The epithelial-mesenchymal transition (EMT) is a complex process in which cell phenotype switches from the epithelial to mesenchymal one. The deregulations of this process have been related with the ...occurrence of different diseases such as lung cancer and fibrosis. In the last decade, several efforts have been devoted in understanding the mechanisms that trigger and sustain this transition process. Adenosine is a purinergic signaling molecule that has been involved in the onset and progression of chronic lung diseases and cancer through the A
2B
adenosine receptor subtype activation, too. However, the relationship between A
2B
AR and EMT has not been investigated, yet. Herein, the A
2B
AR characterization was carried out in human epithelial lung cells. Moreover, the effects of receptor activation on EMT were investigated in the absence and presence of transforming growth factor-beta (TGF-β1), which has been known to promote the transition. The A
2B
AR activation alone decreased and increased the expression of epithelial markers (E-cadherin) and the mesenchymal one (Vimentin, N-cadherin), respectively, nevertheless a complete EMT was not observed. Surprisingly, the receptor activation counteracted the EMT induced by TGF-β1. Several intracellular pathways regulate the EMT: high levels of cAMP and ERK1/2 phosphorylation has been demonstrated to counteract and promote the transition, respectively. The A
2B
AR stimulation was able to modulated these two pathways, cAMP/PKA and MAPK/ERK, shifting the fine balance toward activation or inhibition of EMT. In fact, using a selective PKA inhibitor, which blocks the cAMP pathway, the A
2B
AR-mediated EMT promotion were exacerbated, and conversely the selective inhibition of MAPK/ERK counteracted the receptor-induced transition. These results highlighted the A
2B
AR as one of the receptors involved in the modulation of EMT process. Nevertheless, its activation is not enough to trigger a complete transition, its ability to affect different intracellular pathways could represent a mechanism at the basis of EMT maintenance/inhibition based on the extracellular microenvironment. Despite further investigations are needed, herein for the first time the A
2B
AR has been related to the EMT process, and therefore to the different EMT-related pathologies.
•CALIPER distinguishes between treated and untreated patients during follow-up.•CALIPER correlates with pulmonary function tests at baseline and during follow-up.•CALIPER correlates with prognosis in ...idiopathic pulmonary fibrosis patients.
To investigate the role of a quantitative analysis software (CALIPER) in identifying HRCT thresholds predicting IPF patients’ survival and lung function decline and its role in detecting changes of HRCT abnormalities related to treatment and their correlation with Forced Vital Capacity (FVC).
This retrospective study included 105 patients with a multidisciplinary diagnosis of IPF for whom one HRCT at baseline and concomitant FVC were available.
HRCTs were evaluated with CALIPER and the correlation between FVC and radiological features were assessed. Radiological thresholds for survival prediction and functional decline were calculated for all patients. Fifty-nine patients with at least 2 serial HRCTs were classified into two groups based on treatment. For patients for whom a FVC within 3 months of the HRCT was available (n = 44), the correlation of radiological and clinical progression was evaluated.
The correlation between FVC and CALIPER-derived features at baseline was significant and strong. A baseline CALIPER-derived interstitial lung disease (ILD%) extent higher than 20 % and pulmonary vascular related structures (PVRS%) score greater than 5 % defined a worse prognosis.
A significant progression of CALIPER-derived features in all patients was found with a faster increase in untreated patients. ILD% and PVRS% changes during follow-up demonstrated strong correlations with FVC changes.
CALIPER quantification of fibrosis and vascular involvement could distinguish disease progression in treated versus untreated patients and predict the survival. The changes in CALIPER-derived variables over time were significantly correlated to changes in FVC.
Introduction
Computer-Aided Lung Informatics for Pathology Evaluation and Ratings (CALIPER) software has already been widely used in the evaluation of interstitial lung diseases (ILD) but has not yet ...been tested in patients affected by COVID-19. Our aim was to use it to describe the relationship between Coronavirus Disease 2019 (COVID-19) outcome and the CALIPER-detected pulmonary vascular-related structures (VRS).
Materials and methods
We performed a multicentric retrospective study enrolling 570 COVID-19 patients who performed a chest CT in emergency settings in two different institutions. Fifty-three age- and sex-matched healthy controls were also identified. Chest CTs were analyzed with CALIPER identifying the percentage of VRS over the total lung parenchyma. Patients were followed for up to 72 days recording mortality and required intensity of care.
Results
There was a statistically significant difference in VRS between COVID-19-positive patients and controls (median (iqr) 4.05 (3.74) and 1.57 (0.40) respectively,
p
= 0.0001). VRS showed an increasing trend with the severity of care,
p
< 0.0001. The univariate Cox regression model showed that VRS increase is a risk factor for mortality (HR 1.17,
p
< 0.0001). The multivariate analysis demonstrated that VRS is an independent explanatory factor of mortality along with age (HR 1.13,
p
< 0.0001).
