Functional Progression after Dose Suspension or Discontinuation of Nintedanib in Idiopathic Pulmonary Fibrosis: A Real-Life Multicentre Study

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with rapidly progressive evolution and an unfavorable outcome. Nintedanib (NTD) is an antifibrotic drug that has been shown to be effective in slowing down the progression of the disease. The aim of our study was to examine the efficacy, especially in terms of the functional decline, and the safety profile of NTD in patients treated with the recommended dose and subjects who reduced or suspended the therapy due to the occurrence of adverse reactions. Methods: We conducted a real-life retrospective study based on the experience of NTD use in two centers between 2015 and 2022. Clinical data were evaluated at baseline, at 6 and 12 months after the NTD introduction in the whole population and in subgroups of patients who continued the full-dose treatment, at a reduced dosage, and at the discontinuation of treatment. The following data were recorded: the demographic features, IPF clinical features, NTD therapeutic dosage, tolerability and adverse events, pulmonary function tests (PFTs), the duration of treatment upon discontinuation, and the causes of interruption. Results: There were 54 IPF patients who were included (29.6% females, with a median (IQR) age at baseline of 75 (69.0-79.0) years). Twelve months after the introduction of the NTD therapy, 20 (37%) patients were still taking the full dose, 11 (20.4%) had reduced it to 200 mg daily, and 15 (27.8%) had stopped treatment. Gastrointestinal intolerance predominantly led to the dose reduction (13.0%) and treatment cessation (20.4%). There were two deaths within the initial 6 months (3.7%) and seven (13.0%) within 12 months. Compared to the baseline, the results of the PFTs remained stable at 6 and 12 months for the entire NTD-treated population, except for a significant decline in the DLCO (% predicted value) at both 6 (38.0 ± 17.8 vs. 43.0 ± 26.0; p = 0.041) and 12 months (41.5 ± 15.3 vs. 44.0 ± 26.8; p = 0.048). The patients who continued treatment at the full dose or a reduced dosage showed no significant differences in the FVC and the DLCO at 12 months. Conversely, those discontinuing the NTD exhibited a statistically significant decline in the FVC (% predicted value) at 12 months compared to the baseline (55.0 ± 13.5 vs. 70.0 ± 23.0; p = 0.035). Conclusions: This study highlights the functional decline of the FVC at 12 months after the NTD initiation among patients discontinuing therapy but not among those reducing their dosage

Growth modes of nanoparticle superlattice thin films

We report about the fabrication and characterization of iron oxide nanoparticle thin film superlattices. The formation into different film morphologies is controlled by tuning the particle plus solvent-to-substrate interaction. It turns out that the wetting vs. dewetting properties of the solvent before the self-assembly process during solvent evaporation plays a major role to determine the resulting film morphology. In addition to layerwise growth also three-dimensional mesocrystalline growth is evidenced. The understanding of the mechanisms ruling nanoparticle self-assembly represents an important step toward the fabrication of novel materials with tailored optical, magnetic or electrical transport properties

Functional Progression in Patients with Interstitial Lung Disease Resulted Positive to Antisynthetase Antibodies: A Multicenter, Retrospective Analysis

Antisynthetase syndrome (ASSD) is a rare autoimmune disease characterized by serologic positivity for antisynthetase antibodies. Anti-Jo1 is the most frequent, followed by anti PL-7, anti PL-12, anti EJ, and anti OJ antibodies. The lung is the most frequently affected organ, usually manifesting with an interstitial lung disease (ILD), which is considered the main determinant of prognosis. Some evidences suggest that non-anti-Jo-1 antibodies may be associated with more severe lung involvement and possibly with poorer outcomes, while other authors do not highlight differences between anti-Jo1 and other antisynthetase antibodies. In a multicenter, retrospective, "real life" study, we compared lung function tests (LFTs) progression in patients with ILD associated with anti-Jo1 and non-anti-Jo1 anti-synthetase antibodies to assess differences in lung function decline between these two groups. Therefore, we analyzed a population of 57 patients (56% anti-Jo1 positive), referred to the outpatient Clinic of four referral Centers in Italy (Modena, Monza, Siena, and Trieste) from 2008 to 2019, with a median follow-up of 36 months. At diagnosis, patients showed a mild ventilatory impairment and experienced an improvement of respiratory function during treatment. We did not observe statistically significant differences in LFTs at baseline or during follow-up between the two groups. Moreover, there were no differences in demographic data, respiratory symptoms onset (acute vs. chronic), extrapulmonary involvement, treatment (steroid and/or another immunosuppressant), or oxygen supplementation. Our study highlights the absence of differences in pulmonary functional progression between patients positive to anti-Jo-1 vs. non anti-Jo-1 antibodies, suggesting that the type of autoantibody detected in the framework of ASSD does not affect lung function decline

Domain-wall structure in thin films with perpendicular anisotropy: Magnetic force microscopy and polarized neutron reflectometry study

