Health-related Quality of Life Outcomes of Adalimumab for Patients With Rheumatoid Arthritis in Korea

Objective@#Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disorder that impairs patients’ overall health-related quality of life (HRQOL). In this study, we evaluated the effect of adalimumab in Korean patients with active RA on HRQOL. @*Methods@#Patients included in the study had moderate to severe active RA that did not respond to conventional drugs with a Disease Activity Score of 28 joints ＞3.2 and were biologics-naïve. All patients received adalimumab 40 mg subcutaneously every other week and were followed for 24 weeks. The primary endpoint was the change in baseline Health Assessment Questionnaire Disability Index (HAQ-DI) score at week 24. Secondary endpoints were changes in the EuroQol 5-dimension 3-Level (EQ-5D-3L) baseline score and Short Form 36-Item Health Survey (SF-36) domain scores at weeks 12 and 24 and change in baseline HAQ-DI score at week 12. @*Results@#In total, 91 Korean patients were included. Ninety-three percent of patients were in high disease activity with a baseline mean DAS28 value of 6.1 within all patients. The mean change from baseline in HAQ-DI scores were −0.46 at week 12 and∼0.67 at week 24 (p＜0.0001). Additionally, EQ-5D-3L score at weeks 12 and 24 had significantly improved (p＜0.0001) compared to baseline. SF-36 at weeks 12 and 24 had significantly improved (p＜0.0001, p=0.0001) compared to baseline. @*Conclusion@#Treatment with adalimumab resulted in significant improvement in HAQ-DI, EQ-5D-3L, and SF-36 scores at 12 and 24 weeks in Korean RA patient.

Serum Fibroblast Growth Factor 21 and New-Onset Metabolic Syndrome: KoGES-ARIRANG Study

PURPOSE: Fibroblast growth factor 21 (FGF21) is a crucial metabolic regulator, with multiple favorable effects on glucose homeostasis and lipid metabolism. Since serum FGF21 level has been implicated as a potential marker for the early identification of metabolic syndrome (MetS), we investigated the association between serum FGF21 level and the development of MetS in a population-based prospective study. MATERIALS AND METHODS: We conducted a prospective study of 221 randomly sampled adults without MetS from a general population-based cohort study who were examined from 2005–2008 (baseline) and from 2008–2011 (follow-up). Baseline serum FGF21 levels were analyzed using enzyme-linked immunosorbent assay. RESULTS: During the average 2.8-year follow-up period, 82 participants (36.6%) developed new-onset MetS. Serum FGF21 levels were significantly higher in patients with new-onset MetS than in those without MetS (209.56±226.80 vs. 110.09±81.10, p < 0.01). In multivariate adjusted models, the odds for MetS development were greater in patients with serum FGF21 levels in the highest quartile, compared to those in the lowest quartile (3.84, 95% confidence interval: 1.59–9.28). CONCLUSION: Serum FGF21 level was an independent predictor for new-onset MetS in a population-based prospective study.

Radon Exposure-induced Genetic Variations in Lung Cancers among Never Smokers

BACKGROUND: Lung cancer in never smokers (LCINS) differs etiologically and clinically from lung cancer attributed to smoking. After smoking, radon exposure is the second leading cause and the primary risk factor of lung cancer among never smokers. Exposure to radon can lead to genetic and epigenetic alterations in tumor genomes affecting genes and pathways involved in lung cancer development. The present study sought to explore genetic alterations associated with LCINS exposed to radon gas indoors. METHODS: Genetic associations were assessed via a case-control study of LCINS (39 cases and 30 controls) using next generation sequencing. Associations between genetic mutations and high exposure to radon were investigated by OncoPrint and heatmap graphs. Bioinformatic analysis was conducted using various tools. According radon exposure levels, we divided subjects in two groups of cases and controls. RESULTS: We found that ABL2 rs117218074, SMARCA4 rs2288845, PIK3R2 rs142933317, MAPK1 rs1803545, and androgen receptor (AR) rs66766400 were associated with LCINS exposed to high radon levels. Among these, Chromodomain helicase DNA-binding protein 4 (CHD4) rs74790047, TSC2 rs2121870, and AR rs66766408 were identified as common exonic mutations in both lung cancer patients and normal individuals exposed to high levels of radon indoor. CONCLUSION: We identified that CHD4 rs74790047, TSC2 rs2121870, and AR rs66766408 are found to be common exonic mutations in both lung cancer patients and normal individuals exposed to radon indoors. Further analysis is needed to determine whether these genes are completely responsible for LCINS exposed to residential radon.