Conclusion
Our study suggests that VRS increases with the required intensity of care, and it is an independent explanatory factor for mortality.
Key Points
•
The percentage of vascular-related structure volume (VRS) in the lung is significatively increased in COVID-19 patients.
•
VRS showed an increasing trend with the required intensity of care, test for trend p< 0.0001.
•
Univariate and multivariate Cox models showed that VRS is a significant and independent explanatory factor of mortality.
Thin-slices multi-detector computed tomography (MDCT) plays a key role in the differential diagnosis of interstitial lung disease (ILD). However, thin-slices MDCT has a limited ability to detect ...active inflammation, which is an important target of newly developed ILD drug therapy. Magnetic resonance imaging (MRI), thanks to its multi-parameter capability, provides better tissue characterisation than thin-slices MDCT.Our aim was to summarise the current status of MRI applications in ILD and to propose an ILD-MRI protocol. A systematic literature search was conducted for relevant studies on chest MRI in patients with ILD.We retrieved 1246 papers of which 55 original papers were selected for the review. We identified 24 studies comparing image quality of thin-slices MDCT and MRI using several MRI sequences. These studies described new MRI sequences to assess ILD parenchymal abnormalities, such as honeycombing, reticulation and ground-glass opacity. Thin-slices MDCT remains superior to MRI for morphological imaging. However, recent studies with ultra-short echo-time MRI showed image quality comparable to thin-slices MDCT. Several studies demonstrated the added value of chest MRI by using functional imaging, especially to detect and quantify inflammatory changes.We concluded that chest MRI could play a role in ILD patients to differentiate inflammatory and fibrotic changes and to assess efficacy of new ILD drugs.
Introduction/objectives
Interstitial lung disease (ILD) is frequent and highly disabling in systemic sclerosis (SSc). Magnetic resonance imaging (MRI) is not routinely used to evaluate the lung, due ...to poorer spatial resolution compared to high-resolution computed tomography (HRCT). We aimed to compare lung MRI signal with HRCT and evaluate the role of MRI in predicting ILD progression.
Methods
Thirty SSc patients underwent lung MRI and HRCT. STIR and T1 mapping sequences were acquired before and after gadolinium injection. Patients were classified as
normal
(group 1 with normal HRCT and MRI),
discordant
(group 2 without ILD signs on HRCT but areas of hyperintensity on MRI), and
abnormal
(group 3 with ILD signs on HRCT and areas of hyperintensity on MRI). Patients were followed up for ILD progression.
Results
Mean STIR and T1 values were different between the three groups (
p
< 0.0001). STIR values correlated with HRCT score (
R
= 0.79,
p
< 0.0001), lung ultrasound B-lines (
R
= 0.73,
p
< 0.0001), and %DLco (
R
= − 0.63,
p
= 0.0001). Nine events were recorded during a follow-up of 25 ± 20 months. Continuous STIR values were independently associated with events (HR 1.018; CI 1.005–1.031,
p
= 0.005). A STIR value >90 ms discriminated patients at a higher risk of worsening pulmonary involvement (HR 8.80; CI 1.81–42.74;
p
< 0.007).
Conclusions
Lung MRI can detect SSc-related ILD, with good correlations with other ILD markers. STIR values, independently of HRCT appearance, may predict worsening lung involvement. Lung MRI, although very preliminary, is a promising tool that in a near future could help selecting patients for an early treatment of SSc-related ILD and a more appropriate use of HRCT.
Key points
•
Lung MRI has the potential to differentiate inflammation-predominant
versus
fibrosis-predominant lesions, but it is not currently used in routine clinical practice to assess SSc-related ILD.
•
Lung MRI STIR and T1 values are significantly different between patients with and without SSc-related ILD. STIR values, independently of HRCT appearance, are also able to predict worsening lung involvement over time.
•
These preliminary data suggest that, in a near future, MRI could support the choice for an early treatment of SSc-related ILD, as well as a more appropriate use of HRCT.
EGFR-positive Non-small Cell Lung Cancer (NSCLC) is a dynamic entity and tumor progression and resistance to tyrosine kinase inhibitors (TKIs) arise from the accumulation, over time and across ...different disease sites, of subclonal genetic mutations. For instance, the occurrence of EGFR T790M is associated with resistance to gefitinib, erlotinib, and afatinib, while EGFR C797S causes osimertinib to lose activity. Sensitive technologies as radiomics and liquid biopsy have great potential to monitor tumor heterogeneity since they are both minimally invasive, easy to perform, and can be repeated over patient's follow-up, enabling the extraction of valuable information. Yet, to date, there are no reported cases associating liquid biopsy and radiomics during treatment.
