<div>Abstract<p>Immune-checkpoint-inhibitor (ICI)-associated myotoxicity involves the heart (myocarditis) and skeletal muscles (myositis), which frequently occur concurrently and is highly fatal. We report the results of a strategy that included identification of individuals with severe ICI-myocarditis by also screening for and managing concomitant respiratory muscle involvement with mechanical ventilation, as well as treatment with CTLA4-fusion protein abatacept and the Janus-kinase inhibitor ruxolitinib. Forty cases with definite ICI-myocarditis were included with pathological confirmation of concomitant myositis in the majority of patients. In the first 10 patients, using recommended guidelines, myotoxicity-related fatality occurred in 60%, consistent with historical controls. In the subsequent 30 cases, we instituted systematic screening for respiratory muscle involvement coupled with active ventilation and treatment using ruxolitinib and abatacept. Abatacept dose was adjusted using CD86-receptor occupancy on circulating monocytes. Myotoxicity-related fatality rate was 3.4%(1/30) in these 30 patients vs.60% in 1st quartile(p<0.0001). These clinical results are hypothesis-generating and need further evaluation.</p></div>
Core-needle biopsy guided by ultrasound can be performed for investigating peripheral lymph node (PLN). The aim of this study was to determine the efficacy of this technique in sarcoidosis.Retrospective review of files of all patients in the database of the radiology department of Avicenne university hospital who underwent PLN biopsies guided by ultrasound from January 2008 to June 2011 (n=292). Cases with either granulomas at histology with the procedure or with a final diagnosis of sarcoidosis were included in the study.The histological specimens were adequate in 282 out of 292 cases (96%) showing non-caseating granulomas in 22 cases (n=20 patients with a final diagnosis of sarcoidosis and n=2 patients with tuberculosis). After reviewing clinical files of the 282 patient, 22 were confirmed to have sarcoidosis, at initial presentation (n=19) or later during flare-up or relapse (n=3) with only 2 patients having no granuloma on PLN biopsy. PLN were palpable in 18 cases and only detected by (18F)FDG-PET/CT showing increased PLN uptake in 4 cases. The sensitivity and specificity of adequate biopsy were 91 and 99% and the positive and negative predictive values were 91 and 99%, respectively.Core-needle biopsy guided by ultrasound has a high efficacy for evidencing granulomas in sarcoidosis patients with PLN involvement either clinically palpable or in the presence of (18F)FDG-PET/CT uptake.
Background There are conflicting data regarding the diagnostic performance of chest CT for COVID-19 pneumonia. Disease extent at CT has been reported to influence prognosis. Purpose To create a large publicly available data set and assess the diagnostic and prognostic value of CT in COVID-19 pneumonia. Materials and Methods This multicenter, observational, retrospective cohort study involved 20 French university hospitals. Eligible patients presented at the emergency departments of the hospitals involved between March 1 and April 30th, 2020, and underwent both thoracic CT and reverse transcription-polymerase chain reaction (RT-PCR) testing for suspected COVID-19 pneumonia. CT images were read blinded to initial reports, RT-PCR, demographic characteristics, clinical symptoms, and outcome. Readers classified CT scans as either positive or negative for COVID-19 based on criteria published by the French Society of Radiology. Multivariable logistic regression was used to develop a model predicting severe outcome (intubation or death) at 1-month follow-up in patients positive for both RT-PCR and CT, using clinical and radiologic features. Results Among 10 930 patients screened for eligibility, 10 735 (median age, 65 years; interquartile range, 51-77 years; 6147 men) were included and 6448 (60%) had a positive RT-PCR result. With RT-PCR as reference, the sensitivity and specificity of CT were 80.2% (95% CI: 79.3, 81.2) and 79.7% (95% CI: 78.5, 80.9), respectively, with strong agreement between junior and senior radiologists (Gwet AC1 coefficient, 0.79). Of all the variables analyzed, the extent of pneumonia at CT (odds ratio, 3.25; 95% CI: 2.71, 3.89) was the best predictor of severe outcome at 1 month. A score based solely on clinical variables predicted a severe outcome with an area under the curve of 0.64 (95% CI: 0.62, 0.66), improving to 0.69 (95% CI: 0.6, 0.71) when it also included the extent of pneumonia and coronary calcium score at CT. Conclusion Using predefined criteria, CT reading is not influenced by reader's experience and helps predict the outcome at 1 month. ClinicalTrials.gov identifier: NCT04355507 Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Rubin in this issue.
Abstract Aims Epicardial adipose tissue (EAT) could contribute to the specific atherosclerosis profile observed in premature coronary artery disease (pCAD) characterized by accelerated plaque burden (calcified and non-calcified), high-risk plaque (HRP) features, and ischaemic recurrence. Our aims were to describe EAT volume and density in pCAD compared with asymptomatic individuals matched on cardiovascular risk factors and to study their relationship with coronary plaque severity extension and vulnerability. Methods and results Two hundred and eight patients who underwent coronary computed tomography angiography were analysed. It included 104 consecutive individuals with pCAD (acute or stable obstructive CAD before the age of 45 years) and 104 controls, matched 1:1 on age, sex, and cardiovascular risk factors. EAT volume, volume index (EATi), and density were measured with a semi-automated artificial-intelligence based segmentation method and CAD-RADS V2.0 determined according to guidelines. EAT volume and density were compared across groups, and associations with plaque burden and characteristics were investigated. EAT volume and EATi were significantly higher in patients with pCAD compared with matched controls (71.5 mL/m² [45.7;99.8] vs. 58.5 mL/m² [41.3;81.7] P = 0.002), and EAT density was significantly lower in patients with pCAD compared with matched controls (−82 HU [−87; −79] vs. −82 [−85; −78], P = 0.025). EATi was found to be positively correlated with increasing number of plaques, stenosis severity, and HRP features. Conclusion Patients with pCAD had EAT expansion with a higher lipid concentration, compared with controls matched for traditional risk factors. Increased EAT volume and low EAT density were imaging biomarkers related to severe and potentially vulnerable CAD features.
Immune checkpoint inhibitors (ICI) have constituted a paradigm shift in the management of patients with cancer. Their administration is associated with a new spectrum of immune-related toxicities that can affect any organ. In patients treated with ICI, cardiovascular toxicities, particularly myocarditis, occur with a low incidence (<1%) but with a high fatality rate (30−50%). ICI-related myocarditis has been attributed to an immune infiltration, comprising of T-cells that are positive for CD3+, CD4+, CD8+, and macrophages that are positive for CD68. The diagnosis remains challenging and is made based on clinical syndrome, an electrocardiogram (ECG), biomarker data, and imaging criteria. In most clinical scenarios, endomyocardial biopsy plays a pivotal role in diagnosis, while cardiac magnetic resonance imaging (cMRI) has limitations that should be acknowledged. In this review, we discuss the role of medical imaging in optimizing the management of ICI related myocarditis, including diagnosis, prognostication, and treatment decisions.
