ObjectiveTo evaluate apremilast treatment in patients with active psoriatic arthritis, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents.MethodsPatients (N=505) were randomised (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily. Rescue therapy with apremilast was designated at week 16 for placebo patients not achieving 20% improvement in swollen and tender joint counts. At week 24, the remaining placebo patients were then randomised to apremilast 20 mg twice daily or 30 mg twice daily. The efficacy and safety of apremilast were assessed over 52 weeks.ResultsAt week 16, significantly more patients receiving apremilast 20 mg twice daily (28%) and 30 mg twice daily (41%) achieved 20% improvement in American College of Rheumatology response criteria versus placebo (18%; p=0.0295 and p<0.0001, respectively), and mean decrease in the Health Assessment Questionnaire-Disability Index score was significantly greater with apremilast 30 mg twice daily (−0.20) versus placebo (−0.07; p=0.0073). In patients with baseline psoriasis body surface area involvement ≥3%, significantly more apremilast 30 mg twice daily patients achieved 50% reduction from baseline Psoriasis Area and Severity Index score (41%) versus placebo (24%; p=0.0098) at week 16. At week 52, observed improvements in these measures demonstrated sustained response with continued apremilast treatment. Most adverse events were mild to moderate in severity; the most common were diarrhoea, nausea, headache and upper respiratory tract infection.ConclusionsApremilast demonstrated clinically meaningful improvements in psoriatic arthritis and psoriasis at week 16; sustained improvements were seen with continued treatment through 52 weeks. Apremilast was generally well tolerated and demonstrated an acceptable safety profile.Trial registration numberNCT01212770.

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Objectives. The monocyte-to-lymphocyte ratio (MLR), as a new marker of the systemic inflammatory response, is associated with cardiovascular disease (CVD) mortality in the general population and hemodialysis patients. However, the association between the MLR and CVD mortality in peritoneal dialysis (PD) has received little attention. Methods. In this multicenter retrospective cohort study, 1753 incident PD patients from November 1, 2005, to June 30, 2017, with a baseline MLR were enrolled. The primary endpoint was CVD mortality. The association of MLR with CVD mortality was assessed using a multivariable-adjusted Cox model and the Fine and Gray competing risk model. Results. Of 1753 patients, the mean age was 51.1±14.9 years, 56.9% of patients were male, and the Charlson comorbidity index was 4.29±1.75. During the follow-up period of 31.2±18.4 months, 368 patients died, of which 200 (54.3%) deaths were caused by CVD events. CVD mortality rates for the lowest, middle, and highest MLR tertiles were 70.6, 78.4, and 88.9 per 1000 patient-years, respectively (P<0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log rank=22.41, P<0.001). After adjusting for confounding factors, the highest MLR tertile was significantly associated with a hazard ratio (HR) for CVD mortality of 1.45 (95% confidence interval, 1.13-2.51, P=0.016). The Fine and Gray method analysis showed that using all-cause mortality as competing risk, the highest MLR tertile remained an independent predictor of CVD mortality (HR=1.39, 95% CI 1.10-2.47, P=0.021). Conclusions. Higher MLR levels at the commencement of PD may be independently associated with increased CVD mortality in PD patients.

