BACKGROUND The Centers for Disease Control and Prevention has shifted policy away from using ventilator-associated pneumonia (VAP) and toward using ventilator-associated conditions (VACs) as a marker ...of ICU quality. To date, limited prospective data regarding the incidence of VAC among medical and surgical ICU patients, the ability of VAC criteria to capture patients with VAP, and the potential clinical preventability of VACs are available. METHODS This study was a prospective 12-month cohort study (January 2013 to December 2013). RESULTS We prospectively surveyed 1,209 patients ventilated for ≥ 2 calendar days. Sixty-seven VACs were identified (5.5%), of which 34 (50.7%) were classified as an infection-related VAC (IVAC) with corresponding rates of 7.0 and 3.6 per 1,000 ventilator days, respectively. The mortality rate of patients having a VAC was significantly greater than that of patients without a VAC (65.7% vs 14.4%, P < .001). The most common causes of VACs included IVACs (50.7%), ARDS (16.4%), pulmonary edema (14.9%), and atelectasis (9.0%). Among IVACs, 44.1% were probable VAP and 17.6% were possible VAP. Twenty-five VACs (37.3%) were adjudicated to represent potentially preventable events. Eighty-six episodes of VAP occurred in 84 patients (10.0 of 1,000 ventilator days) during the study period. The sensitivity of the VAC criteria for the detection of VAP was 25.9% (95% CI, 16.7%-34.5%). CONCLUSIONS Although relatively uncommon, VACs are associated with greater mortality and morbidity when they occur. Most VACs represent nonpreventable events, and the VAC criteria capture a minority of VAP episodes.
A number of studies have reported that pathogenic and nonpathogenic foodborne bacteria have the ability to form filaments in microbiological growth media and foods after prolonged exposure to ...sublethal stress or marginal growth conditions. In many cases, nucleoids are evenly spaced throughout the filamentous cells but septa are not visible, indicating that there is a blockage in the early steps of cell division but the mechanism behind filament formation is not clear. The formation of filamentous cells appears to be a reversible stress response. When filamentous cells are exposed to more favorable growth conditions, filaments divide rapidly into a number of individual cells, which may have major health and regulatory implications for the food industry because the potential numbers of viable bacteria will be underestimated and may exceed tolerated levels in foods when filamentous cells that are subjected to sublethal stress conditions are enumerated. Evidence suggests that filament formation under a number of sublethal stresses may be linked to a reduced energy state of bacterial cells. This review focuses on the conditions and extent of filament formation by foodborne bacteria under conditions that are used to control the growth of microorganisms in foods such as suboptimal pH, high pressure, low water activity, low temperature, elevated CO2 and exposure to antimicrobial substances as well as lack a of nutrients in the food environment and explores the impact of the sublethal stresses on the cell's inability to divide.
•Bacteria can form filamentous cells under sublethal stress conditions.•The specific mechanism leading to filament formation may well be different for the different stresses imposed on the cell.•Filamentation may be a result of decreased levels of energy.•Filamentation may lead to an underestimation of health risks.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Sox2 (sex-determining region Y-box protein 2) is a transcription factor regulating pluripotency in embryonic stem cells. Sox2 is aberrantly expressed in breast and other cancers, though its ...biological significance remains widely unexplored. To understand the significance of this aberrancy, we assessed the transcription activity of Sox2 in two Sox2-expressing breast cancer cell lines, MCF7 and ZR751, using a lentiviral Sox2 GFP reporter vector. Surprisingly, Sox2 transcription activity, as measured by GFP expression encoded in a Sox2 reporter construct, was detectable only in a small subset of cells in both cell lines. Purification of GFP+ cells (cells with Sox2 activity) and GFP− cells (cells without Sox2 activity) was enriched for two phenotypically distinct cell populations in both MCF7 and ZR751 cell lines. Specifically, GFP+ cells formed significantly more colonies in methylcellulose and more mammospheres in vitro compared to GFP− cells. These phenotypic differences are directly linked to Sox2 as siRNA knockdown of Sox2 in GFP+ cells abolished these abilities. To provide a mechanistic explanation to our observations, we performed gel shift and chromatin immunoprecipitation studies; Sox2 was found to bind to its DNA binding consensus sequence and the promoters of Cyclin D1 and Nanog (two known Sox2 downstream targets) only in GFP+ cells. GFP+ cells also up-regulated CD49f, phospho-GSK3β, and β-catenin. In summary, we have identified two novel phenotypically distinct cell subsets in two breast cancer cell lines based on their differential Sox2 transcription activity. We demonstrate that Sox2 transcription activity, and not its protein expression alone, underlies the tumorigenicity and cancer stem cell-like phenotypes in breast cancers.
