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We investigated if contrast-enhanced ultrasound (CEUS) may differentiate community acquired pneumonia (CAP) from lung cancer (LC). Among 1374 patients admitted in a 5-year period for lung opacities, 728 (329 CAP and 399 LC) were investigated by CEUS, comparing the time of appearance, disappearance, duration and pattern of distribution of contrast enhancement (CE). The patients with CAP and LC did not differ in terms of age, time of CE appearance, disappearance and duration or CE distribution. Our data show that the timing and pattern of CE detected by chest CEUS does not distinguish between CAP and LC and overly optimistic beliefs on this matter should be abandoned.

Background Colorectal cancer (CRC) harboring BRAF V600E mutation exhibits low response to conventional therapy and poorest prognosis. Due to the emerging correlation between gut microbiota and CRC carcinogenesis, we investigated in serrated BRAF V600E cases the existence of a peculiar fecal microbial fingerprint and specific bacterial markers, which might represent a tool for the development of more effective clinical strategies. Methods By injecting human CRC stem-like cells isolated from BRAF V600E patients in immunocompromised mice, we described a new xenogeneic model of this subtype of CRC. By performing bacterial 16S rRNA sequencing, the fecal microbiota profile was then investigated either in CRC-carrying mice or in a cohort of human CRC subjects. The microbial communities’ functional profile was also predicted. Data were compared with Mann-Whitney U, Welch’s t-test for unequal variances and Kruskal-Wallis test with Benjamini–Hochberg false discovery rate (FDR) correction, extracted as potential BRAF class biomarkers and selected as model features. The obtained mean test prediction scores were subjected to Receiver Operating characteristic (ROC) analysis. To discriminate the BRAF status, a Random Forest classifier (RF) was employed. Results A specific microbial signature distinctive for BRAF status emerged, being the BRAF -mutated cases closer to healthy controls than BRAF wild-type counterpart. In agreement, a considerable score of correlation was also pointed out between bacteria abundance from BRAF -mutated cases and the level of markers distinctive of BRAF V600E pathway, including those involved in inflammation, innate immune response and epithelial-mesenchymal transition. We provide evidence that two candidate bacterial markers, Prevotella enoeca and Ruthenibacterium lactatiformans , more abundant in BRAF V600E and BRAF wild-type subjects respectively, emerged as single factors with the best performance in distinguishing BRAF status (AUROC = 0.72 and 0.74, respectively, 95% confidence interval). Furthermore, the combination of the 10 differentially represented microorganisms between the two groups improved performance in discriminating serrated CRC driven by BRAF mutation from BRAF wild-type CRC cases (AUROC = 0.85, 95% confidence interval, 0.69–1.01). Conclusion Overall, our results suggest that BRAF V600E mutation itself drives a distinctive gut microbiota signature and provide predictive CRC-associated bacterial biomarkers able to discriminate BRAF status in CRC patients and, thus, useful to devise non-invasive patient-selective diagnostic strategies and patient-tailored optimized therapies.

Gliomas represent a disparate group of tumours for which there are to date no cure. Thus, there is a recognized need for new diagnostic and therapeutic approaches based on increased understanding of their molecular nature. We performed the comparison of the microRNA (miRNA) profile of 8 WHO grade II gliomas and 24 higher grade tumours (2 WHO grade III and 22 glioblastomas) by using the Affymetrix GeneChip miRNA Array v. 1.0. A relative quantification method (RT-qPCR) with standard curve was used to confirm the 22 miRNA signature resulted by array analysis. The prognostic performances of the confirmed miRNAs were estimated on the Tumor Cancer Genome Atlas (TCGA) datasets. We identified 22 miRNAs distinguishing grade II gliomas from higher grade tumours. RT-qPCR confirmed the differential expression in the two patients' groups for 13 out of the 22 miRNAs. The analysis of the Glioblastoma Multiforme (GBM) and Lower Grade Glioma (LGG) datasets from TCGA demonstrated the association with prognosis for 6 of those miRNAs. Moreover, in the GBM dataset miR-21 and miR-210 were predictors of worse prognosis in both univariable and multivariable Cox regression analyses (HR 1.19, p = 0.04, and HR 1.18, p = 0.029 respectively). Our results support a direct contribution of miRNAs to glioma cancerogenesis and suggest that miR-21 and miR-210 may play a role in the aggressive clinical behaviour of glioblastomas.

