3 research outputs found
Modulation of the Association Between Age and Death by Risk Factor Burden in Critically Ill Patients With COVID-19.
UNLABELLED: Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death.
DESIGN: Multicenter cohort study.
SETTING: ICUs at 68 hospitals across the United States.
PATIENTS: A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [± 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (
CONCLUSIONS: In a large population of critically ill patients with COVID-19, age had an independent exponential association with death. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and death, but age still had an exponential association with death in subgroups according to the number of risk factors present. Additional studies are needed to identify the mechanisms underpinning why older age confers an increased risk of death in critically ill patients with COVID-19
Positive predictive value of ERBB2 copy number gain by tissue or circulating tumor DNA next-generation sequencing across advanced cancers
BACKGROUND: The correlation of ERBB2 copy number gain (CNG) from tissue or circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) with standard HER2 tissue evaluation is not well understood.
MATERIALS AND METHODS: We retrospectively identified patients with ERBB2 CNG on commercial NGS. We described their clinical-pathologic features and calculated the positive predictive value (PPV) of ERBB2 CNG by NGS for HER2-positivity by IHC and FISH testing.
RESULTS: 176 patients had NGS revealing an ERBB2 CNG (112 by tumor tissue and 91 by ctDNA). The cancer subtypes with the most cases with ERBB2 CNG by NGS were breast (
CONCLUSIONS: ERBB2 CNG by NGS is detected in numerous malignancies for which HER2 testing is not standard. Detection of ERBB2 CNG by tissue NGS and ctDNA has a high PPV for true HER2-positivity by standard IHC and/or FISH testing in breast cancer
pH- and Temperature-Dependent Peptide Binding to the Lactococcus lactis Oligopeptide-Binding Protein A Measured with a Fluorescence Anisotropy Assay
Bacterial ATP-binding cassette transporters
are a superfamily of
transport systems involved in the import of various molecules including
amino acids, ions, sugars, and peptides. In the lactic acid bacteria Lactococcus lactis, the oligopeptide-binding protein
A (OppA) binds peptides for import to support nitrogen metabolism
and cell growth. The OppA protein is of great interest because it
can bind peptides over a broad variety of lengths and sequences; however,
current methods to study peptide binding have employed low throughput,
endpoint, or low dynamic range techniques. Therefore, in this study,
we developed a fluorescence anisotropy-based peptide-binding assay
that can be readily employed to quantify OppA function. To test the
utility of our assay, we characterized the pH dependence of oligopeptide
binding because L. lactis is commonly
used in fermentation and often must survive in low pH environments
caused by lactic acid export. We determined that OppA affinity increases
as pH or temperature decreases, and circular dichroism spectroscopy
further indicated that acidic conditions increase the thermal stability
of the protein, increasing the unfolding transition temperature by
10 °C from pH 8 to pH 6. Thus, our fluorescence anisotropy assay
provides an easy technique to measure peptide binding, and it can
be used to understand molecular aspects of OppA function under stress
conditions experienced during fermentation and other biotechnology
applications