Upadacitinib in patients from China, Brazil, and South Korea with rheumatoid arthritis and an inadequate response to conventional therapy.

AIM: This study assessed the efficacy and safety of upadacitinib (UPA), in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), in Chinese, Brazilian, and South Korean patients with active rheumatoid arthritis (RA) and an inadequate response (IR) to csDMARDs. METHODS: Patients on stable csDMARDs were randomized (1:1) to once-daily UPA 15 mg or matching placebo (PBO) for a 12-week, double-blind period. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 12. RESULTS: In total, 338 patients were randomized and treated, of whom 310 (91.7%) completed the double-blind phase. The study met the primary endpoint of ACR20 at week 12 for UPA 15 mg vs PBO (71.6% vs 31.4%, P < .001), with a treatment difference observed as early as week 1. All ranked and other key secondary endpoints, including more stringent responses such as ACR50, ACR70 (≥50%/70% improvement in ACR criteria), and Disease Activity Score in 28 joints using C-reactive protein <2.6, were met for UPA 15 mg vs PBO. The incidence of serious infections (2.4% vs 0.6%) and herpes zoster (HZ: 1.8% vs 0.6%) was higher with UPA 15 mg vs PBO. There was one case of venous thromboembolism reported in the UPA group. CONCLUSION: UPA 15 mg in combination with csDMARDs demonstrated clinical and functional improvement and an acceptable safety profile over 12 weeks among patients from China, Brazil, and South Korea who had moderately to severely active RA and an IR to csDMARDs.

Feasibility of free-breathing dynamic contrast-enhanced MRI of the abdomen: a comparison between CAIPIRINHA-VIBE, Radial-VIBE with KWIC reconstruction and conventional VIBE.

OBJECTIVE: To evaluate the feasibilities of controlled aliasing in parallel imaging results in higher acceleration with volumetric interpolated breath-hold examination (CAIPIRINHA-VIBE), radial acquisition of VIBE (Radial-VIBE) with k-space-weighted image contrast (KWIC) reconstruction (KWIC-Radial-VIBE) and conventional-VIBE (c-VIBE) for free-breathing dynamic contrast-enhanced (DCE)-MRI of the abdomen. METHODS: 23 prospectively enrolled patients underwent DCE-MRI of the abdomen with CAIPIRINHA-VIBE (n = 10), KWIC-Radial-VIBE (n = 6) or c-VIBE (n = 7). Qualitative image quality of the DCE-MR images and perfusion maps was independently scored by two abdominal radiologists using a 5-point scale (from 1, uninterpretable, to 5, very good). For quantitative analysis, the signal-to-noise ratio (SNR) of the liver and goodness-of-fit (GOF) of the time-intensity curve were measured. RESULTS: In the three tested sequences, DCE-MRI had good temporal (5 s) and spatial resolution (1.48 × 1.48 × 4 mm/voxel). Interobserver agreement in the qualitative analysis was good (ĸ = 0.753; 95% confidence interval, 0.610-0.895). Therefore, the mean scores were used in the data analysis. Overall image quality was comparable between CAIPIRINHA-VIBE (3.52 ± 0.55) and KWIC-Radial-VIBE (3.72 ± 0.37; p = 1.000), and both were significantly better than c-VIBE (2.71 ± 0.34; p < 0.001). Perfusion map quality score was highest with KWIC-Radial-VIBE (4.33 ± 0.65), followed by CAIPIRINHA-VIBE (3.70 ± 0.73) and c-VIBE (3.14 ± 0.66), but without statistical significance between CAIPIRINHA-VIBE and KWIC-Radial-VIBE (p = 0.167). The SNR of the liver and GOF of the time-intensity curve did not significantly differ between the three sequences (p = 0.116 and 0.224, respectively). CONCLUSION: CAIPIRINHA-VIBE and KWIC-Radial-VIBE provide comparably better performance than c-VIBE. Both can be feasible sequences with acceptable good image quality for free-breathing DCE-MRI. ADVANCES IN KNOWLEDGE: CAIPIRINHA-VIBE and KWIC-Radial-VIBE provide comparably better quality of free-breathing DCE-MRIs than c-VIBE.

Increased cell-free DNA concentrations in patients with obstructive sleep apnea.

AIM: Blood concentrations of cell-free DNA, which is considered to be released during apoptosis, are elevated under some pathological conditions such as cardiovascular disease and cancer. The association between obstructive sleep apnea (OSA) and cell-free DNA concentrations has not been reported so far. The purpose of the present study was to examine the association between OSA and plasma DNA concentrations. METHODS: A case-control study was conducted using a total of 164 men aged 39-67 years, who were free of coronary heart disease and cancer. Laboratory-based overnight polysomnography was performed for all participants. RESULTS: On the basis of polysomnography, patients with an apnea-hypopnea index (AHI) = 5-30 events/h were defined as having mild-moderate OSA (n = 33) and those with >30 events/h were defined as having severe OSA (n = 49). All 82 controls had AHI < 5 events/h. Plasma DNA concentrations from all participants were analyzed for the beta-globin gene using fluorescence-based real-time polymerase chain reaction. Patients with severe OSA had significantly higher plasma DNA concentrations than persons with mild-moderate OSA and those without OSA (P < 0.05). AHI was significantly associated with body mass index (P < 0.001), hypertension (P < 0.001), and plasma DNA concentration (P < 0.05). CONCLUSION: After taking into account hypertension and other potential risk factors, persons with high plasma DNA concentrations (>8 microg/L) had approximately fourfold higher odds of OSA than those with low DNA levels. Further data are warranted to confirm the association for men and to evaluate the association for women.