EBUS-TBLC increase the diagnosis rate in different type of peripheral pulmonary lesions.

Background and objective: Recently, endobronchial ultrasonography with guide sheath-guided (EBUS-GS) has been increasingly used in the diagnosis of peripheral pulmonary lesions (PPLs) from human natural orifice. However, the diagnostic rate is still largely dependent on the location of the lesion and the probe. Here, we reported a new procedure to improve the diagnostic rate of EBUS-transbronchial lung cryobiopsy (EBUS-TBLC), which performed under general anesthesia with laryngeal mask airway (LMA) in all of the patients. This study retrospectively evaluated the diagnosis of PPLs with 'blind-ending' type (Type I) and 'pass-through' type procedures (Type II) of EBUS-GS-TBLB or EBUS-TBLC respectively. Methods: Retrospective review of 136 cases performed by EBUS-GS-TBLB or EBUS-TBLC for PPLs over 2 years. Results: A total of 126 cases EBUS-GS-TBLB or EBUS-TBLC were performed during the study period. Among them, 66 (52.4%) were performed Type I and 60 (47.6%) were performed Type II. Clinical baseline characteristics did not differ between two groups. The overall diagnosis rate of 126 patients with EBUS-GS-TBLB or EBUS-TBLC was 73% (92/126), and different method type have significant influence on the diagnostic yield (P = 0.012, x2 = 4.699). Among them, diagnostic yields for Type I with forceps biopsy (n=34), Type I with cryobiopsy (n=32), Type II with forceps biopsy (n=30), and Type II with cryobiopsy (n=30) were 72.5%, 64.5%, 70.4% and 74.2% respectively (Figure 2A). The study further compared the outcomes of different procedures in concentric and eccentric lesion. Diagnostic yields for Type I with eccentric (n=30), Type I with concentric (n=36), Type II with eccentric (n=34), and Type II with concentric (n=26) were 58.2%, 76.9%, 60.2% and 74.8%, respectively (P < 0.05). The incidence of complications in 126 patients was 2.6%. Conclusion: EBUS-GS-TBLB and EBUS-TBLC both are very safe and highly diagnostic technique; different method types have significant influence on the diagnostic yield. Moreover, Type II procedure has higher diagnostic yield. In addition, Type I with eccentric had the lowest diagnosis yield.

New perspective on exploring the predictive factors of blood pressure reduction during CPAP treatment in people with severe OSA and hypertension: a prospective observational study.

BACKGROUND: The predictive factors of blood pressure (BP) response to continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA) are still being explored. We aimed to assess the antihypertensive effect of CPAP considering the obstructive respiratory event-triggered BP surge profiles in 130 subjects with severe OSA and untreated hypertension. METHODS: Nocturnal BP was monitored continuously and synchronised with polysomnography. Event-triggered BP surge profiles were studied: BP surge as the value of event-related systolic BP (SBP) elevation; BP index as the number of BP surge events of ≥10 mm Hg per hour. Patients were then divided into two groups according to the median BP index (high and low BP surge groups) and assigned to 4 weeks of CPAP. Changes in BPs and plasma biomarkers were compared. After the initial evaluation, patients with a better BP response in the high BP surge group were then followed up for the second evaluation at 24 months. RESULTS: Overall, a modest decrease was observed in both office and asleep BPs at the 4-week follow-up; however, BPs dropped more markedly in patients in the high BP surge group than those in the low BP surge group, in both office SBP (5.3 mm Hg vs 2.2 mm Hg, p=0.003) and diastolic BP (4.0 mm Hg vs 1.2 mm Hg, p<0.001), especially the asleep SBP (9.0 mm Hg vs 2.1 mm Hg, p<0.001). For 30 cases in the high BP surge group, optimal BP control was achieved in 60.0% of patients and BP<140/90 mm Hg reached up to 83.3% after 24 months of CPAP. Linear regression revealed that BP index was significantly associated with BP decrease during CPAP treatment. CONCLUSIONS: Our results suggested that high event-triggered BP surge was a sensitive predictor of BP response to CPAP in patients with severe OSA and untreated hypertension. TRIAL REGISTRATION NUMBER: Clinical Trials.gov Identifier: NCT03246022; https://clinicaltrials.gov/ct2/show/NCT03246022?term=NCT+03246022&draw=2&rank=1.

Glucagon-like peptide-1 receptor activation alleviates lipopolysaccharide-induced acute lung injury in mice via maintenance of endothelial barrier function.

Glucagon-like peptide-1 (GLP-1), which is well known for regulating glucose homeostasis, exhibits multiple actions in cardiovascular disorders and renal injury. However, little is known about the effect of GLP-1 receptor (GLP-1R) activation on acute lung injury (ALI). In this study, we investigated the effect of GLP-1R on ALI and the potential underlying mechanisms with the selective agonist liraglutide. Our results show that GLP-1 levels decreased in serum, though they increased in bronchoalveolar lavage fluid (BALF) and lung tissue in a mouse model of lipopolysaccharide (LPS)-induced ALI. Liraglutide prevented LPS-induced polymorphonuclear neutrophil (PMN) extravasation, lung injury, and alveolar-capillary barrier dysfunction. In cultured human pulmonary microvascular endothelial cells (HPMECs), liraglutide protected against LPS-induced endothelial barrier injury by restoring intercellular tight junctions and adherens junctions. Moreover, liraglutide prevented PMN-endothelial adhesion by inhibiting the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and thereafter suppressed PMN transendothelial migration. Furthermore, liraglutide suppressed LPS-induced activation of Rho/NF-κB signaling in HPMECs. In conclusion, our results show that GLP-1R activation protects mice from LPS-induced ALI by maintaining functional endothelial barrier and inhibiting PMN extravasation. These results also suggest that GLP-1R may be a potential therapeutic target for the treatment of ALI.

