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This review discusses the substantial advances that have been made in our understanding of pleural biology and related pathophysiology, as well as in the epidemiology and treatment of parapneumonic effusions, empyema, and malignant pleural effusions.

Background Aggregatibacter species are Gram-negative bacteria typically recognized as oral saprophytes in humans, with invasive infections uncommon in immunocompetent individuals. To the best our knowledge, this is the first reported case of subdural empyema attributed to Aggregatibacter segnis ( A. segnis ). Case presentation A 50-year-old female was transferred to our hospital from a local facility due to headache, fever, and left-sided limb numbness. Initially suspected of subdural hematoma and viral encephalitis, she did not respond well to prior treatment. Cerebral computed tomography and magnetic resonance imaging revealed a subdural lesion in the frontal-temporal region and sinusitis. Virus-related tests, smear, and culture of cerebrospinal fluid (CSF) were negative. Craniotomy was performed to evacuate the subdual empyema, and A. segnis was detected in the culture of pus. The discrepancy between metagenomic next-generation sequencing (mNGS) and culture highlights diagnostic challenges in this pretreated patient. Antibiotic treatment was guided by culture results and mNGS. Clinical symptoms resolved gradually following surgery and administration of antibiotics. Conclusions This rare case suggested that A. segnis should be considered in the diagnosis of subdural empyema. Multimodal diagnostics, prompt neurosurgical management, and individualized antimicrobial stewardship are crucial in managing rare central nervous system infections.

Background Incidence of childhood complicated community acquired pneumonia (cCAP) is increasing worldwide. Necrotising pneumonia (NP), empyema and complicated parapneumonic effusion (CPPE) are the most common local complications. Methods This retrospective observational study describes clinical characteristics, aetiology and management of children hospitalized with cCAP in one of the largest tertiary centers in Egypt, over 5 years (December 2017 till September 2022). Results A total of 158 cases were identified. Seasonal variation was observed, as more cases were hospitalized during Winter and Spring. NP, empyema and CPPE, were diagnosed in 85 (54%), 52 (33%) and 21 (13%) children, respectively. 54 (64%) of children presented with NP had associated empyema or CPPE. The yield of pleural fluid, sputum and blood cultures were 23%, 18% and 17%, respectively. Community acquired MRSA was the predominant causative organism, followed by S pneumoniae . 87% of the patients had pleural interventions. 29 (18%) children received fibrinolytics. Three children presented with CAP and highly septated effusion, developed NP and persistent air leaks following fibrinolytic administration. Patients had prolonged hospitalization (median 17 days). 15 (10%) children had surgery. Children presented with NP had more morbidities and longer length of hospital stay, compared to children presented with CPPE and empyema. ICU admission, mechanical ventilation, severe anemia requiring blood transfusion, broncho-pleural fistula and surgical interventions were significantly higher in NP cohort. We report 5 mortalities, 4 of them below 1 year of age. Conclusions This study describes the largest cohort of children hospitalized with cCAP from Egypt till this date. Management of cCAP remains challenging worldwide and the current guidelines requires updating. Improvement of microbial detection and reporting is needed to promote antimicrobial stewardship.

Abstract Rationale Intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) therapy for pleural infection given at the time of diagnosis has been shown to significantly improve radiological outcomes. Published cases are limited to only a single randomized controlled trial and a few case reports. Objectives Multinational observation series to evaluate the pragmatic “real-life” application of tPA/DNase treatment for pleural infection in a large cohort of unselected patients. Methods All patients from eight centers who received intrapleural tPA/DNase for pleural infection between January 2010 and September 2013 were included. Measured outcomes included treatment success at 30 days, volume of pleural fluid drained, improvement in radiographic pleural opacity and inflammatory markers, need for surgery, and adverse events. Measurements and Main Results Of 107 patients treated, the majority (92.3%) were successfully managed without the need for surgical intervention. No patients died as a result of pleural infection. Most patients (84%) received tPA/DNase more than 24 hours after failing to respond to initial conservative management with antibiotics and thoracostomy. tPA/DNase increased fluid drained from a median of 250 ml (interquartile range [IQR], 100–654) in the 24 hours preceding commencement of intrapleural therapy to 2,475 ml (IQR 1,800–3,585) in the 72 hours following treatment initiation (P < 0.05). We observed a corresponding clearance of pleural opacity on chest radiographs from a median of 35% (IQR 25–31) to 14% (7–28) of the hemithorax (P < 0.001), as well as significant reduction in C-reactive protein (P < 0.05). Pain necessitating escalation of analgesia occurred in 19.6% patients, and nonfatal bleeding occurred in 1.8%. Conclusions This large series of patients who received intrapleural tPA/DNase therapy provides important evidence that the treatment is effective and safe, especially as a “rescue therapy” in patients who do not initially respond to antibiotics and thoracostomy drainage.

