High body mass index and pre-existing autoimmune disease are associated with an increased risk of immune-related adverse events in cancer patients treated with PD-(L)1 inhibitors across different solid tumors

BACKGROUND\nPATIENTS AND METHODS\nRESULTS\nCONCLUSION\nTreatment with anti-PD-(L)1 antibodies, approved for several oncology indications, can lead to immune-related adverse events (irAEs). We aimed to investigate risk factors associated with an increased reporting of irAEs in patients treated with PD-(L)1 inhibitors approved for solid tumor indications.\nA retrospective review was performed of individual data from patients in phase II/III registrational studies for PD-(L)1 inhibitors in solid tumors. Data on baseline characteristics and adverse events were extracted. Univariate and multivariable logistic regression models were used to identify risk factors.\nIn total, 5123 patients were included from 15 studies reporting on the use of four PD-(L)1 inhibitors for five solid tumor indications. Univariate analysis suggested that type of study drug (P 2 [odds ratio (OR) 1.5, 95% confidence interval (CI) 1.2-1.8] in comparison to normal BMI, having an autoimmune disease at baseline (OR 1.8, 95% CI 1.1-2.7), and use of a PD-L1 inhibitor (OR 1.6, 95% CI 1.2-2.0). The latter finding is probably biased due to the selection of the studies in the dataset with complete information on baseline characteristics.\nThis study was conducted using a large dataset of individual patient data from clinical trials comprising multiple solid tumor indications. We demonstrated that patients with obesity and concurrent autoimmune disease were at increased risk of developing irAEs.FWN – Publicaties zonder aanstelling Universiteit Leide

Second Harmonic Generation from Lb Films of PolyIsocyanide)S

Contains fulltext : 10117.pdf (publisher's version ) (Open Access

Mixed Monolayers and Multilayers of Poly(Isocyanide)S with Nonlinear Optically-Active Side-Chains

Contains fulltext : 10551.pdf (publisher's version ) (Open Access

Flexibilized styrene-N-substituted maleimide copolymers. II. Multiblock copolymers prepared from PTHF-based iniferters

This article describes the synthesis and molecular characterization of thermal polymeric iniferters, based on hydroxy-terminated poly(tetrahydrofuran) (PTHF), bearing thiuram disulfide groups along the chain. Thermal polymerization after the addition of styrene (S) and N-methylmaleimide (MI) to these PTHF-based polymeric iniferters yielded segmented PTHF (SMI-block-PTHF)n block copolymers that proved to have a single Tg. The multiblock copolymers were molecularly characterized by elemental analysis, IR, and NMR. The thermal stability, as checked by thermogravimetric analysis, proved to be good up to about 350 °C. A size exclusion chromatography/differential viscosity (DV) analysis showed that the molecular weights of the synthesized single-phase multiblock copolymers were sufficiently high (several times the estimated molecular weight between two adjacent entanglements) to determine the entanglement density from the rubbery plateau modulus, for which the method developed by S. Wu (J Polym Sci Part B: Polym Phys 1989, 27, 723-741) was applied. The entanglement density of flexibilized SMI proved to be about 20-25% higher than that of the nonflexibilized SMI. This increase is disappointing, and more work, based on the described concept, is required to achieve the desired enhancement of the toughness

Linearly Polarized Probes of Surface Chirality

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Langmuir-Blodgett Mono- and Multilayers of Poly(isocyanide)s with Different Sidechains

In this study poly(isocyanide)s, [R-N=C<]n with different sidechains R are used as spreading material to form LB monolayers at the water-air interface. Poly(isocyanide)s are rigid-rod polymers with a stable, helical conformation. One of the aims of this study was to ascertain whether this rigid conformation is sufficient to enable the formation of a stable monolayer on the water surface. We find that different poly(isocyanide)s with non-polar aliphatic substituents are unable to form such stable monolayers. On the other hand, poly((S)-1-acetoxymethylethylisocyanide), a polymer which has polar substituents, does form a stable monolayer. This monolayer can be transferred onto all kinds of substrates by Z-type transfer. Multilayer formation is possible with transfer ratios remaining constant up to at least 40 layers. From IR measurements it follows that the polymer helices are preferentially oriented with their main axis parallel to the transfer direction.

Mixed mono- and multilayers of poly(isocyanide)s with non-linear optically active side chains

The properties and structure of Langmuir-Blodgett mono- and multilayers of several poly(isocyanide)s with non-linear optically active side-chains were studied. These polymers formed very rigid layers or layers which appeared to be unstable. To circumvent this problem they were mixed with other poly(isocyanide)s or with amylose-butyrate. Transmission electron microscopy studies of the polymeric mixtures revealed that phase separation occurred in all cases and that only poly(isocyanide)s substituted with hydrophilic side chains formed monomolecular layers. Depending on the nature of the polymer which was used for mixing, the dye polymers could be deposited with Y- or Z-type transfer. Second-harmonic intensities generated from these films were small in the case of the Y-type multilayered films and moderately high in the case of the Z-type films.

Slow Structural Rearrangement of a Side-Chain Phthalocyanine Methacrylate Polymer at the Air-Water Interface

A polymethacrylate with dodecoxy-substituted phthalocyanine units in the side chains has been used to form Langmuir-Blodgett monolayers at the air-water interface. The monolayers are highly crystalline. They expand slowly even when a constant surface pressure is applied. The structural change coupled with this process has been studied by electron microscopy, electron diffraction, and ellipsometry. It is proposed that the expansion is the result of a change in conformation of the peripheral alkoxy chains on the phthalocyanine rings. The polymer can be deposited on various substrates with Y-type transfer if it is mixed with arachidic acid. The resulting multilayers have been characterized by UV/vis and FT-IR spectroscopies and ellipsometry. No flow-induced orientation was observed during the transfer process.