Proposal for a standardized methodology for performing endobronchial ultrasound-guided mediastinal cryobiopsy: a four-step approach.

Endobronchial ultrasound (EBUS)-guided mediastinal cryobiopsy is a novel technique that increases the accuracy of diagnosing most pathologies that affect the mediastinum. Although EBUS-guided transbronchial needle aspiration (EBUS-TBNA) is the first choice in the diagnosis of mediastinal pathology, mediastinal cryobiopsy offers a larger and higher quality biopsy with minimal artifacts and no crushing when compared to conventional cytological samples obtained through EBUS-TBNA. It is particularly valuable in pathologies where EBUS-TBNA has diagnostic limitations, such as lymphoproliferative diseases, benign granulomatous conditions like sarcoidosis and silicosis, some rare infectious processes, metastases from rare non-pulmonary tumors, and in advanced stages of non-small cell lung cancer (NSCLC) where immunohistochemistry and molecular analysis are essential for personalized treatment. Therefore, mediastinal cryobiopsy seems to play a crucial role in these challenging scenarios. However, there is ongoing debate in the field of interventional pulmonology regarding the best approach for obtaining a mediastinal cryobiopsy. Some interventional pulmonologists use a high-frequency needle knife to create an incision in the tracheobronchial wall adjacent to the mediastinal lesion before inserting the cryoprobe, while others use a needle to create a pathway to the target area. There are also variations in the use of endoscopic or ultrasound imaging for guidance. In this article, we aim to review the current literature on different methods of performing mediastinal cryobiopsy and share our own clinical experience and methodology in a systematic way for its implementation in a safe, fast, and effective way.

Ultrasound in the Study of Thoracic Diseases: Innovative Aspects.

Thoracic ultrasound (TU) has rapidly gained popularity over the past 10 years. This is in part because ultrasound equipment is available in many settings, more training programmes are educating trainees in this technique, and ultrasound can be done rapidly without exposure to radiation. The aim of this review is to present the most interesting and innovative aspects of the use of TU in the study of thoracic diseases. In pleural diseases, TU has been a real revolution. It helps to differentiate between different types of pleural effusions, guides the performance of pleural biopsies when necessary and is more cost-effective under these conditions, and assists in the decision to remove thoracic drainage after talc pleurodesis. With the advent of COVID19, the use of TU has increased for the study of lung involvement. Nowadays it helps in the diagnosis of pneumonias, tumours and interstitial diseases, and its use is becoming more and more widespread in the Pneumology ward. In recent years, TU guided biopsies have been shown to be highly cost-effective, with other advantages such as the absence of radiation and the possibility of being performed at bedside. The use of contrast in ultrasound to increase the cost-effectiveness of these biopsies is very promising. In the study of the mediastinum and peripheral pulmonary nodules, the introduction of echobronchoscopy has brought about a radical change. It is a fully established technique in the study of lung cancer patients. The introduction of elastography may help to further improve its cost-effectiveness. In critically-ill patients, diaphragmatic ultrasound helps in the assessment of withdrawal of mechanical ventilation, and is now an indispensable tool in the management of these patients. In neuromuscular patients, ultrasound is a good predictor of impaired lung function. Currently, in Neuromuscular Disease Units, TU is an indispensable tool. Ultrasound study of the intercostal musculature is also effective in the study of respiratory function, and is widely used in Respiratory Rehabilitation. In Intermediate Care Units, thoracic ultrasound is indispensable for patient management. In these units there are ultrasound protocols for the management of patients with acute dyspnoea that have proven to be very effective.

Ten Issues to Update in Nosocomial or Hospital-Acquired Pneumonia: An Expert Review.