Erratum: Novel Genetic Associations Between Lung Cancer and Indoor Radon Exposure

The original version of the article contained error in the funding statement in Acknowledgements section.

Erratum: Novel Genetic Associations Between Lung Cancer and Indoor Radon Exposure

The original version of this article contained error in the name of the fourth author which was given incorrectly as Hye Run Kim. The author’s name should have been written as Hye Ryun Kim.

Novel Genetic Associations Between Lung Cancer and Indoor Radon Exposure

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide, for which smoking is considered as the primary risk factor. The present study was conducted to determine whether genetic alterations induced by radon exposure are associated with the susceptible risk of lung cancer in never smokers. METHODS: To accurately identify mutations within individual tumors, next generation sequencing was conduct for 19 pairs of lung cancer tissue. The associations of germline and somatic variations with radon exposure were visualized using OncoPrint and heatmap graphs. Bioinformatic analysis was performed using various tools. RESULTS: Alterations in several genes were implicated in lung cancer resulting from exposure to radon indoors, namely those in epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), NK2 homeobox 1 (NKX2.1), phosphatase and tensin homolog (PTEN), chromodomain helicase DNA binding protein 7 (CHD7), discoidin domain receptor tyrosine kinase 2 (DDR2), lysine methyltransferase 2C (MLL3), chromodomain helicase DNA binding protein 5 (CHD5), FAT atypical cadherin 1 (FAT1), and dual specificity phosphatase 27 (putative) (DUSP27). CONCLUSIONS: While these genes might regulate the carcinogenic pathways of radioactivity, further analysis is needed to determine whether the genes are indeed completely responsible for causing lung cancer in never smokers exposed to residential radon.

Gene mutation discovery research of non-smoking lung cancer patients due to indoor radon exposure

Although the incidence and mortality for most cancers such as lung and colon are decreasing in several countries, they are increasing in several developed countries because of an unhealthy western lifestyles including smoking, physical inactivity and consumption of calorie-dense food. The incidences for lung and colon cancers in a few of these countries have already exceeded those in the United States and other western countries. Among them, lung cancer is the main cause of cancer death in worldwide. The cumulative survival rate at five years differs between 13 and 21 % in several countries. Although the most important risk factors are smoking for lung cancer, however, the increased incidence of lung cancer in never smokers(LCINS) is necessary to improve knowledge concerning other risk factors. Environmental factors and genetic susceptibility are also thought to contribute to lung cancer risk. Patients with lung adenocarcinoma who have never smoking frequently contain mutation within tyrosine kinase domain of the epidermal growth factor receptor(EGFR) gene. Also, K-ras mutations are more common in individuals with a history of smoking use and are related with resistance to EFGR-tyrosine kinase inhibitors. Recently, radon(Rn), natural and noble gas, has been recognized as second common reason of lung cancer. In this review, we aim to know whether residential radon is associated with an increased risk for developing lung cancer and regulated by several genetic polymorphisms.

Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study

The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout.

Use of post-operative negative-pressure wound therapy for gouty ulcer / 영남의대학술지

Gouty ulcer can be caused by the accumulation of clumps of uric acid in body tissues that lead to acute or chronic inflammation at sites of accumulation. Furthermore, tophi-inhibiting granulation tissue may form a canal that channels microbial infection from the underlying involved joint space, and thus, presents the risk of osteomyelitis development. Accordingly, gouty ulcer must be treated appropriately. In this case, refractory wounds on gouty ulcers at the left shin and left radial ankle were treated by surgical debridement. Negative-pressure wound therapy was used successfully to prevent post-operative delayed wound healing.

The Impact of CDH13 Polymorphism and Statin Administration on TG/HDL Ratio in Cardiovascular Patients

PURPOSE: Adiponectin is expressed in adipose tissue, and is affected by smoking, obesity, and genetic factors, such as CDH13 polymorphism, contributing to the development of coronary vascular diseases (CVDs). MATERIALS AND METHODS: We investigated the effect of genetic variations of CDH13 (rs3865188) on blood chemistry and adiponectin levels in 345 CVD patients undergoing statin-free or statin treatment. RESULTS: Genetic variation in CDH13 was significantly correlated with several clinical factors, including adiponectin, diastolic blood pressure, triglyceride (TG), and insulin levels. Subjects with the T allele (mutant form) had significantly lower adiponectin levels than those with the A allele. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), TG/high-density lipoprotein cho-lesterol (HDLc) ratio, and HDL3b subtype were markedly decreased in statin treated subjects regardless of having the A or T allele. TG and TG/HDL in the statin-free group with TT genotype of the rs3865188 was higher than in the others but they were not different in the statin-treated subjects. We observed a significant difference in adiponectin levels between patients with the A and T alleles in the statin-free group; meanwhile, no difference in adiponectin levels was noted in the statin group. Plasma levels of other cytokines, leptin, visfatin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), were not different among the CDH13 genotypes according to statin administration. Body mass index (BMI), TG, insulin, HDL3b, and TG/HDL ratio showed negative correlations with adiponectin levels. CONCLUSION: Plasma adiponectin levels and TG/HDL ratio were significantly different according to variants of CDH13 and statin administration in Korean patients with CVD.

