Comorbidities in idiopathic pulmonary fibrosis: an underestimated issue

Idiopathic pulmonary fibrosis (IPF) is a progressive and fibrosing lung disease with a poor prognosis. Between 60% and 70% of IPF patients die of IPF; the remaining causes of death may be due to comorbidities occurring in this ageing population. Interest in the role played by comorbidities in IPF has increased in the past few years. The optimal clinical management of IPF is multifaceted and not only involves antifibrotic treatment, but also vaccinations, oxygen supplementation, evaluation of nutritional status as well as psychological support and patient education. Symptom management, pulmonary rehabilitation, palliative care and treatment of comorbidities represent further areas of clinical intervention. This review analyses the major comorbidities observed in IPF, focusing on those that have the greatest impact on mortality and quality of life (QoL). The identification and treatment of comorbidities may help to improve patients' health-related QoL (i.e. sleep apnoea and depression), while some comorbidities (i.e. lung cancer, cardiovascular diseases and pulmonary hypertension) influence survival. It has been outlined that gathering comorbidities data improves the prediction of survival beyond the clinical and physiological parameters of IPF

Prognostic value of mediastinal lymph node enlargement in chronic interstitial lung disease

PURPOSEMediastinal lymph node (MLN) enlargement detected on chest computed tomography (CT) is frequent in patients with interstitial lung disease (ILD) and is shown in approximately 70% of cases of idiopathic pulmonary fibrosis (IPF). We hypothesized that enlarged MLNs might be a predictor of poor prognosis, associated with lower survival and stronger disease severity.METHODSThis study included patients with idiopathic pulmonary fibrosis (IPF) or nonspecific interstitial pneumonia (NSIP) from January 2009 to December 2018. Baseline chest CT scan and one-year follow-up scan of the patients were reviewed for the extent of lung fibrosis and MLNs. Two radiologists independently assessed MLN diameter and location. Patients with drug toxicity-related ILD, sarcoidosis, chronic hypersensitivity pneumonitis and other rare idiopathic interstitial pneumonias were excluded. The primary endpoint was survival. Secondary endpoints included number of hospitalizations for respiratory causes, lung function evaluated by forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), and lung fibrosis score determined by CT scan.RESULTSWe retrospectively reviewed the medical registries of 110 patients with chronic pulmonary fibrosis (mean age 71 years, 60.4% male). Nine participants were excluded because the CT scans were of poor diagnostic quality for the evaluation of the mediastinum or unavailable for review. The analysis of 101 patients showed that enlarged MLNs (short axis diameter ≥10 mm) were present in 50.5% (n=51) and strongly predicted survival (HR= 2.11, 95% CI 1.12–3.96, p = 0.020). Patients with MLN enlargement experienced greater number of hospitalizations for respiratory causes (mean 2.5 vs. 1.8, p = 0.010) and had significantly worse lung function parameters (FVC, 71% vs. 81%, p = 0.018 and DLCO, 40% vs. 50%, p = 0.001) and a higher lung fibrosis score (50% vs. 39%, p = 0.001).CONCLUSIONIn patients with IPF and NSIP, enlarged MLNs predict survival, are associated with increased number of hospitalizations, and show signs of poorer lung function and more severe fibrosis

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer, studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory, a versatile observatory designed to address the Hot and Energetic Universe science theme, selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), it aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR, browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters. Finally we briefly discuss on the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, and touch on communication and outreach activities, the consortium organisation, and finally on the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental Astronomy with minor editin

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory. Athena is a versatile observatory designed to address the Hot and Energetic Universe science theme, as selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), X-IFU aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over a hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR (i.e. in the course of its preliminary definition phase, so-called B1), browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters, such as the instrument efficiency, spectral resolution, energy scale knowledge, count rate capability, non X-ray background and target of opportunity efficiency. Finally, we briefly discuss the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, touch on communication and outreach activities, the consortium organisation and the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. The X-IFU will be provided by an international consortium led by France, The Netherlands and Italy, with ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Poland, Spain, Switzerland, with additional contributions from the United States and Japan.The French contribution to X-IFU is funded by CNES, CNRS and CEA. This work has been also supported by ASI (Italian Space Agency) through the Contract 2019-27-HH.0, and by the ESA (European Space Agency) Core Technology Program (CTP) Contract No. 4000114932/15/NL/BW and the AREMBES - ESA CTP No.4000116655/16/NL/BW. This publication is part of grant RTI2018-096686-B-C21 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. This publication is part of grant RTI2018-096686-B-C21 and PID2020-115325GB-C31 funded by MCIN/AEI/10.13039/501100011033