Nosocomial pneumonia, or hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) are important health problems worldwide, with both being associated with substantial morbidity and mortality. HAP is currently the main cause of death from nosocomial infection in critically ill patients. Although guidelines for the approach to this infection model are widely implemented in international health systems and clinical teams, information continually emerges that generates debate or requires updating in its management. This scientific manuscript, written by a multidisciplinary team of specialists, reviews the most important issues in the approach to this important infectious respiratory syndrome, and it updates various topics, such as a renewed etiological perspective for updating the use of new molecular platforms or imaging techniques, including the microbiological diagnostic stewardship in different clinical settings and using appropriate rapid techniques on invasive respiratory specimens. It also reviews both Intensive Care Unit admission criteria and those of clinical stability to discharge, as well as those of therapeutic failure and rescue treatment options. An update on antibiotic therapy in the context of bacterial multiresistance, in aerosol inhaled treatment options, oxygen therapy, or ventilatory support, is presented. It also analyzes the out-of-hospital management of nosocomial pneumonia requiring complete antibiotic therapy externally on an outpatient basis, as well as the main factors for readmission and an approach to management in the emergency department. Finally, the main strategies for prevention and prophylactic measures, many of them still controversial, on fragile and vulnerable hosts are reviewed.

Efficacy and Safety of Indwelling Catheter for Malignant Pleural Effusions Related to Timing of Cancer Therapy: A Systematic Review.

INTRODUCTION: To compare the efficacy and safety of indwelling pleural catheters (IPC) in relation with the timing of systemic cancer therapy (SCT) (i.e., before, during, or after SCT) in patients with malignant pleural effusion (MPE). METHODS: Systematic review of randomized controlled trials (RCT), quasi-controlled trials, prospective and retrospective cohorts, and case series of over 20 patients, in which the timing of IPC insertion in relation to that of SCT was provided. Medline (via PubMed), Embase, and Cochrane Library were systematically searched from inception to January 2023. The risk of bias was assessed using the Cochrane Risk of Bias (ROB) tool for RCTs and the ROB in non-randomized studies of interventions (ROBINS-I) for non-randomized designs. RESULTS: Ten studies (n=2907 patients; 3066 IPCs) were included. Using SCT while the IPC was in situ decreased overall mortality, increased survival time, and improved quality-adjusted survival. Timing of SCT had no effect on the risk of IPC-related infections (2.85% overall), even in immunocompromised patients with moderate or severe neutropenia (relative risk 0.98 [95%CI: 0.93-1.03] for patients treated with the combination of IPC and SCT). The inconsistency of the results or the lack of analysis of all outcome measures in relation to the SCT/IPC timing precluded drawing solid conclusions about time to IPC removal or need of re-interventions. CONCLUSIONS: Based on observational evidence, the efficacy and safety of IPC for MPE does not seem to vary depending on the IPC insertion timing (before, during, or after SCT). The data most likely support early IPC insertion.

Multicentre study on the accuracy of lung ultrasound in the diagnosis and monitoring of respiratory sequelae in the medium and long term in patients with COVID-19.

Introduction: Lung ultrasound (LUS) has proven to be a more sensitive tool than radiography (X-ray) to detect alveolar-interstitial involvement in COVID-19 pneumonia. However, its usefulness in the detection of possible pulmonary alterations after overcoming the acute phase of COVID-19 is unknown. In this study we proposed studying the utility of LUS in the medium- and long-term follow-up of a cohort of patients hospitalized with COVID-19 pneumonia. Materials and methods: This was a prospective, multicentre study that included patients, aged over 18 years, at 3 ± 1 and 12 ± 1 months after discharge after treatment for COVID-19 pneumonia. Demographic variables, the disease severity, and analytical, radiographic, and functional clinical details were collected. LUS was performed at each visit and 14 areas were evaluated and classified with a scoring system whose global sum was referred to as the "lung score." Two-dimensional shear wave elastography (2D-SWE) was performed in 2 anterior areas and in 2 posterior areas in a subgroup of patients. The results were compared with high-resolution computed tomography (CT) images reported by an expert radiologist. Results: A total of 233 patients were included, of whom 76 (32.6%) required Intensive Care Unit (ICU) admission; 58 (24.9%) of them were intubated and non-invasive respiratory support was also necessary in 58 cases (24.9%). Compared with the results from CT images, when performed in the medium term, LUS showed a sensitivity (S) of 89.7%, specificity (E) 50%, and an area under the curve (AUC) of 78.8%, while the diagnostic usefulness of X-ray showed an S of 78% and E of 47%. Most of the patients improved in the long-term evaluation, with LUS showing an efficacy with an S of 76% and E of 74%, while the X-ray presented an S of 71% and E of 50%. 2D-SWE data were available in 108 (61.7%) patients, in whom we found a non-significant tendency toward the presentation of a higher shear wave velocity among those who developed interstitial alterations, with a median kPa of 22.76 ± 15.49) versus 19.45 ± 11.39; p = 0.1). Conclusion: Lung ultrasound could be implemented as a first-line procedure in the evaluation of interstitial lung sequelae after COVID-19 pneumonia.

Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy in the diagnosis of mediastinal lesions: safety, feasibility and diagnostic yield - experience in 50 cases.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the technique of choice in the study of mediastinal and hilar lesions; however, it can be affected by the insufficiency of intact biopsy samples, which might decrease its diagnostic yield for certain conditions, thus requiring re-biopsies or additional diagnostic procedures such as mediastinoscopy when the probability of malignancy remains high. Our objectives were to 1) attempt to reproduce this technique in the same conditions that we performed EBUS-TBNA, i.e. in the bronchoscopy suite and under moderate sedation; 2) describe the method used for its execution; 3) determine its feasibility by accessing different lymph node stations applying our method; and 4) analyse the diagnostic yield and its complications. Methods: This was a prospective study of 50 patients who underwent EBUS-TBNA and EBUS-guided transbronchial mediastinal cryobiopsy (TMC) in a single procedure using a 22-G TBNA needle and a 1.1-mm cryoprobe subsequently between January and August 2022. Patients with mediastinal lesions >1 cm were recruited, and EBUS-TBNA and TMC were performed in the same lymph node station. Results: The diagnostic yield was 82% and 96% for TBNA and TMC, respectively. Diagnostic yields were similar for sarcoidosis, while cryobiopsy was more sensitive than TBNA in lymphomas and metastatic lymph nodes. As for complications, there was no pneumothorax and in no case was there significant bleeding. There were no complications during the procedure or in the follow-up of these patients. Conclusions: TMC following our method is a minimally invasive, rapid and safe technique that can be performed in a bronchoscopy suite under moderate sedation, with a higher diagnostic yield than EBUS-TBNA, especially in cases of lymphoproliferative disorders and metastatic lymph nodes or when more biopsy sample is needed for molecular determinations.

Diagnosis and Treatment of Pleural Effusion. Recommendations of the Spanish Society of Pulmonology and Thoracic Surgery. Update 2022.

Pleural effusion (PE) is a common yet complex disease that requires specialized, multidisciplinary management. Recent advances, novel diagnostic techniques, and innovative patient-centered therapeutic proposals have prompted an update of the current guidelines. This document provides recommendations and protocols based on a critical review of the literature on the epidemiology, etiology, diagnosis, prognosis, and new therapeutic options in PE, and addresses some cost-effectiveness issues related to the main types of PE.

Transbronchial biopsy results according to diffuse interstitial lung disease classification. Cryobiopsy versus forceps: MULTICRIO study.

