Assessment of a randomized controlled trial on the safety of pre-placing bronchial balloons in transbronchial lung cryobiopsy for diagnosing interstitial lung disease.

RATIONALE AND OBJECTIVES: Bleeding is a major complication of transbronchial lung cryobiopsy (TBLC), and pre-placing a bronchial balloon is one of the clinical practices used to prevent it, but with very weak evidence, which should be confirmed. This study aimed to conduct whether pre-placing a bronchial balloon in TBLC for diagnosing interstitial lung disease (ILD) is more safety. MATERIALS AND METHODS: In this prospective, single-center, randomized controlled trial, patients with suspected ILD were enrolled and randomly assigned to pre-placed balloon and none-pre-placed balloon groups. The primary outcome was incidence of moderate bleeding in each group. The secondary endpoints were the incidence of severe bleeding, pneumothorax, and other procedural complications. RESULTS: Exactly 250 patients were enrolled between August 2019 and March 2022, with 125 in each group. There were no significant differences in severe bleeding between the none-pre-placed balloon group and pre-placed balloon group (1.6% vs. 0.8%; adjusted p = 0.520), while more moderate bleeding occurred in the none-pre-placed balloon group (26.4% vs. 6.4%, adjusted p = 0.001), as well as more use of hemostatic drug (28.0% vs. 6.4%, adjusted p = 0.001). Three patients in the none-pre-placed balloon group used the bronchial balloon. More samples could be acquired in the pre-placed balloon group than in the none-pre-placed balloon group (3.8 ± 0.9 vs. 3.1 ± 0.9, p < 0.001). There were no significant differences in multidisciplinary discussion (MDD) between the two groups (89.6% vs. 91.2%, adjusted p = 0.182). CONCLUSION: A pre-placed bronchial balloon can reduce the incidence of moderate bleeding and increase the confidence of the bronchoscopists. However, it had no effect on increasing the diagnostic rate of MDD and reducing severe bleeding. REGISTRATION NUMBER: NCT04047667 ( www. CLINICALTRIALS: gov identifier).

The accuracy of electromagnetic navigation bronchoscopy compared to fluoroscopy in navigation of transbronchial lung cryobiopsy in patients with interstitial lung disease.

BACKGROUND: Safely implementing transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD) requires accurate navigation. Traditional fluoroscopy falls short in reducing the risk of post-procedure pneumothorax. The potential of electromagnetic navigation bronchoscopy (ENB) as a more precise navigation method warrants further exploration. METHODS: A prospective cohort study was conducted on ILD patients undergoing TBLC. Patients were assigned either fluoroscopy or ENB for cryoprobe positioning. Navigation accuracy was evaluated using cone beam computed tomography (CBCT) images as the standard. Safety and diagnostic yield were also observed. RESULTS: Seventeen patients underwent TBLC, with 10 guided by fluoroscopy and seven by ENB. Fluoroscopy-guided cryoprobe navigation required more adjustments [9/15 (60%) v.s. 1/9 (11%), p = 0.018] for subsequent TBLC compared to ENB, as confirmed by CBCT images. Clinical characteristics, post-procedure complications, and biopsy specimen size showed no significant differences between the groups. Fourteen patients obtained a pathological diagnosis, and 15 received a multidisciplinary discussion (MDD) diagnosis. In the fluoroscopy group, three patients failed to obtain a pathological diagnosis, and two failed to obtain an MDD diagnosis. CONCLUSIONS: ENB demonstrates significantly superior accuracy in TBLC navigation compared to traditional fluoroscopy when CBCT images are used as a reference. Further studies are necessary to determine the value of ENB in TBLC navigation for ILD patients.

A new avialan theropod from an emerging Jurassic terrestrial fauna.