Lung Cryobiopsy for the Diagnosis of Interstitial Lung Diseases: A Series Contribution to a Debated Procedure

Introduction: Transbronchial cryobiopsy is an alternative to surgical biopsy for the diagnosis of fibrosing interstitial lung diseases, although the role of this relatively new method is rather controversial. Aim of this study is to evaluate the diagnostic performance and the safety of transbronchial cryobiopsy in patients with fibrosing interstitial lung disease. Materials and methods: The population in this study included patients with interstitial lung diseases who underwent cryobiopsy from May 2015 to May 2018 at the Division of Pneumology of San Giuseppe Hospital in Milan and who were retrospectively studied. All cryobiopsy procedures were performed under fluoroscopic guidance using a flexible video bronchoscope and an endobronchial blocking system in the operating room with patients under general anaesthesia. The diagnostic performance and safety of the procedure were assessed. The main complications evaluated were endobronchial bleeding and pneumothorax. All cases were studied with a multidisciplinary approach, before and after cryobiopsy. Results: Seventy-three patients were admitted to this study. A specific diagnosis was reached in 64 cases, with a diagnostic sensitivity of 88%; 5 cases (7%) were considered inadequate, 4 cases (5%) were found to be non-diagnostic. Only one major bleeding event occurred (1.4%), while 14 patients (19%) experienced mild/moderate bleeding events while undergoing bronchoscopy; 8 cases of pneumothorax (10.9%) were reported, of which 2 (2.7%) required surgical drainage. Conclusions: When performed under safe conditions and in an experienced center, cryobiopsy is a procedure with limited complications having a high diagnostic yield in fibrotic interstitial lung disease

The Cryogenic AntiCoincidence detector for ATHENA X-IFU: A program overview

none17noThe ATHENA observatory is the second large-class ESA mission, in the context of the Cosmic Vision 2015 - 2025, scheduled to be launched on 2028 at L2 orbit. One of the two on-board instruments is the X-IFU (X-ray Integral Field Unit): it is a TES-based kilo-pixels order array able to perform simultaneous high-grade energy spectroscopy (2.5 eV at 6 keV) and imaging over the 5 arcmin FoV. The X-IFU sensitivity is degraded by the particles background which is induced by primary protons of both solar and Cosmic Rays origin, and secondary electrons. The studies performed by Geant4 simulations depict a scenario where it is mandatory the use of reduction techniques that combine an active anticoincidence detector and a passive electron shielding to reduce the background expected in L2 orbit down to the goal level of 0.005 cts/cm2/s/keV, so enabling the characterization of faint or diffuse sources (e.g. WHIM or Galaxy cluster outskirts). From the detector point of view this is possible by adopting a Cryogenic AntiCoincidence (CryoAC) placed within a proper optimized environment surrounding the X-IFU TES array. It is a 4-pixels detector made of wide area Silicon absorbers sensed by Ir TESes, and put at a distance < 1 mm below the TES-array. On October 2015 the X-IFU Phase A program has been kicked-off, and about the CryoAC is at present foreseen on early 2017 the delivery of the DM1 (Demonstration Model 1) to the FPA development team for integration, which is made of 1 pixel "bridgessuspended" that will address the final design of the CryoAC. Both the background studies and the detector development work is on-going to provide confident results about the expected residual background at the TES-array level, and the single pixel design to produce a detector for testing activity on 2016/2017. Here we will provide an overview of the CryoAC program, discussing some details about the background assessment having impact on the CryoAC design, the last single pixel characterization, the structural issues, followed by some programmatic aspects.noneMacculi, C.; Argan, A.; D'Andrea, M.; Lotti, S.; Laurenza, M.; Piro, L.; Biasotti, M.; Corsini, D.; Gatti, F.; Torrioli, G.; Fiorini, M.; Molendi, S.; Uslenghi, M.; Mineo, T.; Bulgarelli, A.; Fioretti, V.; Cavazzuti, E.Macculi, C.; Argan, A.; D'Andrea, M.; Lotti, S.; Laurenza, M.; Piro, L.; Biasotti, M.; Corsini, D.; Gatti, F.; Torrioli, G.; Fiorini, M.; Molendi, S.; Uslenghi, M.; Mineo, T.; Bulgarelli, A.; Fioretti, V.; Cavazzuti, E

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services