Endobronchial ultrasound-guided transbronchial needle aspiration under conscious sedation with meperidine and midazolam.

Endobronchial Ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is usually performed under general anesthesia or deep sedation with drugs such as Propofol that, at least in Italy, can be administered only by an anesthesiologist. Aim of the study was to assess conscious sedation feasibility, safety and tolerability using Meperidine and Midazolam as administered by Pulmonologist and relevant impact on the efficiency of the sampling procedures.All patients undergoing EBUS-TBNA from February 2013 to July 2014 were examined retrospectively. Efficiency using Meperidine and Midazolam during EBUS-TBNA has been assessed: completion of lymph-nodal sampling, sampling adequacy, diagnostic yield, cough during endoscopic procedure complications and need for procedure repetition with Anesthesiology assistance. Patient satisfaction and cost/effectiveness were also evaluated. One hundred and thirty-four consecutive patients were considered; 97.7% completed the procedure. In 96.9% of cases the prefixed program of lymph-nodal sampling was accomplished. Sampling adequacy was 92,4%. Diagnostic yield was 55%. In 94.7% of cases cough was absent or did not interfere with EBUS-TBNA. The need to repeat the endoscopic procedure occurred in 6 cases but only in 2 the presence of an Anesthesiologist was required. Patient satisfaction was very high, with 95.9% of subjects reporting they would "definitely return". A 27% cost reduction was calculated. EBUS-TBNA under conscious sedation using Meperidine and Midazolam prescribed and administered by pulmonologist without the Anesthesiologist assistance, revealed to be a safe, well tolerated and cost saving procedure. The efficiency of sampling was good, apart from a relatively low diagnostic yield due to different expertise of operators.

Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein.

SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic. Its high pathogenicity is due to SARS-CoV-2 spike protein (S protein) contacting host-cell receptors. A critical hallmark of COVID-19 is the occurrence of coagulopathies. Here, we report the direct observation of the interactions between S protein and platelets. Live imaging shows that the S protein triggers platelets to deform dynamically, in some cases, leading to their irreversible activation. Cellular cryo-electron tomography reveals dense decorations of S protein on the platelet surface, inducing filopodia formation. Hypothesizing that S protein binds to filopodia-inducing integrin receptors, we tested the binding to RGD motif-recognizing platelet integrins and find that S protein recognizes integrin αvß3. Our results infer that the stochastic activation of platelets is due to weak interactions of S protein with integrin, which can attribute to the pathogenesis of COVID-19 and the occurrence of rare but severe coagulopathies.

Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 Spike protein.

SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic. Its high pathogenicity is due to SARS-CoV-2 spike protein (S protein) contacting host-cell receptors. A critical hallmark of COVID-19 is the occurrence of coagulopathies. Here, we report the direct observation of the interactions between S protein and platelets. Live imaging showed that the S protein triggers platelets to deform dynamically, in some cases, leading to their irreversible activation. Strikingly, cellular cryo-electron tomography revealed dense decorations of S protein on the platelet surface, inducing filopodia formation. Hypothesizing that S protein binds to filopodia-inducing integrin receptors, we tested the binding to RGD motif-recognizing platelet integrins and found that S protein recognizes integrin α v ß 3 . Our results infer that the stochastic activation of platelets is due to weak interactions of S protein with integrin, which can attribute to the pathogenesis of COVID-19 and the occurrence of rare but severe coagulopathies.

Bronchial fibroepithelial polyp: a clinico-radiologic, bronchoscopic, histopathological and in-situ hybridisation study of 15 cases of a poorly recognised lesion.

