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Background: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined., Research Question: What is the bleeding complication risk associated with IET use in pleural infection?, Study Design and Methods: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria., Results: Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 10 9 /L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare., Interpretation: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rationale: In 2018, a systematic review evaluating transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD) was performed to inform American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guidelines on the diagnosis of idiopathic pulmonary fibrosis. Objectives: To perform a new systematic review to inform updated guidelines. Methods: Medline, Excerpta Medica Database, and the Cochrane Central Register of Controlled Trials (CCTR) were searched through June 2020. Studies that enrolled patients with ILD and reported the diagnostic yield or complication rates of TBLC were selected for inclusion. Data was extracted and then pooled across studies via meta-analysis. The quality of the evidence was appraised using the grading of recommendations, assessment, development, and evaluation approach. Results: Histopathologic diagnostic yield (number of procedures that yielded a histopathologic diagnosis divided by the total number of procedures performed) of TBLC was 80% (95% confidence interval [CI], 76-83%) in patients with ILD. TBLC was complicated by bleeding and pneumothorax in 30% (95% CI, 20-41%) and 8% (95% CI, 6-11%) of patients, respectively. Procedure-related mortality, severe bleeding, prolonged air leak, acute exacerbation, respiratory failure, and respiratory infection were rare. The quality of the evidence was very low owing to the uncontrolled study designs, lack of consecutive enrollment, and inconsistent results. Conclusions: Very low-quality evidence indicated that TBLC has a diagnostic yield of approximately 80% in patients with ILD, with manageable complications.

Background: Usual interstitial pneumonia (UIP) is the histopathologic hallmark of idiopathic pulmonary fibrosis (IPF), the prototypical interstitial lung disease (ILD). Diagnosis of IPF requires that a typical UIP pattern be identified by using high-resolution chest computed tomography or lung sampling. A genomic classifier for UIP has been developed to predict histopathologic UIP by using lung samples obtained through bronchoscopy. Objective: To perform a systematic review to evaluate genomic classifier testing in the detection of histopathologic UIP to inform new American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax guidelines. Data Sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched through June 2020. Data Extraction: Data were extracted from studies that enrolled patients with ILD and reported the use of genomic classifier testing. Synthesis: Data were aggregated across studies via meta-analysis. The quality of the evidence was appraised by using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results: Genomic classifier testing had a sensitivity of 68% (95% confidence interval [CI], 55-73%) and a specificity of 92% (95% CI, 81-95%) in predicting the UIP pattern in ILD. Confidence in an IPF diagnosis increased from 43% to 93% in one cohort and from 59% to 89% in another cohort. Agreement levels in categorical IPF and non-IPF diagnoses measured by using a concordance coefficient were 0.75 and 0.64 in the two cohorts. The quality of evidence was moderate for test characteristics and very low for both confidence and agreement. Conclusions: Genomic classifier testing predicts histopathologic UIP in patients with ILD with a specificity of 92% and improves diagnostic confidence; however, sensitivity is only 68%, and testing is not widely available.

Introduction: Bronchoscopic lung volume reduction (BLVR) with endobronchial valves (EBVs) has emerged as an important treatment method for patients with severe chronic obstructive pulmonary disease (COPD). Acute exacerbations of COPD (AECOPD) are a frequent complication following BLVR with EBV. However, there is no consensus on the prevention of AECOPD., Objectives: Our study aims to compare the outcomes of different prophylactic measures on the occurrence of AECOPD after BLVR with EBV., Methods: We conducted a multicenter, retrospective study of patients who underwent BLVR with EBV at six different institutions. Emphasis was directed towards the specific practices aimed at preventing AECOPD: antibiotics, steroids, antibiotics plus steroids, or no prophylaxis. Subgroups were compared, and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated., Results: A total of 170 patients were reviewed. The rate of AECOPD was 21.2% for the full cohort. Patients who received prophylaxis had a significantly lower rate of AECOPD compared with those who did not (16.7% vs. 46.2%; p = 0.001). The rate was lowest in patients who received antibiotics alone (9.2%). There was no significant difference in the rate of AECOPD between patients who received steroids alone or antibiotics plus steroids, compared with the other subgroups. The OR for AECOPD was 4.3 (95% CI: 1.8-10.4; p = 0.001) for patients not receiving prophylaxis and 3.9 (95% CI: 1.5-10.1; p = 0.004) for prophylaxis other than antibiotics alone., Conclusions: Administration of antibiotics after BLVR with EBV was associated with a lower rate of AECOPD. This was not observed with the use of steroids or in combination with antibiotics., (© 2021 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Background: Indwelling pleural catheters (IPC) are increasingly used for management of recurrent (especially malignant) effusions. Pleural infection associated with IPC use remains a concern. Intrapleural therapy with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) significantly reduces surgical referrals in non-IPC pleural infection, but data on its use in IPC-related pleural infection are scarce., Objective: To assess the safety and efficacy of intrapleural tPA and DNase in IPC-related pleural infection., Methods: Patients with IPC-related pleural infection who received intrapleural tPA/DNase in five Australian and UK centers were identified from prospective databases. Outcomes on feasibility of intrapleural tPA/DNase delivery, its efficacy and safety were recorded., Results: Thirty-nine IPC-related pleural infections (predominantly Staphylococcus aureus and gram-negative organisms) were treated in 38 patients; 87% had malignant effusions. In total, 195 doses (median 6 [IQR = 3-6]/patient) of tPA (2.5 mg-10 mg) and DNase (5 mg) were instilled. Most (94%) doses were delivered via IPCs using local protocols for non-IPC pleural infections. The mean volume of pleural fluid drained during the first 72 h of treatment was 3,073 (SD = 1,685) mL. Most (82%) patients were successfully treated and survived to hospital discharge without surgery; 7 required additional chest tubes or therapeutic aspiration. Three patients required thoracoscopic surgery. Pleurodesis developed post-infection in 23/32 of successfully treated patients. No major morbidity/mortality was associated with tPA/DNase. Four patients received blood transfusions; none had systemic or significant pleural bleeding., Conclusion: Treatment of IPC-related pleural infection with intrapleural tPA/DNase instillations via the IPC appears feasible and safe, usually without additional drainage procedures or surgery. Pleurodesis post-infection is common., (© 2021 S. Karger AG, Basel.)

