Background: Idiopathic pulmonary fibrosis (IPF) has common risk factors with cancer and significant similarities in the pathobiology process, both diseases having poor outcomes. Immune checkpoint PD-L1 has become the target of checkpoint inhibitory therapy that unleashes antitumor T cells and has revolutionized cancer treatment. This is a pilot study exploring membrane immune checkpoint PD-L1 expression in human IPF lung tissue samples and its soluble form, soluble PD-L1 (sPD-L1) plasma concentrations in IPF patients, in order to investigate potential role of PD-L1 as an IPF biomarker. Methods: Twelve human IPF lung tissue samples (formalin-fixed, paraffin-embedded) obtained by surgical biopsy, have been tested for PD-L1 expression by PD-L1 IHC 22C3 pharmDx assay, while plasma samples for examination of sPD-L1 forms, PD-L1 (B7-H1/CD274) blood concentration, originated from 23 patients with IPF who did not undergo surgical biopsy. Results: Membrane PD-L1 expression in IPF lung tissue samples was positive to overexpression of PD-L1 in 9 samples out of 12. Only very few cells in the interstitium have shown a discrete PD-L1 expression, but not of a membrane type. As for sPD-L1 forms, we have found elevated concentrations of sPD-L1 in the serum of IPF patients 314.3 ng/L (117.7-483.1 ng/L), significantly higher compared with healthy control group 91.0 ng/L (52.4-119.7 ng/L), P<0.01. Conclusions: For IPF with PD-L1 expression on alveolar macrophages, further studies are necessary to elucidate this phenomenon. Serum sPD-1/PD-L1 is easily detected in clinical practice and should be further evaluated as a potential prognostic or/and predictive biomarker in IPF.

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A dinuclear double end-on azido bridged Ni(II) complex [Ni 2 L 2 (μ-1,1 -N 3 ) 2 (N 3 ) 2 ] (1) with the condensation product of 2-quinolinecarboxaldehyde and trimethylammonium acetohydrazide chloride (Girard's T reagent) (HLCl) has been synthesized and characterized by elemental analysis, IR spectroscopy, single-crystal X-ray diffraction, magnetic measurements and DFT studies. In complex 1 intra-dimer ferromagnetic coupling between Ni 2+ ions (J = +12.0(2) cm -1 ) and inter-dimer antiferromagnetic interaction (δ = -0.8(3) cm -1 ) were observed. DFT-BS calculations provided explanation of ferromagnetic exchange coupling in complex 1.

Background: Several registries of idiopathic pulmonary fibrosis (IPF) have been established to better understand its natural history, though their size and duration of follow-up are limited. Here, we describe the large European MultiPartner IPF Registry (EMPIRE) and validate predictors of long-term survival in IPF. Methods: The multinational prospective EMPIRE registry enrolled IPF patients from 48 sites in 10 Central and Eastern European countries since 2014. Survival from IPF diagnosis until death was estimated, accounting for lefttruncation. The Cox proportional hazards regression model was used to estimate adjusted hazard ratios (HR) of death for prognostic factors, using restricted cubic splines to fit continuous factors. Results: The cohort included 1620 patients (mean age at diagnosis 67.6 years, 71% male, 63% smoking history), including 75% enrolled within 6 months of diagnosis. Median survival was 4.5 years, with 45% surviving 5 years post-diagnosis. Compared with GAP stage I, mortality was higher with GAP stages II (HR 2.9; 95% CI: 2.3-3.7) and III (HR 4.0; 95% CI: 2.8-5.7) while, with redefined cutoffs , the corresponding HRs were 2.7 (95% CI: 1.8-4.0) and 5.8 (95% CI: 4.0-8.3) respectively. Mortality was higher with concurrent pulmonary hypertension (HR 2.0; 95% CI: 1.5-2.9) and lung cancer (HR 2.6; 95% CI: 1.3-4.9). Conclusions: EMPIRE, one of the largest long-term registries of patients with IPF, provides a more accurate confirmation of prognostic factors and co-morbidities on longer term five-year mortality. It also suggests that some fine-tuning of the indices for mortality may provide a more accurate long-term prognostic profile for these patients.

Two Zn(II) complexes with the condensation product of 2-quinolinecarboxaldehyde and trimethylammonium acetohydrazide chloride (Girard's T reagent) (HLCl) and monodentate pseudohalides (azide and cyanate) have been synthesized and characterized by elemental analysis, IR and NMR spectroscopy and single-crystal X-ray diffraction. In both complexes, the coordination surroundings of the Zn(II) ions consist of a deprotonated hydrazone ligand coordinated through an NNO set of donor atoms and two monodentate pseudohalides (N 3or NCO -) at the remaining coordination sites. The Zn(II) complexes showed low to moderate activity against laboratory control strains of pathogenic bacteria and fungi.