Computed Tomography Findings for Predicting Invasiveness of Lung Adenocarcinomas Manifesting as Pure Ground-Glass Nodules.

Purpose: To comprehensively evaluate qualitative and quantitative features for predicting invasiveness of pure ground-glass nodules (pGGNs) using multiplanar computed tomography. Methods: Ninety-three resected pGGNs (16 atypical adenomatous hyperplasia [AAH], 18 adenocarcinoma in situ [AIS], 31 minimally invasive adenocarcinoma [MIA], and 28 invasive adenocarcinoma [IA]) were retrospectively included. Two radiologists analyzed qualitative and quantitative features on three standard planes. Univariable and multivariable logistic regression analyses were performed to identify features to distinguish the pre-invasive (AAH/AIS) from the invasive (MIA/IA) group. Results: Tumor size showed high area under the curve (AUC) for predicting invasiveness (.860, .863, .874, and .893, for axial long diameter [AXLD], multiplanar long diameter, mean diameter, and volume, respectively). The AUC for AXLD (cutoff, 11 mm) was comparable to that of the volume (P = .202). The invasive group had a significantly higher number of qualitative features than the pre-invasive group, regardless of tumor size. Six out of 59 invasive nodules (10.2%) were smaller than 11 mm, and all had at least one qualitative feature. pGGNs smaller than 11 mm without any qualitative features (n = 16) were all pre-invasive. In multivariable analysis, AXLD, vessel change, and the presence or number of qualitative features were independent predictors for invasiveness. The model with AXLD and the number of qualitative features achieved the highest AUC (.902, 95% confidence interval .833-.971). Conclusion: In adenocarcinomas manifesting as pGGNs on computed tomography, AXLD and the number of qualitative features are independent risk factors for invasiveness; small pGGNs (<11 mm) without qualitative features have low probability of invasiveness.

Open channel block of Kv1.4 potassium channels by aripiprazole.

Aripiprazole is a quinolinone derivative approved as an atypical antipsychotic drug for the treatment of schizophrenia and bipolar disorder. It acts as with partial agonist activities at the dopamine D2 receptors. Although it is known to be relatively safe for patients with cardiac ailments, less is known about the effect of aripiprazole on voltage-gated ion channels such as transient A-type K+ channels, which are important for the repolarization of cardiac and neuronal action potentials. Here, we investigated the effects of aripiprazole on Kv1.4 currents expressed in HEK293 cells using a whole-cell patch-clamp technique. Aripiprazole blocked Kv1.4 channels in a concentration-dependent manner with an IC50 value of 4.4 µM and a Hill coefficient of 2.5. Aripiprazole also accelerated the activation (time-to-peak) and inactivation kinetics. Aripiprazole induced a voltage-dependent (δ = 0.17) inhibition, which was use-dependent with successive pulses on Kv1.4 currents without altering the time course of recovery from inactivation. Dehydroaripiprazole, an active metabolite of aripiprazole, inhibited Kv1.4 with an IC50 value of 6.3 µM (p < 0.05 compared with aripiprazole) with a Hill coefficient of 2.0. Furthermore, aripiprazole inhibited Kv4.3 currents to a similar extent in a concentration-dependent manner with an IC50 value of 4.9 µM and a Hill coefficient of 2.3. Thus, our results indicate that aripiprazole blocked Kv1.4 by preferentially binding to the open state of the channels.