Birds are descended from non-avialan theropod dinosaurs of the Late Jurassic period, but the earliest phase of this evolutionary process remains unclear owing to the exceedingly sparse and spatio-temporally restricted fossil record1-5. Information about the early-diverging species along the avialan line is crucial to understand the evolution of the characteristic bird bauplan, and to reconcile phylogenetic controversies over the origin of birds3,4. Here we describe one of the stratigraphically youngest and geographically southernmost Jurassic avialans, Fujianvenator prodigiosus gen. et sp. nov., from the Tithonian age of China. This specimen exhibits an unusual set of morphological features that are shared with other stem avialans, troodontids and dromaeosaurids, showing the effects of evolutionary mosaicism in deep avialan phylogeny. F. prodigiosus is distinct from all other Mesozoic avialan and non-avialan theropods in having a particularly elongated hindlimb, suggestive of a terrestrial or wading lifestyle-in contrast with other early avialans, which exhibit morphological adaptations to arboreal or aerial environments. During our fieldwork in Zhenghe where F. prodigiosus was found, we discovered a diverse assemblage of vertebrates dominated by aquatic and semi-aquatic species, including teleosts, testudines and choristoderes. Using in situ radioisotopic dating and stratigraphic surveys, we were able to date the fossil-containing horizons in this locality-which we name the Zhenghe Fauna-to 148-150 million years ago. The diversity of the Zhenghe Fauna and its precise chronological framework will provide key insights into terrestrial ecosystems of the Late Jurassic.

Imbalanced distribution of regulatory T cells and Th17.1 cells in the peripheral blood and BALF of sarcoidosis patients: relationship to disease activity and the fibrotic radiographic phenotype.

Rationale: Sarcoidosis is a granulomatous interstitial lung disease involving a complex interplay among different cluster of differentiation 4 (CD4+) thymus cell (T-cell) subsets. Originally described as a type 1 T-helper (Th1) inflammatory disease, recent evidence suggests that both effector and regulatory T-cell subgroups play a critical role in sarcoidosis, but this remains controversial. Objectives: We aimed to investigate the distribution of CD4+ T-cell subpopulations in sarcoidosis patients and its potential associations with clinical disease activity and a radiographic fibrotic phenotype. Methods: We measured the frequencies of regulatory T cells (Tregs), Th1, Th17, and Th17.1 cells in the peripheral blood and/or bronchoalveolar lavage fluid (BALF) of 62 sarcoidosis patients, 66 idiopathic pulmonary fibrosis (IPF) patients, and 41 healthy volunteers using flow cytometry. We also measured the changes in these T-cell subpopulations in the blood at the follow-up visits of 11 sarcoidosis patients. Measurements and results: An increased percentage of Tregs was observed in the peripheral blood of sarcoidosis patients, with a positive association to disease activity and a fibrotic radiographic phenotype. We found a higher frequency of Tregs, a lower proportion of Th17.1 cells, and a lower ratio of Th17.1 cells to total Tregs in the peripheral blood of both active and fibrotic sarcoidosis patients, compared with IPF patients or healthy donors. In contrast, a lower frequency of Tregs and a higher proportion of Th17.1 cells was found in the BALF of sarcoidosis patients than in that of IPF patients. There was an imbalance of Tregs and Th17.1 cells between the peripheral blood and BALF in sarcoidosis patients. Following immunoregulatory therapy, the proportion of circulating Tregs in sarcoidosis patients decreased. Conclusion: A higher proportion of Tregs in the peripheral blood of sarcoidosis patients was related to disease activity, fibrotic phenotype, and the need for immunoregulatory therapy. The imbalanced distribution of Tregs and Th17.1 cells in patients' peripheral blood and BALF suggests that the lung microenvironment has an effect on the immunological pathogenesis of sarcoidosis. Therefore, further studies on the functional analysis of Tregs and Th17.1 cells in sarcoidosis patients are warranted.

A 56-Year-Old Man With Cough, Bloody Sputum, and Lithoptysis.

CASE PRESENTATION: A 56-year-old Chinese man, who did not smoke, presented with a 2-month history of cough and bloody sputum. He also complained of fatigue, night sweats, chest pain, and shortness of breath, with no chills or loss of weight. He previously worked as a veterinarian and had been infected with Brucella 30 years ago. Additionally, he had been diagnosed with tuberculous pleurisy and completed a 1-year anti-TB treatment. Subsequently, he had been well until 2 months before the current admission. A chest CT scan showed a cruciform calcification in the mediastinum and some tree-in-bud changes. The results of the purified protein derivative skin test and interferon-gamma release assay for TB were negative. Brucella agglutination test was also negative. On the night of admission, the patient coughed up two silver-white-colored shiny stones and had a fever of up to 38.5 °C on the following days.

Ultrasonic Elastography-guided Pleural Biopsy for the Diagnosis of Pleural Effusion: A Multicenter Prospective Study of Diagnostic Test Performance.

