Necessity of mandatory postoperative intensive care unit management after clipping surgery for unruptured intracranial aneurysms.

OBJECTIVE: Many neurosurgeons routinely perform postoperative intensive care unit (ICU) management after clipping of unruptured intracranial aneurysms (UIAs). However, whether routine postoperative ICU care is necessary remains a clinical question. Therefore, we investigated which factors acted as risk factors that actually required ICU care after microsurgical clipping of unruptured aneurysms. METHODS: We included a total of 532 patients who underwent clipping surgery for UIA between January 2020 and December 2020. The patients were divided into two groups: those who really required ICU care (41 patients, 7.7%) and those who did not (491 patients, 92.3%). A backward stepwise logistic regression model was used to identify factors that were independently associated with ICU care requirement. RESULTS: The mean hospital stay duration and the operation time were significantly longer in the ICU requirement group than in the no ICU requirement group (9.9 ± 10.7 vs. 6.3 ± 3.7 days, p = 0.041), (259.9 ± 128.4 vs. 210.5 ± 46.1 min, p = 0.019). The transfusion rate was significantly higher (p = 0.024) in the ICU requirement group. Multivariable logistic regression analysis identified male sex (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.15-4.76; p = 0.0195), operation time (OR, 1.01; 95% CI, 1.00-1.01; p = 0.0022), and transfusion (OR, 2.35; 95% CI, 1.00-5.51; p = 0.0500) as independent risk factors for requiring ICU care after clipping. CONCLUSIONS: Postoperative ICU management may not be mandatory after clipping surgery for UIAs. Our results suggest that postoperative ICU management may be more required in the male sex, patients with longer operation times, and those who received a transfusion.

In Search of Regional Stability in the Age of Hyper-Uncertainty: The US-China Strategic Competition and the Redesign of Regional Order in East Asia

The US-China strategic competition, combined with other structural changes such as the global spread of COVID-19, climate change, and competition for technological innovation has dramatically increased uncertainty in Asia. Against this backdrop, the strategic competition between the US and China in the 21st century shows profound differences from the hegemonic competition in the past. The systemic consequences of hyper-uncertainty, as we are witnessing, are protectionism, nationalism, and the proliferation of conflicts and disputes between states. A collection of four papers in this special issue systematically examine the way in which the US-China strategic competition combined with other factors amplify the instability of the regional order, and explain the dual dynamics of competition and cooperation that Asian countries demonstrate in responding to US-China strategic competition and redesigning the regional order. The US-China strategic competition further amplified the uncertainty of the world order. Strategic competition has limited their capabilities and willingness to provide the leadership needed to organize transnational cooperation though transnational cooperation is essential to effectively respond to transnational threats.

Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface.

The vast majority of intracellular protein targets are refractory toward small-molecule therapeutic engagement, and additional therapeutic modalities are needed to overcome this deficiency. Here, the identification and characterization of a natural product, WDB002, reveals a therapeutic modality that dramatically expands the currently accepted limits of druggability. WDB002, in complex with the FK506-binding protein (FKBP12), potently and selectively binds the human centrosomal protein 250 (CEP250), resulting in disruption of CEP250 function in cells. The recognition mode is unprecedented in that the targeted domain of CEP250 is a coiled coil and is topologically featureless, embodying both a structural motif and surface topology previously considered on the extreme limits of "undruggability" for an intracellular target. Structural studies reveal extensive protein-WDB002 and protein-protein contacts, with the latter being distinct from those seen in FKBP12 ternary complexes formed by FK506 and rapamycin. Outward-facing structural changes in a bound small molecule can thus reprogram FKBP12 to engage diverse, otherwise "undruggable" targets. The flat-targeting modality demonstrated here has the potential to expand the druggable target range of small-molecule therapeutics. As CEP250 was recently found to be an interaction partner with the Nsp13 protein of the SARS-CoV-2 virus that causes COVID-19 disease, it is possible that WDB002 or an analog may exert useful antiviral activity through its ability to form high-affinity ternary complexes containing CEP250 and FKBP12.