Guowu Zhou

Background and Objectives: Endobronchial ultrasound (EBUS)–guided transbronchial mediastinal cryobiopsy (TBMC) has potential superiority compared with EBUS-guided transbronchial needle aspiration (TBNA) in the diagnosis of patients with intrathoracic sarcoidosis. However, high-quality clinical evidence is lacking. The aim of this study was to compare the efficacy and safety of EBUS-TBMC and EBUS-TBNA in diagnosing patients with intrathoracic sarcoidosis. Methods: A multicenter randomized controlled trial was conducted in patients with suspected stage I/II sarcoidosis. Following identification of the mediastinal lesion via EBUS, TBNA and TBMC were sequentially performed in a randomized order. The granuloma detection rate was the primary outcome. The final diagnosis was based on pathology results and clinical follow-up at 6 months after randomization. Results: A total of 128 patients with suspected stage I/II sarcoidosis were recruited for this study. Among them, 116 patients were diagnosed with sarcoidosis at 6 months after randomization. The granuloma detection rate was 89.8% (95% confidence interval [CI], 83.3–94.5) for EBUS-TBMC and 78.1% (95% CI, 70.0–84.9) for EBUS-TBNA, and the difference was significant ( P < 0.001). The histological quality of the EBUS-TBMC samples was superior to that of the EBUS-TBNA samples ( P < 0.001). Only one case of pneumothorax was detected by chest radiography, which resolved spontaneously without the need for drainage or other interventions. Conclusions: Compared with EBUS-TBNA, EBUS-TBMC had superior granuloma detection rate and histological quality of samples with acceptable safety in patients suspected with stage I/II sarcoidosis.

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.

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.

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. 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. 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. TBLC can lead to an increased chance of establishing a diagnosis, which could significantly improve the patients’ prognosis, with an acceptable safety profile.

Background: Identifying pathologic features is helpful for management of nonresolving ARDS. Transbronchial lung cryobiopsy (TBLC) is a novel biopsy technique which may be comparable 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 in a tertiary medical ICU were included. And a literature search of TBLC for ARDS was performed by searching PubMed, EMBASE, ATS/ERS meeting abstracts and Google Scholar. Data on complications, histologic diagnosis, management changes, and outcomes were analyzed. Results: Five patients underwent TBLC. None of the patients developed pneumothorax although in two patients massive bleeding occurred. 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 resulted in 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 the cases were proven to be DAD. TBLC contributed to management changes in 80% of the patients (20/25). Procedure-related complications consisted of pneumothorax (16%, 4/25), significant bleeding (12%, 3/25), and persistent air leak (8%, 2/25). There were no procedure-related deaths. The follow-up survival rate was 61.9% (13/21). Conclusions: Given its acceptable safety profile and high diagnostic yield, TBLC may be of potential value in patients with nonresolving ARDS.

Mutations in RAD51 gene are believed to be associated with elevated breast cancer risk. However, several case–control studies focusing on the association between RAD51 135G>C and breast cancer risk failed to achieve consensus. To clarify the effect of RAD51 135G>C polymorphism on breast cancer, a meta-analysis was performed. By searching PubMed and EMBASE, a total of 14 case–control studies, containing 12,183 cases and 10,183 controls, were included. The strength of association between RAD51 135G>C polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95% CI). When all the eligible studies were pooled into the meta-analysis, an elevated cancer risk was revealed in additive model (OR, 1.34; 95% CI, 1.01–1.78; P = 0.044) and recessive model (OR, 1.37; 95% CI, 1.03–1.82; P = 0.032). In subgroup analyses by ethnicity, BRCA1/2 mutation status, and family history, a significant association was found only among BRCA2 mutation carriers (additive model: OR, 4.92; 95% CI, 1.11–21.83; P = 0.036; recessive model: OR, 4.88; 95% CI, 1.10–21.67; P = 0.037). Sensitivity analysis did not perturb the results. In conclusion, this meta-analysis suggests that RAD51 variant 135C homozygote is associated with elevated breast cancer risk among BRCA2 mutation carriers.

Methionine synthase reductase (MTRR) is one of the important enzymes involved in the folate metabolic pathway and its functional genetic polymorphisms may be associated with breast cancer risk. However, this relationship remains inconclusive. For better understanding the effect of MTRR A66G polymorphism on breast cancer risk, a meta-analysis was performed. By searching PubMed and EMBASE, a total of six case–control studies, containing 6,084 cases and 6,756 controls, were included. The strength of association between MTRR A66G polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95% CI). The results strongly suggested that there was no significant association between MTRR A66G polymorphism and breast cancer susceptibility in overall comparisons in all genetic models (additive model: OR 1.00, 95% CI 0.89–1.11, P = 0.943; dominant model: OR 1.00, 95% CI 0.91–1.10, P = 0.989; recessive model: OR 1.00, 95% CI 0.91–1.09, P = 0.926). Similarly, in subgroup analyses for ethnicity (Caucasian, Asian and mixed population) and folate intake status (high and low folate intake), the results were negative. Sensitivity analysis demonstrated that omitting any study did not perturb the results. In conclusion, this meta-analysis strongly suggests that MTRR A66G polymorphism is not associated with breast cancer risk, especially in Caucasians and Asians.

A genetic polymorphism at codon 198 in the human glutathione peroxidase 1 gene was reported to be associated with several cancers. However, this relationship remains controversial, especially in breast cancer. For better understanding the effect of GPX1 Pro198Leu polymorphism on breast cancer, a meta-analysis was performed. By searching relevant literatures, a total of six case–control studies, containing 5,509 breast cancer cases and 6,542 healthy controls, were included. The strength of association between GPX1 Pro198Leu polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95%CI). And the results strongly suggested that there was no significant association between variant Leu allele and breast cancer susceptibility in overall comparisons in all genetic models [additive model: OR, 1.04; 95% CI, 0.92–1.18; P = 0.555; dominant model: OR, 1.01; 95% CI, 0.94–1.09; P = 0.777; recessive model: OR, 1.04; 95% CI, 0.92–1.18; P = 0.536]. However in subgroup analysis, an elevated risk in African population with variant Leu allele was revealed in additive (OR, 1.91; 95% CI, 1.02–3.58; P = 0.044) and recessive (OR, 2.09; 95% CI, 1.16–3.76; P = 0.014) genetic model. No apparent association between this polymorphism and different menopausal status (premenopausal and postmenopausal) and the other ethnicities (almost Caucasians) was showed. In conclusion, this meta-analysis strongly suggests that GPX1 Pro198Leu polymorphism is not associated with breast cancer risk in Caucasians, and an elevated risk in Africans needs large-scale investigations to confirm.