Targeting the IL-6 Dependent Phenotype Can Identify Novel Therapies for Cholangiocarcinoma

The need for new therapies for cholangiocarcinoma is highlighted by their poor prognosis and refractoriness to chemotherapy. Increased production of Interleukin-6 promotes cholangiocarcinoma growth and contributes to chemoresistance by activating cell survival mechanisms. We sought to identify biologically active compounds capable of ameliorating the phenotypic effects of IL-6 expression and to explore their potential therapeutic use for cholangiocarcinoma.A genomic signature associated with Interleukin-6 expression in Mz-ChA-1 human malignant cholangiocytes was derived. Computational bioinformatics analysis was performed to identify compounds that induced inverse gene changes to the signature. The effect of these compounds on cholangiocarcinoma growth was then experimentally verified in vitro and in vivo. Interactions with other therapeutic agents were evaluated using median effects analysis.A group of structurally related compounds, nitrendipine, nifedipine and felodipine was identified. All three compounds were cytotoxic to Mz-ChA-1 cells with an IC50 for felodipine of 26 µM, nitrendipine, 44 µM and nifedipine, 15 µM. Similar results were observed in KMCH-1, CC-LP-1 and TFK-1 cholangiocarcinoma cell lines. At a fractional effect of 0.5, all three agents were synergistic with either camptothecin or gemcitabine in Mz-ChA-1 cells in vitro. Co-administration of felodipine and gemcitabine decreased the growth of Mz-ChA-1 cell xenografts in nude athymic mice.Computational bioinformatics analysis of phenotype-based genomic expression can be used to identify therapeutic agents. Using this drug discovery approach based on targeting a defined tumor associated phenotype, we identified compounds with the potential for therapeutic use in cholangiocarcinoma

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Current Status of Transurethral Prostatectomy: A Korean Multicenter Study

Purpose: We aimed to verify the current status of transurethral resection of the prostate (TURP) in Korea. Materials and Methods: The medical records of 1,341 men who underwent TURP in 9 Korean medical centers between 2004 and 2008 were reviewed. The patients were divided into two groups according to time periods: 2004-2005 (group 1) and 2006-2008 (group 2). To verify differences in the two patient groups, age, prostate volume, indications for TURP, preoperative International Prostate Symptom Score (IPSS), and resected tissue weight were evaluated. Results: The mean age of the patients was 71.2 years and the mean IPSS was 22.7. The patients’ characteristics were not significantly different between the two groups. The annual cases of TURP increased over the study period. The proportion of lower urinary tract symptoms (LUTS) as an indication for TURP increased up to 58.3% in group 2 compared with 51.6% in group 1 (p=0.019). However, the proportion of patients who presented with acute urinary retention decreased from 35.5% to 30.3% with marginal statistical significance (p=0.051). Other indications such as hematuria, bladder stone, recurrent urinary tract infection, and hydronephrosis were not significantly different between the groups. The mean resected weights of the prostate were similar (17.5 g in group 1 and 18.3 g in group 2, respectively; p>0.05). Conclusions: TURP has been steadily performed in patients with benign prostatic hyperplasia and it is expected to remain constant. LUTS was the most common indication for TURP in recent years

Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis: a comparison with bacteremia caused by Enterobacteriaceae

BACKGROUND: This study was performed to detect risk factors for Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis. METHODS: A retrospective case–control study was designed to identify risk factors for P. aeruginosa bacteremia in cirrhotic patients. The cases were cirrhotic patients with P. aeruginosa bacteremia and the controls were cirrhotic patients with Enterobacteriaceae bacteremia. RESULTS: Sixty-one cases and the same number of controls were enrolled. In a multivariate analysis, younger age {adjusted odds ratio (aOR) per one year: 0.96, 95% confidence interval: 0.93 - 0.99}, nosocomial acquisition (aOR 3.87, 95% confidence interval: 1.50 - 9.94), preexisting biliary disease (aOR 4.79, 95% confidence interval: 1.92 - 10.47), and recent exposure to immunosuppressive agent (aOR 3.10, 95% confidence interval: 1.23 - 7.82) were associated with P. aeruginosa bacteremia. In the case group the frequency of appropriate initial antibiotic regimens was considerably lower than in the control group: 29.5% vs. 65.6% (P <0.01). However, thirty day mortality did not differ significantly between cases and controls (19.7% vs. 24.6%). CONCLUSIONS: Nosocomial acquisition, preexisting biliary disease, and recent use of immunosuppressive agents are strong predictive factors for P. aeruginosa bacteremia in cirrhotic patients