Usefulness of the Controlled Attenuation Parameter for Detecting Liver Steatosis in Health Checkup Examinees

BACKGROUND/AIMS: The controlled attenuation parameter (CAP) implemented in FibroScan(R) is reported to be a non-invasive means of detecting steatosis (>10% steatosis). We aimed to evaluate the usefulness of CAP in detecting steatosis among health checkup examinees and to assess its correlation with ultrasonography (US). METHODS: Consecutive CAP results were retrospectively collected. A total of 280 subjects were included. RESULTS: Fatty liver was detected in 119 subjects (42.5%) by US, whereas it was detected in 160 subjects (57.1%) by the CAP. The numbers of subjects with S0:S1:S2:S3 steatosis according to the CAP value were 120:59:58:43, respectively. The mean CAP values were 203.34+/-28.39 dB/m for S0, 248.83+/-6.14 dB/m for S1, 274.33+/-8.53 dB/m for S2, and 322.35+/-22.20 dB/m for S3. CAP values were correlated with body weight (r=0.404, p<0.001), body mass index (r=0.445, p<0.001), and the fatty liver grade by US (r=0.472, p<0.001). Among the 161 subjects with normal US findings, steatosis was detected in 65 subjects (40.4%) using the CAP. CONCLUSIONS: The CAP seems to be useful for detecting very low-grade hepatic steatosis in health checkup examinees. Its role in predicting subjects with a risk of metabolic derangement needs to be evaluated.

Usefulness of the Controlled Attenuation Parameter for Detecting Liver Steatosis in Health Checkup Examinees

BACKGROUND/AIMS: The controlled attenuation parameter (CAP) implemented in FibroScan(R) is reported to be a non-invasive means of detecting steatosis (>10% steatosis). We aimed to evaluate the usefulness of CAP in detecting steatosis among health checkup examinees and to assess its correlation with ultrasonography (US). METHODS: Consecutive CAP results were retrospectively collected. A total of 280 subjects were included. RESULTS: Fatty liver was detected in 119 subjects (42.5%) by US, whereas it was detected in 160 subjects (57.1%) by the CAP. The numbers of subjects with S0:S1:S2:S3 steatosis according to the CAP value were 120:59:58:43, respectively. The mean CAP values were 203.34+/-28.39 dB/m for S0, 248.83+/-6.14 dB/m for S1, 274.33+/-8.53 dB/m for S2, and 322.35+/-22.20 dB/m for S3. CAP values were correlated with body weight (r=0.404, p<0.001), body mass index (r=0.445, p<0.001), and the fatty liver grade by US (r=0.472, p<0.001). Among the 161 subjects with normal US findings, steatosis was detected in 65 subjects (40.4%) using the CAP. CONCLUSIONS: The CAP seems to be useful for detecting very low-grade hepatic steatosis in health checkup examinees. Its role in predicting subjects with a risk of metabolic derangement needs to be evaluated.

Genetic Variations of Drug Transporters Can Influence on Drug Response in Patients Treated with Docetaxel Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Dose-limiting toxicities of docetaxel are widely considered to be neutropenia, anemia, skin toxicity, and nausea. One of the factors that limit the use of docetaxel is its unpredictability of inter-individual variation in toxicity. MATERIALS AND METHODS: In order to identify the genetic factors that affect the risk of docetaxel-induced toxicities, we recruited patients who received docetaxel chemotherapy. We genotyped 92 patients with single-nucleotide polymorphisms (SNPs) in 5 genes: CYP3A4 (CYP3A4*1B, CYP3A4*18, and CYP3A4*3), CYP3A5 (CYP3A5*2 and CYP3A5*3), ABCB1 (C1236T, G2677G/T, and C3435T), SLCO1B3 (rs11045585), and ABCC2 (rs12762549). RESULTS: Out of 92 patients, 70 had grade 3 or 4 neutropenia; 4 had grade 1 or 2; and 18 had no toxicity (76.1%, 4.3%, and 19.6%, respectively). The findings of the SNP analysis showed that patients with TT genotype of ABCB1 3435C>T polymorphism showed significantly higher risk of neutropenia and anemia (p=0.029 and p=0.044, respectively). There were significant associations between docetaxel-induced leucopenia and 2677G/T of ABCB1 and rs12762549 of ABCC2 (p=0.025 and p=0.028, respectively). In a multivariate analysis, we observed that patients carrying 2677G>T in ABCB1might be associated with higher risk of chemo-resistance when treated with docetaxel (odds ratio [OR], 6.48; confidence interval, 1.92 to 21.94; p=0.003). In a subgroup analysis of non-small cell lung cancer patients, a significant association of tumor response with G2677T/A (OR, 4.54) in ABCB1 and SLCO1B3 (OR, 9.44) was observed. CONCLUSION: Our data suggest that ABCB1 (2677G/T) and SLCO1B3 (rs11055585) might be major genetic predictors of docetaxel-related toxicities in patients receiving docetaxel chemotherapy.

