Outcomes of intrapleural fibrinolytic and deoxyribonuclease therapy in pleural infection: a systematic review and meta-analysis

Pleural infection remains a common problem with significant associated morbidity and mortality. The current treatment paradigm for pleural infection appears to be shifting as more recent data have suggested that the use of intrapleural fibrinolytic therapy (IPFT) may be adequate for treatment, potentially avoiding the need for surgical intervention in a significant number of patients. The previous Multicenter Intrapleural Sepsis Trial demonstrated improved outcomes when utilizing combined IPFT, however, more recently alterations in this dosing regimen have been explored. Successful retrospective studies have examined the role of extended dosing (more than six sequential doses), concurrent dosing (instilling both medications together as opposed to separate medication dwell times), and daily dosing of intrapleural medications. Although the use of IPFT is likely shifting the management of pleural infection to less surgical intervention, the optimal dosing strategy of intrapleural therapy remains undefined. Within the last few years more data on variations of IPFT have emerged. This data remains of lower quality because of its retrospective nature and future prospective evaluation is required to further define the optimal dosing regimen for IPFT in complicated pleural space infections.

Comparing the outcomes of intrapleural fibrinolytic and DNase therapy versus intrapleural fibrinolytic or DNase therapy: A systematic review and meta-analysis

Intrapleural fibrinolytic therapy for loculated malignant pleural effusion: A systematic review and meta-analysis.

BackgroundPleural infection remains common with an increasing incidence. It is associated with a high morbidity and mortality. Despite chest tube drainage and antibiotic therapy up to 30% of patients will...

Rationale: Pleural infection is frequently encountered in clinical practice and is associated with high morbidity and mortality. Limited evidence exists regarding the optimal treatment. Although both early medical thoracoscopy (MT) and tube thoracostomy with intrapleural instillation of tissue plasminogen activator and human recombinant deoxyribonuclease are acceptable treatments for patients with complicated pleural infection, there is a lack of comparative data for these modes of management.Objectives: The aim of this study was to compare the safety and efficacy of early MT versus intrapleural fibrinolytic therapy (IPFT) in selected patients with multiloculated pleural infection and empyema.Methods: This was a prospective multicenter, randomized controlled trial involving patients who underwent MT or IPFT for pleural infection. The primary outcome was the length of hospital stay after either intervention. Secondary outcomes included the total length of hospital stay, treatment failure, 30-day mortality, and adverse events.Results: Thirty-two patients with pleural infection were included in the study. The median length of stay after an intervention was 4 days in the IPFT arm and 2 days in the MT arm (P = 0.026). The total length of hospital stay was 6 days in the IPFT arm and 3.5 days in MT arm (P = 0.12). There was no difference in treatment failure, mortality, or adverse events between the treatment groups, and no serious complications related to either intervention were recorded.Conclusions: When used early in the course of a complicated parapneumonic effusion or empyema, MT is safe and might shorten hospital stays for selected patients as compared with IPFT therapy. A multicenter trial with a larger sample size is needed to confirm these findings.Clinical trial registered with ClinicalTrials.gov (NCT02973139).

Intrapleural fibrinolytic therapy (IPFT), also known as intrapleural enzymatic therapy (IET), has been utilized for decades to treat pleural infections by expediting drainage in patients with pleural organization. The successful MIST2 trial demonstrated that IPFT improves pleural opacification, reduces hospital stays, and decreases short-term surgical referrals. Despite significant progress, gaps remain in identification of the optimal fibrinolytic agents, dosing, and safety improvements. IPFT is generally recommended for patients with loculation and failed pleural drainage, with a consensus panel advocating for combined tissue plasminogen activator (tPA) and DNase therapy. How each agent may affect the activity or function of the other in the combination remains unclear. While IPFT can reduce the need for surgical intervention, there are relatively few comparative clinical trials to guide initial therapy. Emerging low-dose IPFT treatment approaches may benefit patients who are poor surgical candidates. Personalized IPFT candidate approaches, such as the Fibrinolytic Potential Assay (FPA), could refine dosing and improve outcomes. Additionally, biomarkers like pleural fluid PAI-1 and suPAR concentrations may predict clinical outcomes and guide treatment. New therapeutic agents, including PAI-1 inhibiting peptides and mesothelial profibrogenic targets, are under investigation to enhance IPFT efficacy. These advances hold promise for improving the management of pleural infections and other forms of pleural organization.

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Intrapleural Fibrinolytics Versus Thoracic Surgery for Complicated Pleural Infections: A Systematic Review and Meta-Analysis.

