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Neutrophil functional changes caused by sepsis itself and their time-course variation have not been fully elucidated because previous studies targeted patients who had received therapeutic interventions. We explored the multilateral functions of circulating neutrophils in patients with severe sepsis or septic shock who had not yet undergone interventions, and followed their changes. Patients were treated based on the Surviving Sepsis Campaign Guidelines 2012. Neutrophil functions were evaluated on days 0 (before therapeutic intervention), 3, and 7 in 59 septic patients. The clinical severity score (APACHE II and SOFA) and serum pro-/anti-inflammatory cytokine concentrations of the patients were significantly increased on day 0 and normalized on day 3. However, neutrophil priming state, estimated by measuring the fMLP-stimulated reactive oxygen species, was significantly elevated on day 0, further augmented on day 3, and then returned to day 0 levels on day 7 despite general resolution of the inflammatory response. The expression of CXC chemokine receptor 2 and paired immunoglobulin-like receptor α, assessed as surrogate markers of transmigration and adhesion potency, was suppressed most strongly on day 0 and gradually recovered. To conclude, contrary to the patient's clinical course, neutrophil priming state was augmented most strongly at 3 days after diagnosis of sepsis. Impaired transmigration and excessive adhesion potency were observed most prominently at diagnosis. These observations would partially explain the mechanism of development of multiple organ dysfunction of the host who is subjected to a secondary insult, and may provide an important perspective for the implementation of additional immune-modulating therapy in sepsis.

要旨 症例は61歳男性。自転車で走行中にトラックにはね飛ばされ前医に搬送された。前医で骨盤骨折と診断，血管内治療目的で当院に転院搬送となった。CT検査で心囊気腫・左血気胸・左肺挫傷・肋骨骨折・骨盤骨折を認めた。胸腔ドレーン挿入，血管造影検査施行後に集中治療室管理とした。気胸と心囊気腫を伴った鈍的胸部外傷症例であることから，外傷性心囊破裂を疑いvideo assisted thoracic surgery（VATS）を施行した。しかし胸腔内及び心膜観察が充分に行えず，開胸手術に移行したところ横隔神経背側に最大長約10cmの心囊破裂を認めた。心臓自体に損傷を認めず，破裂部位を非吸収性ポリプロピレン糸にて水平マットレス縫合2針で閉鎖した。外傷性心囊破裂により心ヘルニアとなった場合，循環不全を来し致命的となりえるため緊急手術が必要である。一方，心ヘルニア非合併型外傷性心囊破裂症例では特異的な症状を呈さず，診断も困難である。また遅発性心ヘルニア発症の可能性があり，確実な診断と治療が重要となる。積極的な探査手術により診断・治療に至った心ヘルニア非合併型外傷性心囊破裂の1例を報告する。

During drug discovery, drug candidates are narrowed down over several steps to develop pharmaceutical products. The theoretical chemical space in such steps is estimated to be [Formula: see text]. To cover that space, extensive virtual compound libraries have been developed; however, the compilation of extensive libraries comes at large computational cost. Thus, to reduce the computational cost, researchers have constructed custom-made virtual compound libraries that focus on target diseases. In this study, we develop a system that generates virtual compound libraries from input compounds. When a user inputs a compound, the system recursively applies virtual synthetic reaction rules to the compound to improve its properties. The synthetic pathway can also be traced by the user because the reaction rules in this system are based on real organic synthesis reactions. This system has useful functions for effective drug design, such as structural preservation, allowing the substructures necessary for potency to be maintained. In this paper, to confirm the effect of directional reaction sets, we applied the reaction sets to 100 compounds. Moreover, to confirm that the system can reproduce real synthetic pathways, the synthetic pathways of Ibuprofen and Ofloxacin were explored by inputting isobutyl benzene and 7,8-difluoro-2,3-dihydro-3-methyl-4H-benzoxazine. This application is available at the following URL: http://enh.sekijima-lab.org .

The purpose of this study was to identify computed tomography (CT) findings that predict the need for angioembolization in patients with pelvic fracture.This retrospective cross-sectional study was performed between April 2006 and October 2015 at two urban emergency medical centers in Japan. The study included patients who underwent CT within 3 hours of arrival and were diagnosed with a pelvic fracture. The study outcome was undergoing angioembolization within 24 hours of arrival. Four independent readers blinded to all clinical information interpreted the CT scans for blush, thickness of retroperitoneal hematoma, and diameter and laterality of muscle swelling around the pelvis. Receiver operating characteristics analyses provided area under the receiver-operating characteristic curves (AUROC) and diagnostic indicators at the estimated thresholds including sensitivity, specificity, positive and negative predictive values and diagnostic odds ratio (DOR). The interobserver reliability of all radiographic findings was also evaluated.Fifty-two of 244 eligible patients underwent angioembolization. The predictive ability in terms of DOR was relatively better with blush on CT scan (sensitivity, 0.57; specificity, 0.86; DOR, 8.05) than with laterality of muscle swelling of 12.9 mm or greater (sensitivity, 0.79; specificity, 0.55; DOR, 4.60; AUROC, 0.75) and thickness of retroperitoneal hematoma of 22.7 mm or greater (sensitivity, 0.65; specificity, 0.74; DOR, 5.39; AUROC, 0.73). The interobserver reliability of blush, laterality of muscle swelling, and thickness of retroperitoneal hematoma was 0.43, 0.54, and 0.70, respectively.All of the tested CT findings failed to show both sufficient predictive ability and sufficient interobserver agreement. Further diagnostic accuracy studies to validate these findings or establish a prediction model incorporating these findings are expected.Diagnostic, level V.