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<b><i>Introduction:</i></b> Treatment of interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) often includes systemic corticosteroids. Use of steroid-sparing agents is amenable to avoid potential side effects. <b><i>Methods:</i></b> Functional indices and high-resolution computed tomography (HRCT) patterns of patients with non-IPF ILDs receiving mycophenolate mofetil (MMF) with a minimum follow-up of 1 year were analyzed. Two independent radiologists and a machine learning software system (Imbio 1.4.2.) evaluated HRCT patterns. <b><i>Results:</i></b> Fifty-five (<i>n</i> = 55) patients were included in the analysis (male: 30 [55%], median age: 65.0 [95% CI: 59.7–70.0], mean forced vital capacity %predicted [FVC %pred.] ± standard deviation [SD]: 69.4 ± 18.3, mean diffusing capacity of lung for carbon monoxide %pred. ± SD: 40.8 ± 14.3, hypersensitivity pneumonitis: 26, connective tissue disease-ILDs [CTD-ILDs]: 22, other ILDs: 7). There was no significant difference in mean FVC %pred. post-6 months (1.59 ± 2.04) and 1 year (−0.39 ± 2.49) of treatment compared to baseline. Radiographic evaluation showed no significant difference between baseline and post-1 year %ground glass opacities (20.0 [95% CI: 14.4–30.0] vs. 20.0 [95% CI: 14.4–25.6]) and %reticulation (5.0 [95% CI: 2.0–15.6] vs. 7.5 [95% CI: 2.0–17.5]). A similar performance between expert radiologists and Imbio software analysis was observed in assessing ground glass opacities (intraclass correlation coefficient [ICC] = 0.73) and reticulation (ICC = 0.88). Fourteen patients (25.5%) reported at least one side effect and 8 patients (14.5%) switched to antifibrotics due to disease progression. <b><i>Conclusion:</i></b> Our data suggest that MMF is a safe and effective steroid-sparing agent leading to disease stabilization in a proportion of patients with non-IPF ILDs. Machine learning software systems may exhibit similar performance to specialist radiologists and represent fruitful diagnostic and prognostic tools.

IntroductionMyositis associated interstitial lung disease (ILD) seems to be an under-recognized entity.MethodsIn this multicenter, retrospective study, we recorded between 9/12/2019 and 30/9/2021 consecutive patients who presented in five different ILD centers from two European countries (Greece, France) and received a multidisciplinary diagnosis of myositis associated-ILD. The primary outcome was all-cause mortality over 1 year in specific subgroups of patients. Secondary outcomes included comparison of disease characteristics between patients diagnosed with the amyopathic subtype and patients with evidence of myopathy at diagnosis.ResultsWe identified 75 patients with myositis associated-ILD. Median age (95% CI) at the time of diagnosis was 64.0 (61.0–65.0) years. Antinuclear antibody testing was positive in 40% of the cohort (n = 30/75). Myopathy onset occurred first in 40.0% of cases (n = 30), ILD without evidence of myopathy occurred in 29 patients (38.7%), while 16 patients (21.3%) were diagnosed concomitantly with ILD and myopathy. The commonest radiographic pattern was cellular non-specific interstitial pneumonia (NSIP) and was observed in 29 patients (38.7%). The radiographic pattern of organizing pneumonia was significantly more common in patients diagnosed with the amyopathic subtype compared to patients that presented with myopathy [24.1% (n = 7/29) vs. 6.5% (n = 3/46), p = 0.03]. One year survival was 86.7% in the overall population. Kaplan–Meier analysis demonstrated significantly higher all-cause 1-year mortality in patients with the amyopathic subtype compared to patients with evidence of myopathy [H R 4.24 (95% CI: 1.16–15.54), p = 0.03]. Patients diagnosed following hospitalization due to acute respiratory failure experienced increased risk of 1-year all-cause mortality compared to patients diagnosed in outpatient setting [HR 6.70 (95% CI: 1.19–37.81), p = 0.03]. Finally, patients with positive anti-MDA5 presented with higher 1-year all-cause mortality compared to anti-MDA5 negative patients [HR 28.37 (95% CI: 5.13–157.01), p = 0.0001].ConclusionSpecific ILD radiographic patterns such as NSIP and organizing pneumonia may herald underlying inflammatory myopathies. Hospitalized patients presenting with bilateral organizing pneumonia refractory to antibiotics should be meticulously evaluated for myositis associated-ILD even if there is no overt muscular involvement. Incorporation of ILD radiological patterns in the diagnostic criteria of inflammatory myopathies may lead to timely therapeutic interventions and positively impact patients’ survival.

