Complicated Pleural Infection is Associated With Prolonged Recovery and Reduced Functional Ability.

BACKGROUND: Management of complicated pleural infections (CPIs) had historically been surgical; however, following the publication of the second multicenter intrapleural sepsis trial (MIST-2), combination tissue plasminogen (tPA) and dornase (DNase) offers a less invasive and effective treatment. Our aim was to assess the quality of life (QOL) and functional ability of patients' recovery from a CPI managed with either intrapleural fibrinolytic therapy (IPFT) or surgery. METHODS: We identified 565 patients managed for a CPI between January 1, 2013 and March 31, 2018. There were 460 patients eligible for contact, attempted through 2 phone calls and one mailer. Two questionnaires were administered: the Short Form 36-Item Health Survey (SF-36) and a functional ability questionnaire. RESULTS: Contact was made in 35% (159/460) of patients, and 57% (90/159) completed the survey. Patients had lower QOL scores compared to average US citizens; those managed with surgery had higher scores in physical functioning (surgery: 80, IPFT: 70, P=0.040) but lower pain scores (surgery: 58, IPFT: 68, P=0.045). Of 52 patients who returned to work, 48% (25) reported an impact on their work effectiveness during recovery, similarly between management strategies (IPFT: 50%, 13/26 vs. surgery: 46%, 12/26; P=0.781). CONCLUSION: Patients with a CPI had a lower QOL compared with average US citizens. Surgically managed patients reported improved physical functioning but worse pain compared with patients managed with IPFT. Patients returned to work within 4 weeks of discharge, and nearly half reported their ability to work effectively was impacted by their recovery. With further research into recovery timelines, patients may be appropriately counselled for expectations.

Evaluation of the RAPID score as a predictor of postoperative morbidity and mortality in patients undergoing pulmonary decortication for stage III pleural empyema.

OBJECTIVE: This study aims to correlate the RAPID score with the 3-month survival and surgical results of patients undergoing lung decortication with stage III pleural empyema. METHODS: This was a retrospective study with the population of patients with pleural empyema who underwent pulmonary decortication between January 2019 and June 2022. Data were collected from the institution's database, and patients were classified as low, medium, and high risk according to the RAPID score. The primary outcome was 3-month mortality. Secondary outcomes were the length of hospital stay, readmission rate, and the need for pleural re-intervention. RESULTS: Of the 34 patients with pleural empyema, according to the RAPID score, patients were stratified into low risk (23.5 %), medium risk (47.1 %), and high risk (29.4 %). The high-risk group had a 3-month mortality of 40 %, while the moderate-risk group had a 6.25 % and the low-risk group had no deaths within 90 days, confirming a good correlation with the RAPID score (p < 0.05). Sensitivity and specificity for the primary outcome in the high-risk score were 80.0 % and 79.3 %, respectively. The secondary outcomes did not reach statistical significance. CONCLUSIONS: In this retrospective series, the RAPID score had a good correlation with 3-month mortality in patients undergoing lung decortication. The morbidity indicators did not reach statistical significance. The present data justifies further studies to explore the capacity of the RAPID score to be used as a selection tool for treatment modality in patients with stage III pleural empyema.

Malignant pleural effusion: current understanding and therapeutic approach.

Malignant pleural effusion (MPE) is a common complication of thoracic and extrathoracic malignancies and is associated with high mortality and elevated costs to healthcare systems. Over the last decades the understanding of pathophysiology mechanisms, diagnostic techniques and optimal treatment intervention in MPE have been greatly advanced by recent high-quality research, leading to an ever less invasive diagnostic approach and more personalized management. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. In the next future, because of a better understanding of underlying tumor biology together with more sensitive molecular diagnostic techniques, it is likely that combined diagnostic and therapeutic procedures allowing near total outpatient management of MPE will become popular. This article provides a review of the current advances, new discoveries and future directions in the pathophysiology, diagnosis and management of MPE.

