Persistent Health Problems beyond Pulmonary Recovery up to 6 Months after Hospitalization for COVID-19: A Longitudinal Study of Respiratory, Physical, and Psychological Outcomes.

Rationale: Data on longitudinal recovery after hospitalization for coronavirus disease (COVID-19) currently remain scarce, just as outcomes beyond 3 months of follow-up do. Objectives: To evaluate the sequelae up to 6 months after hospitalization for COVID-19 by considering 1) recovery as it relates to pulmonary function, radiological abnormalities, physical and mental health status, and health-related quality of life (HR-QoL) and 2) the predictors of the most clinically relevant sequelae. Methods: Patients were evaluated at 6 weeks, 3 months, and 6 months after hospitalization by using pulmonary function testing, radiological evaluation, and online questionnaires on the physical and mental health status and HR-QoL. Outcomes were analyzed using repeated-measurement analyses. Results: Ninety-two patients were included (mean age, 58.2 ± 12.3 yr; 58 [63.0%] men). The estimated percentage of patients with impaired forced vital capacity improved from 25% at 6 weeks to 11% at 6 months; for impaired diffusion capacity, this percentage improved from 63% to 46%. Radiologically, ground-glass opacity decreased but fibrosis persisted. The majority of patients (89.1%) still reported one or more symptoms 6 months after discharge. Fatigue decreased significantly over time (P = 0.006). Nonetheless, fatigue remained in 51% of the patients at 6 months. HR-QoL (nearly) normalized in most domains at 6 months, except for physical role functioning, with persistent fatigue and the length of hospitalization being the most important predictors. Conclusions: During the first 6 months after hospitalization for COVID-19, most patients demonstrated continuing recovery across all health domains, but persistent sequelae were frequent. Fatigue was the most frequent residual and persistent symptom up to 6 months after hospitalization, importantly impacting HR-QoL.

The BRAF P.V600E Mutation Status of Melanoma Lung Metastases Cannot Be Discriminated on Computed Tomography by LIDC Criteria nor Radiomics Using Machine Learning.

Patients with BRAF mutated (BRAF-mt) metastatic melanoma benefit significantly from treatment with BRAF inhibitors. Currently, the BRAF status is determined on archival tumor tissue or on fresh tumor tissue from an invasive biopsy. The aim of this study was to evaluate whether radiomics can predict the BRAF status in a non-invasive manner. Patients with melanoma lung metastases, known BRAF status, and a pretreatment computed tomography scan were included. After semi-automatic annotation of the lung lesions (maximum two per patient), 540 radiomics features were extracted. A chest radiologist scored all segmented lung lesions according to the Lung Image Database Consortium (LIDC) criteria. Univariate analysis was performed to assess the predictive value of each feature for BRAF mutation status. A combination of various machine learning methods was used to develop BRAF decision models based on the radiomics features and LIDC criteria. A total of 169 lung lesions from 103 patients (51 BRAF-mt; 52 BRAF wild type) were included. There were no features with a significant discriminative value in the univariate analysis. Models based on radiomics features and LIDC criteria both performed as poorly as guessing. Hence, the BRAF mutation status in melanoma lung metastases cannot be predicted using radiomics features or visually scored LIDC criteria.

Preoperative Chest Computed Tomography Screening for Coronavirus Disease 2019 in Asymptomatic Patients Undergoing Cardiac Surgery.