BACKGROUND: In recent years, transbronchial cryobiopsy (TBCB) has come to be increasingly used in interventional pulmonology units as it obtains larger and better-quality samples than conventional transbronchial lung biopsy (TBLB) with forceps. No multicenter studies have been performed, however, that analyse and compare TBCB and TBLB safety and yield according to the interstitial lung disease (ILD) classification. OBJECTIVES: We compared the diagnostic yield and safety of TBCB with cryoprobe sampling versus conventional TBLB forceps sampling in the same patient. METHOD: Prospective multicenter clinical study of patients with ILD indicated for lung biopsy. Airway management with orotracheal tube, laryngeal mask and rigid bronchoscope was according to the protocol of each centre. All procedures were performed using fluoroscopy and an occlusion balloon. TBLB was followed by TBCB. Complications were recorded after both TBLB and TBCB. RESULTS: Included were 124 patients from 10 hospitals. Airway management was orotracheal intubation in 74% of cases. Diagnostic yield according to multidisciplinary committee results for TBCB was 47.6% and for TBLB was 19.4% (p<0.0001). Diagnostic yield was higher for TBCB compared to TBLB for two groups: idiopathic interstitial pneumonias (IIPs) and ILD of known cause or association (OR 2.5; 95% CI: 1.4-4.2 and OR 5.8; 95% CI: 2.3-14.3, respectively). Grade 3 (moderate) bleeding after TBCB occurred in 6.5% of patients compared to 0.8% after conventional TBLB. CONCLUSIONS: Diagnostic yield for TBCB was higher than for TBLB, especially for two disease groups: IIPs and ILD of known cause or association. The increased risk of bleeding associated with TBCB confirms the need for safe airway management and prophylactic occlusion-balloon use. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02464592.

Endobronchial ultrasound elastography for diagnosing mediastinal and hilar lymph nodes. / Elastografía asociada a la ecografía endobronquial en el estudio de adenopatías hiliares y mediastínicas.

INTRODUCTION: The main objective was to analyze the technical variability of EBUS-elastography in the differentiation of benign and malignant hilar and mediastinal lymph nodes. As a secondary objective, the results of the EBUS-elastography in said differentiation were analyzed, comparing them with the anatomopathological results. MATERIAL AND METHODS: Prospective and analytical study of lymph nodes in which EBUS-elastography was performed. Elastographic variables and their variability were analyzed. RESULTS: 24 patients and 38 lymph nodes were evaluated. Of these, 60.5% had a history of neoplasia, 71% of them were EBUS-elastography with diagnostic intention, 53% were mediastinal staging of lung cancer. Both procedures were performed in 25% of the patients. Lymph nodes were classified into elastographic colour patterns, red being characteristic of elastic tissues and blue of rigid tissues. The lymphadenopathies with apredominantly blue pattern were associated with an anatomopathological result of malignancy (86% vs. 14%, OR 20.4 (3.1 -245.1) p-value = .00015). Malignant lymph nodes presented less colour dispersion in the frequency histograms and a higher ratio of blue pixels and higher strain ratio. These variables showed a variability of 8.7, 9.9 and 31.6% respectively in repetitions in the same adenopathy. Finally, a 66% of consistency was obtained in the event of colour pattern variability (p .0000). CONCLUSIONS: EBUS-elastography is feasible during EBUS and may be helpful in predicting malignant lymph node infiltration. The quantitative elastographic data show low variability in repetitions in the same adenopathy. The strain ratio is the most variable elastographic parameter.

Diagnostic Value of Elastography and Endobronchial Ultrasound in the Study of Hilar and Mediastinal Lymph Nodes.

BACKGROUND: The aim of this study was to explore elastography features and its ability to distinguish between benign and malignant lymph nodes by comparing the results with an anatomopathologic examination used as gold standard. METHODS: Patients were randomized in 2 groups [endobronchial ultrasound (EBUS) and EBUS-elastography]. Echographic characteristics of the lymph nodes were collected in both categories. In the EBUS-elastography group, elastographic data were also determined. RESULTS: A total of 100 lymph nodes were evaluated. Group 1 (EBUS) consisted of 57 lymph nodes. Group 2 (EBUS-elastography) included 43 lymph nodes. In group 2, lymph nodes with predominantly blue pattern were associated with a pathologic determination of malignancy, and the probability of presenting malignant infiltration with this color pattern was 86.7% (P=0.00004). Malignant lymph nodes presented less color dispersion (48.8 vs. 94.8, P=0.00013), higher ratio of blue pixels (66% vs. 32.5%, P=0.016), and higher strain ratio (7.1 vs. 2.48, P=0.005). The cut-off points to distinguish between benign and malignant lymph nodes were 4 for strain ratio, 61 for frequency histograms, and 52 for blue pixel ratio. The area under the curve of the ROC curves were 0.75, 0.83, and 0.87, respectively. Group 2 presented a lower number of nondiagnostic samples (2.3% vs. 21%, P=0.001) and a higher rate of malignant results (42% vs. 16%, P=0.005). CONCLUSION: EBUS-elastography is feasible during EBUS and may be helpful in predicting malignant lymph node infiltration. It could improve anatomopathologic sample collection and increase diagnostic efficiency.

