Radial endobronchial ultrasound - guided bronchoscopy for the diagnosis of peripheral pulmonary lesions: A systematic review and meta-analysis of prospective trials.

Background: The diagnostic yield of radial endobronchial ultrasound (r-EBUS) for the diagnosis of peripheral pulmonary lesions (PPLs) varies between studies and is affected by multiple factors. We aimed to evaluate the efficacy and safety of r-EBUS, and to explore the factors influencing the diagnostic yield of r-EBUS in patients with PPLs. Methods: The PubMed, Web of Science, and EMBASE databases were searched to identify relevant studies that used r-EBUS for diagnosing PPLs from the date of inception to Dec 2022. Meta-analysis was conducted using Review Manager 5.4 and Stata 15.1. Results: An analysis of 46 studies with a total of 7252 PPLs was performed. The pooled diagnostic yield of r-EBUS was 73.4 % (95 % CI: 69.9%-76.7 %), with significant heterogeneity detected among studies (I2 = 90 %, P < 0.001). Further analysis demonstrated PPLs located in the middle or lower lobe, >2 cm in size, malignant in type, solid in appearance on computerized tomography (CT), present in bronchus sign, the within probe location, and the addition of rapid on-site evaluation (ROSE) were associated with increased diagnostic yield, whereas use of a guide sheath (GS), bronchoscopy type, and a multimodality approach failed to influence the outcome. The pooled incidence rates of overall complications, pneumothorax and moderate and severe bleeding were 3.1 % (95 % CI: 2.1%-4.3 %), 0.4 % (95 % CI: 0.1%-0.7 %) and 1.1 % (95 % CI: 0.5%-2.0 %), respectively. Conclusions: r-EBUS has an appreciable diagnostic yield and an excellent safety manifestation when used to deal with PPLs.

Recent progress in radioactive seed implantation brachytherapy of non-small cell lung cancer: a narrative review.

Background and Objective: Brachytherapy, a new form of radiation therapy, has been used to treat lung cancer and consists of two main forms of treatment: endobronchial brachytherapy and radioactive seed implantation brachytherapy (RSI-BT), the latter of which is used to treat non-small cell lung cancer (NSCLC). The use of RSI-BT in the treatment of NSCLC at our centre has yielded some positive results. Methods: To more fully consider the context of this application, we conducted a search of PubMed from 2018 to March 5, 2023. The search included a combination of the MeSH terms: "brachytherapy" and "lung neoplasm". Key Content and Findings: The majority of NSCLC patients who received RSI-BT achieved positive benefits. Most patients had a progression-free survival (PFS) of between 12 and 18 months. Additionally, radioactive particle stent implantation as a specific RSI-BT has shown therapeutic potential in the treatment of malignant airway obstruction. With the application of new technologies, RSI-BT will become more precise, efficient and inexpensive. Conclusions: This review demonstrates that RSI-BT can be therapeutic in the treatment of both early and advanced NSCLC with manageable complications. There have also been reports on the combination of RSI-BT with other therapies, but more research is needed on the combination of RSI-BT with them.

ETV6-NTRK2 Fusion in a Patient With Metastatic Pulmonary Atypical Carcinoid Successfully Treated With Entrectinib: A Case Report and Review of the Literature.

Pulmonary atypical carcinoid (AC) is an extremely rare neuroendocrine tumor. The neurotrophic tropomyosin receptor kinase (NTRK) fusions are reported in only 0.5% of nonsmall cell lung cancer, and are more rare in AC with only one previously reported case. Currently, there is little established evidence on the optimal therapeutic strategies and prognosis for advanced cases. We present a female patient with metastatic AC after complete resection. Due to low expression of somatostatin receptor in this case, somatostatin analogs and peptide receptor radionuclide therapy were not available. After pursuing other alternative treatments, including chemotherapy (ie, carboplatin, etoposide, capecitabine, temozolomide, and paclitaxel), everolimus, and atezolizumab, she returned with significant progression, including innumerable subcutaneous nodules, left pleura metastasis, multiple bone metastases, and brain metastases. New biopsy analysis revealed an ETV6-NTRK2 fusion. She was immediately administered the first-generation tropomyosin receptor kinase inhibitor entrectinib at a dose of 600 mg q.d. A subsequent month of treatment resulted in a complete response in all of the metastatic lung lesions. To date, she has maintained sustained benefit for at least 1 year from initiation of entrectinib. Here, we present the first case of a female patient with metastatic AC harboring the ETV6-NTRK2 fusion, and successfully treated with entrectinib, providing evidence for the application of entrectinib in patients with NTRK-positive AC, and underscoring the critical role of molecular profiling for such cases.

