Dasatinib-induced diffuse alveolar hemorrhage

The BCR-ABL tyrosine kinase inhibitor dasatinib is a potent treatment for chronic myeloid leukemia (CML). However, it is associated with pulmonary toxicities. Commonly reported dasatinib related pulmonary toxicities include pleural effusion, lung parenchymal abnormalities, and pulmonary hypertension. Diffuse alveolar hemorrhage (DAH) during treatment with dasatinib is very rare. To the best of our knowledge there are only two cases reported. Here we report a 57-year-old Caucasian woman who developed acute hypoxic respiratory failure while on dasatinib for treatment of CML. She was diagnosed with DAH suspected to be secondary to dasatinib, after other common etiologies were ruled out. There was full recovery after stopping dasatinib and treatment with corticosteroids. Keywords: Dasatinib, pulmonary toxicity, diffuse alveolar hemorrhage, chronic myeloid leukemia

Symptom Persistence Despite Improvement in Cardiopulmonary Health - Insights from longitudinal CMR, CPET and lung function testing post-COVID-19

Background The longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19. Methods Fifty-eight patients and thirty matched controls underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months. Findings At 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1 (marker of inflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pVO2) on CPET. By 6 months, 53% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (-4.3 mls/m2, P=0.005) decreased and RV ejection fraction (+3.2%, P=0.0003) increased. Native T1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak VO2, although better, were abnormal in patients versus controls. 31% had reduced pVO2 secondary to fatigue and submaximal tests. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures. Interpretation In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health. Funding NIHR Oxford and Oxford Health BRC, Oxford BHF CRE, UKRI and Wellcome Trust.

Widespread Parenchymal Abnormalities and Pulmonary Embolism on Contrast-Enhanced CT Predict Disease Severity and Mortality in Hospitalized COVID-19 Patients

Purpose: Severe COVID-19 is associated with inflammation, thromboembolic disease, and high mortality. We studied factors associated with fatal outcomes in consecutive COVID-19 patients examined by computed tomography pulmonary angiogram (CTPA).Methods: This retrospective, single-center cohort analysis included 130 PCR-positive patients hospitalized for COVID-19 [35 women and 95 men, median age 57 years (interquartile range 51–64)] with suspected pulmonary embolism based on clinical suspicion. The presence and extent of embolism and parenchymal abnormalities on CTPA were recorded. The severity of pulmonary parenchymal involvement was stratified by two experienced radiologists into two groups: lesions affecting ≤50% or >50% of the parenchyma. Patient characteristics, radiological aspects, laboratory parameters, and 60-day mortality data were collected.Results: Pulmonary embolism was present in 26% of the patients. Most emboli were small and peripheral. Patients with widespread parenchymal abnormalities, with or without pulmonary embolism, had increased main pulmonary artery diameter (p < 0.05) and higher C-reactive protein (p < 0.01), D-dimer (p < 0.01), and troponin T (p < 0.001) and lower hemoglobin (p < 0.001). A wider main pulmonary artery diameter correlated positively with C-reactive protein (r = 0.28, p = 0.001, and n = 130) and procalcitonin. In a multivariant analysis, D-dimer >7.2 mg/L [odds ratio (±95% confidence interval) 4.1 (1.4–12.0)] and ICU stay were significantly associated with embolism (p < 0.001). The highest 60-day mortality was found in patients with widespread parenchymal abnormalities combined with pulmonary embolism (36%), followed by patients with widespread parenchymal abnormalities without pulmonary embolism (26%). In multivariate analysis, high troponin T, D-dimer, and plasma creatinine and widespread parenchymal abnormalities on CT were associated with 60-day mortality.Conclusions: Pulmonary embolism combined with widespread parenchymal abnormalities contributed to mortality risk in COVID-19. Elevated C-reactive protein, D-dimer, troponin-T, P-creatinine, and enlarged pulmonary artery were associated with a worse outcome and may mirror a more severe systemic disease. A liberal approach to radiological investigation should be recommended at clinical deterioration, when the situation allows it. Computed tomography imaging, even without intravenous contrast to assess the severity of pulmonary infiltrates, are of value to predict outcome in COVID-19. Better radiological techniques with higher resolution could potentially improve the detection of microthromboses. This could influence anticoagulant treatment strategies, preventing clinical detoriation.