Rationale: The diagnostic yield of traditional ultrasound-guided pleural biopsy remains unsatisfactory, particularly when the pleural thickness is ⩽5 mm and/or no pleural nodules are detected. Pleural ultrasound elastography (UE) has a better diagnostic yield than traditional ultrasound for malignant pleural effusion (MPE). However, studies on UE-guided pleural biopsies are lacking. Objectives: To evaluate the feasibility and safety of UE-guided pleural biopsy. Methods: In this multicenter prospective single-arm trial, patients with pleural effusion whose pleural thickness was ⩽5 mm with no pleural nodules were enrolled between July 2019 and August 2021. The diagnostic yield of UE-guided pleural biopsy for pleural effusion and its sensitivity for detecting MPE were evaluated. Results: Ninety-eight patients (mean age, 62.4 ± 13.2 yr; 65 men) were prospectively enrolled. The diagnostic yield of UE-guided pleural biopsy for making any diagnosis was 92.9% (91/98), and its sensitivity for MPE was 88.7% (55/62). In addition, its sensitivity for pleural tuberculosis was 69.6% (16/23). The rate of postoperative chest pain was acceptable, and there was no pneumothorax. Conclusions: UE-guided pleural biopsy is a novel technique for diagnosing MPE with good diagnostic yield and sensitivity. Clinical trial registered with https://www.chictr.org.cn (ChiCTR2000033572).

Feasibility of transbronchial lung cryobiopsy in patients with veno-venous extracorporeal membrane oxygenation support.

Background: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is essential life support in patients with severe acute hypoxaemic respiratory failure. However, biopsies should be considered for some patients with unknown aetiology. This study aims to evaluate the feasibility of transbronchial lung cryobiopsy (TBLC) in such patients. Methods: All patients with acute hypoxaemic respiratory failure of unknown aetiology who underwent TBLC with VV-ECMO support were retrospectively reviewed. Patients' characteristics, ventilation settings, procedure parameters, complications, pathological diagnosis and survival were summarised and analysed. Results: Eight female and five male patients with VV-ECMO support underwent TBLC. The median age was 58 (interquartile range (IQR) 38-67) years old. Concurrent diseases were present in 10 of the 13 patients, seven of which were immunosuppressed. The median time between biopsy and VV-ECMO establishment was 2.0 (IQR 0.5-6.5) days. No patient died from the procedure. Neither pneumothorax nor severe bleeding occurred in any of the patients. Five of the 13 patients experienced moderate bleeding, and all bleeding events were successfully controlled with prophylactic balloon blockers. Pathological diagnosis by TBLC was obtained in all patients, and the diagnosis of diffuse alveolar damage was made in nine of them. Conclusions: In patients with VV-ECMO support, the TBLC procedure is generally safe when standardised bleeding prophylaxis is in place. TBLC contributes to identifying underlying aetiologies in patients with acute hypoxaemic respiratory failure of unknown aetiology.

The associations of radiological features of high-resolution computed tomography with the outcomes of transbronchial cryobiopsy in interstitial lung diseases: A cohort study.

Background: Transbronchial cryobiopsy (TBCB) is a critical procedure in the diagnosis of interstitial lung diseases (ILD). The associations between high-resolution computed tomography (HRCT) features and outcomes of TBCB were unknown. Methods: This study was conducted as a single-center prospective cohort study between September 2018 and January 2020 (NCT04047667). HRCT was obtained before performing TBCB. The clinical and radiological characteristics, complications, pathological and multidisciplinary discussion (MDD) diagnoses were recorded. The relationships between HRCT features and outcomes of TBCB were analyzed. Results: TBCB was performed on 216 ILD patients. The radiological features usually interstitial pneumonia (UIP) or probable UIP, indeterminate for UIP, ground-glass opacities (GGO) and cysts were found in 55 (25.5%), 38 (17.6%), 84 (38.9%) and 9 (4.2%) patients, respectively. And 118 (54.6%) patients had high HRCT score (involved lung proportion ≥50%) in the biopsied lobe. Multivariate analysis suggested radiological probable UIP pattern may be an independent risk factor for moderate bleeding (OR = 4.304; 95% CI: 1.383-13.393; P = 0.012), while GGO may be a protective factor from moderate bleeding (OR = 0.173, 95% CI: 0.043-0.687; P = 0.013). The pathological diagnostic yield in patients presenting cysts on HRCT was significantly lower than others (44.4 vs. 87.9%; P = 0.009). While performing TBCB in the lobe with high HRCT score increased pathological diagnostic yield (91.5 vs. 79.6%; P = 0.022). Neither pneumothorax nor MDD diagnostic yields were found to be associated with HRCT features. Conclusions: HRCT features were associated with moderate bleeding and pathological diagnosis. Pre-TBCB assessments of HRCT pattern and scores were helpful for bronchoscopists to make a better patient selection and procedure planning.