Rituximab for Rheumatoid Arthritis Following TNF-alpha Inhibitor Associated Splenic Tuberculosis

One of the most important adverse effects of a tumor necrosis factor (TNF)-alpha inhibitor is the reactivation of tuberculosis. Most of them occur in the lung, but sometimes they can be found in other organs. Moreover, the proper management of active rheumatoid arthritis (RA) in patients with anti-TNF-alpha associated tuberculosis is still in debate. We present the case of a seropositive RA patient who showed good response with rituximab, an anti-CD20 monoclonal antibody, after developing splenic tuberuculosis, following treatment with TNF-alpha inhibitor. Confirming a diagnosis of splenic tuberculosis is difficult and can be delayed due to its nonspecific symptoms and rare occurrence. This case suggests that splenic tuberculosis should be doubted in RA patients treated with TNF-alpha inhibitor, and that rituximab may be considered as an alternative treatment option in RA patients with anti-TNF-alpha associated tuberculosis.

A Case of Refractory Behcet's Uveitis Improving after Insertion of Fluocinolone Acetonide Implant

Behcet's disease (BD) is systemic vasculitis that can manifest severely debilitating. Despite the understanding mechanisms of overall BD, there are remains many questions in various critical manifestations and treatments. The ocular manifestation is characterized by a prototype of chronic relapsing and persistent uveitis. The main treatment is topical corticosteroid, and topical nonsteroidal anti-inflammatory drugs in mild uveitis. The recurrent and severe uveitis could be treated with ocular corticosteroid injections, and systemic corticosteroid for inducing long-lasting suppression of the inflammation. Systemic corticosteroids should rapidly be tapered within weeks for avoiding side effects. Recent advances have led to the development of sustained-release corticosteroid devices using different corticosteroids. We present a case of 67-year-old woman who received a fluocinolone acetonide implant for recurrent Behcet's uveitis. She was successfully treated with implant and the uveitis became quiescent within a month.

A Case of Systemic Lupus Erythematosus-Associated Hemophagocytic Lymphohistiocytosis Treated Successfully with an Etoposide Infusion / 대한내과학회지

Hemophagocytic lymphohistiocytosis (HLH) can develop following strong activation of the immune system and the cardinal symptoms are a prolonged fever, hematological abnormalities, hepatosplenomegaly, and hemophagocytosis. HLH can be classified as primary or secondary HLH, associated with infections, malignancy and autoimmune disease. There is no consensus on the primary treatment regimen in systemic lupus erythematosus (SLE)-associated HLH. We experienced a case of SLE-associated HLH in a previously healthy adult. She was initially treated with intravenous immunoglobulin, cyclosporine, and high-dose steroid, but had a poor clinical response. After intravenous etoposide, the patient stabilized and has been followed for 1 year without reactivation of the HLH or SLE.

Immunohistochemical Study for the Syndecan-2 in Cutaneous Melanoma and Pigmented Nevus / 대한피부과학회지

BACKGROUND: Melanoma is a malignant neoplasm originating from melanocytes. It has been recently suggested that syndecan-2 may contribute to the aggressive phenotype and metastatic potential of melanoma in cell line studies. However, there is no quantitative analysis of syndecan-2 expression using human melanoma tissue. OBJECTIVE: This study aimed to examine the specific expression of syndecan-2 in human melanoma tissue. METHODS: A total of 35 sections of formalin-fixed, paraffin-embedded tissues were investigated for syndecan-2 expression using immunohistochemical staining. Also, a total of 6 tissues and two kinds of cell lines were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) and western blot. RESULTS: Immunohistochemical staining of 23 cases of melanoma tissue was done, and in 5 cases (21.7%), strong expression of syndecan-2 was seen. Also, syndecan-2 was detected in human melanoma tissue and MNT-1 melanoma cells by RT-PCR and western blot analysis. CONCLUSION: We suggest that syndecan-2 expression is increased in melanoma compared to nevus. The results of this study may help to explain the clinical features of melanoma and syndecan-2.