The golden key to open mystery boxes of SMARCA4-deficient undifferentiated thoracic tumor: focusing immunotherapy, tumor microenvironment and epigenetic regulation.

SMARCA4-deficient undifferentiated thoracic tumor is extremely invasive. This tumor with poor prognosis is easily confused with SMARCA4-deficent non-small cell lung cancer or sarcoma. Standard and efficient treatment has not been established. In this review, we summarized the etiology, pathogenesis and diagnosis, reviewed current and proposed innovative strategies for treatment and improving prognosis. Immunotherapy, targeting tumor microenvironment and epigenetic regulator have improved the prognosis of cancer patients. We summarized clinicopathological features and immunotherapy strategies and analyzed the progression-free survival (PFS) and overall survival (OS) of patients with SMARCA4-UT who received immune checkpoint inhibitors (ICIs). In addition, we proposed the feasibility of epigenetic regulation in the treatment of SMARCA4-UT. To our knowledge, this is the first review that aims to explore innovative strategies for targeting tumor microenvironment and epigenetic regulation and identify potential benefit population for immunotherapy to improve the prognosis.

Chronic Obstructive Pulmonary Disease and Non-Small Cell Lung Cancer an association.

Objectives: Lung cancer is known to be associated with chronic obstructive pulmonary disease. Moreover; nutritional status is associated with chronic obstructive disease treatment and lung cancer. Our aim was to evaluate the interaction of the COPD status and treatment of non-small cell lung cancer. Methods: Eighty-two patients were enrolled in our multicenter study. Chronic obstructive disease stage, spirometry and treatment was recorded along with the treatment and Body Mass Index (BMI), Mediterranian Diet Score, Pack Years, Basic Metabolsim (RMR) (kcal/day), VO2 (ml/min), Ve (lt/min) and Physical Activity. The statistical analysis was performed using the JMP 14.3 (SAS Inc 2018) software. Results: The drug pairs showed a steady and unchanged by time health condition for 48 patients. Overall, 31 patients were recorded with worse COPD health conditions. The one-way ANOVA clearly indicated that chemotherapy induced the best FEV1-difference conditions with a positive effect of 8.56 mean FEV volume, the combined treatment simply did not have an effect (-0.9), while immunotherapy and patients receiving radiation decreased their FEV1 volume down to -4.23 and -5.15 mean values. Conclusions: Patients receiving chemotherapy alone had their chronic obstructive disease improved with less drugs and exacerbations, while patients receiving immunotherapy had their chronic obstructive disease stable, while all other treatment combinations worsened the patients chronic obstructive disease. Nutritional status did not affect the chronic obstructive disease of these patients in any way.

Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. From In vitro to In vivo.

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept. Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5µm in mass median aerodynamic diameter. Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces. Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly).

Ablation for Single Pulmonary Nodules, Primary or Metastatic. Εndobronchial Ablation Systems or Percutaneous.

Single pulmonary nodules are a difficult to diagnose imagining artifact. Currently novel diagnostic tools such as Radial-EBUS with or not C-ARM flouroscopy, electromagnetic navigation systems, robotic bronchoscopy and cone beam-compuer tomography (CBCT) can assist in the optimal guidance of biopsy equipment. After diagnosis of lung cancer or metastatic disease as pulmonary nodule, then surgery or ablation methods as local treatment can be applied. The percutaneous ablation systems under computed tomography guidance with radiofrequency, microwave, cryo and thermosphere have been used for several years. In the past 10 years extensive research has been made for endobronchial ablation systems and methods. We will present and comment on the two different ablation methods and present up to date data.

A Generic Strategy to Create Mechanically Interlocked Nanocomposite/Hydrogel Hybrid Electrodes for Epidermal Electronics.