BACKGROUND & AIMS: New oral therapeutic agents are needed for patients with ulcerative colitis (UC) who are unresponsive or intolerant to conventional therapy. METHODS: We performed a double-blind, phase 2 trial of adults with active UC for 3 months or more who were naïve to biologic therapy or had been failed by, could not tolerate, or had contraindications to conventional therapies. The study was performed at 61 sites in 14 countries (screening from January 2015 through May 2017). Patients were randomly assigned to groups given apremilast 30 mg (n [ 57), apremilast 40 mg (n [ 55), or placebo (n [ 58) twice daily for 12 weeks; patients were then randomly assigned to groups that received apremilast, 30 or 40 mg twice daily, for an additional 40 weeks. Endoscopies were performed and biopsies were collected during the screening phase, at week 12, and at week 52. Blood and fecal samples were also collected and analyzed throughout the study. The primary endpoint was clinical remission at week 12, defined as a total Mayo score of 2 or less, with no individual subscore above 1. RESULTS: Clinical remission was achieved at week 12 by 31.6% of patients in the 30 mg apremilast group and 12.1% of patients in the placebo group (P [ .01). However, only 21.8% of patients in the 40 mg apremilast group achieved clinical remission at week 12 (P [ .27 compared with placebo). Differences in clinical remission between the 30 mg and 40 mg apremilast groups were associated with differences in endoscopic improvement. Both apremilast groups had similar improvements from baseline in Mayo score components (stool frequency score, rectal bleeding score, physician's global assessment). The 30 mg and 40 mg apremilast groups had greater median percent reductions in C-reactive protein (measured by a high-sensitivity blood test) and fecal calprotectin through week 12 than the placebo group. At week 52, clinical remission was achieved by 40.4% of patients initially assigned to the apremilast 30 mg group and 32.7% of patients initially assigned to the apremilast 40 mg group. The most frequent apremilast-associated adverse events were headache and nausea. CONCLUSIONS: Although the primary endpoint of clinical remission was not met in this phase 2 trial, a greater proportion of patients with active UC who received apremilast (30 mg or 40 mg) had improvements in clinical and endoscopic features, and markers of inflammation, at 12 weeks. Clinical remission was maintained to week 52 in up to 40% of patients who continued apremilast until that time point. ClinicalTrials.gov no: NCT02289417

BackgroundTo investigate the association between the ratio of apolipoprotein B (apo B) / apolipoprotein A1 (apo A1) with all-cause mortality and cardiovascular events in peritoneal dialysis (PD) patients.MethodsEight hundred and sixty incident PD patients were enrolled from November 1, 2005, to February 28, 2017, and followed until May 31, 2017. Outcomes were all-cause mortality and cardiovascular events. Associations between the apo B/apo A1 ratio with all-cause mortality and cardiovascular events were evaluated using multivariable-adjusted Cox models.ResultsOf the 860 patients, the mean age was 49.9 ± 14.5 years, 57.6% were men, and 19.3% were diabetic patients. The median apo B/apo A1 ratio was 0.65 (range: 0.22–2.24). During a median follow-up period of 27 months (interquartile range, 13 – 41 months), 202 deaths, and 145 cardiovascular events were recorded. After adjustment for age, sex, body mass index, diabetes, cardiovascular disease, systolic blood pressure, total Kt/V, estimated glomerular filtration rate, hemoglobin level, neutrophil to lymphocyte ratio and albumin, triglyceride, and cholesterol, as well as the use of lipid-lowering agents, the highest apo B/apo A1 ratio tertile was significantly associated with a hazard ratio for all-cause mortality of 1.60 (95% CI: 1.02 to 2.49, P = 0.040) and for cardiovascular events of 2.04 (95% CI: 1.21 to 3.44, P = 0.008).ConclusionAn increased apo B/apo A1 ratio was independently associated with all-cause mortality and cardiovascular events in PD patients.

BackgroundPeriodontal disease is common among adults and is associated with an increasing risk of chronic kidney disease (CKD). We aimed to investigate the prevalence and risk factors of CKD in patients with periodontal disease in China.MethodsIn the current cross-sectional study, patients with periodontal disease were included from Guangdong Provincial Stomatological Hospital between March 2011 and August 2011. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, the presence of albuminuria, or hematuria. All patients with periodontal disease underwent a periodontal examination, including periodontal probing pocket depth, gingival recession, and clinical attachment level by Florida Probe. They completed a questionnaire and had blood and urine samples taken. The adjusted prevalence of indicators of kidney damage was calculated and risk factors associated with CKD were analyzed.ResultsA total of 1392 patients with periodontal disease were invited to participate this study and 1268 completed the survey and examination. After adjusting for age and sex, the prevalence of reduced eGFR, albuminuria, and hematuria was 2.7% (95% CI 1.7–3.7), 6.7% (95% CI 5.5–8.1) and 10.9% (95% CI 9.2–12.5), respectively. The adjusted prevalence of CKD was 18.2% (95% CI 16.2–20.3). Age, male, diabetes, hypertension, history of CKD, hyperuricemia, and interleukin-6 levels (≥7.54 ng/L) were independent risk factors for reduced eGFR. Female, diabetes, hypertension, history of CKD, hyperuricemia, high level of cholesterol, and high sensitivity C-reactive protein (hsCRP) (≥1.03 mg/L) and TNF-α levels (≥1.12 ng/L) were independently associated with an increased risk of albuminuria. Female, lower education (