In this case series, seven patients with metastatic EGFR-positive NSCLC have been monitored during target therapy. Plasma-derived cell free DNA (cfDNA) was analyzed by a digital droplet PCR (ddPCR), while radiomic analyses were performed using the validated LifeX® software on computed tomography (CT)-images. The dynamics of EGFR mutations in cfDNA was compared with that of radiomic features. Then, for each EGFR mutation, a radiomic signature was defines as the sum of the most predictive features, weighted by their corresponding regression coefficients for the least absolute shrinkage and selection operator (LASSO) model. The receiver operating characteristic (ROC) curves were computed to estimate their diagnostic performance. The signatures achieved promising performance on predicting the presence of EGFR mutations (R
= 0.447, p <0.001 EGFR activating mutations R
= 0.301, p = 0.003 for T790M; and R
= 0.354, p = 0.001 for activating plus resistance mutations), confirmed by ROC analysis.
To our knowledge, these are the first cases to highlight a potentially promising strategy to detect clonal heterogeneity and ultimately identify patients at risk of progression during treatment. Together, radiomics and liquid biopsy could detect the appearance of new mutations and therefore suggest new therapeutic management.
Chest X-ray (CXR) is the most important technique for performing chest imaging, despite its well-known limitations in terms of scope and sensitivity. These intrinsic limitations of CXR have prompted ...the development of several artificial intelligence (AI)-based software packages dedicated to CXR interpretation. The online database "AI for radiology" was queried to identify CE-marked AI-based software available for CXR interpretation. The returned studies were divided according to the targeted disease. AI-powered computer-aided detection software is already widely adopted in screening and triage for pulmonary tuberculosis, especially in countries with few resources and suffering from high a burden of this disease. AI-based software has also been demonstrated to be valuable for the detection of lung nodules detection, automated flagging of positive cases, and post-processing through the development of digital bone suppression software able to produce digital bone suppressed images. Finally, the majority of available CE-marked software packages for CXR are designed to recognize several findings, with potential differences in sensitivity and specificity for each of the recognized findings.
Smoking is the main risk factor for lung cancer (LC), which is the leading cause of cancer-related death worldwide. Independent randomized controlled trials, governmental and inter-governmental task ...forces, and meta-analyses established that LC screening (LCS) with chest low dose computed tomography (LDCT) decreases the mortality of LC in smokers and former smokers, compared to no-screening, especially in women. Accordingly, several Italian initiatives are offering LCS by LDCT and smoking cessation to about 10,000 high-risk subjects, supported by Private or Public Health Institutions, envisaging a possible population-based screening program. Because LDCT is the backbone of LCS, Italian radiologists with LCS expertise are presenting this position paper that encompasses recommendations for LDCT scan protocol and its reading. Moreover, fundamentals for classification of lung nodules and other findings at LDCT test are detailed along with international guidelines, from the European Society of Thoracic Imaging, the British Thoracic Society, and the American College of Radiology, for their reporting and management in LCS. The Italian College of Thoracic Radiologists produced this document to provide the basics for radiologists who plan to set up or to be involved in LCS, thus fostering homogenous evidence-based approach to the LDCT test over the Italian territory and warrant comparison and analyses throughout National and International practices.
The role of total plasma cell-free DNA (cfDNA) in lung cancer (LC) screening with low-dose computed tomography (LDCT) is uncertain. We hypothesized that cfDNA could support differentiation between ...malignant and benign nodules observed in LDCT. The baseline cfDNA was measured in 137 subjects of the ITALUNG trial, including 29 subjects with screen-detected LC (17 prevalent and 12 incident) and 108 subjects with benign nodules. The predictive capability of baseline cfDNA to differentiate malignant and benign nodules was compared to that of Lung-RADS classification and Brock score at initial LDCT (iLDCT). Subjects with prevalent LC showed both well-discriminating radiological characteristics of the malignant nodule (16 of 17 were classified as Lung-RADS 4) and markedly increased cfDNA (mean 18.8 ng/mL). The mean diameters and Brock scores of malignant nodules at iLDCT in subjects who were diagnosed with incident LC were not different from those of benign nodules. However, 75% (9/12) of subjects with incident LC showed a baseline cfDNA ≥ 3.15 ng/mL, compared to 34% (37/108) of subjects with benign nodules (p = 0.006). Moreover, baseline cfDNA was correlated (p = 0.001) with tumor growth, measured with volume doubling time. In conclusion, increased baseline cfDNA may help to differentiate subjects with malignant and benign nodules at LDCT.
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