consumption were assessed for 72 hours. RESULTS: There was no significant difference in time to first bowel movement (80.1 ± 42.2 vs. 82.5 ± 40.4 hours; P = 0.830), time to first flatus (64.7 ± 38.5 vs. 70.0 ± 31.2 hours; P = 0.568), length of hospital stay (9 [8–13] vs. 11 [9–14) days; P = 0.531], nor postoperative pain scores in the lidocaine vs. control groups. Cumulative opioid consumption was significantly lower in the lidocaine vs. the control group from 24 hours onwards. At 72 hours, cumulative opioid consumption (µg fentanyl) in the lidocaine group (1,570 [825–3,587]) was over 40% lower than in the placebo group (2,730 [1,778–5,327]; P = 0.039). CONCLUSIONS: A 48-hour low-dose i.v. lidocaine infusion does not significantly speed the return of bowel function in patients undergoing elective open colorectal surgery. It was associated with reduced postoperative opioid consumption, but not with earlier hospital discharge, or lower pain scores.
Adult ; Analgesia, Patient-Controlled ; Analgesics, Opioid ; Anesthetics, Local ; Colorectal Surgery ; Fentanyl ; Flatulence ; Humans ; Ileus ; Length of Stay ; Lidocaine ; Pain, Postoperative ; Prospective Studies

BACKGROUND: Although intravenous (i.v.) lidocaine is used as a perioperative analgesic in abdominal surgery, evidence of efficacy is limited. The infusion dose and duration remain unclear. This study aimed to investigate the effect of a longer low-dose 48-hour infusion regimen on these outcomes. METHODS: Fifty-eight adults undergoing elective open colorectal surgery were randomized into the lidocaine group (1.5 mg/kg bolus followed by 1 mg/kg/h infusion for 48 hours) and control group. After surgery, patients were given a fentanyl patient-controlled analgesia machine and time to first bowel movement (primary outcome) and flatus were recorded. Postoperative pain scores and fentanyl consumption were assessed for 72 hours. RESULTS: There was no significant difference in time to first bowel movement (80.1 ± 42.2 vs. 82.5 ± 40.4 hours; P = 0.830), time to first flatus (64.7 ± 38.5 vs. 70.0 ± 31.2 hours; P = 0.568), length of hospital stay (9 [8–13] vs. 11 [9–14) days; P = 0.531], nor postoperative pain scores in the lidocaine vs. control groups. Cumulative opioid consumption was significantly lower in the lidocaine vs. the control group from 24 hours onwards. At 72 hours, cumulative opioid consumption (µg fentanyl) in the lidocaine group (1,570 [825–3,587]) was over 40% lower than in the placebo group (2,730 [1,778–5,327]; P = 0.039). CONCLUSIONS A 48-hour low-dose i.v. lidocaine infusion does not significantly speed the return of bowel function in patients undergoing elective open colorectal surgery. It was associated with reduced postoperative opioid consumption, but not with earlier hospital discharge, or lower pain scores.

OBJECTIVE: Interleukin (IL)-17 is a pro-inflammatory cytokine that has pleiotropic effects on multiple target cells and thereby contributes to the development of immune-mediated inflammatory disorders. However, the role of IL-17 in the humoral immune response has not been clearly elucidated. METHODS: Mice deficient in IL-17A (IL-17A knockout [KO] mice) and wild type (WT) C57BL/6 mice were compared. Distinct B cell (mature/precursor and marginal zone/follicular) and plasma cell populations were compared using fluorescence-activated cell sorting (FACS) and confocal immunostaining. Immunoglobulin production was assessed by enzyme-linked immunosorbent assay. RESULTS: There was no difference in B cell and plasma cell populations between IL-17A KO and WT mice. However, after T cell-dependent antigen challenge, IL-17A KO mice produced lower levels of immunoglobulin (Ig)G1 than wild-type animals. IL-17A KO mice also showed reduced germinal center (GC) formation and lower expression of activation-induced cytidine deaminase, the essential enzyme for class switch recombination (CSR). IL-17 had no effect on the proliferation or survival of naïve B cells in in vitro functional studies. However, IL-17 treatment promoted naïve B cell differentiation into plasma cells in synergy with IL-4, although IL-17 alone had no effect. CONCLUSION: Our findings suggest that IL-17 contributes to the humoral immune response by enhancing GC formation, CSR to IgG1, and plasma cell differentiation in synergy with IL-4.
Animals ; B-Lymphocytes ; Cell Differentiation ; Cytidine Deaminase ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Germinal Center* ; Immunity, Humoral ; Immunoglobulin G ; Immunoglobulins* ; In Vitro Techniques ; Interleukin-17* ; Interleukin-4 ; Interleukins ; Mice* ; Plasma Cells ; Recombination, Genetic