Evaluation of the RAPID score as a predictor of postoperative morbidity and mortality in patients undergoing pulmonary decortication for stage III pleural empyema

Abstract Objective: This study aims to correlate the RAPID score with the 3-month survival and surgical results of patients undergoing lung decortication with stage III pleural empyema. Methods: This was a retrospective study with the population of patients with pleural empyema who underwent pulmonary decortication between January 2019 and June 2022. Data were collected from the institution's database, and patients were classified as low, medium, and high risk according to the RAPID score. The primary outcome was 3-month mortality. Secondary outcomes were the length of hospital stay, readmission rate, and the need for pleural re-intervention. Results: Of the 34 patients with pleural empyema, according to the RAPID score, patients were stratified into low risk (23.5 %), medium risk (47.1 %), and high risk (29.4 %). The high-risk group had a 3-month mortality of 40 %, while the moderate-risk group hada 6.25 % and the low-risk group had no deaths within 90days, confirmingagood correlation with the RAPID score (p < 0.05). Sensitivity and specificity for the primary outcome in the high-risk score were 80.0 % and 79.3%, respectively. The secondary outcomes did not reach statistical significance. Conclusions: In this retrospective series, the RAPID score had a good correlation with 3-month mortality in patients undergoing lung decortication. The morbidity indicators did not reach statistical significance. The present data justifies further studies to explore the capacity of the RAPID score to be used as a selection tool for treatment modality in patients with stage III pleural empyema.

Early Video-assisted Thoracoscopic Surgery or Intrapleural Enzyme Therapy 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-nonsurgery trial as well as the key outcome measures that are important to identify relevant patient-centered outcomes in a subsequent RCT. Methods: The MIST-3 (third Multicenter Intrapleural Sepsis Trial) was a prospective multicenter RCT involving eight U.K. centers combining on-site and off-site surgical services. The study enrolled all patients with a confirmed diagnosis of pleural infection and randomized those with ongoing pleural sepsis after an initial period (as long as 24 h) of standard care to one of three treatment arms: continued standard care, early IET, or a surgical opinion with regard to early VATS. The primary outcome was feasibility based on >50% of eligible patients being successfully randomized, >95% of randomized participants retained to discharge, and >80% of randomized participants retained to 2 weeks of follow-up. The analysis was performed per intention to treat. Measurements and Main Results: Of 97 eligible patients, 60 (62%) were randomized, with 100% retained to discharge and 84% retained to 2 weeks. Baseline demographic, clinical, and microbiological characteristics of the patients were similar across groups. Median times to intervention were 1.0 and 3.5 days in the IET and surgery groups, respectively (P = 0.02). Despite the difference in time to intervention, length of stay (from randomization to discharge) was similar in both intervention arms (7 d) compared with standard care (10 d) (P = 0.70). There were no significant intergroup differences in 2-month readmission and further intervention, although the study was not adequately powered for this outcome. Compared with VATS, IET demonstrated a larger improvement in mean EuroQol five-dimension health utility index (five-level edition) from baseline (0.35) to 2 months (0.83) (P = 0.023). One serious adverse event was reported in the VATS arm. Conclusions: This is the first multicenter RCT of early IET versus early surgery in pleural infection. Despite the logistical challenges posed by the coronavirus disease (COVID-19) pandemic, the study met its predefined feasibility criteria, demonstrated potential shortening of length of stay with early surgery, and signals toward earlier resolution of pain and a shortened recovery with IET. The study findings suggest that a definitive phase III study is feasible but highlights important considerations and significant modifications to the design that would be required to adequately assess optimal initial management in pleural infection.The trial was registered on ISRCTN (number 18,192,121).

Does the time to diagnosis and treatment influence outcome in adults with pleural infections.

Objective: To investigate the effect of early diagnosis and intervention in adult patients with complicated parapneumonic pleural effusion or pleural empyema and the impact on outcomes. Methods: A systematic review based on a literature search of the PubMed database was performed. Results: Eleven eligible studies were included; nine observational studies and two randomised controlled trials totalling a study population of 10,717 patients. The studies were conducted from 1992 to 2018, all in Europe and Northern America except one. Results varied between studies, but a trend towards better outcome in patients with shorter duration of symptoms and quicker initiation of treatment was found. We found that duration of symptoms before treatment may affect length of hospital stay, rate of conversion to open surgery, and frequency of complications. Conclusion: We found that an earlier intervention in adults suffering from complicated parapneumonic pleural effusion and pleural empyema may potentially improve the outcome of patients in terms of length of stay, conversion to open surgery, and general complications following treatment, but not regarding mortality. Further studies are required to specify the timing of each intervention, and direct comparison in early management of interventions.

Achieving Molecular Profiling in Pleural Biopsies: A Multicenter, Retrospective Cohort Study.

