The impact of CMV reactivation on mortality after chimeric antigen receptor T-cell therapy.

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Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study

Background To evaluate inter-multidisciplinary team agreement for the diagnosis of diffuse parenchymal lung disease (DPLD). Methods Seven multidisciplinary meetings (MDTMs) consisting of at least one clinician, radiologist and pathologist, from 7 different countries evaluated 70 cases of diffuse lung disease in a two-stage process. First, the clinician, radiologist and pathologist (when lung biopsy was performed) evaluated each case and chose likelihoods (censored at 5% and summing to 100% in each case) for each of their differential diagnoses, without inter-disciplinary consultation. A full MDTM with review of all clinical, radiologic and pathologic data followed this. Interobserver agreement and inter-MDTM agreement for diagnosis was calculated using Cohen's kappa coefficient or weighted kappa coefficient where appropriate. Findings Inter-MDTM agreement for first choice diagnoses was acceptable (κ = 0.50). Idiopathic pulmonary fibrosis made up 18% of all MDTM first choice diagnoses. Diagnostic likelihoods for MDTM differential diagnoses were converted to a 5-point scale (0 = condition not included in the differential diagnosis, 1 = low probability (5-25%), 2 = intermediate probability (30-65%), 3 = high probability (70-95%), and 4 = pathognomonic (100%)). Inter-MDTM agreement on diagnostic likelihoods was good for idiopathic pulmonary fibrosis (IPF) (κw = 0.71) and connective tissue disease related interstitial lung disease (CTD-ILD) (κw = 0.73), only moderate for non-specific interstitial pneumonia (NSIP) (κw = 0.42) and poor for hypersensitivity pneumonitis (HP) (κw = 0.29). MDTMs, clinicians and radiologists respectively gave high confidence diagnoses of IPF (>65% likelihood) in 77.3%, 64.6% and 66.3% of cases. The prognostic significance of a first choice diagnosis of IPF versus not IPF was evaluated for MDTMs, clinicians and radiologists. Greater prognostic significance was demonstrated for an MDTM diagnosis of IPF as compared to individual clinician's diagnosis of IPF in 5/7 MDTMs, radiologist's diagnosis of IPF in 4/7 MDTMs. Interpretation Agreement between MDTMs for diagnosis in diffuse lung disease is acceptable and good for a diagnosis of IPF. This is validated by the greater prognostic significance of an IPF diagnosis made by MDTMs as compared to individual clinicians or radiologists. Furthermore, MDTMs made the diagnosis of IPF with higher confidence and more frequently than clinicians or radiologists. MDTM agreement for diagnosis of NSIP and hypersensitivity pneumonitis is poor, indicating a need for international consensus on diagnostic criteria for these diseases

IN-SYNC. V. Stellar Kinematics and Dynamics in the Orion A Molecular Cloud

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Safety of nintedanib added to pirfenidone treatment for idiopathic pulmonary fibrosis

We assessed safety and tolerability of treatment with pirfenidone (1602-2403 mg day-1) and nintedanib (200-300 mg day-1) in patients with idiopathic pulmonary fibrosis (IPF). This 24-week, single-arm, open-label, phase IV study (ClinicalTrials.gov identifier NCT02598193) enrolled patients with IPF with forced vital capacity % pred ≫50% and diffusing capacity of the lung for carbon monoxide % pred ≫30%. Before initiating nintedanib, patients had received pirfenidone for ≫16 weeks and tolerated a stable dose of ≫1602 mg day-1 for ≫28 days. The primary end-point was the proportion of patients who completed 24 weeks of combination treatment on pirfenidone (1602- 2403 mg day-1) and nintedanib (200-300 mg day-1). Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither. 89 patients were enrolled; 73 completed 24 weeks of treatment (69 meeting the primary end-point) and 16 discontinued treatment prematurely (13 due to TEAEs). 74 patients had 418 treatment-related TEAEs, of which diarrhoea, nausea and vomiting were the most common. Two patients had serious treatmentrelated TEAEs. Combined pirfenidone and nintedanib use for 24 weeks was tolerated by the majority of patients with IPF and associated with a similar pattern of TEAEs expected for either treatment alone. These results encourage further study of combination treatment with pirfenidone and nintedanib in patients with IPF