Adjudicated myocarditis and multisystem illness trajectory in healthcare workers post-COVID-19.

BACKGROUND: We investigated the associations of healthcare worker status with multisystem illness trajectory in hospitalised post-COVID-19 individuals. METHODS AND RESULTS: One hundred and sixty-eight patients were evaluated 28-60 days after the last episode of hospital care. Thirty-six (21%) were healthcare workers. Compared with non-healthcare workers, healthcare workers were of similar age (51.3 (8.7) years vs 55.0 (12.4) years; p=0.09) more often women (26 (72%) vs 48 (38%); p<0.01) and had lower 10-year cardiovascular risk (%) (8.1 (7.9) vs 15.0 (11.5); p<0.01) and Coronavirus Clinical Characterisation Consortium in-hospital mortality risk (7.3 (10.2) vs 12.7 (9.8); p<0.01). Healthcare worker status associated with less acute inflammation (peak C reactive protein 48 mg/L (IQR: 14-165) vs 112 mg/L (52-181)), milder illness reflected by WHO clinical severity score distribution (p=0.04) and shorter duration of admission (4 days (IQR: 2-6) vs 6 days (3-12)).In adjusted multivariate logistic regression analysis, healthcare worker status associated with a binary classification (probable/very likely vs not present/unlikely) of adjudicated myocarditis (OR: 2.99; 95% CI (1.01 to 8.89) by 28-60 days postdischarge).After a mean (SD, range) duration of follow-up after hospital discharge of 450 (88) days (range 290, 627 days), fewer healthcare workers died or were rehospitalised (1 (3%) vs 22 (17%); p=0.038) and secondary care referrals for post-COVID-19 syndrome were common (42%) and similar to non-healthcare workers (38%; p=0.934). CONCLUSION: Healthcare worker status was independently associated with the likelihood of adjudicated myocarditis, despite better antecedent health. Two in five healthcare workers had a secondary care referral for post-COVID-19 syndrome. TRIAL REGISTRATION NUMBER: NCT04403607.

Initial experience of 3 Tesla versus conventional field strength magnetic resonance imaging of small functioning pituitary tumours.

BACKGROUND: Higher field strength magnetic resonance imaging (MRI) is becoming increasingly available and offers improved image quality; however, the clinical usefulness of this technique for the demonstration of surgically treatable functional pituitary adenomas has not been clearly established. OBJECTIVE: To determine whether 3 Tesla (3T) MRI improves the detection of ACTH- and GH-secreting microadenomas over conventional imaging at field strengths of up to 1·5 Tesla (1·5T). DESIGN: Data sets from postgadolinium T1-weighted MRI at 1·5T and 3T were blinded, randomly ordered and assessed for the presence of pituitary tumour by two radiologists. Where possible, lesion signal difference to noise ratio (SDNR) was calculated for quantitative comparison. Imaging diagnoses were correlated with subsequent surgical and histological findings. PATIENTS: Twenty-four patients (10 men, 14 women) with biochemical evidence of Cushing's disease (19) or acromegaly (5) were identified over a 5-year period. RESULTS: 1·5T MRI gave a clear diagnosis of 12 pituitary tumours, all confirmed at 3T. Four additional definite lesions and one suspicious case were correctly identified at 3T. Histological correlation in 21 cases showed sensitivity improving from 54% with 1·5T to 85% with 3T. Radiologists' subjective image preference favoured 3T in 92%. Quantitative difference between tumour and parenchymal signal was significantly greater at 3T (mean SDNR -7·9 [3T] and -2·8 [1·5T], paired t-test P < 0·05). CONCLUSIONS: 3T MRI appears to offer increased conspicuity and detection of GH- and ACTH-secreting pituitary microadenomas. It is potentially clinically useful when 1·5T imaging is negative or equivocal.

Early Contrast Enhancement: A novel magnetic resonance imaging biomarker of pleural malignancy.

