Clinical Characteristics, Management, and Outcomes of Cancer Patients With Coronavirus Disease 2019 Admitted to the ICU.

Adult patients with cancer have a greater likelihood of developing severe illness and death from coronavirus disease 2019 compared with patients without cancer. We sought to characterize the clinical characteristics and outcomes of cancer patients who tested positive for severe acute respiratory syndrome coronavirus 2 and were admitted to the ICU at the peak of the first wave of the pandemic in the United States. DESIGN: A single-center retrospective cohort study. SETTING: Two medical-surgical ICUs of a tertiary-care cancer center. PATIENTS/SUBJECTS: All consecutive adult patients (≥ 18 yr) with current or past (< 2 yr) diagnosis of cancer who were admitted to the ICU with coronavirus disease 2019 between March 1, and June 30, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, and laboratory data of 89 critically ill cancer patients were extracted from electronic medical records. Median age was 65 years (interquartile range, 57-70 yr), 66% were White, and 58% male. Approximately a third of patients had three or more comorbidities. Fifty-one patients (57%) had solid tumors, and 38 (42%) had hematologic malignancies. Sixty-one patients (69%) received cancer-directed therapy within the previous 90 days. Sixty patients (67%) required mechanical ventilation, 56% required prone positioning, 28% underwent tracheostomy, and 71% required vasopressors. Hospital mortality was 45% (40/89). Among those who required mechanical ventilation, mortality was 53% (32/60). Hospital mortality was significantly higher among patients with hematologic malignancies, higher severity of illness and organ failure scores, need for invasive mechanical ventilation and vasopressor therapy, lower hemoglobin and platelet count, and higher d-dimer levels at ICU admission. ICU and hospital length of stay were 10 and 26 days, respectively. At 9-month follow-up, the mortality rate was 54% (48/89). CONCLUSIONS: We report the largest case series and intermediate-term follow-up of cancer patients with coronavirus disease 2019 who were admitted to the ICU. Hospital mortality was 45%. Intermediate-term outcome after hospital discharge was favorable.

Widespread nanoparticle-assay interference: implications for nanotoxicity testing.

The evaluation of engineered nanomaterial safety has been hindered by conflicting reports demonstrating differential degrees of toxicity with the same nanoparticles. The unique properties of these materials increase the likelihood that they will interfere with analytical techniques, which may contribute to this phenomenon. We tested the potential for: 1) nanoparticle intrinsic fluorescence/absorbance, 2) interactions between nanoparticles and assay components, and 3) the effects of adding both nanoparticles and analytes to an assay, to interfere with the accurate assessment of toxicity. Silicon, cadmium selenide, titanium dioxide, and helical rosette nanotubes each affected at least one of the six assays tested, resulting in either substantial over- or under-estimations of toxicity. Simulation of realistic assay conditions revealed that interference could not be predicted solely by interactions between nanoparticles and assay components. Moreover, the nature and degree of interference cannot be predicted solely based on our current understanding of nanomaterial behaviour. A literature survey indicated that ca. 95% of papers from 2010 using biochemical techniques to assess nanotoxicity did not account for potential interference of nanoparticles, and this number had not substantially improved in 2012. We provide guidance on avoiding and/or controlling for such interference to improve the accuracy of nanotoxicity assessments.

Inhibition of enzyme activity by nanomaterials: potential mechanisms and implications for nanotoxicity testing.

The objective of this study was to investigate whether nanoparticle-exposure affects enzyme function and to determine the mechanisms responsible. Silicon, Au, and CdSe nanoparticles were synthesized in house and their physicochemical properties were characterized. The activity of purified lactate dehydrogenase (LDH) was inhibited or abolished by all nanoparticles tested. Inhibition was dependent upon particle core and surface-functional group composition. Inhibition of LDH was absent in crude tissue homogenates, in the presence of albumin, and at the isoelectric point of the protein, indicating that nanoparticles bind non-specifically to abundant proteins via a charge interaction. Circular dichroism spectroscopy suggests that the structure of LDH may be altered by nanoparticles in a manner different from that of bulk controls. We present new data on the specific physicochemical properties of nanoparticles that may lead to bioactivity and highlight a number of potentially serious problems with common nanotoxicity testing methods.

Exploration of organic acid chain length on water-soluble silicon quantum dot surfaces.

Surface functionalization of silicon quantum dots influences oxidation of the silicon core while affording control of physical properties and maintaining optical stability. An effective method for surface modification is photochemical hydrosilylation in which the hydride-terminated Si surface is reacted with an unsaturated C-C bond resulting in a covalent Si-C bond at the surface. The physical properties (e.g., reactivity and solvent compatibility) of the nanocrystals are thus dictated by those of the pendant functional group. Water-soluble nanoparticles can be produced by extending polar functional groups, such as carboxylic acids, from the surface. Previous literature reports have shown acrylic acid to be an attractive starting material for creating water-soluble Si nanocrystals. To date, a detailed study of the effects of differing surface groups (i.e., carboxylic acids of varying carbon chain lengths) has not been offered. Here, we investigate the effects of carboxylic acid surface moieties with increasing carbon chain length on various silicon nanocrystal properties. Oxidative and optical stability was improved by increasing the length of the carbon spacer between the silicon surface and the polar carboxylic acid group. As well, increased chain length was found to enhance nanocrystal dispersibility in polar solvents. Of important note, however, the use of acrylic acid as a precursor led to poly(acrylic acid) formation under the reaction conditions studied, leading to anomalous behavior compared to precursors with longer carbon chains.