Background: Electromagnetic navigation bronchoscopy (ENB) is a minimally invasive technology for the diagnosis of peripheral pulmonary nodules. However, ENB is limited by the lack of real-time confirmation of various biopsy devices. Cone-beam computed tomography (CBCT) could increase diagnostic yield by allowing real-time confirmation to overcome the inherent divergence of nodule location., Objectives: The aim of this study was to assess the diagnostic yield of ENB plus CBCT as compared with ENB alone for biopsy of peripheral lung nodules., Method: We conducted a retrospective study of patients undergoing ENB before and after the implementation of CBCT. Data from 62 consecutive patients with lung nodules located in the outer two-thirds of the lung who underwent ENB and combined ENB-CBCT were collected. Radial endobronchial ultrasound was used during all procedures as well. Diagnostic yield was defined as the presence of malignancy or benign histological findings that lead to a specific diagnosis., Results: Thirty-one patients had ENB-CBCT, and 31 patients had only ENB for peripheral lung lesions. The median size of the lesion for the ENB-CBCT group was 16 (interquartile range (IQR) 12.6-25.5) mm as compared to 21.5 (IQR 16-27) mm in the ENB group (p = 0.2). In the univariate analysis, the diagnostic yield of ENB-CBCT was 74.2% and ENB 51.6% (p = 0.05). Following multivariate regression analysis adjusting for the size of the lesion, distance from the pleura, and presence of bronchus sign, the odds ratio for the diagnostic yield was 3.4 (95% CI 1.03-11.26, p = 0.04) in the ENB-CBCT group as compared with ENB alone. The median time for the procedure was shorter in patients in the ENB-CBCT group (74 min) than in those in the ENB group (90 min) (p = 0.02). The rate of adverse events was similar in both groups (6.5%, p = 0.7)., Conclusions: The use of CBCT might increase the diagnostic yield in ENB-guided peripheral lung nodule biopsies. Future randomized clinical trials are needed to confirm such findings., (© 2021 S. Karger AG, Basel.)

Mechanisms involved in the association between hyperhomocysteinemia and vascular occlusive diseases remain unclear. Homocysteine (Hcy) may disturb calcium (Ca(2+) ) cytosolic regulation in endothelial cells, a process that can directly affect the synthesis of vasoactive substances, such as nitric oxide (NO). We have investigated the effect of acute and chronic incubation with high concentrations of Hcy (100 and 500 μmol/L) on the changes in the intracellular Ca(2+) concentration ([Ca(2+) ]i ) induced by ATP, using primary cultures of human umbilical vein endothelial cells (HUVEC). The changes in [Ca(2+) ]i , expressed as ΔFt /Fb , were measured using the microspectrofluorimetric technique with Fluo-3 as Ca(2+) indicator. HUVEC acutely exposed to Hcy did not produce significant effects on any of the parameters studied. However, chronic exposition (24 h) caused a significant decrease in the speed of store-mediated Ca(2+) entry, expressed as (ΔFt /Fb )/t (s(-1) ). Exposure of HUVEC to 100 and 500 µmol/L Hcy gave significantly lower values (0.019 ± 0.002 s(-1) , n = 5 and 0.021 ± 0.004 s(-1) , n = 6, respectively) compared to the controls (0.046 ± 0.004 s(-1) , n = 8, P < 0.003). This was detected only when the sustained phase of the ATP-induced [Ca(+2) ]i increase was isolated. These results demonstrate that high concentrations of Hcy can affect the mechanisms involved in [Ca(2+) ]i regulation of HUVEC, and that alteration occurs specifically in the sustained phase, which has been directly associated with NO synthesis., (© 2013 International Federation for Cell Biology.)

Column leaching experiments were conducted to test the ability of Chilean volcanic soils in retaining the mineral constituents and metals in sewage sludge and sludge ash that were incorporated into the soils. Small or negligible amounts of the total content of Pb, Fe, Cr, Mn, Cd, and Zn (0 to <2%), and more significant amounts of mineral constituents such as Na (7-9%), Ca (7-13%), PO4 (4-10%), and SO4 (39-46%) in the sludge and sludge ash were readily soluble. When they were incorporated on the surface layer of the soils and leached with 12 pore volumes of water over a 3 month period of time, less than 0.1% of the total amount of heavy metals and PO4 in the sludge and sludge ash were collected in the drainage water. Cation exchange selectivity, specific anion adsorption and solubility are the processes that cause the reduction of leaching. The volcanic soils were capable of retaining the mineral constituents, P, and metals in applied sewage sludge and sludge ash and gradually released them as nutrients for plant growth.