► Sox2 was transcriptionally active only in a small subset of breast cancer cells. ► Cells with Sox2 activity formed significantly more colonies in colony formation. ► Cells with Sox2 activity formed significantly more mammospheres. ► Cells with Sox2 activity and without Sox2 activity are biochemically different. ► Sox2 transcription activity but not its protein expression promotes tumorigenicity.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Pregnant people with coronavirus disease 2019 (COVID-19) experience higher risk for severe disease and adverse pregnancy outcomes, but no pharmacokinetic (PK) data exist to ...support dosing of COVID-19 therapeutics during pregnancy. We report PK and safety data for intravenous remdesivir in pregnancy. Methods IMPAACT 2032 was a phase 4 prospective, open-label, nonrandomized opportunistic study of hospitalized pregnant and nonpregnant women receiving intravenous remdesivir as part of clinical care. Intensive PK sampling was performed on infusion days 3, 4, or 5 with collection of plasma and peripheral blood mononuclear cells (PBMCs). Safety data were recorded from first infusion through 4 weeks after last infusion and at delivery. Geometric mean ratios (GMR) (90% confidence intervals CI) of PK parameters between pregnant and nonpregnant women were calculated. Results Fifty-three participants initiated remdesivir (25 pregnant; median gestational age, 27.6 weeks; interquartile range, 24.9–31.0 weeks). Plasma exposures of remdesivir, its 2 major metabolites (GS-704277 and GS-441524), and the free remdesivir fraction were similar between pregnant and nonpregnant participants. Concentrations of the active triphosphate (GS-443902) in PBMCs increased 2.04-fold (90% CI, 1.35–3.03) with each additional infusion in nonpregnant versus pregnant participants. Three adverse events in nonpregnant participants were related to treatment (1 grade 3; 2 grade 2 resulting in treatment discontinuation). There were no treatment-related adverse pregnancy outcomes or congenital anomalies detected. Conclusions Plasma remdesivir PK parameters were comparable between pregnant and nonpregnant women, and no safety concerns were identified based on our limited data. These findings suggest no dose adjustments are indicated for intravenous remdesivir during pregnancy. Clinical Trials Registration NCT04582266.
The COVID-19 pandemic exposed the limitations of global health systems' abilities to manage the rapid spread of a novel infectious disease, which was exacerbated by shortages of respiratory ...protective devices and other critical personal protective equipment (PPE). An advisory panel of experienced health-care professionals with backgrounds in Occupational and Environmental Health and Safety (OEHS), Infection Prevention, Nursing, and Clinical Application Specialists convened to discuss challenges and strategies associated with the selection and use of respiratory protective devices as experienced during the first year of the COVID-19 pandemic. This discussion led to the following recommendations: 1) the need for clear communication of alternative respiratory protection selection and use recommendations in accordance with US regulatory and agency guidance; 2) the need for collaboration between Infection Prevention, OEHS, clinical staff, supply chain/materials management, emergency preparedness, executive leadership, and finance; 3) the need for adequate stockpiling, inventory rotation, and diverse respiratory protection options to accommodate the majority of health-care workers; 4) the need for efficient and innovative strategies to communicate evolving regulatory, agency, and facility recommendations and to deliver appropriate training on respiratory protection; and 5) the need for additional research on respiratory protection use - involving filtering facepiece respirators (FFRs) as well as other respirator types designed to be reused - to balance infection prevention best practices with a sustainable process. In conclusion, these considerations may offer guidance and identify areas for research on preparedness, communication, education, and training to enhance the preparation of health-care facilities including community-based health-care organizations for unexpected public health events. Keywords: COVID-19, personal protective equipment, PPE, filtering facepiece respirator, infection prevention, environmental health and safety, nursing
Background The National Healthcare Safety Network (NHSN) has recently supported efforts to shift surveillance away from ventilator-associated pneumonia to ventilator-associated events (VAEs) to ...decrease subjectivity in surveillance and minimize concerns over clinical correlation. The goals of this study were to compare the results of an automated surveillance strategy using the new VAE definition with a prospectively performed clinical application of the definition. Methods All patients ventilated for ≥2 days in a medical and surgical intensive care unit were evaluated by 2 methods: retrospective surveillance using an automated algorithm combined with manual chart review after the NHSN's VAE methodology and prospective surveillance by pulmonary physicians in collaboration with the clinical team administering care to the patient at the bedside. Results Overall, a similar number of events were called by each method (69 vs 67). Of the 1,209 patients, 56 were determined to have VAEs by both methods (κ = .81, P = .04). There were 24 patients considered to be a VAE by only 1 of the methods. Most discrepancies were the result of clinical disagreement with the NHSN’s VAE methodology. Conclusions There was good agreement between the study teams. Awareness of the limitations of the surveillance definition for VAE can help infection prevention personnel in discussions with critical care partners about optimal use of these data.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In 2013, a before-and-after intervention study was conducted to evaluate the effect 24-hour intensivist coverage on length of stay and rates of catheter-associated urinary tract infection, ...central-line associated blood stream infection, and ventilator-associated events. Intensivist coverage for 24 hours did not decrease length of stay or result in a decrease in any specific infection rate.
PDF