Transbronchial lung biopsy versus transbronchial lung cryobiopsy in critically ill patients with undiagnosed acute hypoxemic respiratory failure: a comparative study.

BACKGROUND: In patients with acute hypoxemic respiratory failure whose diagnosis is not established after initial evaluation, obtaining a histopathological diagnosis may improve the patients' prognosis. This study aims to compare the safety profile and diagnostic yields between transbronchial lung biopsy (TBLB) and transbronchial lung cryobiopsy (TBLC) in these patients. METHODS: A retrospective comparative study was conducted in a 26-bed intensive care unit over a 5-year period. The consecutive patients with acute hypoxemic respiratory failure who underwent TBLB or TBLC were included to determine the potential etiology. Patients characteristics, procedure related complications, pathological and multidisciplinary discussion (MDD) diagnostic yields, treatment modification and 28-day survival were analyzed. Prognostic factors were identified by Cox regression analysis. RESULTS: Forty-five and 25 consecutive patients underwent TBLB and TBLC, respectively. The patients underwent TBLC were more critical. There was no significant difference in overall procedure related complications of patients underwent TBLB and TBLC [15.6% (7/45) vs 28.0% (7/25), p = 0.212]. The rate of pathological diagnostic yield [72.0% (18/25) vs 37.8% (17/45), p = 0.006], MDD diagnostic yield [84.0% (21/25) vs 55.6% (25/45), p = 0.016] and subsequent treatment modification [84.0% (21/25) vs 57.8% (26/45), p = 0.025] in patients underwent TBLC were significantly higher than those in patients underwent TBLB. Multivariate analysis revealed that MDD diagnosis [HR 0.193 (95% CI 0.047-0.792), p = 0.022] and treatment modification [HR 0.204 (95% CI 0.065-0.638), p = 0.006] may be prognostic protective factors. CONCLUSIONS: TBLC can lead to an increased chance of establishing a diagnosis, which could significantly improve the patients' prognosis, with an acceptable safety profile.

Safety and accuracy of transbronchial lung cryobiopsy in diagnosing desquamative interstitial pneumonia.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is a new technique to obtain specimens for diagnosis of interstitial lung disease (ILD) in recent years. The objective of this study is to evaluate the safety and the diagnostic accuracy of TBLC in patients of desquamative interstitial pneumonia (DIP). METHODS: In this study twelve patients confirmed with DIP were selected from January 2019 to December 2020 at the department of pulmonary and critical care medicine in China-Japan Friendship Hospital. All cases underwent TBLC in a hybrid cone beam CT (CBCT) operation room with a single general anesthesia. The definitive diagnosis was made by a multidisciplinary team that involved clinicians, radiologists and pathologists. This study analyzed the biopsy sample surface areas, main complications and the consistency between TBLC pathology and multidisciplinary discussion (MDD) diagnosis for DIP. RESULTS: An average of 3.1 ± 1.1 specimens were obtained per patient. The mean surface area of the specimen was 23.7 ± 6.1 mm2 . None of the cases had pneumothorax or massive hemorrhage. Ten cases (83.3%) had no or mild bleeding and two cases (16.7%) had moderate bleeding. All cases had the typical pathologic characteristics of DIP, which was highly consistent with the diagnosis of MDD. CONCLUSION: TBLC can obtain sufficient samples for the pathological diagnosis of DIP, which has high security and accuracy in experienced specialist centers.

Clinicopathologic features and BRAF mutation status of tracheal glomus tumors - Characterization of 4 cases and the distinction from low-grade neuroendocrine tumors.

