Amino acids (AAs) are necessary nutrients which act not only as building blocks in protein synthesis but also in crucial anabolic cellular signaling pathways. It has been demonstrated that SLC7A5 is a critical transporter that mediates uptake of several essential amino acids in highly proliferative tumors and activated T cells. However, the dynamics and relevance of SLC7A5 activity in monocytes/macrophages is still poorly understood. We provide evidence that SLC7A5-mediated leucine influx contributes to pro-inflammatory cytokine production via mTOR complex 1 (mTORC1)-induced glycolytic reprograming in activated human monocytes/macrophages. Moreover, expression of SLC7A5 is significantly elevated in monocytes derived from patients with rheumatoid arthritis (RA), a chronic inflammatory disease, and was also markedly induced by LPS stimulation of both monocytes and macrophages from healthy individuals. Further, pharmacological blockade or silencing of SLC7A5 led to a significant reduction of IL-1β downstream of leucine-mediated mTORC1 activation. Inhibition of SLC7A5-mediated leucine influx was linked to downregulation of glycolytic metabolism as evidenced by the decreased extracellular acidification rate, suggesting a regulatory role for this molecule in glycolytic reprograming. Furthermore, the expression of SLC7A5 on circulating monocytes from RA patients positively correlated with clinical parameters, suggesting that SLC7A5-mediated AA influx is related to inflammatory conditions.

Background Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibrosis of the skin and the involvement of multiple internal organs. Previous studies reported poorer health-related quality of life (HRQoL) in patients with SSc compared with the general population. However, very little is known about how HRQoL in SSc patients compares with that in patients with other systemic autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjogren’s syndrome (SjS). Thus, the main aim of this study was to compare HRQoL in SSc patients, patients with other rheumatic diseases, and the general population. Methods In this cross-sectional study, patients from the rheumatology clinics of Seoul National University Hospital with SSc, RA, SLE, and SjS were enrolled via a random sampling technique. HRQoL was captured by the Short Form (36) health survey (SF-36), the Short Form Six-Dimensional health index (SF-6D), and the EuroQol Five-Dimensional descriptive system (EQ-5D). Demographic characteristics and standardized disease activity for each disease were also obtained. Previously reported data from 600 healthy Koreans were used for the healthy controls. An ANCOVA test was used to compare the SF-36, SF-6D, and EQ-5D values between study subjects with adjustments for age, sex, disease duration, comorbidities, and disease activity status. Results One hundred twenty patients were included in each of the SSc, RA, SLE, and SjS cohorts. Patients with rheumatic diseases had significantly lower SF-36, SF-6D, and EQ-5D scores than healthy controls (all P < 0.001). After statistical adjustments, SSc patients reported significantly lower mental component summary (MCS) scores than patients with RA ( P < 0.001) or SLE ( P = 0.001). Specifically, the mental health and general health domains were significantly lower in SSc patients than reported in RA or SLE patients ( P < 0.001 and P = 0.001, respectively, in both domains). In SSc patients, higher modified Rodnan skin scores (mRSS) correlated with lower MCS scores. Conclusions SSc patients report poorer HRQoL than patients with RA or SLE. The extent of skin involvement is associated with poorer HRQoL in SSc patients. Trial registration NCT03257878 . Registered 22 August 2017 Electronic supplementary material The online version of this article (10.1186/s13075-019-1842-x) contains supplementary material, which is available to authorized users.

Earlier re-evaluation might be possible when a patient's initial NST-TSH levels and maximal or 2-year LT4 doses are low, as both are important predictors of successful trial-off therapy in CH patients. When the initial serum level of free T4 is above the average value in neonates with mildly elevated TSH levels, TFTs may be more likely to normalize on their own.

PurposeGonadotropin-releasing hormone agonist (GnRHa) is known for improving final adult height in patients with central precocious puberty (CPP). This study aimed to investigate the age of menarche and near adult height in girls with CPP who had been treated with GnRHa.MethodsIn this retrospective study, we reviewed the medical records of 71 Korean girls with CPP who had started menarche or reached over 13 years of bone age after long-term GnRHa treatment. We estimated near adult height using the Bayley-Pinneau method and identified the age of menarche in girls with CPP.ResultsMean chronological and bone age at menarche were 11.9±0.7 and 12.8±0.4 years, respectively. The period between menarche and the end of treatment was 14.0±5.6 months. Posttreatment near adult height was 163.8±4.7 cm, which was significantly greater than pretreatment predicted adult height (158.7±4.1 cm).ConclusionGnRHa treatment in girls with CPP could improve final adult height and made the age of menarche close to that of the general population.

Background/Aims: Using a nationwide cohort, we investigated the cancer risk in Korean patients with gout.Methods: Data were obtained from the Korean National Health Insurance Service Database. Patients with gout were defined as those aged ≥ 20 years who were diagnosed with gout and received anti-gout medication (allopurinol, colchicine, and benzbromarone) between 2008 and 2010. Patients with nail disorders were randomly assigned to a control group (1:1 ratio) after frequency matching for age and sex. Cancer incidence was then investigated between 2012 and 2018. Cox proportional hazard regression analysis was used to investigate the association between gout and cancer after adjusting for concomitant diseases.Results: This study included 179,930 patients with gout and an equal number of matched controls. The incidence of overall cancer was higher in patients with gout than in controls (incidence rate ratio, 1.08). Cox proportional hazards regression analysis showed that gout was associated with a hazard ratio of 1.053 (95% confidence interval ,1.031 to 1.077) after adjusting for concomitant diseases.Conclusions: Gout was associated with a significantly high risk of cancer, especially esophageal, stomach, colon, liver, pancreatic, lung, ovarian, renal, and bladder cancers.