POS0325 RADIOMIC BIOMARKER OF PULMONARY VASCULAR RELATED STRUCTURES PREDICTS MORTALITY IN SYSTEMIC SCLEROSIS

Background:Quantitative computed tomography (QCT) extracts features from high-resolution CT scans and quantifies lung parenchymal and vascular abnormalities which may not be discernable by qualitative review. The threshold values of individual parenchymal abnormalities and vascular features measured by QCT methods which associate with mortality in systemic sclerosis (SSc) are currently unknown.Objectives:To determine whether QCT measures, specifically pulmonary parenchymal abnormalities and pulmonary vascular related structures (PVRS), can predict mortality in SSc and to determine the optimal quantitative thresholds for those parameters.Methods:A total of 133 subjects (76% women) meeting 2013 ACR/EULAR classification criteria for SSc with a baseline CT within 3 years of diagnosis were retrospectively identified for inclusion. CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating) was used to quantitatively measure volume of ground glass opacities (GGO), reticular densities, and honeycombing (HC). Total interstitial lung disease (ILD) was the summation of these features. PVRS was also quantified using CALIPER. Values for each feature were expressed as a percentage of total lung volume. Cox models evaluated the hazard ratio (HR) for mortality for each parameter adjusting for age at SSc diagnosis, sex, diffuse SSc subtype, and history of smoking. The optimal thresholds for mortality prediction for each parameter were determined using consensus between 4 methods: Contal and O’Quigley Method, Cox Model Hazard Ratio, Cox Model Wald P-value, and False Discovery Rate. The c-statistic was used to assess each models’ ability to predict mortality.Results:Mean ±SD for age at SSc diagnosis was 61 ± 13 years and length of follow-up was 4.7 ± 3.0 years. There were 32 deaths (24%). A Cox model including age (HR 1.05, 95% CI: 1.01-1.09), female sex (HR 0.49, 95% CI: 0.22-1.08), diffuse SSc subtype (HR 1.50, 95% CI: 0.69-3.30), and history of smoking (HR 2.09, 95% CI: 0.97-4.53) (Model 1) significantly predicted mortality (C-statistic 0.72, 95% CI: 0.63-0.81). Adjusting for Model 1, reticular densities% (HR 1.19, 95% CI: 1.05-1.35), total ILD% (HR 1.02, 95% CI: 1.00-1.03), and PVRS% (HR 1.19, 95% CI: 1.05-1.35) were associated with mortality on univariable analyses; GGO% (HR 1.01, 95% CI: 0.98-1.04) was not significantly associated with mortality. The optimal thresholds for mortality prediction were then determined and were as follows: GGO=20%, reticular densities=8%, total ILD=20%, and PVRS=5%. While the risk of mortality was significantly increased in subjects with GGO ≥20% (HR 2.70, 95% CI: 1.21-6.05), reticular densities ≥8% (HR 4.64, 95% CI: 1.68-12.81), and total ILD ≥20% (2.59, 95% CI: 1.12-5.99), these baseline thresholds did not improve upon mortality prediction when added individually to Model 1 (C-statistic 0.73 for each). PVRS ≥5%, which had an over six-fold increase in mortality (HR 6.42, 95% CI: 2.60-15.88), did improve mortality prediction when added to Model 1 (C-statistic 0.78, 95% CI: 0.70-0.86).Conclusion:PVRS strongly associates with early mortality in patients with SSc and represents a novel radiomic biomarker that provides prognostic information on mortality beyond pulmonary parenchymal abnormalities. CALIPER derived PVRS quantifies CT data through a function that defines connected tubular branching structures. This extracts pulmonary arteries and veins from the adjacent parenchyma but could potentially also include regions of adjoining of fibrosis.1 Larger studies examining the association between PVRS and progression of cardiopulmonary disease are warranted.References:[1]Jacob J, Bartholmai BJ, Rajagopalan S, et al. Predicting Outcomes in Idiopathic Pulmonary Fibrosis Using Automated Computed Tomographic Analysis. Am J Respir Crit Care Med 2018;198:767-76.Acknowledgements:This project was supported by the Mayo Clinic Margaret Harvey Schering Clinician Career Development Award.Disclosure of Interests:Alicia Hinze: None declared, Yasser Radwan: None declared, Mamoun Elnagar: None declared, Reto Kurmann: None declared, Shreyasee Amin: None declared, Robert Vassallo Grant/research support from: Pfizer, Bristol Myers Squibb, Sun Pharma, Cynthia S. Crowson: None declared, Brian Bartholmai Consultant of: AstraZenica, Boehringer Ingelheim, Promedior LLC (all <$5,000 annually)