The study by Kiranantawat et al. “Clinical role, safety and diagnostic accuracy of percutaneous transthoracic needle biopsy in the evaluation of pulmonary consolidation” highlights how “pulmonary consolidation can be safely evaluated with CT-guided percutaneous needle biopsy”. Even if we agree about the role of CT guidance, we would like to point out how Thoracic Ultrasound could be better than CT for biopsy of subpleural lesions that could easily be detected and reached with this “real-time” and quicker technique.

Background. Limited studies and observations conducted on a too small number of patients prevent determining the actual clinical utility of pulmonary contrast-enhanced ultrasound (CEUS). The aim of the present study was to examine the efficacy of contrast enhancement (CE) arrival time (AT) and other dynamic CEUS findings for differentiating between malignant and benign peripheral lung lesions. Methods. 317 inpatients and outpatients (215 men, 102 women; mean age: 52 years) with peripheral pulmonary lesions were included in the study and underwent pulmonary CEUS. Patients were examined in a sitting position after receiving an intravenous injection of 4.8 mL of sulfur hexafluoride microbubbles stabilized by a phospholipid shell as ultrasound contrast agent (SonoVue—Bracco; Milan, Italy). Each lesion was observed for at least 5 min in real-time and the following temporal characteristics of enhancement were detected: the arrival time (AT) of microbubbles in the target lesion; the enhancement pattern; the wash-out time (WOT) of microbubbles. Results were then compared in light of the definitive diagnosis of community acquired pneumonia (CAP) or malignancies, which was not known at the time of CEUS examination. All malignant cases were diagnosed by histological results, while pneumonia was diagnosed on the basis of clinical and radiological follow-up, laboratory findings and, in some cases, histology. Results. CE AT has not been shown to differ between benign and malignant peripheral pulmonary lesions. The overall diagnostic accuracy and sensibility of a CE AT cut-off value < 10 s in discriminating benign lesions were low (diagnostic accuracy: 47.6%; sensibility: 5.3%). Poor results were also obtained in the sub-analysis of small (mean diameter < 3 cm) and large (mean diameter > 3 cm) lesions. No differences were recorded in the type of CE pattern showed between benign and malignant peripheral pulmonary lesions. In benign lesions we observed a higher frequency of delayed CE wash-out time (WOT) > 300 s. Anyhow, a CE WOT cut-off value > 300 s showed low diagnostic accuracy (53.6%) and sensibility (16.5%) in discriminating between pneumonias and malignancies. Similar results were also obtained in the sub-analysis by lesion size. Squamous cell carcinomas showed a more delayed CE AT compared to other histopathology subtypes. However, such a difference was statistically significant with undifferentiated lung carcinomas. Conclusions. Due to an overlap of CEUS timings and patterns, dynamic CEUS parameters cannot effectively differentiate between benign and malignant peripheral pulmonary lesions. Chest CT remains the gold standard for lesion characterization and the eventual identification of other pneumonic non-subpleural localizations. Furthermore, in the case of malignancy, a chest CT is always needed for staging purposes.

We provide a pictorial essay examining the preliminary data of an ongoing study whose primary aim is to assess the usefulness and safety of video-assisted thoracic surgery ultrasound (VATS-US) in the identification of different lung diseases. We studied 14 patients (five women and nine men with a mean age of 56.2 ± 8.4 SD years) with indication for VATS. All patients underwent pre-operative imaging of the chest using high-resolution computed-tomography, contrast-enhanced computed-tomography, and/or positron emission tomography and transthoracic ultrasound. VATS-US was performed under general anesthesia with single-lung ventilation through double-lumen endotracheal intubation in all patients, and the Esaote MyLab 25 laparoscope probe with flexible tip and a linear array transducer at frequencies 8.0–12.0 MHz was used. The final histological diagnoses in our cohort were cancer (three cases), usual interstitial pneumonia (five cases), nonspecific interstitial pneumonia (two cases), and hypersensitivity pneumonitis (one case). In patients with pulmonary fibrosis, the VATS-US showed a thick hyperechoic pleural line and no B-lines. Regarding cancer nodules, the VATS-US images showed a uniform hypoechogenic pattern with jagged margins. In patients with hamartochondroma and histocytosis X, VATS-US showed a mixed hyperechoic structure of the margins. In conclusion, we described the US semeiotics of various lung disorders assessed during VATS by reporting the preliminary data of the first study which applies the methodology systematically to all patients undergoing the surgery procedure. Final results from the study will further elucidate how the technique could be of use during the VATS procedure.

