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Am J Respir Crit Care Med
Am J Respir Crit Care Med
ajrccm
American Journal of Respiratory and Critical Care Medicine
1073-449X
1535-4970
American Thoracic Society

202402-0412LE
10.1164/rccm.202402-0412LE
Correspondence
MIST-3 Is Well Worth an Echo!
Ravaglia Claudia 1 2
Magrini Nicola 3
Poletti Venerino 1 2 4
1 Department of Medical and Surgical Sciences, Bologna University, Bologna, Italy;
2 Pulmonology Unit, G. B. Morgagni Hospital, Forli, Italy;
3 Romagna Health Authority, NHS Clinical Governance Unit, Forli, Italy; and
4 Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
Correspondence and requests for reprints should be addressed to Claudia Ravaglia, M.D., Department of Medical and Surgical Sciences (DIMEC), Bologna University; Pulmonology Unit, G. B. Morgagni Hospital, Via C. Forlanini 34, 47121, Forlì, Italy. Email: claudiaravaglia79@gmail.com.
11 7 2024
1 9 2024
11 7 2024
210 5 694695
Copyright © 2024 by the American Thoracic Society
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0. For commercial usage and reprints, please e-mail Diane Gern (dgern@thoracic.org).
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pmcTo the Editor:

We read with great interest the recently published paper by Bedawi and colleagues regarding the MIST-3 study (Third Multicenter Intrapleural Sepsis Trial) (1). This study was well designed to assess the feasibility of early randomization of patients with pleural infection to a surgical versus nonsurgical intervention (early video-assisted thoracoscopic surgery or intrapleural enzyme therapy, respectively). The authors aimed to randomize all patients enrolled (regardless of fitness for surgery) to define a subsequent definitive randomized controlled trial. The subject is of great interest because pleural infection outcomes are poor (2), despite the broad-spectrum antibiotics and invasive treatment (3), and better acute management is needed.

MIST-3 is evaluating which is preferable: surgical thoracoscopy or intrapleural enzyme therapy with tissue plasminogen activator and DNase. However, medical thoracoscopy has recently been proposed as an effective and safe minimally invasive technique for the treatment of complicated parapneumonic effusion and empyema (4), mainly in frail patients (e.g., elderly with comorbidities) who cannot undergo general anesthesia and surgical procedures (5). Although current guidelines do not recommend medical thoracoscopy for pleural empyema (3), we believe this is already a best standard pneumological practice in tertiary care hospitals, and this option could be considered for MIST-3 as a possible arm when available 24/7.

As the authors mention, strengths of the MIST-3 study include standardized pleural infection diagnostic criteria and definition of treatment failure. Pleural infection was defined when pleural fluid on sampling was macroscopically purulent, positive on Gram staining or culture for bacterial infection, or with a pH 7.2 (1, 3). Randomization of patients was stratified by baseline RAPID risk score (renal, age, fluid purulence, infection source, dietary albumin score) (6), and a mixed-effects model adjusting for treatment and RAPID category was fitted for continuous outcomes (1). This stratification approach, however, did not include ultrasound evaluation, and ultrasound was not considered in the staging of the patients (2). Ultrasound features are crucial for pleural empyema classification into different stages: an exudative phase (free-flowing effusion), a fibrinopurulent phase (fibrin deposition over the pleural surface and viscous effusion with tendency to loculate), and an organizing phase (fibrous thickening of the visceral pleura with fibrous pleural adhesions causing trapped lung) (2). The efficacy and safety of pleural empyema treatment have recently been assessed after patient stratification by chest ultrasound, and significant differences in terms of outcome and response to treatment have been found to be related to different ultrasound features of pleural effusion (4, 5). We understand that planning for a phase III MIST-3 (possibly at an international level) is underway, and we propose that ultrasonography should be included in the early evaluation of all patients with pleural infection and that medical thoracoscopy should be considered as one additional arm where the procedure is currently available.

Originally Published in Press as DOI: 10.1164/rccm.202402-0412LE on July 11, 2024

Author disclosures are available with the text of this letter at www.atsjournals.org.
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References

1. Bedawi EO Stavroulias D Hedley E Blyth KG Kirk A De Fonseka D et al. 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 Am J Respir Crit Care Med 2023 208 1305 1315 37820359
2. Bedawi EO Ricciardi S Hassan M Gooseman MR Asciak R Castro-Añón O et al. ERS/ESTS statement on the management of pleural infection in adults Eur Respir J 2023 61 2201062 36229045
3. Roberts ME Rahman NM Maskell NA Bibby AC Blyth KG Corcoran JP et al. British Thoracic Society guideline for pleural disease Thorax 2023 78 1143 1156 37553157
4. Brutsche MH Tassi GF Gyorik S Gokcimen M Renard C Marchetti GP et al. Treatment of sonographically stratified multiloculated thoracic empyema by medical thoracoscopy Chest 2005 128 3303 3309 16304276
5. Ravaglia C Ghirotti C Puglisi S Piciucchi S Gurioli C Fabbri E et al. Medical thoracoscopy and intrapleural fibrinolytic therapy for the management of pleural empyema: a cohort study Respiration 2023 102 46 54 36398454
6. Corcoran JP Psallidas I Gerry S Piccolo F Koegelenberg CF Saba T et al. Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study Eur Respir J 2020 56 2000130 32675200