BACKGROUND/AIMS: We investigated whether transthoracic echocardiography-suspected pulmonary hypertension (PH) affects survival in systemic lupus erythematosus (SLE) patients and examined factors associated with PH occurrence and survival. METHODS: This retrospective single-center study included 154 Korean SLE patients fulfilling the American College of Rheumatology criteria (January 1995 to June 2013). Student t test, Mann-Whitney U test, Kaplan-Meier curves, and log-rank tests were used for comparisons. RESULTS: A total of 35 SLE patients with PH (SLE/PH+) and 119 without PH (SLE/PH-) were analyzed. Higher percentages of interstitial lung disease, Raynaud's phenomenon (RP), World Health Organization functional classification III/IV, and cardiomegaly were found in SLE/PH+ compared to SLE/PH-. Furthermore, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was significantly higher in SLE/PH+ (2.46 +/- 1.245 vs. 1.00 +/- 1.235), whereas survival rates were significantly higher in SLE/PH- in log-rank tests (p = 0.001). In multivariate analysis, the adjusted mortality hazard ratio (HR) for SLE/PH+ patients was 3.10. Subgroup analysis demonstrated a higher percentage of lupus nephritis in the SLE/PH+ patients who died (p = 0.039) and low complement-3 levels (p = 0.007). In univariate analysis, the mortality HR for SLE/PH+ patients with lupus nephritis was 4.62, whereas the presence of RP decreased the mortality risk in multivariate analysis; adjusted HR, 0.10. CONCLUSIONS: PH is an independent factor predicting survival in SLE patients. The presence of lupus nephritis resulted in an increased trend for mortality, whereas coexistence of RP was associated with a better survival prognosis in SLE/PH+ patients.
Adolescent ; Adult ; Cardiomegaly/diagnosis/epidemiology ; Chi-Square Distribution ; Female ; Humans ; Hypertension, Pulmonary/diagnosis/*mortality ; Kaplan-Meier Estimate ; Lung Diseases, Interstitial/diagnosis/mortality ; Lupus Erythematosus, Systemic/diagnosis/*mortality ; Lupus Nephritis/diagnosis/mortality ; Male ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Raynaud Disease/diagnosis/epidemiology ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Young Adult

The aim of the current study is to identify patients without osteoporosis who met the criteria of the fracture risk assessment tool (FRAX) of the National Osteoporosis Foundation (NOF) only. The incidence of fractures was investigated in patients who met only the FRAX criteria of the NOF and patients who presented osteoporosis. Five hundred and forty five patients with rheumatoid arthritis who visited a single center were recruited in Korea. In the follow-up period of median 30 months, the new onset of fractures was investigated. Of 223 patients who have no osteoporosis, 39 (17.4%) satisfied the FRAX criteria for pharmacological intervention. During the follow-up period, 2 new onset fractures occurred in patients who met only the FRAX criteria and 22 new onset fractures did in patients with osteoporosis by bone mineral density. The incidence rate for new onset fractures of patients who met only the FRAX criteria was with 295.93 per 10,000 person-years higher than in the general population with 114.99 per 10,000 person-years. Patients who met the FRAX criteria of the NOF only need pharmacological intervention because their numbers of incidence for new onset fractures are similar to those of patients with osteoporosis by BMD.
Age Distribution ; Aged ; Arthritis, Rheumatoid/diagnosis/*epidemiology ; Causality ; Comorbidity ; Computer Simulation ; Female ; Humans ; Incidence ; Male ; Middle Aged ; *Models, Statistical ; Osteoporotic Fractures/diagnosis/*epidemiology ; *Proportional Hazards Models ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Factors ; Sensitivity and Specificity ; Sex Distribution

Epigenetics is defined as an inheritable effect that influences gene activity, but does not involve a change in DNA sequence. Epigenetic gene regulation has an essential role in determining individual gene function and activity in each specific cell type. Epigenetics includes four predominant mechanisms: DNA methylation, histone modification, nucleosome positioning and microRNA (miRNA). These mechanisms influence gene expression, cell differentiation, proliferation, DNA repair and replication. Epigenetic modifications are far more sensitive to environmental stimuli than DNA sequence alterations. Candidate gene approaches have identified a small set of genes that undergo epigenetic changes, such as aberrant DNA demethylation, histone modification, as well as regulation by miRNA in rheumatic diseases. It is well known that T cells from patients with SLE or RA, as well as synovial fibroblasts from individuals with RA, have sequences undergoing DNA hypomethylation and/or histone modifications. In addition, miRNA regulates the gene expression by pairing with its target mRNAs and is often deregulated in systemic rheumatic diseases. High-throughput approaches are necessary for screening the epigenetic alterations, and it is essential to screen the specific tissue and cell types that are relevant to the disease pathogenesis. Identification of cell-specific targets of the epigenetic deregulation in rheumatic disorders will provide clinical markers for the diagnosis, disease progression and response to therapy. Our understanding of epigenetics is in its infancy. New generation of pharmaceuticals, which manipulate the epigenome to the switch targeted genes on or off are under investigation. The new field of repairing or optimizing the epigenome through epigenetic modifier and/or diet is wide open.
Autoimmune Diseases ; Base Sequence ; Biomarkers ; Cell Differentiation ; Diet ; Disease Progression ; DNA ; DNA Methylation ; DNA Repair ; Epigenomics ; Fibroblasts ; Gene Expression ; Histone Code ; Histones ; Humans ; Mass Screening ; MicroRNAs ; Nucleosomes ; Rheumatic Diseases ; RNA, Messenger ; T-Lymphocytes