ObjectiveThe aim of the present study was to assess the degree and impact of patient selection of patients with intermittent claudication undergoing supervised exercise therapy in Randomized Controlled Trials (RCTs) by describing commonly used exclusion criteria, and by comparing baseline characteristics and treatment response measured as improvement in maximum walking distance of patients included in RCTs and patients treated in standard care.MethodsWe compared data from RCTs with unselected standard care data. First, we systematically reviewed RCTs that investigated the effect of supervised exercise therapy in patients with intermittent claudication. For each of the RCTs, we extracted and categorized the eligibility criteria and their justifications. To assess whether people in RCTs (n = 1,440) differed from patients treated in daily practice (n = 3,513), in terms of demographics, comorbidity and walking capacity, we assessed between group-differences using t-tests. To assess differences in treatment response, we compared walking distances at three and six months between groups using t-tests. Differences of ≥15% were set as a marker for a clinically relevant difference.ResultsAll 20 included RCTs excluded large segments of patients with intermittent claudication. One-third of the RCTs eligibility criteria were justified. Despite, the numerous eligibility criteria, we found that baseline characteristics were largely comparable. A statistically significant and (borderline) clinically relevant difference in treatment response after three and six months between trial participants and standard care patients was found. Improvements in maximum walking distance after three and six months were significantly and clinically less in trial participants.ConclusionsThe finding that baseline characteristics of patients included in RCTs and patients treated in standard care were comparable, may indicate that RCT eligibility criteria are used implicitly by professionals when referring patients to standard physiotherapy care. The larger treatment response reported in standard physiotherapy care compared to clinical trials, might suggest that scientific studies underestimate the benefits of supervised exercise therapy in patients with intermittent claudication.

IntroductionIntroduction: Small burns with a total body surface area (TBSA) of < 20% account for the large majority (92%) of burn injury hospital admissions. Autologous skin cell suspension (ASCS) is a novel treatment for acute thermal burn injuries – including small burns -- that is associated with significantly lower donor skin requirements than split-thickness skin grafts, the traditional standard of care (SOC). The ASCS treatment indication was recently expanded from adult patients to include pediatric patients. Previously modeled analyses suggested that ASCS use is associated with a lower hospital length of stay (LOS) and costs savings versus SOC. This study evaluated whether real-world data (RWD) corroborate these findings in small burns and in both adult and pediatric populations.MethodsMethods: Data were collected from January 2019 through August 2020 from 500 facilities in the United States. Adult patients (age ≥ 21) and pediatric patients (< age 21) receiving inpatient burn treatment with ASCS were identified and matched to patients receiving SOC based on sex, age, TBSA < 20%, and comorbidities. Based on typical BEACON model outcomes, LOS was assumed to account for 70% of total costs and was used as a proxy to assess the data. LOS was assumed to cost $7,554 per day. Mean LOS and costs were calculated for the ASCS and SOC adult and pediatric cohorts. The incremental revenue associated with changes in inpatient capacity was also analyzed.ResultsResults: A total of 151 ASCS and 2,243 SOC adult cases and 19 ASCS and 341 SOC pediatric cases were identified. In adults, the SOC cohort had a higher percentage of patients with TBSA < 20% than the ASCS cohort (82.9% vs. 55.0%). For small burns, sixty-three matches were made for each adult cohort, and seven matches were made for each pediatric cohort. For adults, LOS was 18.5 days with ASCS use and 20.6 days with SOC use (difference: 2.1 days [10.2%]). For pediatrics, the ASCS LOS was 18.6 days, and the SOC LOS was 21.4 days (difference: 2.9 days [15.4%]). This difference led to cost savings of $15,587.62 per adult ASCS patient. Total cost savings with ASCS adult patients were $22,268.03 per patient. The reduced LOS with ASCS adult patients resulted in an increased capacity of 2.0 inpatients per bed per year, which was estimated to increase hospital revenue by $83,894 per burn unit bed annually. Pediatric cost results and savings were similar.ConclusionsConclusion: This RWD analysis shows that small burn treatment with ASCS is associated with reduced LOS and substantial cost savings compared with SOC in both adult and pediatric populations, supporting the validity of previous model projections. ASCS use may also significantly increase hospital revenue related to increased inpatient capacity.

Introduction: Pleural infections are a significant cause of mortality. Intrapleural fibrinolytic therapy (IPFT) utilising alteplase and dornase is a treatment option for patients unsuitable for surgery. The optimal dose of alteplase is unknown, and factors affecting treatment success in an Asian population are unclear. We sought to determine the factors affecting treatment success in Tan Tock Seng Hospital, Singapore and evaluate the efficacy of lower doses of IPFT. Method: A retrospective analysis of patients with pleural infections treated with IPFT between July 2016 and November 2023 was performed. Treatment success was defined as survival without surgery at 3 months. Data, including patient demographics; comorbidities; RAPID (renal, age, purulence, infection source and dietary factor) scores; and radiological characteristics, were extracted from medical records and analysed. Linear mixed effects model and logistic regression were performed to determine factors affecting treatment success. Results: A total of 131 cases were analysed. Of these, 51 (38.9%) reported positive pleural fluid culture, and the most common organism was Streptoccocus anginosus. Mean age was 65 years (standard deviation [SD] 15.5). Mean time from chest tube insertion to first dose of IPFT was 10.2 days (SD 11.5). Median starting dose of alteplase was 5 mg. Treatment success was reported in 112 cases (85.5%). There were no significant differences between the alteplase dose and radiological clearance. Patient age (odds ratio [OR] 0.94, confidence interval [CI] 0.89–0.98) and interval between chest tube insertion to first dose (OR 0.95, CI 0.91–0.99) were statistically significant variables for the treatment success. Conclusion: Lower starting doses of alteplase remain effective in the treatment of pleural infection. Early IPFT may result in better outcomes.

Tunneled Pleural Catheters for the Treatment of Patients With Pleural Infection and a Nonexpandable Lung: A Single-Center Case Series

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