BACKGROUND: Glomus tumors are uncommon and mostly benign mesenchymal neoplasms of the perivascular family. To date, only a few cases of glomus tumors occurring in the trachea have been reported. Tracheal glomus tumors simulated low-grade neuroendocrine tumors on clinical and histomorphological examination, so the differential diagnosis between these two entities is very necessary. The latest studies showed that BRAF mutation may be associated with a malignant phenotype of glomus tumors. METHODS: We investigated the clinical, histopathologic, immunohistochemical, and BRAF V600E mutation status of four cases of tracheal glomus tumors. RESULTS: The cases showed a female predilection (male:female, 1:3) with a median age of 35.5. All of the cases had the typical morphological characteristics of glomus tumors, such as uniform round tumor cells with nest-like distribution surrounding thin-walled vessels; two of them met the malignant diagnostic criteria based on the 5th edition of WHO classification, including marked nuclear atypia and any level of mitotic activity. Immunohistochemistry showed diffusely positive for vimentin (4/4), α-SMA (4/4) and collagen IV (4/4), variably reactive for synaptophysin (3/4) and SSTR2 (2/2), and negative for AE1/AE3 (0/4) and chromogranin A (0/4). Three tested cases harbored no BRAF V600E mutation. Three follow-up cases were alive and free of disease with an average follow-up of 89.3 months. CONCLUSIONS: Tracheal glomus tumors are rare mesenchymal tumors that have overlapping morphologic and immunohistochemical features with neuroendocrine neoplasms. Our cases highlight the importance of careful histomorphological examination and comprehensive immunohistochemical study in reaching a correct diagnosis of glomus tumors of the trachea. Other than BRAF mutation, malignant glomus tumors may have a complex mutational profile.

The effect of 1.9-mm versus 2.4-mm probes in transbronchial cryobiopsies for interstitial lung diseases: a prospective analysis.

BACKGROUND: Transbronchial cryobiopsy (TBCB) is critical procedure in the diagnosis interstitial lung diseases (ILD). The procedure utilizes cryoprobes of different sizes (1.9-mm or 2.4-mm probes). This study aimed to compare the effect of different cryoprobe types on the outcomes of TBCB. METHODS: This study was analyzed from an updated single-center prospective cohort study between September 2018 and January 2020 (NCT04047667). TBCB was performed in patients with ILD using 1.9-mm or 2.4-mm cryoprobes. The size and quality of specimens, complications, and histopathological and multidisciplinary discussion (MDD) diagnoses were compared between the cryoprobes. RESULTS: TBCB was performed on 52 and 164 patients with 1.9- and 2.4-mm cryoprobes, respectively. The specimens obtained using the 2.4-mm probe were significantly larger than those obtained with the 1.9-mm probe (surface area: 24.6 vs. 22.0 mm2, P<0.001). Both percentages of grossly and microscopically qualified specimens acquired with the 2.4-mm probe were significantly higher than those obtained with the 1.9-mm probe (grossly qualified: 80.1% vs. 66.7%, P<0.001; microscopically qualified: 99.4% vs. 90.4%, P=0.003). No significant differences were found in the incidence of pneumothorax (3.7% vs. 0.0%, P=0.360) or the risk of moderate bleeding (9.1% vs. 11.5%, P=0.612) between the two groups. Additionally, no significant differences were observed in the pathological or MDD diagnostic yields. Multivariate analysis indicated that pathological diagnostic yield in patients with microscopically qualified specimens was significantly higher than that with unqualified specimens. CONCLUSIONS: Specimens obtained using the 2.4-mm probe were of significantly better size and quality than those obtained using the 1.9-mm probe. No significant differences were observed between the two probes with respect to the safety profile and diagnostic yield.

Transbronchial lung cryobiopsy may be of value for nonresolving acute respiratory distress syndrome: case series and systematic literature review.

