Clinical outcomes following inpatient penicillin allergy testing: A systematic review and meta-analysis.

BACKGROUND: A documented penicillin allergy is associated with increased morbidity including length of hospital stay and an increased incidence of resistant infections attributed to use of broader-spectrum antibiotics. The aim of the systematic review was to identify whether inpatient penicillin allergy testing affected clinical outcomes during hospitalization. METHODS: We performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library over the past 20 years. Inpatients having a documented penicillin allergy that underwent penicillin allergy testing were included. RESULTS: Twenty-four studies met eligibility criteria. Study sample size was between 24 and 252 patients in exclusively inpatient cohorts. Penicillin skin testing (PST) with or without oral amoxicillin challenge was the main intervention described (18 studies). The population-weighted mean for a negative PST was 95.1% [CI 93.8-96.1]. Inpatient penicillin allergy testing led to a change in antibiotic selection that was greater in the intensive care unit (77.97% [CI 72.0-83.1] vs 54.73% [CI 51.2-58.2], P<.01). An increased prescription of penicillin (range 9.9%-49%) and cephalosporin (range 10.7%-48%) antibiotics was reported. Vancomycin and fluoroquinolone use was decreased. Inpatient penicillin allergy testing was associated with decreased healthcare cost in four studies. CONCLUSIONS: Inpatient penicillin allergy testing is safe and effective in ruling out penicillin allergy. The rate of negative tests is comparable to outpatient and perioperative data. Patients with a documented penicillin allergy who require penicillin should be tested during hospitalization given its benefit for individual patient outcomes and antibiotic stewardship.

MicroRNA-185 suppresses tumor growth and progression by targeting the Six1 oncogene in human cancers.

Homeobox genes encode transcription factors that are essential for normal development and are often dysregulated in cancers. The molecular mechanisms that cause their misregulation in cancers are largely unknown. In this study, we investigate the mechanism by which the Six1 homeobox protein, which has a crucial role during development, is frequently deregulated in several poor outcome, aggressive, metastatic adult human cancers, including breast cancer, ovarian cancer, hepatocellular carcinoma and pediatric malignancies such as rhabdomyosarcoma and Wilms' tumor. Our results reveal that miRNA-185 translationally represses Six1 by binding to its 3'-untranslated region. Analyses of ovarian cancers, pediatric renal tumors and multiple breast cancer cell lines showed decreased miR-185 expression, paralleling an increase in Six1 levels. Further investigation revealed that miR-185 impedes anchorage-independent growth and cell migration, in addition to suppressing tumor growth in vivo, implicating it to be a potent tumor suppressor. Our results indicate that miR-185 mediates its tumor suppressor function by regulating cell-cycle proteins and Six1 transcriptional targets c-myc and cyclin A1. Furthermore, we show that miR-185 sensitizes Six1-overexpressing resistant cancer cells to apoptosis in general and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in particular. Together, our findings suggest that the altered expression of the novel tumor suppressor miR-185 may be one of the central events that leads to dysregulation of oncogenic protein Six1 in human cancers.