BACKGROUND: Pleural biopsy findings offer greater diagnostic sensitivity in malignant pleural effusions compared with pleural fluid. The adequacy of pleural biopsy techniques in achieving molecular marker status has not been studied, and such information (termed "actionable" histology) is critical in providing a rational, efficient, and evidence-based approach to diagnostic investigation. RESEARCH QUESTION: What is the adequacy of various pleural biopsy techniques at providing adequate molecular diagnostic information to guide treatment in malignant pleural effusions? STUDY DESIGN AND METHODS: This study analyzed anonymized data on 183 patients from four sites across three countries in whom pleural biopsy results had confirmed a malignant diagnosis and molecular profiling was relevant for the diagnosed cancer type. The primary outcome measure was adequacy of pleural biopsy for achieving molecular marker status. Secondary outcomes included clinical factors predictive of achieving a molecular diagnosis. RESULTS: The median age of patients was 71 years (interquartile range, 63-78 years), with 92 of 183 (50%) male. Of the 183 procedures, 105 (57%) were local anesthetic thoracoscopies (LAT), 12 (7%) were CT scan guided, and 66 (36%) were ultrasound guided. Successful molecular marker analysis was associated with mode of biopsy, with LAT having the highest yield and ultrasound-guided biopsy the lowest (LAT vs CT scan guided vs ultrasound guided: LAT yield, 95%; CT scan guided, 86%; and ultrasound guided, 77% [P = .004]). Biopsy technique and size of biopsy sample were independently associated with successful molecular marker analysis. LAT had an adjusted OR for successful diagnosis of 30.16 (95% CI, 3.15-288.56; P = .003) and biopsy sample size an OR of 1.18 (95% CI, 1.02-1.37) per millimeter increase in tissue sample size (P < .03). INTERPRETATION: Although previous studies have shown comparable overall diagnostic yields, in the modern era of targeted therapies, this study found that LAT offers far superior results to image-guided techniques at achieving molecular profiling and remains the optimal diagnostic tool.

ERS/ESTS statement on the management of pleural infection in adults.

Pleural infection is a common condition encountered by respiratory physicians and thoracic surgeons alike. The European Respiratory Society (ERS) and European Society of Thoracic Surgeons (ESTS) established a multidisciplinary collaboration of clinicians with expertise in managing pleural infection with the aim of producing a comprehensive review of the scientific literature. Six areas of interest were identified: 1) epidemiology of pleural infection, 2) optimal antibiotic strategy, 3) diagnostic parameters for chest tube drainage, 4) status of intrapleural therapies, 5) role of surgery and 6) current place of outcome prediction in management. The literature revealed that recently updated epidemiological data continue to show an overall upwards trend in incidence, but there is an urgent need for a more comprehensive characterisation of the burden of pleural infection in specific populations such as immunocompromised hosts. There is a sparsity of regular analyses and documentation of microbiological patterns at a local level to inform geographical variation, and ongoing research efforts are needed to improve antibiotic stewardship. The evidence remains in favour of a small-bore chest tube optimally placed under image guidance as an appropriate initial intervention for most cases of pleural infection. With a growing body of data suggesting delays to treatment are key contributors to poor outcomes, this suggests that earlier consideration of combination intrapleural enzyme therapy (IET) with concurrent surgical consultation should remain a priority. Since publication of the MIST-2 study, there has been considerable data supporting safety and efficacy of IET, but further studies are needed to optimise dosing using individualised biomarkers of treatment failure. Pending further prospective evaluation, the MIST-2 regimen remains the most evidence based. Several studies have externally validated the RAPID score, but it requires incorporating into prospective intervention studies prior to adopting into clinical practice.

Malignant pleural effusion: Updates in diagnosis, management and current challenges.

Malignant pleural effusion (MPE) is a common condition which often causes significant symptoms to patients and costs to healthcare systems. Over the past decade, the management of MPE has progressed enormously with large scale, randomised trials answering key questions regarding optimal diagnostic strategies and effective management strategies. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. The future goals for providing improved care for patients lies in changing the treatment paradigm from a generic pathway to personalised care, based on probability of malignancy type and survival. This article reviews the current evidence base, new discoveries and future directions in the diagnosis and management of MPE.

Intrapleural fibrinolysis and DNase versus video-assisted thoracic surgery (VATS) for the treatment of pleural empyema (FIVERVATS): protocol for a randomised, controlled trial - surgery as first-line treatment.

