Weaning from mechanical ventilation: a cross-sectional study of reference values and the discriminative validity of aging

[Purpose] To evaluate pre-extubation variables and check the discriminative validity of age as well as its correlation with weaning failure in elderly patients. [Subjects and Methods] Two hundred thirty-nine consecutive patients (48% female) who were on mechanical ventilation and had undergone orotracheal intubation were divided into four subgroups according to their age: <59 years, 60–69 years, 70–79 years, and >80 years old. The expiratory volume (V_E), respiratory frequency (f), tidal volume (V_T), and respiratory frequency/tidal volume ratio (f/V_T) were used to examine differences in weaning parameters between the four subgroups, and age was correlated with weaning failure. [Results] The rate of weaning failure was 27.8% in patients aged >80 years and 22.1% in patients aged <60 years old. Elderly patients presented higher f/V_T and f values and lower V_T values. The areas under the receiver operating characteristic curves for f/V_T ratio were smaller than those published previously. [Conclusion] Our results indicate that aging influences weaning criteria without causing an increase in weaning failure.Key words: Weaning, Mechanical ventilation, Aging     

Musashi2 sustains the mixed-lineage leukemia–driven stem cell regulatory program

Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. Leukemia cells exhibit a dysregulated developmental program as the result of genetic and epigenetic alterations. Overexpression of the RNA-binding protein Musashi2 (MSI2) has been previously shown to predict poor survival in leukemia. Here, we demonstrated that conditional deletion of Msi2 in the hematopoietic compartment results in delayed leukemogenesis, reduced disease burden, and a loss of LSC function in a murine leukemia model. Gene expression profiling of these Msi2-deficient animals revealed a loss of the hematopoietic/leukemic stem cell self-renewal program and an increase in the differentiation program. In acute myeloid leukemia patients, the presence of a gene signature that was similar to that observed in Msi2-deficent murine LSCs correlated with improved survival. We determined that MSI2 directly maintains the mixed-lineage leukemia (MLL) self-renewal program by interacting with and retaining efficient translation of Hoxa9, Myc, and Ikzf2 mRNAs. Moreover, depletion of MLL target Ikzf2 in LSCs reduced colony formation, decreased proliferation, and increased apoptosis. Our data provide evidence that MSI2 controls efficient translation of the oncogenic LSC self-renewal program and suggest MSI2 as a potential therapeutic target for myeloid leukemia.     

Antibiofilm Peptides Increase the Susceptibility of Carbapenemase-Producing Klebsiella pneumoniae Clinical Isolates to β-Lactam Antibiotics

Multidrug-resistant carbapenemase-producing Klebsiella pneumoniae (KpC) strains are becoming a common cause of infections in health care centers. Furthermore, Klebsiella can develop multicellular biofilms, which lead to elevated adaptive antibiotic resistance. Here, we describe the antimicrobial and antibiofilm activities of synthetic peptides DJK-5, DJK-6, and 1018 against five KpC isolates. Using static microplate assays, it was observed that the concentration required to prevent biofilm formation by these clinical isolates was below the MIC for planktonic cells. More-sophisticated flow cell experiments confirmed the antibiofilm activity of the peptides against 2-day-old biofilms of different KpC isolates, and in some cases, the peptides induced significant biofilm cell death. Clinically relevant combinations of DJK-6 and β-lactam antibiotics, including the carbapenem meropenem, also prevented planktonic growth and biofilm formation of KpC strain1825971. Interestingly, peptide DJK-6 was able to enhance, at least 16-fold, the ability of meropenem to eradicate preformed biofilms formed by this strain. Using peptide DJK-6 to potentiate the activity of β-lactams, including meropenem, represents a promising strategy to treat infections caused by KpC isolates.     

In Vitro Activity of Daptomycin in Combination with β-Lactams,Gentamicin, Rifampin,and Tigecycline against Daptomycin-Nonsusceptible Enterococci

Enterococci that are nonsusceptible (NS; MIC > 4 μg/ml) to daptomycin are an emerging clinical concern. The synergistic combination of daptomycin plus beta-lactams has been shown to be effective against vancomycin-resistant Enterococcus (VRE) species in vitro. This study systematically evaluated by in vitro time-kill studies the effect of daptomycin in combination with ampicillin, cefazolin, ceftriaxone, ceftaroline, ertapenem, gentamicin, tigecycline, and rifampin, for a collection of 9 daptomycin-NS enterococci that exhibited a broad range of MICs and different resistance-conferring mutations. We found that ampicillin plus daptomycin yielded the most consistent synergy but did so only for isolates with mutations to the liaFSR system. Daptomycin binding was found to be enhanced by ampicillin in a representative isolate with such mutations but not for an isolate with mutation to the yycFGHIJ system. In contrast, ampicillin enhanced the killing of the LL-37 human antimicrobial peptide against daptomycin-NS E. faecium with either the liaFSR or yycFGHIJ mutation. Antagonism was noted only for rifampin and tigecycline and only for 2 or 3 isolates. These data add support to the growing body of evidence indicating that therapy combining daptomycin and ampicillin may be helpful in eradicating refractory VRE infections.     

Hospital Elder Life Program in the Real World: The Many Uses of the Hospital Elder Life Program Website

The Hospital Elder Life Program (HELP) can prevent delirium, a common condition in older hospitalized adults associated with substantial morbidity, mortality, and healthcare costs. In 2011, HELP transitioned to a web‐based dissemination model to provide accessible resources, including implementation materials; information for healthcare professionals, patients, and families; and a searchable reference database. It was hypothesized that, although intended to assist sites to establish HELP, the resources that the HELP website offer might have broader applications. An e‐mail was sent to all HELP website registrants from September 10, 2012, to March 15, 2013, requesting participation in an online survey to examine uses of the resources on the website and to evaluate knowledge diffusion related to these resources. Of 102 responding sites, 73 (72%) completed the survey. Thirty‐nine (53%) had implemented and maintained an active HELP model. Twenty‐six (35%) sites had used the HELP website resources to plan for implementation of the HELP model and 35 (50%) sites to implement and support the program during and after launch. Sites also used the resources for the development of non‐HELP delirium prevention programs and guidelines. Forty‐five sites (61%) used the website resources for educational purposes, targeting healthcare professionals, patients, families, or volunteers. The results demonstrated that HELP resources were used for implementation of HELP and other delirium prevention programs and were also disseminated broadly in innovative educational efforts across the professional and lay communities.