Hormone refractory metastatic prostate cancer remains an incurable disease. We found that high expression levels of the chemokine receptor CXCR4 correlated with the presence of metastatic disease in prostate cancer patients. Positive staining for CXCL12, the ligand for CXCR4, was mainly present in the tumor-associated blood vessels and basal cell hyperplasia. Subcutaneous xenografts of PC3 and 22Rv1 prostate tumors that overexpressed CXCR4 in NOD/SCID mice were two- to threefold larger in volume and weight vs. controls. Moreover, blood vessel density, functionality, invasiveness of tumors into the surrounding tissues, and metastasis to the lymph node and lung were significantly increased in these tumors. Neutralizing the interactions of CXCL12/CXCR4 in vivo with CXCR4 specific antibodies inhibited the CXCR4-dependent tumor growth and vascularization. In vitro, CXCL12 induced the proliferation and VEGF secretion but not migration of PC3 and 22Rv1 cells overexpressing CXCR4. Similar effects of CXCR4 overexpression on tumor growth in vivo were also noted in two breast cancer lines, suggesting that the observed effect of CXCR4 is not unique to prostate tumor cells. Thus high levels of the chemokine receptor CXCR4 induce a more aggressive phenotype in prostate cancer cells and identify CXCR4 as a potential therapeutic target in advanced cases of metastatic prostate cancer.
Extended-spectrum -lactamase (ESBL)-producing Enterobacteriaceae are pathogens that may lead to a spectrum of clinical syndromes. We aimed to identify predictors and outcomes of ESBL bacteremia upon hospital admission (UHA) in a nationwide prospective study. Thus, a multicenter prospective study was conducted in 10 Israeli hospitals. Adult patients with bacteremia due to Enterobacteriaceae diagnosed within 72 h of hospitalization were included. Patients with ESBL producers (cases) were compared to those with non-ESBL producers (controls), and a 1:1 ratio was attempted in each center. A case-control study to identify predictors and a cohort study to identify outcomes were conducted. Bivariate and multivariate logistic regressions were used for analyses. Overall, 447 patients with bacteremia due to Enterobacteriaceae were recruited: 205 cases and 242 controls. Independent predictors of ESBL were increased age, multiple comorbid conditions, poor functional status, recent contact with health care settings, invasive procedures, and prior receipt of antimicrobial therapy. In addition, patients presenting with septic shock and/or multiorgan failure were more likely to have ESBL infections. Patients with ESBL producers suffered more frequently from a delay in appropriate antimicrobial therapy (odds ratio [OR], 4.7; P, <0.001) and had a higher mortality rate (OR, 3.5; P, <0.001). After controlling for confounding variables, both ESBL production (OR, 2.3; P, 9.1) and a delay in adequate therapy (OR, 0.05; P, 0.001) were significant predictors for mortality and other adverse outcomes. We conclude that among patients with bacteremia due to Enterobacteriaceae UHA, those with ESBL producers tend to be older and chronically ill and to have a delay in effective therapy and severe adverse outcomes. Efforts should be directed to improving the detection of patients with ESBL bacteremia UHA and to providing immediate appropriate therapy.Enterobacteriaceae producing extended-spectrum -lactameses (ESBL) pose a major worldwide threat (27). These pathogens are resistant to all penicillins and cephalosporins and often are coresistant to multiple other classes of antibiotics (2). Thus, therapeutic options to treat infections with these pathogens are limited (27). The Infectious Diseases Society of America has listed ESBL-producing Enterobacteriaceae as pathogens necessitating the urgent development of new and novel therapeutics (37). While infections caused by ESBLproducing strains have been acquired primarily in hospitals and health care institutions, recent reports from multiple parts of the world show that these pathogens now have a role in community-acquired infections as well (2,3,5,6,8,9,12,15,19,27,29,30,32,38). The burden of these infections is enormous, and compared to bacteremia caused by non-ESBL-producing Enterobacteriaceae, infections caused by ESBL producers are associated with a significantly higher mortality rate, 6 additional days of hospitalization, and approximately $10,000 in additional costs per case (35,36).There ...
NCC in travelers is a rare phenomenon commonly presenting as seizure disorder manifesting months to years post-travel. Antihelminthic therapy followed by 12 to 24 months of antiepileptic therapy resulted in complete resolution of symptoms in our patients.
Background Among the many medical challenges presented by the COVID-19 pandemic, management of the majority of patients in community outpatient settings is crucial. The aim of this study was to describe the characteristics and outcomes among confirmed COVID-19 cases who were managed at three settings: two outpatient settings and one inpatient. Methods A retrospective database cohort study was conducted in a large Israeli Health Maintenance Organization. All COVID-19 cases diagnosed between 28 February 2020 and 20 July 2020 were included. Cases in the community settings were managed through a nationwide remote monitoring center, using preliminary telehealth triage and 24/7 virtual care. Outcome parameters included hospital admission, disease severity, need for respiratory support and mortality. Results About 5448 cases, aged range 0–97 years, were enrolled; 88.7% were initially managed as outpatient either at home or in designated hotels, 3.1 and 2.1% of them, respectively, later required hospitalization. The main reason for hospitalization was dyspnea; 12 were diagnosed with severe disease; 56 patients (1.3%) died, five (0.1%) of whom were initially allocated to the outpatient settings. Conclusions Care for appropriately selected COVID-19 patients in the community provides a safe and effective option. This can contribute to reducing the hospitalization burden, with no evidence of increased morbidity or mortality.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.