INTRODUCTION: Pleural empyema is a frequent disease with a high morbidity and mortality. Current standard treatment includes antibiotics and thoracic ultrasound (TUS)-guided pigtail drainage. Simultaneously with drainage, an intrapleural fibrinolyticum can be given. A potential better alternative is surgery in terms of video-assisted thoracoscopic surgery (VATS) as first-line treatment. The aim of this study is to determine the difference in outcome in patients diagnosed with complex parapneumonic effusion (stage II) and pleural empyema (stage III) who are treated with either VATS surgery or TUS-guided drainage and intrapleural therapy (fibrinolytic (Alteplase) with DNase (Pulmozyme)) as first-line treatment. METHODS AND ANALYSIS: A national, multicentre randomised, controlled study. Totally, 184 patients with a newly diagnosed community acquired complicated parapneumonic effusion or pleural empyema are randomised to either (1) VATS procedure with drainage or (2) TUS-guided pigtail catheter placement and intrapleural therapy with Actilyse and DNase. The total follow-up period is 12 months. The primary endpoint is length of hospital stay and secondary endpoints include for example, mortality, need for additional interventions, consumption of analgesia and quality of life. ETHICS AND DISSEMINATION: All patients provide informed consent before randomisation. The research project is carried out in accordance with the Helsinki II Declaration, European regulations and Good Clinical Practice Guidelines. The Scientific Ethics Committees for Denmark and the Danish Data Protection Agency have provided permission. Information about the subjects is protected under the Personal Data Processing Act and the Health Act. The trial is registered at www. CLINICALTRIALS: gov, and monitored by the regional Good clinical practice monitoring unit. The results of this study will be published in peer-reviewed journals and presented at various national and international conferences. TRIAL REGISTRATION NUMBER: NCT04095676.

Role of thoracic ultrasonography in pleurodesis pathways for malignant pleural effusions (SIMPLE): an open-label, randomised controlled trial.

BACKGROUND: Pleurodesis is done as an in-patient procedure to control symptomatic recurrent malignant pleural effusion (MPE) and has a success rate of 75-80%. Thoracic ultrasonography has been shown in a small study to predict pleurodesis success early by demonstrating cessation of lung sliding (a normal sign seen in healthy patients, lung sliding indicates normal movement of the lung inside the thorax). We aimed to investigate whether the use of thoracic ultrasonography in pleurodesis pathways could shorten hospital stay in patients with MPE undergoing pleurodesis. METHODS: The Efficacy of Sonographic and Biological Pleurodesis Indicators of Malignant Pleural Effusion (SIMPLE) trial was an open-label, randomised controlled trial done in ten respiratory centres in the UK and one respiratory centre in the Netherlands. Adult patients (aged ≥18 years) with confirmed MPE who required talc pleurodesis via either a chest tube or as poudrage during medical thorascopy were eligible. Patients were randomly assigned (1:1) to thoracic ultrasonography-guided care or standard care via an online platform using a minimisation algorithm. In the intervention group, daily thoracic ultrasonography examination for lung sliding in nine regions was done to derive an adherence score: present (1 point), questionable (2 points), or absent (3 points), with a lowest possible score of 9 (preserved sliding) and a highest possible score of 27 (complete absence of sliding); the chest tube was removed if the score was more than 20. In the standard care group, tube removal was based on daily output volume (per British Thoracic Society Guidelines). The primary outcome was length of hospital stay, and secondary outcomes were pleurodesis failure at 3 months, time to tube removal, all-cause mortality, symptoms and quality-of-life scores, and cost-effectiveness of thoracic ultrasonography-guided care. All outcomes were assessed in the modified intention-to-treat population (patients with missing data excluded), and a non-inferiority analysis of pleurodesis failure was done in the per-protocol population. This trial was registered with ISRCTN, ISRCTN16441661. FINDINGS: Between Dec 31, 2015, and Dec 17, 2019, 778 patients were assessed for eligibility and 313 participants (165 [53%] male) were recruited and randomly assigned to thoracic ultrasonography-guided care (n=159) or standard care (n=154). In the modified intention-to-treat population, the median length of hospital stay was significantly shorter in the intervention group (2 days [IQR 2-4]) than in the standard care group (3 days [2-5]; difference 1 day [95% CI 1-1]; p<0·0001). In the per-protocol analysis, thoracic ultrasonography-guided care was non-inferior to standard care in terms of pleurodesis failure at 3 months, which occurred in 27 (29·7%) of 91 patients in the intervention group versus 34 (31·2%) of 109 patients in the standard care group (risk difference -1·5% [95% CI -10·2% to 7·2%]; non-inferiority margin 15%). Mean time to chest tube removal in the intervention group was 2·4 days (SD 2·5) versus 3·1 days (2·0) in the standard care group (mean difference -0·72 days [95% CI -1·22 to -0·21]; p=0·0057). There were no significant between-group differences in all-cause mortality, symptom scores, or quality-of-life scores, except on the EQ-5D visual analogue scale, which was significantly lower in the standard care group at 3 months. Although costs were similar between the groups, thoracic ultrasonography-guided care was cost-effective compared with standard care. INTERPRETATION: Thoracic ultrasonography-guided care for pleurodesis in patients with MPE results in shorter hospital stay (compared with the British Thoracic Society recommendation for pleurodesis) without reducing the success rate of the procedure at 3 months. The data support consideration of standard use of thoracic ultrasonography in patients undergoing MPE-related pleurodesis. FUNDING: Marie Curie Cancer Care Committee.