Background Though the roles of microRNAs (miRNAs) in renal diseases have been extensively investigated, a thorough screening and comparison of miRNAs among different types of chronic kidney disease (CKD) has never been performed. Methods The intrarenal miRNAs were profiled from fresh kidney tissues of patients with biopsy-proven minimal change disease (MCD), focal segmental glomerular sclerosis (FSGS) and diabetic nephropathy (DN) by using microarray. Commonly dysregulated miRNAs were validated by real-time PCR using paraffin-embedded renal tissues from all three types of CKD patients as well as mouse unilateral ureteral obstruction (UUO) model. Two novel miRNAs were selected and annotations of their target genes were performed using GO and KEGG pathway enrichment analysis. Biological functions of three two candidate miRNAs were explored in TGF-β1-induced cell model using human kidney proximal tubular cells (HK-2). Results The kidney biopsy samples of three disease types represent different levels of damage and fibrosis, which were the mildest in MCD, moderate in FSGS, and the most severe in DN. 116 miRNAs were identified to be commonly dysregulated, including 40 up-regulated and 76 down-regulated in CKD tissues as compared with healthy donor kidney biopsy tissues. Two novel miRNAs, hsa-miR-3607-3p and hsa-miR-4709-3p, were verified as consistently differentially expressed among all three types of patient samples as well as in mouse model. In vitro, hsa-miR-3607-3p was repressed while hsa-miR-4709-3p was induced by TGF-β1 treatment. Inhibition of hsa-miR-3607-3p or overexpression of hsa-miR-4709-3p promoted TGF-β1-induced migration and F-actin assembling in HK-2 cells, which are characteristics of epithelial–mesenchymal transition (EMT). Further study identified that ITGB8 and CALM3 were the bona fide target genes of hsa-miR-3607-3p and hsa-miR-4709-3p respectively. Conclusions The present identify a unique miRNAs profile that probably relates to the common fibrosis process of CKD. Results of our study suggest that hsa-miR-3607-3p and hsa-miR-4709-3p may represent as promising therapeutic targets against kidney fibrosis. Electronic supplementary material The online version of this article (10.1186/s12882-019-1512-x) contains supplementary material, which is available to authorized users.

Background Elevated aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is an independent risk factor for cardiovascular disease (CVD) among the general population. However, an association between AST/ALT ratio and CVD mortality in patients on peritoneal dialysis (PD) has received little attention. Methods A total of 2224 incident PD patients from multi-centers were enrolled from November 1, 2005, to June 30, 2017, in this retrospective cohort study. The primary endpoint was CVD mortality. Eligible patients were divided into high and normal groups according to the AST/ALT ratio cut-off for CVD mortality with the receiver operating characteristic (ROC) curve. The associations between the AST/ALT ratio and CVD mortality were evaluated by the Cox regression model. Results Of eligible 1579 patients with a mean age of 49.3 ± 14.6 years, 55.4% of patients were male, 18.1% of patients had diabetes, and 64.2% of patients had hypertension. The prevalence of a high AST/ALT ratio was 76.6% in the cohort population. During a follow-up period with 4659.6 patient-years, 316 patients died, of which 193 (61.1%) deaths were caused by CVD episodes. The incidence of CVD mortality in the high group was significantly higher than that in the normal group (13.1% versus 9.2%, P = 0.024). Cumulative CVD mortality rates were significantly different between the two groups by Kaplan-Meier analysis [hazards ratio (HR) = 1.50, 95% confidence index (CI) 1.09–2.07, P = 0.014]. After adjusting for confounding factors, a higher AST/ALT ratio was independently associated with an increased risk of CVD mortality compared with their counterparts (HR = 1.43, 95%CI 1.08–2.41, P = 0.002). Conclusions PD patients with high baseline AST/ALT ratio levels may be at a significant risk of CVD mortality.