EPHA3 regulates the multidrug resistance of small cell lung cancer via the PI3K/BMX/STAT3 signaling pathway

Tumor Biology - Multidrug resistance (MDR) is a major obstacle to the treatment of small cell lung cancer (SCLC). EPHA3 has been revealed to be the most frequently mutated Eph receptor gene in lung...     

A descriptive pharmacokinetic/pharmacodynamic analysis of continuous infusion ceftazidime-avibactam in a case series of critically ill renal patients treated for documented carbapenem-resistant Gram-negative bloodstream infections and/or ventilator-associated pneumonia

ObjectivesTo describe the pharmacokinetic/pharmacodynamic (PK/PD) behaviour of continuous infusion (CI) ceftazidime-avibactam and the microbiological outcome in a case series of critically ill renal patients treated for documented carbapenem-resistant Gram-negative (CR-GN) bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP).MethodsCritically ill patients with different degrees of renal function who were treated with CI ceftazidime-avibactam for documented CR-GN infections, and who underwent therapeutic drug monitoring from April 2021 to March 2022, were retrospectively assessed. Ceftazidime and avibactam concentrations were determined at steady-state, and the free fraction (fC_ss) was calculated. The joint PK/PD target of ceftazidime-avibactam was considered as optimal when both C_ss/MIC ratio for ceftazidime ≥4 (equivalent to 100%fT>_4xMIC) and C_ss/C_T ratio for avibactam >1 (equivalent to 100% fT>C_T of 4.0 mg/L) were simultaneously achieved (quasi-optimal if only one of the two was achieved, and suboptimal if neither of the two was achieved). The relationship between ceftazidime-avibactam PK/PD targets and microbiological outcome was assessed.ResultsTen patients with documented CR-GN infections (5 BSIs, 4 VAP, 1 BSI+VAP) were retrieved. The joint PK/PD targets of ceftazidime-avibactam were optimal and quasi-optimal in eight and two cases, respectively. Microbiological failure occurred in two patients (one with VAP, one with BSI+VAP), one of whom developed ceftazidime-avibactam resistance. Both underwent renal replacement therapy, and failed despite attaining optimal joint PK/PD target and receiving fosfomycin co-treatment.ConclusionCI administration may enable optimal joint PK/PD targets of ceftazidime-avibactam to be achieved in most critical renal patients with CR-GN infections, and may help to minimize the risk of microbiological failure.     

Frailty as a predictor of adverse outcomes in hospitalized older adults: A systematic review and meta-analysis

Frailty syndrome is prevalent among hospitalized older adults as are the occurrence of adverse outcomes. This systematic review and meta-analysis investigated whether frailty in older adults at hospital admission predicts adverse outcomes. Manual (ProQuest, conferences annals and references) and electronic searches (PUBMED, EMBASE, Web of Science, Lilacs, CINAHL, PsycINFO and Google Scholar) were performed. We included prospective studies of hospitalized older adults. Primary outcomes were functional decline at hospital discharge and mortality after discharge. Other data were considered secondary outcomes. Methodological quality was evaluated by the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Twenty-eight papers were included, corresponding to 19 cohorts (5 cohorts for functional decline and 16 for mortality), with moderate to good methodological quality. Being frail [RR: 1.32 (95%CI: 1.04; 1.67)] and pre-frail [RR: 1.51 (95%CI: 1.05; 2.17)] are risk factors for functional decline compared with being nonfrail. Frail individuals had a relative risk for in-hospital mortality and mortality in medium- and long-term compared to nonfrail (in-hospital RR: 8.20, medium RR: 9.49 and long RR: 7.94) and pre-frail (in-hospital RR: 3.19, medium RR: 3.31 and long RR: 3.72). The overall mortality risk in frail individuals is 3.49 and 2.14 times compared to nonfrail and pre-frail, respectively. Length of hospital stay was higher for frail older adults (13.5 days) compared with pre-frail (10.5 days) and nonfrail (8.3 days). Therefore, being frail at hospital admission is a risk factor for in-hospital mortality, long hospital stay, functional decline at hospital discharge, and mortality in the medium- and long-term.     

Genomic and biological characterization of the Vibrio alginolyticus-infecting “Podoviridae” bacteriophage,vB_ValP_IME271

Virus Genes - As an opportunist pathogen, Vibrio alginolyticus (V. alginolyticus), causes disease in marine animals. Bacterial contamination of seafood is not uncommon, and phage therapy is...     

Schistosomal myelitis: findings at MR imaging

Schistosomal spinal cord involvement is a rare complication of infection by Schistosoma mansoni. This work reports the MR imaging findings in a patient with schistosomal myelitis involving the lower spinal cord and conus medullaris. MR imaging showed a focal mass with a slightly nodular surface and which had peripheral enhancement after contrast administration. The MR appearance of this complication of schistosomal infection is important to recognize so that early medical therapy can be started in an attempt to maximize neurologic recovery.     

基于Oncomine数据库分析分泌性磷蛋白1在肝细胞癌中的表达及临床意义

目的 分析分泌性磷蛋白1(SPP1)在肝细胞癌中的表达,探索其对肝癌患者预后的影响.方法 基于Oncomine数据库,对肝细胞癌中的SPP1差异表达情况进行分析,探讨其意义;利用Kaplan Meier-Plotter在线分析工具,对患者生存情况进行分析;基于String数据库在线构建蛋白互作网络.结果 在筛选到的4项...