The Frequency, Risk Factors, and Management of Complications From Pleural Procedures.

Pleural disease is a common presentation and spans a heterogeneous population across broad disease entities; a common feature is the requirement for interventional procedures. Despite the frequency of such procedures, there is little consensus on rates of complications and risk factors associated with such complications. This narrative review was based on a structured search of the literature. Searches were limited to 2010 onward, in recognition of the transformation in procedural complications following the mainstream use of thoracic ultrasound. Procedures of interest were limited to thoracocentesis, intercostal drains, indwelling pleural catheters (IPCs), and local anesthetic thoracoscopy. A total of 4,308 studies were screened, and 48 studies were identified for inclusion. Iatrogenic pneumothorax remains the most common complication following thoracocentesis (3.3%; 95% CI, 3.2-3.4), although pneumothorax requiring intervention was rare (0.3%; 95% CI, 0.2-0.4) when the procedure was ultrasound guided. Drain blockage and displacement were the most common complications following intercostal drain insertion (6.3% and 6.8%, respectively). IPC-related infections can be a significant problem (5.8%; 95% CI, 5.1-6.7). However, most cases can be managed without removal of the IPC. Local anesthetic thoracoscopy has an overall mortality of 0.1% (95% CI, 0.03-0.3). Data on safety and complication rates in procedural interventions are limited by methodologic problems, and novel methods to study this topic should be considered. Although complications remain rare events, once encountered, they have the potential to rapidly escalate. It is of paramount importance for operators to prepare and have in place plans for such events to ensure high quality and, above all, safe care.

Parapneumonic Effusion and Empyema.

The rising incidence and high morbidity of pleural infection remain a significant challenge to health care systems worldwide. With distinct microbiology and treatment paradigms from pneumonia, pleural infection is an area in which the evidence base has been rapidly evolving. Progress in recent years has revolved around characterizing the microbiome of pleural infection and the addition of new strategies such as intrapleural enzyme therapy to the established treatment pathway of drainage and antibiotics. The future of improving outcomes lies with personalizing treatment, establishing optimal timing of intrapleural agents and surgery, alongside wider use of risk stratification to guide treatment.

Recent Insights into the Management of Pleural Infection.

Pleural infection in adults has considerable morbidity and continues to be a life-threatening condition. The term "pleural infection" encompasses complicated parapneumonic effusions and primary pleural infections, and includes but is not limited to empyema, which refers to collection of pus in the pleural cavity. The incidence of pleural infection in adults has been continuously increasing over the past two decades, particularly in older adults, and most of such patients have comorbidities. Management of pleural infection requires prolonged duration of hospitalization (average 14 days). There are recognized differences in microbial etiology of pleural infection depending on whether the infection was acquired in the community or in a health-care setting. Anaerobic bacteria are acknowledged as a major cause of pleural infection, and thus anaerobic coverage in antibiotic regimens for pleural infection is mandatory. The key components of managing pleural infection are appropriate antimicrobial therapy and chest-tube drainage. In patients who fail medical therapy by manifesting persistent sepsis despite standard measures, surgical intervention to clear the infected space or intrapleural fibrinolytic therapy (in poor surgical candidates) are recommended. Recent studies have explored the role of early intrapleural fibrinolytics or first-line surgery, but due to considerable costs of such interventions and the lack of convincing evidence of improved outcomes with early use, early intervention cannot be recommended, and further evidence is awaited from ongoing studies. Other areas of research include the role of routine molecular testing of infected pleural fluid in improving the rate of identification of causative organisms. Other research topics include the benefit of such interventions as medical thoracoscopy, high-volume pleural irrigation with saline/antiseptic solution, and repeated thoracentesis (as opposed to chest-tube drainage) in reducing morbidity and improving outcomes of pleural infection. This review summarizes current knowledge and practice in managing pleural infection and future research directions.

