Critical analysis of the utility of initial pleural aspiration in the diagnosis and management of suspected malignant pleural effusion

INTRODUCTION:Current guidelines recommend an initial pleural aspiration in the investigation and management of suspected malignant pleural effusions (MPEs) with the aim of establishing a diagnosis, identifying non-expansile lung (NEL) and, at times, providing a therapeutic procedure. A wealth of research has been published since the guidelines suggesting that results and outcomes from an aspiration may not always provide sufficient information to guide management. It is important to establish the validity of these findings in a 'real world' population. METHODS:A retrospective analysis was conducted of all patients who underwent pleural fluid (PF) sampling, in a single centre, over 3 years to determine the utility of the initial aspiration. RESULTS:A diagnosis of MPE was confirmed in 230/998 (23%) cases, a further 95/998 (9.5%) were presumed to represent MPE. Transudative biochemistry was found in 3% of cases of confirmed MPE. Positive PF cytology was only sufficient to guide management in 45/140 (32%) cases. Evidence of pleural thickening on CT was associated with both negative cytology (χ2 1df=26.27, p<0.001) and insufficient samples (χ2 1df=10.39, p=0.001). In NEL 44.4% of patients did not require further procedures after pleurodesis compared with 72.7% of those with expansile lung (χ2 1df=5.49, p=0.019). In patients who required a combined diagnostic and therapeutic aspiration 106/113 (93.8%) required further pleural procedures. CONCLUSIONS:An initial pleural aspiration does not achieve either definitive diagnosis or therapy in the majority of patients. A new pathway prioritising symptom management while reducing procedures should be considered

Clinical characteristics of chylothorax: results from the International Collaborative Effusion database

BackgroundChylothorax is an uncommon medical condition for which limited data are available regarding the contemporary aetiology, management and outcomes. The goal of this study was to better define these poorly characterised features.MethodsThe medical records of adult patients diagnosed with chylothorax at 12 centres across Europe, America and South Africa from 2009-2021 were retrospectively reviewed. Descriptive and inferential statistics were performed.Results77 patients (median age 69 years, male to female ratio 1.5) were included. Subacute dyspnoea was the most typical presenting symptom (66%). The commonest cause of chylothorax was malignancy (68.8%), with lymphoma accounting for 62% of these cases. Other aetiologies were trauma (13%), inflammatory/miscellaneous conditions (11.7%) and idiopathic cases (6.5%). At the initial thoracentesis, the pleural fluid appeared milky in 73%, was exudative in 89% and exhibited triglyceride concentrations >100 mg·dL-1 in 88%. Lymphangiography/lymphoscintigraphy were rarely ordered (3%), and demonstration of chylomicrons in pleural fluid was never ascertained. 67% of patients required interventional pleural procedures. Dietary measures were infrequently followed (36%). No patient underwent thoracic duct ligation or embolisation. Morbidity included infections (18%), and thrombosis in malignant aetiologies (16%). The 1-year mortality was 47%. Pleural fluid protein >3.5 mg·dL-1 (sub-distribution hazard ratio (SHR) 4.346) or lactate dehydrogenase -1 (SHR 10.21) increased the likelihood of effusion resolution. Pleural fluid protein ≤3.5 mg·dL-1 (HR 4.047), bilateral effusions (HR 2.749) and a history of respiratory disease (HR 2.428) negatively influenced survival.ConclusionChylothoraces have a poor prognosis and most require pleural interventions. Despite the standard recommendations, lymphatic imaging is seldom used, nor are dietary restrictions followed

Efficacy of Small versus Large-Bore Chest Drain in Pleural Infection: A Systematic Review and Meta-Analysis