COVID-19 in a pediatric cohort—retrospective review of chest computer tomography findings

Background Radiological features of the novel 2019 coronavirus disease (COVID-19) have been mainly described in adults. Available literature states that imaging findings in children are similar but less pronounced. The aim of this study is to describe and illustrate the chest computer tomography (CT) features of pediatric COVID-19. Results This retrospective study was based on the review of all the chest CTs performed in pediatric patients with confirmed COVID-19 disease between March 8th and May 26th 2020 (n = 24). The presence of comorbidities and coinfection was assessed, as well as timing of CT examination in relation to the onset of symptoms. CT findings were categorized as typical, indeterminate, atypical, and negative for COVID-19 according to International Expert Consensus Statement on Chest Imaging in Pediatric COVID-19 Patient Management. This study found that CT findings were abnormal in 17 (71%) patients, with 5 (21%), 9 (38%), and 3 (13%) patients considered to have typical, indeterminate, and atypical findings, respectively. The most common CT patterns were multiple ground-glass opacities (58%), followed by consolidations (50%). Six patients showed predominantly peripheral distribution of parenchymal abnormalities. A halo sign was identified in 3 patients and a perilobular pattern was identified in one of the cases with typical findings. Conclusions Chest CT findings in children infected with SARS-CoV-2 can be subtle or absent. Besides recognizing typical findings, radiologists should be able to identify features that favor different or concomitant diagnosis.

Humoral responses to SARS-CoV-2 by healthy and sick dogs during the COVID-19 pandemic in Spain

COVID-19 is a zoonotic disease caused by SARS-CoV-2. Infections of animals with SARS-CoV-2 have recently been reported, and an increase of severe lung pathologies in domestic dogs has also been detected by veterinarians in Spain. Therefore, further descriptions of the pathological processes in those animals that show symptoms similar to those described in humans affected by COVID-19 would be highly valuable. The potential for companion animals to contribute to the continued transmission and community spread of this known human-to-human disease is an urgent issue to be considered. Forty animals with pulmonary pathologies were studied by chest X-ray, ultrasound analysis, and computed tomography. Nasopharyngeal and rectal swabs were analyzed to detect canine pathogens, including SARS-CoV-2. An additional twenty healthy dogs living in SARS-CoV-2-positive households were included. Immunoglobulin detection by several immunoassays was performed. Our findings show that sick dogs presented severe alveolar or interstitial patterns with pulmonary opacity, parenchymal abnormalities, and bilateral lesions. The forty sick dogs were negative for SARS-CoV-2 but Mycoplasma spp. was detected in 26 of 33 dogs. Five healthy and one pathological dog presented IgG against SARS-CoV-2. Here we report that despite detecting dogs with α-SARS-CoV-2 IgG, we never obtained a positive RT-qPCR for SARS-SoV-2, not even in dogs with severe pulmonary disease; suggesting that even in the case of canine infection, transmission would be unlikely. Moreover, dogs living in COVID-19-positive households could have been more highly exposed to infection with SARS-CoV-2.