BACKGROUND: Identification of pathologic features is helpful for the management of nonresolving acute respiratory distress syndrome (ARDS). Transbronchial lung cryobiopsy (TBLC) is a novel biopsy technique that may have comparable utility to surgical biopsy. The aim of this study was to assess the value of TBLC in patients with nonresolving ARDS. METHODS: All patients with nonresolving ARDS who underwent TBLC from January 2019 to August 2019 in a tertiary medical ICU were included. In addition, a literature search of TBLC for ARDS was performed by searching PubMed, EMBASE, ATS/ERS/APSR meeting abstracts, ClinicalTrials.gov , and Google Scholar. Data on complications, histologic diagnosis, management changes, and outcomes were analysed. RESULTS: Five patients (three women and two men) underwent TBLC. None of the patients developed pneumothorax, although two patients developed massive bleeding, which was controlled by continuous occlusion using bronchial blockers. There were no procedure-related deaths. Diffuse alveolar damage (DAD) and alternative histologic patterns were found in two and three patients, respectively, resulting in management changes in all cases. The literature search yielded four studies, which together with the present study comprised data from 25 cases in which TBLC was used in nonresolving ARDS. The summary diagnostic yield was 92% (23/25). Only 44% (11/25) of cases were proven to be DAD. TBLC contributed to management changes in 80% of patients (20/25). Procedure-related complications consisted of pneumothorax (16%, 4/25), significant bleeding (12%, 3/25), and persistent air leaks (8%, 2/25). There were no procedure-related deaths. The follow-up survival rate was 61.9% (13/21). CONCLUSIONS: The complications of TBLC in selected patients with nonresolving ARDS may be acceptable. The procedure may have a high diagnostic yield and can lead to a re-evaluation of the diagnosis as well as changes in patient management. Further investigations with larger sample sizes are required.

NOGO-B promotes EMT in lung fibrosis via MMP14 mediates free TGF-beta1 formation.

Idiopathic pulmonary fibrosis (IPF) is a lung disease with an extremely poor prognosis. Epithelial mesenchymal transition (EMT) appearing on the airway epithelial cell plays an essential role in the formation and development of Idiopathic pulmonary fibrosis. In this paper, Bleomycin (BLM)-induced mice model combined with bioinformatics analysis were employed to elucidate the potential mechanism of EMT in pulmonary fibrosis. The obtained results showed that endoplasmic reticulum protein Nogo-b may promote MMP14-mediated proprotein maturation of TGF-ß1, accelerating the release of free TGF-ß1 in type II airway epithelial cells A549, subsquently, induce the epithelial-mesenchymal transition (EMT) of the cell. In all, the overexpression of Nogo-b play a role in the course of pulmonary fibrosis by influencing the EMT ability of cells.

Anti-PD-1/PD-L1 antibody therapy for pretreated advanced nonsmall-cell lung cancer: A meta-analysis of randomized clinical trials.

BACKGROUND: Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC. METHODS: Randomized clinical trials were retrieved by searching the PubMed, EMBASE, ASCO meeting abstract, clinicaltrial.gov, and Cochrane library databases. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the overall response rate and adverse events (AEs) were calculated by STATA software. RESULTS: Three randomized clinical trials involving 1141 pretreated patients with advanced NSCLC were included. These trials all compared the efficacy and safety of anti-PD-1/PD-L1 antibodies (nivolumab and MPDL3280A) with docetaxel. The results suggested that, for all patients, anti-PD-1/PD-L1 therapy could acquire a greater overall response (odds ratio = 1.50, 95% CI: 1.08-2.07, P = 0.015, P for heterogeneity [Ph] = 0.620) and longer OS (HR = 0.71, 95% CI: 0.61-0.81, P < 0.001, Ph = 0.361) than docetaxel, but not PFS (HR = 0.83, 95% CI: 0.65-1.06, P = 0.134; Ph = 0.031). Subgroup analyses according to the tumor PD-L1 expression level showed that anti-PD-1/PD-L1 therapy could significantly improve both OS and PFS in patients with high expressions of PD-L1, but not in those with low expressions. Generally, the rates of grade 3 or 4 AEs of anti-PD-1/PD-L1 therapy were significantly lower than that of docetaxel. However, the risks of pneumonitis and hypothyroidism were significantly higher. CONCLUSION: Anti-PD-1/PD-L1 antibody therapy may significantly improve the outcomes for pretreated advanced NSCLC patients, with a better safety profile than docetaxel.

Flexible bronchoscopy-induced massive bleeding: A 12-year multicentre retrospective cohort study.