Stretchable electronics are crucial enablers for next-generation wearables intimately integrated into the human body. As the primary compliant conductors used in these devices, metallic nanostructure/elastomer composites often struggle to form conformal contact with the textured skin. Hybrid electrodes have been consequently developed based on conductive nanocomposite and soft hydrogels to establish seamless skin-device interfaces. However, chemical modifications are typically needed for reliable bonding, which can alter their original properties. To overcome this limitation, this study presents a facile fabrication approach for mechanically interlocked nanocomposite/hydrogel hybrid electrodes. In this physical process, soft microfoams are thermally laminated on silver nanowire nanocomposites as a porous interface, which forms an interpenetrating network with the hydrogel. The microfoam-enabled bonding strategy is generally compatible with various polymers. The resulting interlocked hybrids have a 28-fold improved interfacial toughness compared to directly stacked hybrids. These electrodes achieve firm attachment to the skin and low contact impedance using tissue-adhesive hydrogels. They have been successfully integrated into an epidermal sleeve to distinguish hand gestures by sensing muscle contractions. Interlocked nanocomposite/hydrogel hybrids reported here offer a promising platform to combine the benefits of both materials for epidermal devices and systems.

Ultrastretchable Electrically Self-Healing Conductors Based on Silver Nanowire/Liquid Metal Microcapsule Nanocomposites.

Stretchable conductive nanocomposites are essential for deformable electronic devices. These conductors currently face significant limitations, such as insufficient deformability, significant resistance changes upon stretching, and drifted properties during cyclic deformations. To tackle these challenges, we present an electrically self-healing and ultrastretchable conductor in the form of bilayer silver nanowire/liquid metal microcapsule nanocomposites. These nanocomposites utilize silver nanowires to establish their initial excellent conductivity. When the silver nanowire networks crack during stretching, the microcapsules are ruptured to release the encased liquid metal for recovering the electrical properties. This self-healing capability allows the nanocomposite to achieve ultrahigh stretchability for both uniaxial and biaxial strains, minor changes in resistance during stretching, and stable resistance after repetitive deformations. The conductors have been used to create skin-attachable electronic patches and stretchable light-emitting diode arrays with enhanced robustness. These developments provide a bioinspired strategy to enhance the performance and durability of conductive nanocomposites.

A prediction model for risk of low oxygen saturation in patients with post-tuberculosis tracheobronchial stenosis during bronchoscopy.

BACKGROUND: Low oxygen saturation (LOS) is a frequent occurrence for patients with post-tuberculosis tracheobronchial stenosis (PTTS) during bronchoscopic procedures. However, there are currently no systematic assessment tools to predict LOS risk in PTTS patients during bronchoscopy. OBJECTIVES: This study aimed to develop an effective preoperative predictive model to guide clinical practice. DESIGN: Retrospective cohort study. METHODS: Data was retrospectively collected from PTTS patients who underwent bronchoscopic interventions between January 2017 and December 2022. Among all patients included in this study, patients between January 2017 and December 2021 were used as training cohort for the logistic regression model, and patients between January 2022 and December 2022 were utilized as validation cohort for internal validation. We used consistency index (C-index), goodness-of-fit test and calibration plot to evaluate the model performance. RESULTS: A total of 465 patients who met the inclusion criteria were enrolled in the study. The overall incidence of LOS was 26.0% (121/465). Comorbidity, degree of stenosis, bronchoscopist level, thermal ablation therapy, balloon dilation, and airway stenting, as independent risk factors for the presence of LOS, were used to construct the nomogram prediction model. The C-index of training cohort was 0.827 (95% CI, 0.786-0.869), whereas that of validation cohort was 0.836 (95% CI, 0.757-0.916), combining with the results of the calibration plot and goodness-of-fit test, demonstrating that this model had good predictive ability. CONCLUSION: The predictive model and derived nomogram with good predictive ability has been developed to preoperatively predict the risk of LOS in PTTS patients during bronchoscopy, allowing for individualized interventions for high-risk patients.

CD147 promotes breast cancer migration and invasion by inducing epithelial-mesenchymal transition via the MAPK/ERK signaling pathway.