Ferromagnetic domain patterns and three-dimensional domain-wall configurations in thin CoCrPt films with perpendicular magnetic anisotropy were studied in detail by combining magnetic force microscopy and polarized neutron reflectometry with micromagnetic simulations. With the first method, lateral dimension of domains with alternative magnetization directions normal to the surface and separated by domain walls in 20-nm-thick CoCrPt films were determined in good agreement with micromagnetic simulations. Quantitative analysis of data on reflectometry shows that domain walls consist of a Bloch wall in the center of the thin film, which is gradually transformed into a pair of Néel caps at the surfaces. The width and in-depth thickness of the Bloch wall element, transition region, and Néel caps are found consistent with micromagnetic calculations. A complex structure of domain walls serves to compromise a competition between exchange interactions, keeping spins parallel, magnetic anisotropy orienting magnetization normal to the surface, and demagnetizing fields, promoting in-plane magnetization. It is shown that the result of such competition strongly depends on the film thickness, and in the thinner CoCrPt film (10 nm thick), simple Bloch walls separate domains. Their lateral dimensions estimated from neutron scattering experiments agree with micromagnetic simulations.Microelectronics Advanced Research Corporation (MARCO)United States. Defense Advanced Research Projects Agenc

Prolonged hospitalisation for immigrants and high risk patients with positive smear pulmonary tuberculosis.

Background and objective. Tuberculosis (TB) occurring in immigrants and resistance to drugs are major problems for TB control in Western countries. Directly observed therapy (DOT) reduces disease transmission, but this approach may have poor results among illegal immigrants. Our aim was to evaluate a prolonged hospitalisation programme to improve early outcome of TB treatment in high risk patients. Methods. All the consecutive adult patients with sputum smear-positive pulmonary TB admitted to 2 Italian referral TB Centres were evaluated. Hospital-based DOT was provided to high risk patients up-to smear conversion. Demographic, microbiological and clinical conditions, as potential factors associated with confirmed smear conversion at 60 and 90 days of anti-tuberculous therapy were evaluated. Results. 122 patients were studied, 45.9% of them were immigrants (20% illegal) from high-prevalence TB countries. HIV testing was negative in all cases. Twelve patients had M. tuberculosis resistant to ≥ 1 first-line anti-tuberculous agents. The rate of defaulting from TB treatment was 7.3%. Sputum smear became negative in 84.4% cases after 60 days and 93.3% cases after 90 days. At such time, smear conversion rates were similar among different high risk subgroups such as illegal immigrants (95.9%), legal foreign-born (92.5%) and Italian persons (94.8%). Persistent sputum smear positivity was independently correlated with the extent of pulmonary lesions at 60 (p<0.0001) and 90 days (p=0.038) of hospital-based DOT. Conclusions. These findings suggest that prolonged hospitalisation for illegal immigrants and high risk TB patients, may positively influence the early outcome of TB treatment despite of drug resistance and legal status

Nintedanib Treatment for Idiopathic Pulmonary Fibrosis Patients Who Have Been Switched from Pirfenidone Therapy: A Retrospective Case Series Study

BACKGROUND: The efficacy and effectiveness of nintedanib as a first-line therapy in idiopathic pulmonary fibrosis (IPF) patients have been demonstrated by clinical trials and real-life studies. Our aim was to examine the safety profile and effectiveness of nintedanib when it is utilized as a second-line treatment in subjects who have discontinued pirfenidone. METHODS: The medical charts of 12 patients who were switched from pirfenidone to nintedanib were examined retrospectively. The drug's safety was defined by the number of adverse events (AEs) that were reported; disease progression was evaluated based on the patient's vital status and changes in forced vital capacity (FVC) at 12-month follow-up. RESULTS: The numbers of patients experiencing AEs and of the AEs per patient in our study group didn't significantly differ with respect to a group of 56 individuals who were taking nintedanib as a first-line therapy during the study period (5/12 vs. 22/56; p = 0.9999, and 0.00 (0.00-1.00) vs. 0.00 (0.00-3.00); p = 0.517, respectively). Two out of the 3 patients who had been switched to nintedanib due to a rapid disease progression showed stabilized FVC values. CONCLUSIONS: Nintedanib was found to have an acceptable safety profile in the majority of the IPF patients switched from pirfenidone. Prospective studies are warranted to determine if the drug can effectively delay disease progression in these patients

Quest for barley canopy architecture genes in the hortillus population and whealbi germplasm collection