Purpose: The purpose of the present study was to specifically evaluate the effectiveness and safety of real-time ultrasound-guided thoracentesis in a case series of pleural effusion. Patients and methods: An observational prospective study was conducted. From February 2018 to December 2019, a total of 361 consecutive real-time transthoracic ultrasound (TUS)-guided thoracentesis were performed in the Unit of Diagnostic and Interventional Ultrasound of the Research Hospital “Fondazione Casa Sollievo della Sofferenza” of San Giovanni Rotondo, Foggia, Italy. The primary indication for thoracentesis was therapeutic in all the cases (i.e., evacuation of persistent small/moderate pleural effusions to avoid super-infection; drainage of symptomatic moderate/massive effusions). For completeness, further diagnostic investigations (including chemical, microbiological, and cytological analysis) were conducted. All the procedures were performed by two internists with more than 30 years of experience in interventional ultrasound using a multifrequency convex probe (3–8 MHz). For pleural effusions with a depth of 2–3 cm measured at the level of the costo-phrenic sinus was employed a dedicated holed convex-array probe (5 MHz). Results: In all the cases, the attempts at thoracentesis were successful, allowing the achievement of the therapeutic purpose of the procedure (i.e., the complete drying of the pleural space or the withdrawal of fluid till a “safe” quantity [a mean of 1.5 L, max 2 L] producing relief from symptoms) regardless of the initial extent of the pleural effusion. There were only 3 cases of pneumothorax, for a prevalence rate of complications in this population of 0.83%. No statistical difference was recorded in the rate of pneumothorax according to the initial amount of pleural fluid in the effusion (p = 0.12). All the pleural effusions classified as transudates showed an anechoic TUS appearance. Only the exudative effusions showed a complex nonseptated or a hyperechoic TUS appearance. However, an anechoic TUS pattern was not unequivocally associated with transudates. Some chronic transudates have been classified as exudates by Light’s criteria, showing also a complex nonseptated TUS appearance. The cytological examination of the drained fluid allowed the detection of neoplastic cells in 15.89% cases. On the other hand, the microbiological examination of effusions yielded negative results in all the cases. Conclusions: Real-time TUS-guided thoracentesis is a therapeutically effective and safe procedure, despite the diagnostic yield of the cytological or microbiological examinations on the collected liquid being very low. Future blinded randomized studies are required to definitely clarify the actual benefit of the real-time TUS-guided procedure over percussion-guided and other ultrasound-based procedures.

Purpose: The aim of this study was to assess whether new-generation shear wave elastography (SWE) is suitable for the characterization of lung subpleural lesions.Methods: In total, 190 consecutive patients with subpleural lung lesions received ultrasonography and SWE. Patients with suspected malignancy underwent ultrasound-guided transthoracic needle biopsy. Final diagnoses were made on the basis of patients’ clinical course, microbiological studies, and histological results. SWE was also performed in 25 healthy volunteers.Results: We found no statistically significant differences in stiffness between lung carcinomas, lung metastases, and pneumonia (P=0.296) or between different histological types of lung cancer (P=0.393). Necrosis was associated with reduced stiffness in pneumonia. Excluding necrotic lesions, pneumonia showed higher stiffness than lung carcinomas (2.95±0.68 m/s vs. 2.60±0.54 m/s, P=0.006). Chronic pneumonia showed increased stiffness (3.03±0.63 m/s), probably due to the presence of fibrotic tissue on histology. Pleural effusion was associated with a statistically significant reduction in stiffness, both in lung carcinomas (P=0.004) and lung metastases (P=0.002). The presence of air in healthy lung tissue may lead to incorrect speed estimates due to shear wave reflection (very high values, 14.64±2.19 m/s).Conclusion: Transthoracic SWE could not distinguish lung malignancy from pneumonia, or between different histological types of lung carcinomas. In particular, SWE seems unable to resolve the clinical dilemma of chronic subpleural consolidations.

Baló’s concentric sclerosis is a rare variant of multiple sclerosis. It belongs to the group of primary inflammatory central nervous system demyelinating diseases having no clear etiology. Peculiar radiological findings on magnetic resonance imaging are alternating rings of demyelinated and myelinated axons resembling an “onion bulb.” We report on a case of a patient with cocaine abuse who presented with Balò’s-like acute multifocal leukoencephalopathy supported by histological and radiological findings. The abuse of cocaine and its most frequent adulterant, levamisole, may induce ischemic or hemorrhagic stroke and metabolic or multifocal inflammatory leukoencephalopathy. Only a few studies described levamisole-induced leukoencephalopathy mimicking Balò round lesions. Nevertheless, it has not yet been established the correlation between them; it might also be possible that the cocaine/levamisole addiction represents just a coincidence in some of those patients affected by Balò sclerosis disease.