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Background: Sepsis is the most common cause of death in hospitals, and intra-abdominal infection (IAI) accounts for a large portion of the causes of sepsis. We investigated the clinical outcomes and factors influencing mortality of patients with sepsis due to IAI. Methods: This post-hoc analysis of a prospective cohort study included 2126 patients with sepsis who visited 16 tertiary care hospitals in Korea (September 2019–February 2020). The analysis included 219 patients aged > 19 years who were admitted to intensive care units owing to sepsis caused by IAI. Results: The incidence of septic shock was 47% and was significantly higher in the non-survivor group (58.7% vs 42.3%, p = 0.028). The overall 28-day mortality was 28.8%. In multivariable logistic regression, after adjusting for age, sex, Charlson Comorbidity Index, and lactic acid, only coagulation dysfunction (odds ratio: 2.78 [1.47–5.23], p = 0.001) was independently associated, and after adjusting for each risk factor, only simplified acute physiology score III (SAPS 3) (p < 0.001) and continuous renal replacement therapy (CRRT) (p < 0.001) were independently associated with higher 28-day mortality. Conclusions: The SAPS 3 score and acute kidney injury with CRRT were independently associated with increased 28-day mortality. Additional support may be needed in patients with coagulopathy than in those with other organ dysfunctions due to IAI because patients with coagulopathy had worse prognosis. [ABSTRACT FROM AUTHOR]

Background: Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity. Methods: We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples. Results: We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep_VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep_VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data. Conclusions: This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: The poor performance of conventional techniques used in cardiovascular disease patients requiring hemodialysis or arterial bypass grafting has prompted tissue engineers to search for clinically appropriate off-the-shelf vascular grafts. Most patients with cardiovascular disease lack suitable autologous tissue because of age or previous surgery. Commercially available vascular grafts with diameters of < 5 mm often fail because of thrombosis and intimal hyperplasia. Result: Here, we tested tubular biodegradable poly-e-caprolactone/polydioxanone (PCL/PDO) electrospun vascular grafts in a rat model of aortic interposition for up to 12 weeks. The grafts demonstrated excellent patency (100%) confirmed by Doppler Ultrasound, resisted aneurysmal dilation and intimal hyperplasia, and yielded neoarteries largely free of foreign materials. At 12 weeks, the grafts resembled native arteries with confluent endothelium, synchronous pulsation, a contractile smooth muscle layer, and co-expression of various extracellular matrix components (elastin, collagen, and glycosaminoglycan). Conclusions: The structural and functional properties comparable to native vessels observed in the neoartery indicate their potential application as an alternative for the replacement of damaged small-diameter grafts. This synthetic off-the-shelf device may be suitable for patients without autologous vessels. However, for clinical application of these grafts, long-term studies (> 1.5 years) in large animals with a vasculature similar to humans are needed. [ABSTRACT FROM AUTHOR]

In the original publication of this article [1], there are mistakes in Fig. 4d. The corrected Fig. 4 should be: [ABSTRACT FROM AUTHOR]

Background: Androgen receptor (AR)-targeted treatments improve the survival of castration-resistant prostate cancer (CRPC) patients; however, secondary resistance to these agents ultimately occurs in virtually all patients. Therefore, alternative therapeutic targets are urgently needed. Since growing evidence demonstrates that WNT/β-catenin signaling plays an important role in CRPC, the antitumor activity and mechanism of action of CWP232291, a small molecule β-catenin inhibitor, were investigated in prostate cancer. Methods: We assessed the antitumor activity of CWP232291 in prostate cancer cell lines and primary cells derived from CRPC patients. The effect of CWP232291 on apoptotic cell death, endoplasmic reticulum (ER) stress, cell viability, and WNT/β-catenin signaling was evaluated by flow cytometry, western blotting, luciferase reporter assay, and fluorescence microscopy. Antitumor efficacy was assessed in two CRPC xenograft mouse models. Results: CWP232291 induced ER stress, resulting in upregulation of the proapoptotic protein CHOP and activation of caspase-3-dependent apoptosis. In addition, CWP232291 suppressed the expression of β-catenin by affecting WNT-dependent transcriptional activity, and downregulated AR and its splice variants in prostate cancer cells. Antitumor activity was observed in prostate cancer cells in vitro and ex vivo, and antitumor efficacy was observed in vivo. Conclusions: Beyond providing preclinical evidence of therapeutic efficacy for the novel small molecule β-catenin inhibitor CWP232291 in CRPC, our results show that inducing ER stress and targeting WNT/β-catenin signaling may be a novel strategy against CRPC. [ABSTRACT FROM AUTHOR]