Clinical significance of chest CT for the exclusion of COVID-19 in pre-admission screening: Is it worthwhile using chest CT with reverse-transcription polymerase chain reaction test?

BACKGROUND: A single reverse-transcription polymerase chain reaction (RT-PCR) test is not sufficient to exclude COVID-19 in hospital pre-admission screening. However, repeated RT-PCR tests are time-consuming. This study investigates the utility of chest computed tomography (CT) for COVID-19 screening in asymptomatic patients. METHODS: Between April 2020 and March 2021, RT-PCR testing and chest CT were performed to screen COVID-19 in 10 823 asymptomatic patients prior to admission. Chest CT findings were retrospectively evaluated using the reporting system of the Radiological Society of North America. Using RT-PCR results as a reference, we assessed the diagnostic efficacy of chest CT during both the low- and high-prevalence periods of the COVID-19 pandemic. RESULTS: Following a positive RT-PCR test, 20 asymptomatic patients (0.18%) were diagnosed with COVID-19; in the low-prevalence period, 5 of 6556 patients (0.076%) were positive; and in the high-prevalence period, 15 of 4267 patients (0.35%) were positive. Of the 20 asymptomatic COVID-19 positive patients, chest CT results were positive for COVID-19 pneumonia in 8 patients. Chest CT results were false-positive in 185 patients (1.7% false-positive rate, and 60% false-negative rate). Pneumonia that was classified as a "typical appearance" of COVID-19 reported as false-positives in 36 of 39 patients (92.3%). Across the study period, the diagnostic efficacy of "typical appearance" on chest CT were characterized by a sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of 15%, 99.7%, 99.7%, 7.7%, and 99.8%; 20%, 99.6%, 99.6%, 4%, and 99.9%; and 13.3%, 99.7%, 99.7%, 14.3%, and 99.7%, in the entire study, low-, and high-prevalence periods, respectively. CONCLUSIONS: Addition of chest CT to RT-PCR testing provides no benefit to the detection of COVID-19 in asymptomatic patients.

The G Protein Signal-Biased Compound TRV130; Structures, Its Site of Action and Clinical Studies.

Opioid agonists elicit their analgesic action mainly via µ opioid receptors; however, their use is limited because of adverse events including constipation and respiratory depression. It has been shown that analgesic action is transduced by the G protein-mediated pathway whereas adverse events are by the ß-arrestin-mediated pathway through µ opioid receptor signaling. The first new-generation opioid TRV130, which preferentially activates G protein- but not ß-arrestin-mediated signal, was constructed and developed to reduce adverse events. TRV130 and other G protein-biased compounds tend to elicit desirable analgesic action with less adverse effects. In clinical trials, the intravenous TRV130 (oliceridine) was evaluated in Phase I, II and III clinical studies. Here we review the discovery and synthesis of TRV130, its main action as a novel analgesic having less adverse events, its up-to-date status in clinical trials, and additional concerns about TRV130 as demonstrated in the literature.

Possible biased analgesic of hydromorphone through the G protein-over ß-arrestin-mediated pathway: cAMP, CellKey™, and receptor internalization analyses.

Morphine, fentanyl, and oxycodone are widely used as analgesics, and recently hydromorphone has been approved in Japan. Although all of these are selective for µ-opioid receptors (MORs) and have similar structures, their analgesic potencies and adverse effects (AEs) are diverse. Recent molecular analyses of MOR signaling revealed that the G protein-mediated signaling pathway causes analgesic effects and the ß-arrestin-mediated signaling pathway is responsible for AEs. We used several cell-based analyses that selectively measure cellular responses activated by either G protein- or ß-arrestin-mediated pathways. GloSensor™ cAMP, CellKey™, and receptor internalization assays were performed with four different types of cells stably expressing differentially labelled MOR. EC50 values measured by cAMP and CellKey™ assays had potencies in the order fentanyl ≤ hydromorphone < morphine ≤ oxycodone, all also exhibiting full agonist responses. However, in the internalization assay, only fentanyl elicited a full agonist response. Hydromorphone had the strongest potency next to fentanyl; however, contribution of the ß-arrestin-mediated pathway was small, suggesting that its effect could be biased toward the G protein-mediated pathway. Based on these properties, hydromorphone could be chosen as an effective analgesic.

Optimal diagnostic method using multidetector-row computed tomography for predicting lymph node metastasis in colorectal cancer.

BACKGROUND: Prediction of nodal involvement in colorectal cancer is an important aspect of preoperative workup to determine the necessity of preoperative treatment and the adequate extent of lymphadenectomy during surgery. This study aimed to investigate newer multidetector-row computed tomography (MDCT) findings for better predicting lymph node (LN) metastasis in colorectal cancer. METHODS: Seventy patients were enrolled in this study; all underwent MDCT prior to surgery and upfront curative resection for colorectal cancer. LNs with a short-axis diameter (SAD) ≥ 4 mm were identified on MDCT images, and the following measures were recorded by two radiologists independently: two-dimensional (2D) SAD, 2D long-axis diameter (LAD), 2D ratio of SAD to LAD, 2D CT attenuation value, three-dimensional (3D) SAD, 3D LAD, 3D SAD to LAD ratio, 3D CT attenuation value, LN volume, and presence of extranodal neoplastic spread (ENS), as defined by indistinct nodal margin, irregular capsular enhancement, or infiltration into adjacent structures. RESULTS: Forty-six patients presented 173 LNs with a SAD ≥ 4 mm, while 24 patients exhibited pathologically confirmed LN metastases. Receiver operating characteristic analysis revealed that 2D LAD was the most sensitive measure for LN metastases with an area under the curve of 0.752 (cut-off value, 7.05 mm). When combined with CT findings indicating ENS, 2D LAD (> or ≤ 7 mm) showed enhanced predictive power for LN metastases (area under the curve, 0.846; p < 0.001). CONCLUSIONS: LAD in axial MDCT imaging is the most sensitive measure for predicting colorectal LN metastases, especially when MDCT findings of ENS are observed.

Neuropeptide oxytocin enhances µ opioid receptor signaling as a positive allosteric modulator.

Oxytocin (OT) is a 9-amine neuropeptide that plays an essential role in mammalian labor, lactation, maternal bonding, and social affiliation. OT has been reported to exert an analgesic effect in both humans and animals, and the results of certain animal experiments have shown that the analgesic effect of OT is partially blocked by opioid receptor antagonists. To investigate the relationship between OT and µ opioid receptor (MOR), we evaluated how OT affects MOR in vitro by performing an electrical impedance-based receptor biosensor assay (CellKey™ assay), an intracellular cAMP assay, and a competitive receptor-binding analysis by using cells stably expressing human MOR and OT receptor. In both the CellKey™ assay and the intracellular cAMP assay, OT alone exerted no direct agonistic effect on human MOR, but treatment with 10-6 M OT markedly enhanced the MOR signaling induced by 10-6 M endomorphin-1, ß-endorphin, morphine, fentanyl, and DAMGO. Moreover, in the competitive receptor-binding assay, 10-6 M OT did not alter the affinity of endomorphin-1 or morphine for MOR. These results suggest that OT could function as a positive allosteric modulator that regulates the efficacy of MOR signaling, and thus OT might represent a previously unrecognized candidate analgesic agent.