Due to the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov-2), an efficient COVID-19 screening strategy is required for patients undergoing cardiac surgery. The objective of this prospective observational study was to evaluate the role of preoperative computed tomography (CT) screening for COVID-19 in a population of COVID-19 asymptomatic patients scheduled for cardiac surgery. Between the 29th of March and the 26th of May 2020, patients asymptomatic for COVID-19 underwent a CT-scan the day before surgery, with reverse-transcriptase polymerase-chain reaction (RT-PCR) reserved for abnormal scan results. The primary endpoint was the prevalence of abnormal scans, which was evaluated using the CO-RADS score, a COVID-19 specific grading system. In a secondary analysis, the rate of abnormal scans was compared between the screening cohort and matched historical controls who underwent routine preoperative CT-screening prior to the SARS-Cov-2 outbreak. Of the 109 patients that underwent CT-screening, an abnormal scan result was observed in 7.3% (95% confidence interval: 3.2-14.0%). One patient, with a normal screening CT, was tested positive for COVID-19, with the first positive RT-PCR on the ninth day after surgery. A rate of preoperative CT-scan abnormalities of 8% (n = 8) was found in the unexposed historical controls (P > 0.999). In asymptomatic patients undergoing cardiac surgery, preoperative screening for COVID-19 using computed tomography will identify pulmonary abnormalities in a small percentage of patients that do not seem to have COVID-19. Depending on the prevalence of COVID-19, this results in an unfavorable positive predictive value of CT screening. Care should be taken when considering CT as a screening tool prior to cardiac surgery.

Desquamative interstitial pneumonia: a systematic review of its features and outcomes.

BACKGROUND: Desquamative Interstitial Pneumonia (DIP) is a rare form of idiopathic interstitial pneumonia (IIP). Data on clinical features, aetiology, prognosis and effect of treatment strategies are limited. We aimed to collect all published cases to better characterise DIP. METHODS: A systematic literature search was performed for all original cases of adult patients with histopathologically-confirmed DIP. Individual patient data were extracted and summarised. RESULTS: We included 68 individual cases and 13 case series reporting on 294 cases. Most common presenting symptoms were dyspnoea and cough. Pulmonary function showed a restrictive pattern (71%) with decreased diffusion capacity. We found a high incidence (81%) of ever smoking in patients with DIP and 22% of patients had other (occupational) exposures. Characteristic features on high-resolution computed tomography (HRCT) scan were bilateral ground-glass opacities with lower lobe predominance (92%). Treatment and duration of treatment widely varied. Initial response to treatment was generally good, but definitely not uniformly so. A significant proportion of patients died (25% of individual cases) or experienced a relapse (18% of individual cases). CONCLUSION: DIP remains an uncommon disease, frequently but not always related to smoking or other exposures. Furthermore, DIP behaves as a progressive disease more often than generally thought, possibly associated with different underlying aetiology.

A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients.

BACKGROUND: Nivolumab is administered in a weight-based or fixed-flat dosing regimen. For patients with non-small cell lung cancer (NSCLC), a potential exposure-response relationship has recently been reported and may argue against the current dosing strategies. The primary objectives were to determine nivolumab pharmacokinetics (PK) and to assess the relationship between drug clearance and clinical outcome in NSCLC, melanoma, and renal cell cancer (RCC). METHODS: In this prospective observational cohort study, individual estimates of nivolumab clearance and the impact of baseline covariates were determined using a population-PK model. Clearance was related to best overall response (RECISTv1.1), and stratified by tumor type. RESULTS: Two-hundred-twenty-one patients with metastatic cancer receiving nivolumab-monotherapy were included of whom 1,715 plasma samples were analyzed. Three baseline parameters had a significant effect on drug clearance and were internally validated in the population-PK model: gender, BSA, and serum albumin. Women had 22% lower clearance compared to men, while the threshold of BSA and albumin that led to > 20% increase of clearance was > 2.2m2 and < 37.5 g/L, respectively. For NSCLC, drug clearance was 42% higher in patients with progressive disease (mean: 0.24; 95% CI: 0.22-0.27 L/day) compared to patients with partial/complete response (mean: 0.17; 95% CI: 0.15-0.19 L/day). A similar trend was observed in RCC, however, no clearance-response relationship was observed in melanoma. CONCLUSIONS: Based on the first real-world population-PK model of nivolumab, covariate analysis revealed a significant effect of gender, BSA, and albumin on nivolumab clearance. A clearance-response relationship was observed in NSCLC, with a non-significant trend in RCC, but not in melanoma. Individual pharmacology of nivolumab in NSCLC appears important and should be prospectively studied.