INTRODUCTION: Pleural Malignancy (PM) is often occult on subjective radiological assessment. We sought to define a novel, semi-objective Magnetic Resonance Imaging (MRI) biomarker of PM, targeted to increased tumour microvessel density (MVD) and applicable to minimal pleural thickening. MATERIALS AND METHODS: 60 consecutive patients with suspected PM underwent contrast-enhanced 3-T MRI then pleural biopsy. In 58/60, parietal pleura signal intensity (SI) was measured in multiple regions of interest (ROI) at multiple time-points, generating ROI SI/time curves and Mean SI gradient (MSIG: SI increment/time). The diagnostic performance of Early Contrast Enhancement (ECE; which was defined as a SI peak in at least one ROI at or before 4.5 min) was compared with subjective MRI and Computed Tomography (CT) morphology results. MSIG was correlated against tumour MVD (based on Factor VIII immunostain) in 31 patients with Mesothelioma. RESULTS: 71% (41/58) patients had PM. Pleural thickening was <10 mm in 49/58 (84%). ECE sensitivity was 83% (95% CI 61-94%), specificity 83% (95% CI 68-91%), positive predictive value 68% (95% CI 47-84%), negative predictive value 92% (78-97%). ECE performance was similar or superior to subjective CT and MRI. MSIG correlated with MVD (r = 0.4258, p = .02). DISCUSSION: ECE is a semi-objective, perfusion-based biomarker of PM, measurable in minimal pleural thickening. Further studies are warranted.

The diagnostic performance of routinely acquired and reported computed tomography imaging in patients presenting with suspected pleural malignancy.

OBJECTIVES: Contrast-enhanced computed tomography (CT) provides essential cross-sectional imaging data in patients with suspected pleural malignancy (PM). The performance of CT in routine practice may be lower than in previously reported research. We assessed this relative to 'real-life' factors including use of early arterial-phase contrast enhancement (by CT pulmonary angiography (CTPA)) and non-specialist radiology reporting. MATERIALS AND METHODS: Routinely acquired and reported CT scans in patients recruited to the DIAPHRAGM study (a prospective, multi-centre observational study of mesothelioma biomarkers) between January 2014 and April 2016 were retrospectively reviewed. CT reports were classified as malignant if they included specific terms e.g. "suspicious of malignancy", "stage M1a" and benign if others were used e.g. "indeterminate", "no cause identified". All patients followed a standard diagnostic algorithm. The diagnostic performance of CT (overall and based on the above factors) was assessed using 2×2 Contingency Tables. RESULTS: 30/345 (9%) eligible patients were excluded (non-contrast (n=13) or non-contiguous CT (n=4), incomplete follow-up (n=13)). 195/315 (62%) patients studied had PM; 90% were cyto-histologically confirmed. 172/315 (55%) presented as an acute admission, of whom 31/172 (18%) had CTPA. Overall, CT sensitivity was 58% (95% CI 51-65%); specificity was 80% (95% CI 72-87%). Sensitivity of CTPA (performed in 31/315 (10%)) was lower (27% (95% CI 9-53%)) than venous-phase CT (61% (95% CI 53-68%) p=0.0056). Sensitivity of specialist thoracic radiologist reporting was higher (68% (95% CI 55-79%)) than non-specialist reporting (53% (95% CI 44-62%) p=0.0488). Specificity was not significantly different. CONCLUSION: The diagnostic performance of CT in routine clinical practice is insufficient to exclude or confirm PM. A benign CT report should not dissuade pleural sampling where the presence of primary or secondary pleural malignancy would alter management. Sensitivity is lower with non-thoracic radiology reporting and particularly low using CTPA.

Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information. METHODS AND ANALYSIS: Serum and plasma (for SOMAscan and fibulin-3, respectively) will be collected at presentation, prior to pleural biopsy/pleurodesis, from 83 to 120 patients with MPM, at least 480 patients with non-MPM pleural disease and 109 asbestos-exposed controls. Final numbers of MPM/non-MPM cases will depend on the incidence of MPM in the study population (estimated at 13-20%). Identical sampling and storage protocols will be used in 22 recruiting centres and histological confirmation sought in all cases. Markers will be measured using the SOMAscan proteomic assay (SomaLogic) and a commercially available fibulin-3 ELISA (USCN Life Science). The SE in the estimated sensitivity and specificity will be <5% for each marker and their performance will be compared with serum mesothelin. Blood levels will be compared with paired pleural fluid levels and MPM tumour volume (using MRI) in a nested substudy. The prognostic value of each marker will be assessed and a large bioresource created. ETHICS AND DISSEMINATION: The study has been approved by the West of Scotland Research Ethics Committee (Ref: 13/WS/0240). A Trial Management Group meets on a monthly basis. Results will be published in peer-reviewed journals, presented at international meetings and disseminated to patient groups. TRIAL REGISTRATION NUMBER: ISRCTN10079972, Pre-results.