COVID-19 in patients with lung cancer.

BACKGROUND: Patients with lung cancers may have disproportionately severe coronavirus disease 2019 (COVID-19) outcomes. Understanding the patient-specific and cancer-specific features that impact the severity of COVID-19 may inform optimal cancer care during this pandemic. PATIENTS AND METHODS: We examined consecutive patients with lung cancer and confirmed diagnosis of COVID-19 (n = 102) at a single center from 12 March 2020 to 6 May 2020. Thresholds of severity were defined a priori as hospitalization, intensive care unit/intubation/do not intubate ([ICU/intubation/DNI] a composite metric of severe disease), or death. Recovery was defined as >14 days from COVID-19 test and >3 days since symptom resolution. Human leukocyte antigen (HLA) alleles were inferred from MSK-IMPACT (n = 46) and compared with controls with lung cancer and no known non-COVID-19 (n = 5166). RESULTS: COVID-19 was severe in patients with lung cancer (62% hospitalized, 25% died). Although severe, COVID-19 accounted for a minority of overall lung cancer deaths during the pandemic (11% overall). Determinants of COVID-19 severity were largely patient-specific features, including smoking status and chronic obstructive pulmonary disease [odds ratio for severe COVID-19 2.9, 95% confidence interval 1.07-9.44 comparing the median (23.5 pack-years) to never-smoker and 3.87, 95% confidence interval 1.35-9.68, respectively]. Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies did not impact severity. Human leukocyte antigen supertypes were generally similar in mild or severe cases of COVID-19 compared with non-COVID-19 controls. Most patients recovered from COVID-19, including 25% patients initially requiring intubation. Among hospitalized patients, hydroxychloroquine did not improve COVID-19 outcomes. CONCLUSION: COVID-19 is associated with high burden of severity in patients with lung cancer. Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity.

Approaching the size limit of organometallic layers: synthesis and characterization of highly ordered silver-thiolate lamellae with ultra-short chain lengths.

Approaching the ultimate limits of material sizes provides a route for designing new functional materials with extraordinary properties. We report the first systematic synthesis and characterization study of a wide range of highly ordered silver alkanethiolate (AgSCnH2n+1 or AgSCn, n = 1-16) aliphatic lamellae. Single crystalline multilayer AgSCn are synthesized by a modified solution reaction method. Hot toluene recrystallization or Ostwald ripening enhances the structural ordering of the lamellar crystals. This work approaches the chain length limit of aliphatic lamellae by synthesizing highly ordered AgSCn (n = 1-3) with extremely short chains. All lamellae form single crystals with well-registered interlayer interfaces, similar to other alkyl-based lamellae but different from polyethylene lamellae. AgSC2 with a layer thickness of 1.08 nm is the thinnest organometallic layer ever reported. The composition, morphology, decomposition and structure of the lamellae are comprehensively studied. A new method quantifies the composition of the residual Ag and Ag2S contents after the decomposition of the AgSCn: all of the Ag, none of the C and a fraction of the S remain in the residue. The structural orderings of the AgSCn crystals, which are probed by electron diffraction for the first time, are characterized in terms of chain conformation, interlayer lamellar ordering and intralayer lattice ordering. All AgSCn (n = 2-16) layers, except AgSC1, possess a common lattice packing and the same inorganic network structure.

Size effect and odd-even alternation in the melting of single and stacked AgSCn layers: synthesis and nanocalorimetry measurements.

We report a systematic study of melting of layered lamella of silver alkanethiolates (AgSCn). A new synthesis method allows us to independently change the thickness of the crystal in two ways-by modulating chain length (n = 7-18) and by stacking these crystals to a specific layer number (m = 1-10). This method produces magic size lamella, having a well-spaced discrete melting point, Tm, distribution. Nanocalorimetry shows stepwise increases in Tm, as the lamella thickness increases by integer increments of chain length. The relationship between Tm and the inverse thickness follows the linear scaling law of Gibbs-Thomson effect. Layer stacking dramatically changes the degree and nature of size-effect melting. There is odd/even effect in stacked 2, 3, and 4 layers. Tm values of single-layer and multilayer samples do not show noticeable odd/even alternation. We develop a phenomenological model of size effect based on the cumulative excess free energy, G(excess), contributions of four spatially separate regions of the crystal: surface, Ag-S central plane, substrate interface, and interlayer interface. The selective appearance of the odd/even effect is due to the significant stabilization (1.4 kJ/mol) of interlamellae interfaces of odd-chain samples, possibly due to registration/packing. Stabilization occurs only for the mobile lamellae situated close to the free surface, and thus 2-layer samples show the highest degree of stabilization. X-ray diffraction shows that the chains are tilted 18° with respect to the basal plane normal but that the van der Waals gap is 0.3 Å smaller for crystals with odd chains.

Synthesis and characterization of single-layer silver-decanethiolate lamellar crystals.

We report the synthesis of silver-decanethiolate (AgSC10) lamellar crystals. Nanometer-sized Ag clusters grown on inert substrates react with decanethiol vapor to form multilayer AgSC10 lamellar crystals with both layer-by-layer and in-plane ordering. The crystals have strong (010) texture with the layers parallel to the substrates. The synthesis method allows for a precise control of the number of layers. The thickness of the lamellae can be manipulated and systematically reduced to a single layer by decreasing the amount of Ag and lowering the annealing temperature. The single-layer AgSC10 lamellae are two-dimensional crystals and have uniform thickness and in-plane ordering. These samples were characterized with nanocalorimetry, atomic force microscopy (AFM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray reflectivity (XRR), Fourier transform infrared spectroscopy (FTIR), and Rutherford backscattering spectroscopy (RBS).

Self-assembly and ripening of polymeric silver-alkanethiolate crystals on inert surfaces.

We characterize and compare the reaction of alkanethiol with Ag continuous planar thin films and Ag islands on inert substrates. Ag islands generate a significantly larger (3-fold) amount of alkanethiolate than continuous Ag films at comparable conditions. The reaction with planar Ag thin films produces alkanethiol self-assembled monolayers (SAMs), whereas the reaction with Ag islands yields two dissimilar products depending on the size of the islands. Small Ag islands are more likely to be converted into multilayer silver-alkanethiolate (AgSR) crystals, while larger Ag islands form monolayer-protected clusters (MPCs). The AgSR lamellar crystals are initially small having only a few layers. However, during thermal annealing, ripening occurs that generates large AgSR lamellae having diameters of 1 microm and thickness up to 30 layers. Atomic force microscopy shows the single-layer step-heights of individual crystals which match the layer thickness obtained via X-ray diffraction analysis. The crystals have facets and flat terraces with extended area, and have a strong preferred orientation (010) normal to the substrate surface. The MPCs move laterally upon annealing and reorganize into a single-layer network with their separation distance approximately equal to the length of an extended alkyl chain.