Continuous oxygen saturation and risk of retinopathy of prematurity in a Japanese cohort

Kubota H., Fukushima Y., Kawasaki R., et al. Continuous oxygen saturation and risk of retinopathy of prematurity in a Japanese cohort. British Journal of Ophthalmology , bjo-2023-324225 (2024); https://doi.org/10.1136/bjo-2023-324225.Background/aims : We assessed the associations between retinopathy of prematurity (ROP) and continuous measurements of oxygen saturation (SpO2), and developed a risk prediction model for severe ROP using birth data and SpO2 data. Methods : This retrospective study included infants who were born before 30 weeks of gestation between August 2009 and January 2019 and who were screened for ROP at a single hospital in Japan. We extracted data on birth weight (BW), birth length, gestational age (GA) and minute-by-minute SpO2 during the first 20 days from the medical records. We defined four SpO2 variables using sequential measurements. Multivariate logistic regression was used to develop a model that combined birth data and SpO2 data to predict treatment-requiring ROP (TR-ROP). The model’s performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results : Among 350 infants, 83 (23.7%) required ROP treatment. The SpO2 variables in infants with TR-ROP differed significantly from those with non-TR-ROP. The average SpO2 and high SpO2 showed strong associations with GA (r=0.73 and r=0.70, respectively). The model incorporating birth data and the four SpO2 variables demonstrated good discriminative ability (AUC=0.83), but it did not outperform the model incorporating BW and GA (AUC=0.82). Conclusion Data obtained by continuous SpO2 monitoring demonstrated valuable associations with severe ROP, as well as with GA. Differences in the distribution of average SpO2 and high SpO2 between infants with TR-ROP and non-TR-ROP could be used to establish efficient cut-off values for risk determination

The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis

C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with beta 2-glycoprotein I (beta 2GPI), implicating oxLDL/P2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/beta 2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/R2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and beta 2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of adierosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/beta 2GPI complexes correlated with total cholesterol and hemoglobin Al c. Thus, the generation of CRP/oxLDL/beta 2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/R2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis

Immunological Microenvironment Predicts the Survival of the Patients with Hepatocellular Carcinoma Treated with Anti-PD-1 Antibody

Introduction: Although immune checkpoint inhibitors (ICIs) have been considered as promising agents for the treatment of advanced hepatocellular carcinoma (HCC), previous clinical trials revealed that the response to anti-programmed cell death protein 1 (anti-PD-1) monotherapy was as low as 20%. Identifying subgroups that respond well to ICIs is clinically important. Here, we studied the prognostic factors for anti-PD-1 antibody treatment based on the molecular and immunological features of HCC. Methods: Patients who were administered anti-PD1 antibody for advanced HCC at Kindai University Hospital were included. Clinicopathological backgrounds and antitumor responses were examined in 34 cases where tumor tissues before treatment were available. Transcriptome analysis was performed using 40 HCC samples obtained from surgical resection, and immune status was compared between 20 HCCs with activating mutations in β-catenin and those without the mutations using transcriptome-based immunogram. Results: Univariate analysis showed that the disease control rate was significantly better in patients with α-fetoprotein < 400 ng/mL, negative for β-catenin/glutamate synthetase (GS) staining, high combined positive score (CPS) of programmed death-ligand 1 (PD-L1), and increased infiltration of CD8+ cells in tumor tissues. Among them, negative staining of β-catenin/GS, CPS of PD-L1 ≥ 1, and high degree of CD8+ tumor-infiltrating lymphocytes (TILs) were significantly associated with longer survival in both progression-free survival (PFS) and overall survival (OS). The combination of these factors well stratified the survival of the patients on anti-PD-1 antibody in both PFS and OS (p < 0.0001 and p = 0.0048 for PFS and OS, respectively). In addition, the immunogram revealed that tumor-carrying mutations in β-catenin showed downregulation of immune-related genes, especially in those related to priming and activation by dendritic cells, interferon-γ response, inhibitory molecules, and regulatory T cells. Discussion/Conclusion: The combined score including Wnt/β-catenin activation, CPS of PD-L1, and degree of CD8+ TILs in HCC is informative for predicting the response to ICI in HCC cases. Constitutive activation of β-catenin can induce an immune cold phenotype with downregulation of immune-related genes, and immunohistochemistry-based evaluation is beneficial for identifying the subgroup that shows a good response to ICI

Interfacial properties of polystyrene thin films as revealed by neutron reflectivity

We have studied the glass transition temperature (Tg) and molecular mobility of polystyrene (PS) thin films near the interface between the polymer thin film and substrate with bilayer thin films consisting of surface hydrogenated PS (h-PS) and bottom deuterated PS (d-PS) using neutron reflectivity. With decreasing the thickness of the bottom d-PS layer, Tg near the interface between the polymer thin film and substrate increased compared to bulk Tg and a drastic increase of Tg was observed for the bottom d-PS layer <155 Å thick. The orientation of polymer chains at the interface is supposed to be related to the increase of Tg near the interface between the polymer and substrate. The polymer chain mobility decreased with thickness even for the bottom d-PS layer with no discernible change of Tg. It is considered that the numerous contacts between polymer chains and substrate are related to the decrease of mobility near the interface between the polymer thin film and substrate

Distributions of glass-transition temperature and thermal expansivity in multilayered polystyrene thin films studied by neutron reflectivity

We performed neutron reflectivity measurements on multilayered polymer thin films consisting of alternatively stacked deuterated polystyrene (d-PS) and hydrogenated polystyrene (h-PS) layers ∼200 Å thick as a function of temperature covering the glass-transition temperature Tg, and we found a wide distribution of Tg as well as a distribution of the thermal expansivity α within the thin films, implying the dynamic heterogeneity of the thin films along the depth direction. The reported anomalous film thickness dependences of Tg and α were reasonably understood in terms of the distributions, showing that the surface mobile layer and the bottom hard interfacial layer are, respectively, responsible for the depressions of Tg and α with decreasing film thickness. The molecular mobility in each layer is also discussed in relation to the distribution of Tg, based on the results on mutual diffusion at the layer interface