BACKGROUND: CD147, a transmembrane glycoprotein, has been implicated in various cancer-related processes but its role in breast cancer remains poorly understood. Herein, we investigated the expression of CD147 in different breast cancer cell lines and explored its functional roles, including migration, invasion, drug resistance and modulation of key proteins associated with cancer progression. METHODS: The expression of CD147 was assessed in MCF-10 A, BT549, MDA-MB-231 and MCF-7 breast cancer cell lines using qRT-PCR and Western blotting, following which lyposome transfections were performed, leading overexpression of CD147 in BT549 cells and knockdown of CD147 in MCF-7 cells. Scratch assays and Transwell invasion and were performed to evaluate the cells' migration and invasion abilities. Sensitivity to 5-FU was determined via CCK-8 assays, and the expression of Snail1, E-cadherin, Vimentin, MMP-9 and the MAPK/ERK pathway were analyzed by qRT-PCR and Western blotting. RESULTS: Compared with normal beast epithelial cells, CD147 was highly expressed in all breast cancer cell lines, with the highest overexpression observed in MCF-7 cells and the lowest overexpression observed in BT549 cells. Overexpression of CD147 in BT549 cells increased, migration, invasion, viability and resistance to 5-FU of BT549 cells, while CD147 knockdown in MCF-7 cells reduced these properties of MCF-7 cells. Furthermore, CD147 influenced the expression of Snail1, Vimentin, E-cadherin, and MMP-9, suggesting its involvement in epithelial-mesenchymal transition (EMT) regulation. The MAPK/ERK pathway was activated by CD147 in BT549 cells, as indicated by increased p-MEK/MEK ratio and p-ERK/ERK ratio. In contrast, CD147 silencing in MCF-7 cells resulted in reduced p-MEK/MEK ratio and p-ERK/ERK ratio. CONCLUSION: In summary, our findings suggest CD147 as a potential therapeutic target in breast cancer treatment, particularly in cases where drug resistance and metastasis are concerns, worthy of further explorations.

Transbronchial lung cryobiopsy for peripheral pulmonary lesions. A narrative review.

An increasing number of peripheral pulmonary lesions (PPLs) requiring tissue verification to establish a definite diagnosis for further individualized management are detected due to the growing adoption of lung cancer screening by chest computed tomography (CT), especially low-dose CT. However, the morphological diagnosis of PPLs remains challenging. Transbronchial lung cryobiopsy (TBLC) that can retrieve larger specimens with more preserved cellular architecture and fewer crush artifacts in comparison with conventional transbronchial forceps biopsy (TBFB), as an emerging technology for diagnosing PPLs, has been demonstrated to have the potential to resolve the clinical dilemma pertaining to currently available sampling devices (e.g., forceps, needle and brush) and become a diagnostic cornerstone for PPLs. Of note, with the introduction of the 1.1 mm cryoprobe that will be more compatible with advanced bronchoscopic navigation techniques, such as radial endobronchial ultrasound (r-EBUS), virtual bronchoscopic navigation (VBN) and electromagnetic navigation bronchoscopy (ENB), the use of TBLC is expected to gain more popularity in the diagnosis of PPLs. While much remains for exploration using the TBLC technique for diagnosing PPLs, it can be envisaged that the emergence of additional studies with larger data accrual will hopefully add to the body of evidence in this field.

Predictive value of the resistance of the probe to pass through the lesion in the diagnosis of peripheral pulmonary lesions using radial probe endobronchial ultrasound with a guide sheath.

Background: Transbronchial lung biopsy guided by radial probe endobronchial ultrasonography with a guide sheath (EBUS-GS-TBLB) is becoming a significant approach for diagnosing peripheral pulmonary lesions (PPLs). We aimed to explore the clinical value of the resistance of the probe to pass through the lesion in the diagnosis of PPLs when performing EBUS-GS-TBLB, and to determine the optimum number of EBUS-GS-TBLB. Methods: We performed a prospective, single-center study of 126 consecutive patients who underwent EBUS-GS-TBLB for solid and positive-bronchus-sign PPLs where the probe was located within the lesion from September 2019 to May 2022. The classification of probe resistance for each lesion was carried out by two bronchoscopists independently, and the final result depended on the bronchoscopist responsible for the procedures. The primary endpoint was the diagnostic yield according with the resistance pattern. The secondary endpoints were the optimum number of EBUS-GS-TBLB and factors affecting diagnostic yield. Procedural complications were also recorded. Results: The total diagnostic yield of EBUS-GS-TBLB was 77.8%, including 83.8% malignant and 67.4% benign diseases (P=0.033). Probe resistance type II displayed the highest diagnostic yield (87.5%), followed by type III (81.0%) and type I (61.1%). A significant difference between the diagnostic yield of malignant and benign diseases was detected in type II (P = 0.008), whereas others did not. Although most of the malignant PPLs with a definitive diagnosis using EBUS-GS-TBLB in type II or type III could be diagnosed in the first biopsy, the fourth biopsy contributed the most sufficient biopsy samples. In contrast, considerably limited tissue specimens could be obtained for each biopsy in type I. The inter-observer agreement of the two blinded bronchoscopists for the classification of probe resistance was excellent (κ = 0.84). Conclusion: The probe resistance is a useful predictive factor for successful EBUS-GS-TBLB diagnosis of solid and positive-bronchus-sign PPLs where the probe was located within the lesion. Four serial biopsies are appropriate for both probe resistance type II and type III, and additional diagnostic procedures are needed for type I.