Barley grains are predominantly used for animal feed and malting, and breeding traditionally focused on increase of grain yield by partitioning biomass from straw to grains. The increasing demand for renewable energy sources makes straw, and specially barley straw characterized by the largest content of carbohydrates among the cereals, a valuable product for its potential conversion into biofuels and other products. The BarPLUS project aims at finding genes, alleles and candidate lines related to barley canopy architecture and photosynthesis, to maximize barley biomass and yield (https://barplus.wordpress.com/). In this framework, our research group focuses on identifying genes and alleles controlling tillering, leaf size and leaf angle traits in barley by exploiting both induced and natural allelic variation. Using a forward genetics approach, we screened the HorTILLUS population (Szurman-Zubrzycka et al., 2018) under both field and controlled conditions, identifying 5 mutants with increased tillering and/or erect leaves. After crossing with four reference cultivars, pools of F2 wild-type and mutant plants were selected to map and identify the underlying genes by exome sequencing (Mascher et al., 2014). In parallel, TILLING of the HorTILLUS population identified four lines carrying mutations in the LBO (Lateral branching oxidoreductase) gene involved in tiller number. In order to explore also natural genetic variation, we are taking advantage of the \u2018WHEALBI\u2019 germplasm collection, which includes 403 exome sequenced diverse accessions (BustosKorts et al., 2019): a field trial on a subset of 240 lines (Fiorenzuola d\u2019Arda, Italy) allowed us to conduct a preliminary genome wide association study based on high-throughput phenotyping for leaf angle (PocketPlant3D smartphone app) and quantitative image-analysis for leaf size. Results will be compared with those from a greenhouse experiment on the same 240 accessions to analyze a wide range of morphological traits and identify associated markers and genomic regions

A Real-Life Multicenter National Study on Nintedanib in Severe Idiopathic Pulmonary Fibrosis

Background: Two therapeutic options are currently available for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. To date, there is still insufficient data on the efficacy of these 2 agents in patients with more severe disease. Objectives: This national, multicenter, retrospective real-life study was intended to determine the impact of nintedanib on the treatment of patients with severe IPF. Methods: All patients included had severe IPF and had to have at least 6 months of follow-up before and at least 6 months of follow-up after starting nintedanib. The aim of the study was to compare the decline in lung function before and after treatment. Patient survival after 6 months of therapy with nintedanib was assessed. Results: Forty-one patients with a forced vital capacity (FVC) 6450% and/or a diffusing capacity of the lung for carbon monoxide (DLCO) 6435% predicted at the start of nintedanib treatment were enrolled. At the 6-month follow-up, the decline of DLCO (both absolute and % predicted) was significantly reduced compared to the pretreatment period (absolute DLCO at the -6-month, T0, and +6-month time points (5.48, 4.50, and 5.03 mmol/min/kPa, respectively, p = 0.03; DLCO% predicted was 32.73, 26.54, and 29.23%, respectively, p = 0.04). No significant beneficial effect was observed in the other functional parameters analyzed. The 1-year survival in this population was 79%, calculated from month 6 of therapy with nintedanib. Conclusions: This nationwide multicenter experience in patients with severe IPF shows that nintedanib slows down the rate of decline of absolute and % predicted DLCO but does not have significant impact on FVC or other lung parameters

Accuracy of right atrial pressure estimation using a multi-parameter approach derived from inferior vena cava semi-automated edge-tracking echocardiography: a pilot study in patients with cardiovascular disorders

The echocardiographic estimation of right atrial pressure (RAP) is based on the size and inspiratory collapse of the inferior vena cava (IVC). However, this method has proven to have limits of reliability. The aim of this study is to assess feasibility and accuracy of a new semi-automated approach to estimate RAP. Standard acquired echocardiographic images were processed with a semi-automated technique. Indexes related to the collapsibility of the vessel during inspiration (Caval Index, CI) and new indexes of pulsatility, obtained considering only the stimulation due to either respiration (Respiratory Caval Index, RCI) or heartbeats (Cardiac Caval Index, CCI) were derived. Binary Tree Models (BTM) were then developed to estimate either 3 or 5 RAP classes (BTM3 and BTM5) using indexes estimated by the semi-automated technique. These BTMs were compared with two standard estimation (SE) echocardiographic methods, indicated as A and B, distinguishing among 3 and 5 RAP classes, respectively. Direct RAP measurements obtained during a right heart catheterization (RHC) were used as reference. 62 consecutive \u2018all-comers\u2019 patients that had a RHC were enrolled; 13 patients were excluded for technical reasons. Therefore 49 patients were included in this study (mean age 62.2\ua0\ub1\ua015.2\ua0years, 75.5% pulmonary hypertension, 34.7% severe left ventricular dysfunction and 51% right ventricular dysfunction). The SE methods showed poor accuracy for RAP estimation (method A: misclassification error, ME\ua0=\ua051%, R2\ua0=\ua00.22; method B: ME\ua0=\ua069%, R2\ua0=\ua00.26). Instead, the new semi-automated methods BTM3 and BTM5 have higher accuracy (ME\ua0=\ua014%, R2\ua0=\ua00.47 and ME\ua0=\ua022%, R2\ua0=\ua00.61, respectively). In conclusion, a multi-parametric approach using IVC indexes extracted by the semi-automated approach is a promising tool for a more accurate estimation of RAP