Background: Pleural infection represents a significant clinical challenge worldwide. Although prompt drainage of pleural fluid is thought to play a key role in pleural infection management, the optimal size of intrapleural catheter has yet to be defined. Objectives: The aim of this systematic review and meta-analysis was to summarize data on efficacy and complications of small-bore drain (SBD), defined as ≤14F, in comparison to large-bore drain (LBD) in patients with pleural infection. Method: We searched MEDLINE and Embase for all studies reporting outcomes of interest published up to October 2021. Two authors reviewed selected full text to identify studies according to predefined eligibility criteria. Summary estimates were derived using the random-effects model. Results: Twelve original studies were included for qualitative analysis and 7 of these for quantitative analysis. The surgical referral rate of SBD and LBD were, respectively, 0.16 (95% confidence interval [CI], 0.12-0.21) and 0.20 (95% CI, 0.10-0.32), the pooled mortality were 0.12 (95% CI, 0.05-0.21) and 0.20 (95% CI, 0.10-0.32), and the length of hospital stay was 24 days in both groups. Data on complications suggest similar proportions of tube dislodgement. Intensity of pain was evaluated in one study only, reporting higher scores for LBD. Conclusions: This systematic review and meta-analysis provide the first synthesis of data on performance of SBD and LBD in management of pleural infection, and, overall, clinical outcomes and complications did not substantially differ, although the limited number of studies and the absence of dedicated randomized trials does limit the reliability of results

Chest Drain Fall-Out Rate According to Suturing Practices: A Retrospective Direct Comparison

Background: Chest drains often become displaced and require replacement, adding unnecessary risks to patients. Simple measures such as suturing of the drain may reduce fall-out rates; however, there is no direct data to demonstrate this and no standardized recommended practice that is evidence based. Objectives: The study aimed to analyze the rate of chest drain fall out according to suturing practice. Methods: Retrospective analysis of all chest drain insertions (radiology and pleural teams) in 2015–2016. Details of chest drain fall out were collected from patient electronic records. Drain “fall out” was pre-hoc defined as the drain tip becoming dislodged outside the pleural cavity unintentionally before a clinical decision was taken to remove the drain. Results: A total of 369 chest drains were inserted: sutured (n = 106, 28.7%; 44 male [41.5%], median age 74 [interquartile range (IQR) 21] years), and unsutured (n = 263, 71.3%; 139 male [52.9%], median age 68 [IQR 21] years). Of the sutured drains, 7 (6.6%) fell out after a mean of 3.3 days (SD 2.6) compared to 39 (14.8%; p = 0.04) unsutured drains falling out after a mean of 2.7 days (SD 2.0; p = 0.8). Conclusions: Within the limits of this retrospective analysis, these results suggest that suturing of drains is associated with lower fall-out rates

The Biological Role of Pleural Fluid PAI-1 and Sonographic Septations in Pleural Infection: Analysis of a Prospectively Collected Clinical Outcome Study

RATIONALE: Sonographic septations are assumed to be important clinical predictors of outcome in pleural infection but the evidence for this is sparse. The inflammatory and fibrinolysis-associated intrapleural pathway(s) leading to septation formation have not been studied in a large cohort of pleural fluid (PF) samples with confirmed pleural infection, matched with ultrasound and clinical outcome data. OBJECTIVES: To assess the presence and severity of septations against baseline PF Plasminogen-Activator Inhibitor-1 (PAI-1) and other inflammatory and fibrinolysis-associated proteins as well as to correlate these with clinically important outcomes. METHODS: We analysed 214 pleural fluid samples from the PILOT study, a prospective observational pleural infection study, for inflammatory and fibrinolysis-associated proteins using the Luminex platform. Multivariate regression analyses were utilised to assess association of pleural biological markers with septation presence and severity (on ultrasound), and clinical outcomes. RESULTS: PF PAI-1 level was the only protein independently associated with septation presence (p=<0.001) and septation severity (p=0.003). PF PAI-1 levels were associated with increased length of stay (LOS) (p=0.048) and increased 12-month mortality (p=0.003). Sonographic septations alone had no relation to clinical outcomes. CONCLUSIONS: In a large and well characterised cohort, this is the first study to associate pleural biological parameters with a validated sonographic septation outcome in pleural infection. PF PAI-1 is the first biomarker to demonstrate an independent association with mortality. While PF PAI-1 plays an integral role in driving septation formation, septations themselves are not associated with clinically important outcomes. These novel findings now require prospective validation

Early Video Assisted Thoracoscopic Surgery (VATS) or Intrapleural Enzyme Therapy (IET) in Pleural Infection – A Feasibility Randomized Controlled Trial (The Third Multicenter Intrapleural Sepsis Trial – MIST-3)