Inhaled nintentanib, pirfenidone and macitentan for pulmonary fibrosis: a laboratory experiment.

Aim: Idiopathic pulmonary fibrosis is a rare disease with few efficient drugs in the market. The consequences of this disease are mainly respiratory failure and pulmonary hypertension. Materials & methods: In our experiment we used the drugs pirfenidone, nintetanib and macitentan. We performed nebulization experiments with three jet nebulizers and three ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5 µm in mass median aerodynamic diameter. Results: Pirfenidone versus nintetanib had smaller droplet size formation at both inhaled technologies (1.37 < 2.23 and 1.92 < 3.11, jet and ultrasound respectively). Discussion: Pirfenidone and nintetanib can be administered as aerosol in any type of nebulization system.

Long non-coding RNA PANDAR promoted radiation and cisplatin-induced DNA damage repair through ATR/CHK1 in NSCLC.

BACKGROUND: DNA-damaging agents, including radiation and platinum-based chemotherapy, are indispensable treatments for non-small cell lung cancer (NSCLC) patients. However, cancer cells tend to be resistant to both radiation and chemotherapy, thus resulting in treatment failure or recurrence. The purpose of this study was to explore the effect and mechanism of long non-coding RNA (lncRNA) PANDAR (promoter of CDKN1A antisense DNA damage-activated RNA) on NSCLC sensitivity to radiation and chemotherapy. METHODS: Cell counting kit (CCK-8), colony formation and flow cytometry were respectively performed to determine the cell cycle and apoptosis of NSCLC cells treated with γ-ray radiation and cisplatin. The extent of DNA damage was evaluated using a comet assay and immunofluorescence staining against γH2AX. In addition, we explored the role of PANDAR in DNA damage response pathways through western blot analysis. Finally, a nude mouse subcutaneous xenograft model was established to assess the sensitivity to radiation and chemotherapy in vivo. RESULTS: In cell experiments, PANDAR knockdown can increase the sensitivity of NSCLC cells to radiation and cisplatin. The CCK-8 results showed that cell viability was significantly increased in the overexpression group after radiation and cisplatin treatments. The overexpression group also showed more colonies, less apoptosis and DNA damage, and G2/M phase arrest was aggravated to provide the time necessary for DNA repair. Contrary to PANDAR overexpression, the trends were reversed in the PANDAR knockdown group. Furthermore, PANDAR knockdown inhibited radiation and cisplatin-activated phosphorylation levels of ATR and CHK1 in NSCLC cells. Finally, our in vivo model showed that targeting PANDAR significantly sensitized NSCLC to radiation and cisplatin. CONCLUSION: Our study showed that PANDAR knockdown promoted sensitivity to radiation and cisplatin in NSCLC by regulating the ATR/CHK1 pathway, thus providing a novel understanding as well as a therapeutic target for NSCLC treatment. In NSCLC cells, lncRNA PANDAR negatively regulates sensitivity to radiation and cisplatin. PANDAR can promote the repair of radiation and cisplatin-induced DNA damage and activation of the G2/M checkpoint through the ATR/CHK1 pathway. PANDAR knockdown results in defects in DNA damage repair accompanied by more cell apoptosis.

Nootkatone attenuates airway inflammation in asthmatic mice through repressing ROS-induced NLRP3 inflammasome activation.