Pleural Fluid Has Pro-Growth Biological Properties Which Enable Cancer Cell Proliferation.

OBJECTIVES: Patients with malignant pleural mesothelioma (MPM) or pleural metastases often present with malignant pleural effusion (MPE). This study aimed to analyze the effect of pleural fluid on cancer cells. MATERIALS AND METHODS: Established patient-derived cancer cell cultures derived from MPE (MPM, breast carcinoma, lung adenocarcinoma) were seeded in 100% pleural fluid (exudate MPM MPE, transudate MPE, non-MPE transudate fluid) and proliferation was monitored. In addition, the establishment of new MPM cell cultures, derived from MPE specimens, was attempted by seeding the cells in 100% MPE fluid. RESULTS: All established cancer cell cultures proliferated with similar growth rates in the different types of pleural fluid. Primary MPM cell culture success was similar with MPE fluid as with full culture medium. CONCLUSIONS: Pleural fluid alone is adequate for cancer cell proliferation in vitro, regardless of the source of pleural fluid. These results support the hypothesis that pleural fluid has important pro-growth biological properties, but the mechanisms for this effect are unclear and likely not malignant effusion specific.

Advances in pleural infection and malignancy.

Pleural infection and malignancy are among the most common causes of pleural disease and form the mainstay of pleural practice. There has been significant research and increase in scientific understanding in these areas in the past decade. With regard to pleural infection, the rising incidence remains worrying. An increased awareness allowing earlier diagnosis, earlier escalation of therapy and the use of validated risk stratification measures may improve outcomes. In pleural malignancy, research has enabled clinicians to streamline patient pathways with focus on reducing time to diagnosis, definitive management of malignant pleural effusion and achieving these with the minimum number of pleural interventions. Trials comparing treatment modalities of malignant pleural effusion continue to highlight the importance of patient choice in clinical decision-making. This article aims to summarise some of the most recent literature informing current practice in these two areas.

Diagnostic Yield and Safety of Image-Guided Pleural Biopsy: A Systematic Review and Meta-Analysis.

BACKGROUND: Diagnostic yield (DY) and safety of computed tomography (CT)- and thoracic ultrasound (TUS)-guided biopsies in the diagnosis of pleural lesions have been investigated in a number of studies, but no synthesis of data from the literature has ever been performed. OBJECTIVES: We aimed to provide the first systematic review and meta-analysis on the DY and safety of CT- versus TUS-guided biopsy in the diagnosis of pleural lesions. METHOD: We searched MEDLINE and EMBASE for all studies reporting outcomes of interest published up to April 2018. Two authors reviewed all titles/abstracts and retrieved selected full text to identify studies according to predefined selection criteria. Summary estimates were derived using the random-effects model. Cumulative meta-analysis assessed the influence of increasing adoption of the procedures over time. RESULTS: Thirty original studies were included in the present review; the number of studies on TUS-guided biopsy was almost three-fold higher than those on CT-guided biopsy. The pooled DYs of the 2 procedures were overall excellent and differed <10%, being 84% for TUS-guided biopsy and 93% for CT-guided biopsy. Safety profiles were reassuring for both the techniques, being 7 and 3% for CT- and TUS-guided biopsy, respectively. DY of ultrasound technique significantly improved over time, while no time effect was observed for CT-guided biopsy. CONCLUSIONS: Data show that CT- and TUS-guided biopsies in the diagnosis of pleural lesions are both excellent procedures, without meaningful differences in DYs and safety. Considering that TUS is non-ionizing and easily performed at the bedside, it should be the preferred approach in presence of adequate skills.