Rationale: Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized controlled trial (RCT). Objectives: To establish the feasibility of randomization in a surgery versus non-surgery trial as well as the key outcome measures which are important to identify relevant patient-centered outcomes in a RCT. Methods: MIST-3 was a prospective multicenter RCT. All-comers with a confirmed diagnosis of pleural infection were enrolled and those with ongoing pleural sepsis after up to 24-hours of standard care were randomized to one of 3 arms; continued standard care, IET, or surgical opinion for VATS. The analysis was by intention to treat, despite some participants in the VATS arm not being fit enough to undergo surgical intervention. Main Results: Of 97 eligible patients, 60 (62%) participants were randomized. Despite a difference in time-to-intervention, length of stay was similar in both arms. There were no significant inter-group differences in 2-month readmission and further intervention. Compared to VATS, IET demonstrated a greater improvement in mean EQ-5D-5L health utility index at 2 months from baseline. Conclusion: This is the first multicenter RCT of early IET vs early surgery in pleural infection. Despite logistical challenges posed by the COVID-19 pandemic, the study met its predefined feasibility criteria. Potential shortening of LOS with early surgery, and signals toward earlier resolution of pain and shortened recovery with IET were demonstrated. The study findings suggest that a definitive study is feasible and required to assess optimal initial management. Clinical trial registration available at www.isrctn.com, ID: ISRCTN18192121

Correction to: Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

International audienceIn this article, the name of the GLORIA-AF investigator Anastasios Kollias was given incorrectly as Athanasios Kollias in the Acknowledgements. The original article has been corrected

Patterns of oral anticoagulant use and outcomes in Asian patients with atrial fibrillation: a post-hoc analysis from the GLORIA-AF Registry

Background: Previous studies suggested potential ethnic differences in the management and outcomes of atrial fibrillation (AF). We aim to analyse oral anticoagulant (OAC) prescription, discontinuation, and risk of adverse outcomes in Asian patients with AF, using data from a global prospective cohort study. Methods: From the GLORIA-AF Registry Phase II-III (November 2011-December 2014 for Phase II, and January 2014-December 2016 for Phase III), we analysed patients according to their self-reported ethnicity (Asian vs. non-Asian), as well as according to Asian subgroups (Chinese, Japanese, Korean and other Asian). Logistic regression was used to analyse OAC prescription, while the risk of OAC discontinuation and adverse outcomes were analysed through Cox-regression model. Our primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). The original studies were registered with ClinicalTrials.gov, NCT01468701, NCT01671007, and NCT01937377. Findings: 34,421 patients were included (70.0&nbsp;±&nbsp;10.5 years, 45.1% females, 6900 (20.0%) Asian: 3829 (55.5%) Chinese, 814 (11.8%) Japanese, 1964 (28.5%) Korean and 293 (4.2%) other Asian). Most of the Asian patients were recruited in Asia (n&nbsp;=&nbsp;6701, 97.1%), while non-Asian patients were mainly recruited in Europe (n&nbsp;=&nbsp;15,449, 56.1%) and North America (n&nbsp;=&nbsp;8378, 30.4%). Compared to non-Asian individuals, prescription of OAC and non-vitamin K antagonist oral anticoagulant (NOAC) was lower in Asian patients (Odds Ratio [OR] and 95% Confidence Intervals (CI): 0.23 [0.22-0.25] and 0.66 [0.61-0.71], respectively), but higher in the Japanese subgroup. Asian ethnicity was also associated with higher risk of OAC discontinuation (Hazard Ratio [HR] and [95% CI]: 1.79 [1.67-1.92]), and lower risk of the primary composite outcome (HR [95% CI]: 0.86 [0.76-0.96]). Among the exploratory secondary outcomes, Asian ethnicity was associated with higher risks of thromboembolism and intracranial haemorrhage, and lower risk of major bleeding. Interpretation: Our results showed that Asian patients with AF showed suboptimal thromboembolic risk management and a specific risk profile of adverse outcomes; these differences may also reflect differences in country-specific factors. Ensuring integrated and appropriate treatment of these patients is crucial to improve their prognosis. Funding: The GLORIA-AF Registry was funded by Boehringer Ingelheim GmbH