Nootkatone (NKT) exhibits potential pharmacological activities including anti-oxidation and anti-inflammation. Nevertheless, little is known about the roles of NKT in asthmatic airway inflammation. In the study, mice were sensitized and challenged with ovalbumin (OVA) to establish experimental allergic asthma model. After treatment with NKT, lung tissues, peripheral blood, and bronchoalveolar lavage fluid (BALF) were collected to assess inflammatory cytokines, oxidative stress, and pathological alternations. The effects of NKT on regulating reactive oxygen species (ROS)-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation was assessed in IL-13-treated BEAS-2B cell model. We found that NKT treatment decreased the production of Th2 inflammatory cytokines (IL-4, IL-5, and IL-13) in BALF and IgE levels in serum, and alleviated inflammatory cell penetration, goblet cell proliferation, collagen accumulation, and mucus hypersecretion in lung tissues. NKT treatment mitigated oxidative stress and NLRP3 inflammasome activation in asthmatic mice. IL-13 treatment induced oxidative stress and NLRP3-mediated pyroptosis in BEAS-2B bronchial epithelial cells, whereas these effects were blocked by NKT. NKT protected against airway remodeling, as indicated by decreased epithelial-mesenchymal transition. Taken together, these results demonstrate that NKT mitigates asthmatic airway inflammation by inhibiting ROS-triggered NLRP3 activation and may be a potential agent for treating asthma.

Endobronchial Radiofrequency Ablation for pulmonary nodules with Radial-Ebus and Navigation: Pros and Cons.

Introduction: Pulmonary nodules are common in the everyday clinical practice. There is always a diagnostic issue with this imaging finding. Based on the size we can use a variety of imaging and diagnostic techniques. Moreover; in the case of primary lung cancer or metastasis we can use radiofrequency ablation endobronchially. Patients and Methods: We used the radial-endobronchial ultrasound with C-arm and Archemedes, Bronchus electromagnetic navigation in order to acquire biopsy sample and we also used rapid on-site evaluation as a rapid diagnosis for pulmonary nodules. After rapid diagnosis we used the radiofrequency ablation catheter in order to ablate central pulmonary nodules. Results: Both techniques provide efficient navigation, however, with the Bronchus system less time is needed. The new radiofrequency ablation catheter provides efficient results in central lesions with low watts ≤40. Conclusion: We provided in our research a protocol to diagnose and treat such lesions. Future larger studies will provide more data on this subject.

Application of bronchoscopy in the diagnosis and treatment of peripheral pulmonary lesions in China: a national cross-sectional study.

Background: Bronchoscopy has gradually become valuable armamentarium in evaluating and applying endoscopic therapy to peripheral pulmonary lesions (PPLs) around the world. We aimed to make a comprehensive understanding of the application of bronchoscopy in the diagnosis and treatment of PPLs in China. Methods: A cross-sectional survey was carried out in China between January 2022 and March 2022. The survey was in the form of an online questionnaire which was filled in with real-time data by the respondents. Results: A total of 347 doctors from 284 tertiary hospitals (81.8%) and 63 secondary general hospitals (18.2%) were included in the data analysis. More than half of the surveyed doctors (55.0%) had independently performed respiratory endoscopy for 5-15 years. Higher proportions of hospitals with a fixed nursing team, anesthesiologists and rapid on-site evaluation (ROSE) during bronchoscopic procedures were performed in tertiary hospitals than those in secondary general hospitals (P<0.001 each). There were 316 hospitals (91.7%) eligible for performing biopsies of PPLs less than 30mm, while more than 300 PPLs biopsies were performed in only 78 hospitals (24.7%) per year. Radial probe endobronchial ultrasound (r-EBUS) (50.3%) was the commonest type of technique used in the guidance of a bronchoscope to PPLs, followed by navigational bronchoscopy (30.3%) and cone beam CT (CBCT) (17.0%). Although two thirds of the surveyed hospitals had at least one bronchoscopic guidance devices, the actual utilization of these devices was not high due to high capital costs and absence of training. To note, more diagnostic procedures and allocated devices were concentrated in the southeast region and coastal cities. Furthermore, therapeutic bronchoscopic interventions for peripheral lung cancer and/or high-risk PPLs could be performed in 124 (35.7%) of the 347 involved hospitals. Conclusions: Bronchoscopy for the diagnosis of PPLs has been carried out in most hospitals in China and yields in different hospitals and regions varied greatly. To date, only a few hospitals in China can develop therapeutic bronchoscopy for PPLs.

Gumarontinib in patients with non-small-cell lung cancer harbouring MET exon 14 skipping mutations: a multicentre, single-arm, open-label, phase 1b/2 trial.