Image enhancement technology in bronchoscopy: a prospective multicentre study in lung cancer.

INTRODUCTION: Patients with lung cancer may present with additional lesions in the central airways. Earlier studies have shown a relationship between vessel diameter, pattern and grade of malignancy. High-definition (HD+) bronchoscopy with image enhancement techniques (i-scan) detected more vascular abnormalities but correlation with pathology has not yet been established. METHODS: In this investigator-initiated, randomised, controlled, crossover, multicentre study in patients with suspected lung cancer, a HD+ bronchoscopy was performed with i-scan1 and i-scan2 settings in random order. Biopsies, visual grade and vascular pattern classification were obtained by endoscopists and blinded evaluation. RESULTS: In 107 patients, vascular patterns were classified in 48 tumours. Abrupt-ending vessels were predominantly found in squamous cell carcinoma but overall correlation between vessel pattern and histology was not significant (p=0.339). Additional lesions were detected in 35 patients (33%) with a correlation between vessel pattern and high-grade (pre-)invasive lesions (p<0.001). In 8.4% of the patients, relevant second lesions were detected which determined treatment and staging in 3% of all patients. Interobserver agreement was excellent for visual grading of the airway epithelium, but low for classifying vascular patterns. No significant detection rate difference was found by blinded and unblinded evaluation. CONCLUSION: HD+ bronchoscopy with i-scan image enhancement readily detects additional lesions. In one-third of all the patients, additional lesions were detected. Their vascular pattern correlates to pathology outcome, but the interobserver correlation for vascular pattern classification is low. These lesions were relevant in 8.4% and affected treatment and work-up in 3% of the cases. TRIAL REGISTRATION NUMBER: NCT02285426; Results.

[A randomised study of midazolam for sedation in flexible bronchoscopy]. / Eficacia del midazolam para la sedación en la broncoscopia flexible. Un estudio aleatorizado.

INTRODUCTION: Flexible bronchoscopy (FB) is a procedure which is not usually tolerated well by the patient. This makes the examination more difficult, often needing repetition with the subsequent lowering of diagnostic performance. OBJECTIVE: The principal aim of our study is to analyse whether the use of a local anaesthetic with midazolam whilst performing an FB improves the quality of examination in terms of patient tolerance. Also of interest was to find out if this would improve the acceptance of a second or further FB, and the satisfaction of the bronchoscopist in performing these examinations. PATIENTS AND METHODS: A randomised, double blind and controlled with placebo, prospective study has been carried out to assess the use of midazolam. This included 152 patients, randomised into two groups: Group A-79 (51.9%) patients who received midazolam before the FB, and Group B-73 (49.1%) patients who received placebo. The patients were given a questionnaire about different aspects of perception of the procedure after the respiratory endoscopy and another was given to the bronchoscopist. RESULTS: Both groups started off with a similar assessment of fear and nervousness. Group A gave a much higher score than Group B referring to variables related to symptoms and feeling. Patient cooperation assessed by the bronchoscopist was similar in both groups, although the length of the procedure and difficulty was higher in group B. CONCLUSION: Our results show that patients sedated with midazolam tolerate FB better, remember less of the procedure itself and have a better predisposition to repeat the procedure. The bronchoscopist has less difficulties during the procedure and shortens the time using the same techniques during the bronchoscopy. The lack of severe complications and these results suggest the use of sedation with midazolam as routine during FB.