BACKGROUND AND OBJECTIVE: Although massive bleeding is the most life-threatening complication caused by flexible bronchoscopy, data on flexible bronchoscopy-induced massive bleeding are scarce, and the associated clinical characteristics and prognostic factors are unknown. METHODS: This was a multicentre retrospective cohort study of all patients who underwent flexible bronchoscopy in 33 tertiary hospitals from January 2001 to June 2013. The clinical characteristics and outcomes were collected and analysed. RESULTS: A total of 194 patients with massive bleeding were identified among 520 343 patients who underwent flexible bronchoscopy. The average blood loss reached up to 378 mL. The overall incidence and mortality were 0.037% and 0.004%, respectively, and the overall fatality was 10.8%. The risk of massive bleeding induced by therapeutic bronchoscopies was significantly higher than that induced by diagnostic bronchoscopies (incidence: 0.059% vs 0.031%, P < 0.001; mortality: 0.012% vs 0.003%, P < 0.001; fatality: 20% vs 8.4%, P = 0.068). Multivariate analysis showed that age ≥65 years, tracheal bleeding, blood loss ≥500 mL and occurrence of shock were independent factors predicting poor outcome, while emergency surgery was an independent protective factor. Re-bleeding occurred in six patients, resulting in three deaths within a month. CONCLUSION: Flexible bronchoscopy-induced massive bleeding is rare but life-threatening. Age, bleeding location, bleeding volume, circulation condition and emergency surgery were independent prognostic factors.

Temporary placement of metallic stent could lead to long-term benefits for benign tracheobronchial stenosis.

BACKGROUND: The permanent placement of metallic stent for benign tracheobronchial stenosis (BTS) was controversial. This study was conducted to evaluate the long-term outcomes of temporary placement of metallic stent for BTS. METHODS: The BTS patients who received temporary placement of retrievable self-expanded metallic stents were included between 2008 and 2011. Pre-stenting and follow-up respiratory status was analyzed. And symptom recurrence-free survival (SRFS) was assessed. RESULTS: A total of 49 stents were successfully temporarily placed in 40 consecutive BTS patients whose etiologies included endobronchial tuberculosis (EBTB) (n=22), post-tracheostomy stenosis (n=10), post-intubation stenosis (n=6) and post radiotherapy stricture (n=2). All stents were removed integrally after a median 18 days' stenting period, without major complications. During the median 27 months follow-up period after stent removal, a total of 22 patients were free of recurrence. And the overall 3-year SRFS rate was 52.0%. According to the etiology, the 3-year SRFS rates were 59.1% and 42.9% in the patients with EBTB and non-EBTB, respectively. Compared with pre-stenting, the follow-up internal diameter of stricture, Hugh-Jones scale, 6-minute walk test (6MWT) and percentage of forced expiratory volume in one second (FEV1%) were significantly improved. Multivariate analysis suggested that granulation tissue growth and tracheobronchial malacia might be independent factors of poor prognosis. CONCLUSIONS: Temporary placement of retrievable metallic stent may be an alternative treatment for BTS patients.

Overexpression of response gene to complement 32 (RGC32) promotes cell invasion and induces epithelial-mesenchymal transition in lung cancer cells via the NF-κB signaling pathway.

Response gene to complement 32 (RGC32) is a novel cellular protein that has been reported to be expressed aberrantly in multiple types of human tumors. However, the role of RGC32 in cancer is still controversial, and the molecular mechanisms by which RGC32 contributes to the development of cancer remain largely unknown. In the present study, we constructed a recombinant expression vector pCDNA3.1-RGC32 and transfected it into human lung cancer A549 cells. Stable transformanted cells were identified by real-time PCR and Western blot analysis. Functional analysis showed that forced overexpression of RGC32 increased invasive and migration capacities of lung cancer cells in vitro, and induced the acquisition of epithelial-mesenchymal transition (EMT) phenotype, as demonstrated by the spindle-like morphology, downregulation of E-cadherin, and upregulation of Vimentin, Fibronectin, Snail and Slug. Also, overexpression of RGC32 increased expression and activities of matrix metalloproteinase (MMP)-2 and MMP-9 in A549 cells. Furthermore, the downregulation of E-cadherin induced by RGC32 was remarkably attenuated by nuclear factor-κB (NF-κB) inhibitor BAY 11-7028 and small interfering RNA targeting NF-κB p65, suggesting a role of the NF-κB signaling pathway in RGC32-induced EMT. Taken together, our data suggest that RGC32 promotes cell migration and invasion and induces EMT in lung cancer cells via the NF-κB signaling pathway.