Background: Approximately 3-4% of patients with non-small-cell lung cancer (NSCLC) have MET exon 14 (METex14) skipping mutations. We report primary results from the phase 2 stage of a phase 1b/2 study of gumarontinib, a selective, potent, oral MET inhibitor, in patients with METex14 skipping mutation-positive (METex14-positive) NSCLC. Methods: The single-arm, multicentre, open-label, phase 2 stage of the GLORY study was conducted at 42 centres across China and Japan. Adults with locally advanced or metastatic METex14-positive NSCLC received oral gumarontinib 300 mg once daily in continuous 21-day cycles until disease progression, intolerable toxicity, or withdrawal of consent. Eligible patients had failed one or two prior lines of therapy (not including a MET inhibitor), were ineligible for/refused chemotherapy, and had no genetic alterations targetable with standard therapies. The primary endpoint was objective response rate in patients with a valid baseline tumour assessment, by blinded independent review. The study was registered at ClinicalTrials.gov (NCT04270591). Findings: Between Aug 2, 2019 and Apr 28, 2021, 84 patients were enrolled and received gumarontinib (median follow-up 13.5 months [IQR 8.7-17.1]), at data cut-off (Apr 28, 2022) five patients whose METex14 status could not be confirmed by a central laboratory were excluded from the efficacy analysis. The objective response rate was 66% (95% CI 54-76) overall (n = 79), 71% (95% CI 55-83) in treatment-naïve patients (n = 44), and 60% (95% CI 42-76) in previously-treated patients (n = 35). The most common treatment-related adverse events (any grade) were oedema (67/84 patients, 80%) and hypoalbuminuria (32/84, 38%). Grade ≥3 treatment-emergent adverse events occurred in 45 (54%) patients. Treatment-related adverse events leading to permanent discontinuation occurred in 8% (7/84) of patients. Interpretation: Gumarontinib monotherapy had durable antitumour activity with manageable toxicity in patients with locally advanced or metastatic METex14-positive NSCLC when used in first line or later. Funding: Haihe Biopharma Co., Ltd. Supported in part by grants from the National Science and Technology Major Project of China for "Clinical Research of Gumarontinib, a highly selective MET inhibitor" (2018ZX09711002-011-003); the National Natural Science Foundation of China (82030045 to S.L. and 82172633 to YF.Y); Shanghai Municipal Science & Technology Commission Research Project (19411950500 to S.L.); Shanghai Shenkang Action Plan (16CR3005A to S.L.) and Shanghai Chest Hospital Project of Collaborative Innovation (YJXT20190105 to S.L.).

Positron Emission-Computed Tomography, Cryobiopsy versus Bronchoalveolar Lavage and Computed Tomography Findings for Interstitial Lung Disease: A Long-Term Follow-Up.

Background and Objectives: Interstitial lung diseases have always been an issue for pulmonary and rheumatology physicians. Computed tomography scans with a high-resolution protocol and bronchoalveolar lavage have been used along with biochemical blood tests to reach a diagnosis. Materials and Methods: We included 80 patients in total. First, all patients had their diagnosis with computed tomography of the thorax, serological/ immunological blood tests and bronchoalveolar lavage. However; after 3 months, all were divided into 2 groups: those who had bronchoalveolar lavage again and those who had cryobiopsy instead of bronchoalveolar lavage (40/40). Positron emission-computed tomography was also performed upon the first and second diagnosis. The patients' follow-up was 4 years from diagnosis. Results: Patients suffered most from chronic obstructive pulmonary disease (56, 70%), while lung cancer was rarely encountered in the sample (7, 9.75%). Age distribution ranged between 53 and 68 years with a mean value of 60 years. The computed tomography findings revealed 25 patients with typical diagnosis (35.2%), 17 with interstitial pulmonary fibrosis (23.9%) and 11 with probable diagnosis (11%). The cryobiopsy technique led to a new diagnosis in 28 patients (35% of the total sample). Patients who had a new diagnosis with cryobiopsy had a mean survival time of 710 days (<1460). Positron emission-computed tomography SUV uptake was positively associated with the cryobiopsy technique/new disease diagnosis and improved all respiratory functions. Discussion: Positron emission-computed tomography is a tool that can be used along with respiratory functions for disease evaluation. Conclusions: Cryobiopsy is a safe tool for patients with interstitial lung disease and can assist in the diagnosis of interstitial lung diseases. The survival of patients was increased in the cryobiopsy group versus only bronchoalveolar lavage for disease diagnosis.