Functional associations of pleuroparenchymal fibroelastosis and emphysema with hypersensitivity pneumonitis.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) has been described in hypersensitivity pneumonitis (HP) yet its functional implications are unclear. Combined pulmonary fibrosis and emphysema (CPFE) has occasionally been described in never-smokers with HP, but epidemiological data regarding its prevalence is sparse. CTs in a large HP cohort were therefore examined to identify the prevalence and effects of PPFE and emphysema. METHODS: 233 HP patients had CT extents of interstitial lung disease (ILD) and emphysema quantified to the nearest 5%. Lobar percentage pleural involvement of PPFE was quantified on a 4-point categorical scale: 0 = absent, 1 = affecting <10%, 2 = affecting 10-33%, 3 = affecting >33%. Marked PPFE reflected a total lung score of ≥3/18. Results were evaluated against FVC, DLco and mortality. RESULTS: Marked PPFE prevalence was 23% whilst 23% of never-smokers had emphysema. Following adjustment for patient age, gender, smoking status, and ILD and emphysema extents, marked PPFE independently linked to reduced baseline FVC (p = 0.0002) and DLco (p = 0.002) and when examined alongside the same covariates, independently linked to worsened survival (p = 0.01). CPFE in HP demonstrated a characteristic functional profile of artificial lung volume preservation and disproportionate DLco reduction. CPFE did not demonstrate a worsened outcome when compared to HP patients without emphysema beyond that explained by CT extents of ILD and emphysema. CONCLUSIONS: PPFE is not uncommon in HP, and is independently associated with impaired lung function and increased mortality. Emphysema was identified in 23% of HP never-smokers. CPFE appears not to link to a malignant microvascular phenotype as outcome is explained by ILD and emphysema extents.

Bone suppression increases the visibility of invasive pulmonary aspergillosis in chest radiographs.

OBJECTIVE: Chest radiographs (CXR) are an important diagnostic tool for the detection of invasive pulmonary aspergillosis (IPA) in critically ill patients, but their diagnostic value is limited by a poor sensitivity. By using advanced image processing, the aim of this study was to increase the value of chest radiographs in the diagnostic work up of neutropenic patients who are suspected of IPA. METHODS: The frontal CXRs of 105 suspected cases of IPA were collected from four institutions. Radiographs could contain single or multiple sites of infection. CT was used as reference standard. Five radiologists and two residents participated in an observer study for the detection of IPA on CXRs with and without bone suppressed images (ClearRead BSI 3.2; Riverain Technologies). The evaluation was performed separately for the right and left lung, resulting in 78 diseased cases (or lungs) and 132 normal cases (or lungs). For each image, observers scored the likelihood of focal infectious lesions being present on a continuous scale (0-100). The area under the receiver operating characteristics curve (AUC) served as the performance measure. Sensitivity and specificity were calculated by considering only the lungs with a suspiciousness score of greater than 50 to be positive. RESULTS: The average AUC for only CXRs was 0.815. Performance significantly increased, to 0.853, when evaluation was aided with BSI (p = 0.01). Sensitivity increased from 49% to 66% with BSI, while specificity decreased from 95% to 90%. CONCLUSION: The detection of IPA in CXRs can be improved when their evaluation is aided by bone suppressed images. BSI improved the sensitivity of the CXR examination, outweighing a small loss in specificity.

Burden of atherosclerosis improves the prediction of coronary heart disease but not cerebrovascular events: the Rotterdam Study.