Glucagon-like peptide-1 (GLP-1) mediates the protective effects of dipeptidyl peptidase IV inhibition on pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a progressive disease leading to death ultimately. Our recently published data demonstrated that inhibiting dipeptidyl peptidase IV (DPP-4) alleviated pulmonary vascular remodeling in experimental PH. However, whether glucagon-like peptide-1 (GLP-1) mediated the protective effect of DPP-4 inhibition (DPP-4i) on PH is unclear. RESULTS: In the present study, GLP-1 receptor antagonist (exendin-3) abolished the protective effects of DPP-4 inhibitor (sitagliptin) on right ventricular systolic pressure (RVSP) and pulmonary vascular remodeling (PVR) in monocrotaline (MCT, 60 mg/kg)-induced PH in rat. Notably, activation of GLP-1 receptor by GLP-1 analogue liraglutide directly attenuated RVSP and PVR in MCT-induced PH, as well as bleomycin- and chronic hypoxia-induced PH. Moreover, liraglutide potently inhibited MCT-induced inflammation and suppressed MCT-induced down-regulation of vascular endothelial marker (VE-cadherin and vWF) in lung. In vitro studies showed liraglutide reversed TGF-ß1 (5 ng/ml) combining IL-1ß (5 ng/ml) induced endothelial-mesenchymal transition (EndMT) in human umbilical vein endothelial cells (HUVECs), which could be abolished by GLP-1 receptor antagonist (exendin-3). Furtermore, liraglutide suppressed TGF-ß1-IL-1ß-induced phosphorylation of both Smad3 and ERK1/2. CONCLUSIONS: Our data suggest that GLP-1 mediated the protective effects of DPP-4i on pulmonary vascular and RV remodeling in experimental PH, which may be attributed to the inhibitory effect on EndMT.

Glucagon-Like Peptide-1 Mediates the Protective Effect of the Dipeptidyl Peptidase IV Inhibitor on Renal Fibrosis via Reducing the Phenotypic Conversion of Renal Microvascular Cells in Monocrotaline-Treated Rats.

Chronic kidney diseases are characterized by renal fibrosis with excessive matrix deposition, leading to a progressive loss of functional renal parenchyma and, eventually, renal failure. Renal microcirculation lesions, including the phenotypic conversion of vascular cells, contribute to renal fibrosis. Here, renal microcirculation lesions were established with monocrotaline (MCT, 60 mg/kg). Sitagliptin (40 mg/kg/d), a classical dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuated the renal microcirculation lesions by inhibiting glomerular tuft hypertrophy, glomerular mesangial expansion, and microvascular thrombosis. These effects of sitagliptin were mediated by glucagon-like peptide-1 receptor (GLP-1R), since they were blocked by the GLP-1R antagonist exendin-3 (Ex-3, 40 ug/kg/d). The GLP-1R agonist liraglutide showed a similar renal protective effect in a dose-independent manner. In addition, sitagliptin, as well as liraglutide, alleviated the MCT-induced apoptosis of renal cells by increasing the expression of survival factor glucose-regulated protein 78 (GRP78), which was abolished by the GLP-1R antagonist Ex-3. Sitagliptin and liraglutide also effectively ameliorated the conversion of vascular smooth muscle cells (SMCs) from a synthetic phenotype to contractile phenotype. Moreover, sitagliptin and liraglutide inhibited endothelial-mesenchymal transition (EndMT) via downregulating transforming growth factor-ß1 (TGF-ß1). Collectively, these findings suggest that DPP-4 inhibition can reduce microcirculation lesion-induced renal fibrosis in a GLP-1-dependent manner.

Apatinib as a third- or further- line treatment in patients with advanced NSCLC harboring wild-type EGFR.

OBJECTIVES: This study was conducted to evaluate the efficacy and safety of apatinib in advanced NSCLC patients with EGFR wild-type who have failed more than second-line chemotherapy. MATERIALS AND METHODS: We retrospectively analyzed patients with EGFR wild-type advanced NSCLC who were treated with apatinib from January 2014 to August 2016. Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and adverse events (AEs) were reveiwed and evaluated. Univariate and multivariate analyses were performed to determine the prognostic factors. RESULTS: 36 patients were evaluable for safety and efficacy. 6 patients obtained partial response, and 21 showed stable disease. The ORR and DCR were 16.7% and 75%, respectively. The median PFS and OS were 4.5 months and 8.2 months, respectively. Prognostic variable for a longer OS was good performance status (p = 0.015). Most adverse reactions were mild or moderate. CONCLUSIONS: Apatinib should be recommended as a third- or further- line therapy in advanced NSCLC patients with EGFR wild-type due to its better efficacy and tolerable toxicity.