Background: Tocilizumab and baricitinib have proven efficacy in COVID-19. There were no randomized-controlled trials comparing these compounds in patients with COVID-19. Materials/Patients and Methods: In this open label, randomized controlled trial, we assigned 251 patients with COVID-19 and PaO2/FiO2<200 to receive either tocilizumab (n=126) or baricitinib (n=125) plus standard of care. To determine whether baricitinib was non-inferior to tocilizumab, we assessed if the upper boundary of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.50. The primary outcome was mechanical ventilation or death by day 28. Secondary outcomes included time to hospital discharge by day 28 and change in WHO progression scale at day 10. Results: Baricitinib was non-inferior to tocilizumab for the primary composite outcome of mechanical ventilation or death by day 28 (HR 0.83, 95% CI: 0.56 to 1.21, p=0.001 for non-inferiority). Baricitinib was non-inferior to tocilizumab for the time to hospital discharge within 28 days (discharged alive- tocilizumab: 52.4% vs baricitinib: 58.4%; HR 0.85, (95% CI: 0.61 to 1.18), p<0.001 for non-inferiority). There was no significant difference between baricitinib and tocilizumab arm in the change in WHO scale at day 10 [0.0 (95% CI: 0.0 to 0.0) vs 0.0 (95% CI: 0.0 to 1.0), p=0.83]. Conclusion: Baricitinib was non-inferior to tocilizumab with regards to the composite outcome of mechanical ventilation or death by day 28 and the time to discharge by day 28 in patients with severe COVID-19. Cost-effectiveness should be taken into account to avoid a dramatic upswing in health system budgets.

IntroductionPost-acute sequelae of COVID-19 seem to be an emerging global crisis. Machine learning radiographic models have great potential for meticulous evaluation of post-COVID-19 interstitial lung disease (ILD).MethodsIn this multicenter, retrospective study, we included consecutive patients that had been evaluated 3 months following severe acute respiratory syndrome coronavirus 2 infection between 01/02/2021 and 12/5/2022. High-resolution computed tomography was evaluated through Imbio Lung Texture Analysis 2.1.ResultsTwo hundred thirty-two (n = 232) patients were analyzed. FVC% predicted was ≥80, between 60 and 79 and &lt;60 in 74.2% (n = 172), 21.1% (n = 49), and 4.7% (n = 11) of the cohort, respectively. DLCO% predicted was ≥80, between 60 and 79 and &lt;60 in 69.4% (n = 161), 15.5% (n = 36), and 15.1% (n = 35), respectively. Extent of ground glass opacities was ≥30% in 4.3% of patients (n = 10), between 5 and 29% in 48.7% of patients (n = 113) and &lt;5% in 47.0% of patients (n = 109). The extent of reticulation was ≥30%, 5–29% and &lt;5% in 1.3% (n = 3), 24.1% (n = 56), and 74.6% (n = 173) of the cohort, respectively. Patients (n = 13, 5.6%) with fibrotic lung disease and persistent functional impairment at the 6-month follow-up received antifibrotics and presented with an absolute change of +10.3 (p = 0.01) and +14.6 (p = 0.01) in FVC% predicted at 3 and 6 months after the initiation of antifibrotic.ConclusionPost-COVID-19-ILD represents an emerging entity. A substantial minority of patients presents with fibrotic lung disease and might experience benefit from antifibrotic initiation at the time point that fibrotic-like changes are “immature.” Machine learning radiographic models could be of major significance for accurate radiographic evaluation and subsequently for the guidance of therapeutic approaches.