AIMS: Since atherosclerosis is a systemic process, risk prediction would benefit from targeting multiple components of cardiovascular disease simultaneously. To this end, it is useful to examine the predictive value of non-invasive measures of atherosclerosis in various vascular beds for both coronary heart disease (CHD) and cerebrovascular disease. METHODS AND RESULTS: Between September 2003 and February 2006, 2153 asymptomatic participants (69.6±6.6 years) from the Rotterdam Study underwent a multi-detector computed tomography scan. During a median follow-up of 3.5 years, 58 CHD events (myocardial infarction and CHD death) and 52 cerebrovascular events (TIA and stroke) occurred. Participants were classified into low (<5%), intermediate (5-10%), and high (>10%) 5-year risk categories based on a refitted Framingham risk model. The model was extended by coronary, aortic arch, or carotid calcium and reclassification percentages were calculated. For the outcome CHD, the C-statistic improved from 0.693 for the Framingham refitted model to 0.743, 0.740, and 0.749 by addition of coronary, aortic arch, and carotid calcium, respectively. Reclassification was most substantial in the intermediate risk group where addition of coronary calcium reclassified 56% of persons [net reclassification improvement (NRI): 15%; P<0.01)]. Adding aortic arch calcium led to a reclassification of 32% of persons (NRI: 8%; P=0.01) and adding carotid calcium reclassified 51% (NRI: 9%; P=0.02). In contrast, calcification in any of the three vascular beds did not improve cerebrovascular risk prediction. CONCLUSION: Coronary, aortic arch, and carotid artery calcification significantly improved risk prediction of CHD but not of cerebrovascular events.

Carotid, aortic arch and coronary calcification are related to history of stroke: the Rotterdam Study.

OBJECTIVE: Multidetector computed tomography (MDCT), which has been mainly used to study coronary atherosclerosis, also enables non-invasive measurement of carotid and aortic atherosclerosis and might be suitable for screening in the general population. The aim of this study was to investigate the associations of carotid artery, aortic arch and coronary artery calcification as assessed by MDCT, with presence of stroke. METHODS: The study was embedded in the population-based Rotterdam Study and comprises 2521 persons (mean age 69.7±6.8 years, 48% males) that underwent an MDCT scan. History of stroke was reported by 96 persons. We used multivariable logistic regression to investigate the associations of calcification in the carotid arteries, aortic arch, and coronary arteries with presence of stroke. RESULTS: We found strong and graded associations of prevalent stroke with carotid artery (OR quartile 4 versus 1 (95% CI): 5.0 (2.2-11.0)), aortic arch (3.3 (1.5-7.4)) and coronary artery calcification (3.1 (1.3-7.3)), independent of cardiovascular risk factors. Only the association of carotid artery calcification with presence of stroke was independent of calcification in the other two vessel beds. CONCLUSION: In this population-based study, we found a strong and graded association of prevalent stroke with carotid artery, aortic arch and coronary artery calcification, independent of cardiovascular risk factors. After additional adjustment for calcification in the other vessel beds, prevalent stroke was still significantly related to carotid calcification, but no longer to aortic arch or coronary calcification.

Association between calcification in the coronary arteries, aortic arch and carotid arteries: the Rotterdam study.

OBJECTIVE: The present study was performed to examine the prevalence of and associations between calcification in the coronary arteries, aortic arch and carotid arteries, assessed by multislice computed tomography (MSCT), in an elderly population. METHODS AND RESULTS: This study was part of the population-based Rotterdam study. From October 2003 until July 2004, subjects underwent a 16-slice MSCT scan. Calcification was quantified by calculating the Agatston, volume and mass score. Current analyses were performed in 600 subjects (mean age 74 years). The prevalences of calcification in the coronary and carotid arteries were higher in men compared to women. However, aortic arch calcification was more prevalent among women. In men, correlation coefficients based on the Agatston score ranged from 0.40 (between coronary and aortic arch calcification) to 0.54 (between aortic arch and carotid calcification) (p<0.001). Correlation coefficients for women ranged from 0.30 (between coronary and aortic arch calcification) to 0.40 (between coronary and carotid calcification) (p<0.001). CONCLUSIONS: While the prevalences of calcification in the coronary and the carotid arteries were higher in men compared to women, aortic arch calcification was more prevalent among women. Moderate to strong correlations between calcification in different vessel beds were found.