TT Mutant Homozygote of Kruppel-like Factor 5 Is a Key Factor for Increasing Basal Metabolic Rate and Resting Metabolic Rate in Korean Elementary School Children

We investigated the contribution of genetic variations of KLF5 to basal metabolic rate (BMR) and resting metabolic rate (RMR) and the inhibition of obesity in Korean children. A variation of KLF5 (rs3782933) was genotyped in 62 Korean children. Using multiple linear regression analysis, we developed a model to predict BMR in children. We divided them into several groups; normal versus overweight by body mass index (BMI) and low BMR versus high BMR by BMR. There were no differences in the distributions of alleles and genotypes between each group. The genetic variation of KLF5 gene showed a significant correlation with several clinical factors, such as BMR, muscle, low-density lipoprotein cholesterol, and insulin. Children with the TT had significantly higher BMR than those with CC (p = 0.030). The highest muscle was observed in the children with TT compared with CC (p = 0.032). The insulin and C-peptide values were higher in children with TT than those with CC (p= 0.029 vs. p = 0.004, respectively). In linear regression analysis, BMI and muscle mass were correlated with BMR, whereas insulin and C-peptide were not associated with BMR. In the high-BMR group, we observed that higher muscle, fat mass, and C-peptide affect the increase of BMR in children with TT (p < 0.001, p < 0.001, and p = 0.018, respectively), while Rohrer's index could explain the usual decrease in BMR (adjust r2 = 1.000, p < 0.001, respectively). We identified a novel association between TT of KLF5 rs3782933 and BMR in Korean children. We could make better use of the variation within KLF5 in a future clinical intervention study of obesity.

Clinical Significance of Subjective Foamy Urine / 전남의대학술지

Foamy urine is widely regarded as a sign of proteinuria. However, there is no objective definition of foamy urine and there are no reports on the proportion of involved patients who have overt proteinuria or microalbuminuria. We performed this study to investigate this proportion and to identify possible risk factors for these two conditions. We reviewed all new outpatients from 1 November 2011 to 30 April 2012 and identified patients complaining of foamy urine. Their demographic data and medical records were examined. In particular, we tabulated the patients' spot urinary protein to creatinine ratio, spot urinary microalbumin to creatinine ratio (ACR), blood urea nitrogen (BUN), and serum levels of creatinine (Cr), uric acid, calcium, phosphate, and glucose. In addition, we calculated estimated glomerular filtration rates (eGFRs) by using the CKD-EPI equation. We also performed risk factor analysis with the Chi-squared test and by logistic regression. Seventy-two patients (6.3% of total new outpatients) complained of foamy urine; of these, there were 59 males with a median age of 65.5 years (range, 36-87 years). Of the 72 patients, 16 (22.2%) had overt proteinuria. We found that diabetes, poor renal function (high Cr, BUN, low eGFR), increased serum phosphate, and increased serum glucose were associated with overt proteinuria. Multiple logistic regression analysis showed that serum Cr and serum phosphate were associated with overt proteinuria. The ACR was available for 38 patients, and in this subgroup, 12 (31.6%) showed microalbuminuria or overt proteinuria. In this subgroup, a high serum Cr was the only statistically significant risk factor. Among patients who complained of foamy urine, approximately 20% had overt proteinuria, and increased serum Cr and phosphate were statistically significant risk factors.

Necrotizing Fasciitis of the Thigh Secondary to Radiation Colitis in a Rectal Cancer Patient

Necrotizing fasciitis usually occurs after dermal injury or through hematogenous spread. To date, few cases have been reported as necrotizing fasciitis of the thigh secondary to rectal perforation in rectal cancer patients. A 66-year-old male complained of pelvic and thigh pain and subsequently developed necrotizing fasciitis in his right thigh. Four years earlier, he had undergone a low anterior resection and radiotherapy due to of rectal cancer. An ulcerative lesion had been observed around the anastomosis site during the colonoscopy that had been performed two months earlier. Pelvic computed tomography and sigmoidoscopy showed rectal perforation and presacral abscess extending to buttock and the right posterior thigh fascia. Thus, the necrotizing fasciitis was believed to have occurred because of ulcer perforation, one of the complications of chronic radiation colitis, at the anastomosis site. When a rectal-cancer patient complains of pelvic and thigh pain, the possibility of a rectal perforation should be considered.