Relation of serum uric acid levels to readmission and mortality in patients with heart failure.

Data on the association between uric acid (UA) levels and clinical outcomes, such as readmission and mortality, in patients with heart failure are scarce. This study explores whether UA exhibits an independent association with the composite endpoint (clinical outcome during 6 months after discharge, including mortality and 6-month readmission) in patients with chronic heart failure while controlling for other covariates. This study was an observational retrospective study. A cohort of 1943 consecutive patients diagnosed with chronic heart failure, who were admitted between December 2016 and June 2019, was included in the study. Data were sourced from PhysioNet. The independent variable analyzed was the UA level, and the dependent variable was a composite endpoint comprising mortality and 6-month readmission. The study had 1943 participants, of which 91.04% were aged more than 60 years and 58.05% were female. The fully-adjusted model yielded a positive correlation between UA levels (per 10 µmol/L) and the composite endpoint as well as readmission, following adjustment for confounding variables (HR = 1.01, 95% CI 1.00-1.01). Notably, a non-linear relationship was observed between UA levels and the composite endpoint, particularly readmission, with a J-shaped correlation observed between UA levels and both the composite endpoint and readmission. Overall, we found that the serum UA levels at admission were independently and positively associated with the risk of the composite endpoint (clinical outcomes during 6 months after discharge), especially readmission after adjusting other covariates. A J-shaped relationship was observed between UA levels and the composite endpoint and readmission.

Quantitative Comparison of Cephalogram and Cone-Beam Computed Tomography in the Evaluation of Alveolar Bone Thickness of Maxillary Incisors.

OBJECTIVE: This study aims to quantitatively compare cephalogram and cone-beam computed tomography (CBCT) when evaluating maxillary central incisor alveolar bone thickness. METHODS: We used 30 sets of lateral cephalograms and CBCT images that were recorded at the same time. Labial, buccal, and overall alveolar bone thicknesses were measured on three measurement lines of the forward-most incisor in lateral cephalograms and four maxillary incisors in CBCT images. Paired t-test, interclass correlation coefficient analysis, one-way analysis of variance (ANOVA), and Bland-Altman analysis were used to assess cephalometrically measured alveolar bone thickness of maxillary incisors and compare these measurements with those made using CBCT images. RESULTS: Significant differences were observed between cephalometric and CBCT-based measurements of maxillary incisor alveolar bone thickness; most values showed mild or moderate correlation between the two methods. In most cases, cephalometric measurements were greater than CBCT-based measurements. Bland-Altman plots and ANOVA revealed that measurement bias increased when measurement lines moved apically. Alveolar bone thickness was always overestimated on cephalograms. CONCLUSION: Maxillary incisor alveolar bone thickness is always overestimated on cephalograms compared with CBCT-based measurements, with the overestimations ranging from 0.3 to 1.3 mm. Cephalometric measurement bias increases when measurement lines move apically. Thus, CBCT should be recommended when the accurate evaluation of alveolar bone thickness is warranted.

Structural basis of the therapeutic anti-PD-L1 antibody atezolizumab.

Monoclonal antibodies targeting PD-1/PD-L1 signaling pathway have achieved unprecedented success in cancer treatment over the last few years. Atezolizumab is the first PD-L1 monoclonal antibody approved by US FDA for cancer therapy; however the molecular basis of atezolizumab in blocking PD-1/PD-L1 interaction is not fully understood. Here we have solved the crystal structure of PD-L1/atezolizumab complex at 2.9 angstrom resolution. The structure shows that atezolizumab binds the front beta-sheet of PD-L1 through three CDR loops from the heavy chain and one CDR loop from the light chain. The binding involves extensive hydrogen-bonding and hydrophobic interactions. Notably there are multiple aromatic residues from the CDR loops forming Pi-Pi stacking or cation-Pi interactions within the center of the binding interface and the buried surface area is more than 2000 Å2, which is the largest amongst all the known PD-L1/antibody structures. Mutagenesis study revealed that two hot-spot residues (E58, R113) of PD-L1 contribute significantly to the binding of atezolizumab. The structure also shows that atezolizumab binds PD-L1 with a distinct heavy and light chain orientation and it blocks PD-1/PD-L1 interaction through competing with PD-1 for the same PD-L1 surface area. Taken together, the complex structure of PD-L1/atezolizumab solved here revealed the molecular mechanism of atezolizumab in immunotherapy and provides basis for future monoclonal antibody optimization and rational design of small chemical compounds targeting PD-L1 surface.