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1.
Am J Crit Care ; 30(4): e71-e79, 2021 07 01.
Article in English | MEDLINE | ID: mdl-34195781

ABSTRACT

BACKGROUND: Few population-based studies assess the impact of cancer on sepsis incidence and mortality. OBJECTIVES: To evaluate epidemiological trends of sepsis in patients with cancer. METHODS: This retrospective cohort study included adults (≥20 years old) identified using sepsis-indicator International Classification of Diseases codes from the Nationwide Inpatient Sample database (2006-2014). A generalized linear model was used to trend incidence and mortality. Outcomes in patients with cancer and patients without cancer were compared using propensity score matching. Cox regression modeling was used to calculate hazard ratios for mortality rates. RESULTS: The study included 13 996 374 patients, 13.6% of whom had cancer. Gram-positive infections were most common, but the incidence of gram-negative infections increased at a greater rate. Compared with patients without cancer, those with cancer had significantly higher rates of lower respiratory tract (35.0% vs 31.6%), intra-abdominal (5.5% vs 4.6%), fungal (4.8% vs 2.9%), and anaerobic (1.2% vs 0.9%) infections. Sepsis incidence increased at a higher rate in patients with cancer than in those without cancer, but hospital mortality rates improved equally in both groups. After propensity score matching, hospital mortality was higher in patients with cancer than in those without cancer (hazard ratio, 1.25; 95% CI, 1.24-1.26). Of patients with sepsis and cancer, those with lung cancer had the lowest survival (hazard ratio, 1.65) compared with those with breast cancer, who had the highest survival. CONCLUSIONS: Cancer patients are at high risk for sepsis and associated mortality. Research is needed to guide sepsis monitoring and prevention in patients with cancer.


Subject(s)
Neoplasms , Sepsis , Adult , Hospital Mortality , Humans , Incidence , Neoplasms/complications , Neoplasms/epidemiology , Retrospective Studies , Sepsis/epidemiology , Sepsis/mortality , United States , Young Adult
2.
Dev Biol ; 448(2): 210-225, 2019 04 15.
Article in English | MEDLINE | ID: mdl-30365920

ABSTRACT

Electroporation-based assays were used to test whether the myogenic regulatory factor (MRF) of Ciona intestinalis (CiMRF) interferes with endogenous developmental programs, and to evaluate the importance of its unusual N-terminus for muscle development. We found that CiMRF suppresses both notochord and endoderm development when it is expressed in these tissues by a mechanism that may involve activation of muscle-specific microRNAs. Because these results add to a large body of evidence demonstrating the exceptionally high degree of functional conservation among MRFs, we were surprised to discover that non-ascidian MRFs were not myogenic in Ciona unless they formed part of a chimeric protein containing the CiMRF N-terminus. Equally surprising, we found that despite their widely differing primary sequences, the N-termini of MRFs of other ascidian species could form chimeric MRFs that were also myogenic in Ciona. This domain did not rescue the activity of a Brachyury protein whose transcriptional activation domain had been deleted, and so does not appear to constitute such a domain. Our results indicate that ascidians have previously unrecognized and potentially novel requirements for MRF-directed myogenesis. Moreover, they provide the first example of a domain that is essential to the core function of an important family of gene regulatory proteins, one that, to date, has been found in only a single branch of the family.


Subject(s)
Ciona intestinalis/genetics , Myogenic Regulatory Factors/chemistry , Myogenic Regulatory Factors/metabolism , Amino Acid Sequence , Animals , Conserved Sequence , Endoderm/embryology , Endoderm/metabolism , Gene Expression Regulation, Developmental , Green Fluorescent Proteins/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Muscle Development/genetics , Muscles/metabolism , Notochord/embryology , Notochord/metabolism , Promoter Regions, Genetic/genetics , Protein Domains , Structure-Activity Relationship
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