BACKGROUND AND AIMS: Bronchial fibroepithelial polyp is an uncommon, poorly recognised lesion, lacking clear diagnostic criteria at histology, but possibly mimicking neoplastic growth on clinico-radiologic and histopathological grounds. The aim of this study was to define the clinico-pathological features, bronchoscopic appearance and treatment of bronchial fibroepithelial polyp. METHODS: We collected the largest series of bronchial fibroepithelial polyps (15 consecutive cases), including clinico-pathological, bronchoscopic, radiologic and histological features. RESULTS: Overall, there were 13 males and 2 females, with a mean age of 68 years at diagnosis. Eight patients were asymptomatic, whereas four presented with haemoptysis, two with fever, cough and pneumonia-like opacity, and one with dry recurrent cough. Mean size of the lesion was 6.5 mm (range, 2-20 mm) without any prevalence for segmental bronchi. Lesions larger than 10 mm were always symptomatic and visible at computed tomography scans. At bronchoscopy, the lesion appeared as a firm endobronchial nodule with hard consistency and glistening, whitish, smooth surface. A multilobulated and sepimentated surface was observed in the largest polyps. Whatever the size, histological features were quite similar in all cases, consisting in a polypoid lesion with a dense, collagenous, hypocellular stroma with some thin-walled, ectatic vessels and a regular respiratory mucosa on surface. In-situ hybridisation with human papillomavirus probe was negative in all the eight tested cases. CONCLUSION: Despite the benign behaviour of bronchial fibroepithelial polyps, it is important to fix some robust diagnostic criteria in order to avoid misdiagnoses leading to unnecessary aggressive treatment. Differential diagnosis mainly includes inflammatory polyps, hamartomas and papillomas.

Endobronchial metastasis: an epidemiologic and clinicopathologic study of 174 consecutive cases.

PURPOSE: Endobronchial metastases from extrapulmonary solid tumors are a rare event and currently available epidemiological and clinico-pathological data mainly derive from anecdotal case reports. METHODS: A series of 174 consecutive cases of endobronchial metastases from extrathoracic solid tumors were collected over a period of 18 years. Immunohistochemistry was performed in 115 cases. Complete imaging features were available in 81 patients, and analysis of the latency period between primitive tumor diagnosis and occurrence of endobronchial metastasis was obtained. RESULTS: Among all bronchoscopic examinations performed in the same period for malignancy, a mean of 5.6 cases per year consisted of endobronchial metastases (range 2-17 cases), with a statistically significant increase when comparing the periods 1992-2000 (65 cases, 37%) and 2001-2009 (109 cases, 63%) (p = 0.05). Overall, 4% of endobronchial biopsies for suspected malignancy disclosed an endobronchial metastasis from extrapulmonary tumor. Breast (52 cases, 30%), colorectal (42 cases, 24%), renal (14%), gastric (6%) and prostate (4.5%) cancers and melanoma (4.5%) were the most common metastatic neoplasms presenting as endobronchial mass. One-hundred fifty-four cases were identified after the primitive tumor diagnosis (metachronous cases, 89%), 11 cases were simultaneously evidenced in extrapulmonary and endobronchial sites (synchronous cases, 6%), while 9 occult metastatic cases (5%) first presented as endobronchial mass (anachronous cases). Overall, mean latency from extrapulmonary tumor diagnosis and endobronchial metastasis was 136 months (range, 1-300 months). The most frequent symptoms were dyspnea (23%), cough (15%) and haemoptysis (12%), while 26% of patients were totally asymptomatic. At radiology, 53% presented as multiple pulmonary nodules, while other cases presented as hilar and mediastinal mass, single peripheral nodule, atelectasis or pleural effusion. CONCLUSIONS: Endobronchial metastases from extrapulmonary tumors account for about 4% of all bronchoscopic biopsies performed for suspected malignancy and in 5% of the cases the metastasis is the first manifestation of the neoplasm.

"Dry" pleural mesothelioma successfully diagnosed on endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA).

The acquisition of histologic material is obligatory in order to establish the diagnosis of malignant pleural mesothelioma (MPM). In particular, tissue acquisition in cases of "dry" MPM (focal pleural thickening without pleural effusion or mediastinal lymph node involvement) is usually performed via a thoracoscopic pleural biopsy. In contrast, the techniques for performing echoendoscopic (transbronchial or transesophageal) needle aspiration of pleural lesions have only rarely been reported due to the theoretical limitations of tissue acquisition in such cases. We herein report the first case of "dry" MPM successfully diagnosed via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in a 73-year-old man presenting with a pleural mass in the right costovertebral recess, adjacent to the carina. The patient underwent radical resection, and a definitive pathological examination confirmed the diagnosis of epithelioid MPM.