Background Video-assisted thoracic surgery decortication for phase 3 thoracic empyema is widely accepted, but its optimal timing has not been established. We aim to investigate and assess this timing, in terms of overall survival, for chronic empyema. Methods Two hundred four patients with pneumonia-caused phase 3 empyema were treated with video-assisted thoracic surgery decortication over 10-years at Changhua Christian Hospital. The 90-day post-operative survival status was analyzed, and we compared the survivor group versus the non-survivor group. A receiver operating characteristic curve was used to identify the optimal decortication timing. Results A comparison between survivors and non-survivors showed statistical differences among age ( p =0.004), presence of cardiovascular disease ( p =0.018), presence of end-stage renal disease ( p =0.002), duration to surgery ( p =0.013), length of intensive care unit stay ( p =0.010), and overall length of hospital stay ( p =0.015). ROC curve analysis determined the cut-off for video-assisted thoracic surgery decortication, based on optimal 90-day post-operative survival, to be 7.5 days after hospitalization; mortality increases threefold thereafter (14.2% vs 44.6%, p <0.001). Multivariate analysis revealed that age, end-stage renal disease, pleural effusion pH≦7.2 and duration to surgery >7.5 days negatively impacted 90-day post-operative survival. Conclusions Patients receiving decortication surgery within 7.5 days of hospital admission had better overall survival.

In this randomized trial involving 454 patients with pleural infections that required antibiotic therapy and chest-tube drainage, there was no benefit from the use of intrapleural streptokinase in terms of survival, the need for surgery, the length of the hospital stay, or the resolution of radiographic abnormalities. In this trial involving 454 patients with pleural infections, there was no benefit from the use of intrapleural streptokinase in terms of survival, the need for surgery, the length of the hospital stay, or the resolution of radiographic abnormalities. Pleural infection develops in about 65,000 patients each year in the United States and the United Kingdom. 1 Approximately 15 percent of patients die, 2 which is similar to the death rate among patients hospitalized with pneumonia, 3 , 4 and 15 to 40 percent require surgical drainage of the infected pleural space. 2 , 5 The median duration of inpatient care is 15 days, with 20 percent of patients remaining in the hospital for a month or longer. 2 Apart from antibiotic therapy, treatment in patients with pleural infection consists mainly of drainage of the infected pleural fluid, and the intrapleural administration of fibrinolytic drugs is . . .

Background Fungal empyema is an uncommon disease and is associated with a high mortality rate. Surgical intervention is suggested in stage II and III empyema. However, there were no studies that reported the outcomes of surgery for fungal empyema. Methods This study is a retrospective analysis in a single institute. Patients with empyema thoracis who underwent thoracoscopic decortication between January 2012 and December 2021 were included in the study. We separated the patients into a fungal empyema group and a bacterial empyema group according to culture results. We used 1:3 propensity score matching to reduce selection bias. Results There were 1197 empyema patients who received surgery. Of these, 575 patients showed positive culture results and were enrolled. Twenty-eight patients were allocated to the fungal empyema group, and the other 547 patients were placed in the bacterial empyema group. Fungal empyema showed significantly longer intensive care unit stay (16 days vs. 3 days, p = 0.002), longer median ventilator usage duration (20.5 days vs. 3 days, p = 0.002), longer hospital stay duration (40 days vs. 17.5 days, p < 0.001) and a higher 30-day mortality rate (21.4% vs. 5.9%, p < 0.001). Fungal empyema revealed significantly poorer 1-year survival rate than bacterial empyema before matching (p < 0.001) but without significant difference after matching. Conclusions The fungal empyema patients had much worse surgical outcomes than the bacterial empyema patients. Advanced age and high Charlson Comorbidity Index score are independent predictors for poor prognosis. Prompt surgical intervention combined with the use of antifungal agents was the treatment choice for fungal empyema.

Purpose Subdural empyema (SDE) is a rare but potentially serious complication following chronic subdural hematoma (CSDH) evacuation. This study aimed to establish the incidence of postoperative SDE, identify risk factors for its development, characterize the bacterial pathogens involved, and evaluate optimal surgical management strategies. Methods Patients aged ≥ 15 years who underwent CSDH evacuation at the Karolinska University Hospital between 2006 and 2022 were retrospectively screened for postoperative SDE. Logistic regression analyses were used to identify predictors of SDE development and treatment failure. Results Among 2656 operations for CSDH, 37 (1.4%) resulted in postoperative SDE. Independent predictors of SDE were larger CSDH diameter (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.06 – 1.17, p  < 0.001) and Cloxacillin prophylaxis during index CSDH-surgery (OR 4.63, 95% CI 2.19 – 11.0, p  < 0.001). Hemiparesis (54%) and wound infection (30%) were the most common SDE symptoms, and fever was frequently absent. Cutibacterium acnes was the most common bacterial isolate, identified in 76% of cases. Craniotomy was more effective than burr-hole evacuation for managing SDE, with the latter showing a higher risk of reoperation (OR 11.5, 95% CI 1.72 – 230, p =  0.032). The median antibiotic treatment duration was 48 days (interquartile range 35–77). One-year mortality did not differ significantly between patients with and without SDE (8.1% vs. 12%, p =  0.618). Conclusion A larger CSDH diameter and Cloxacillin prophylaxis significantly increased the risk of postoperative SDE. Craniotomy was more effective than burr-hole evacuation for SDE management, and one-year mortality was not elevated in patients who developed an SDE.

Background A randomized controlled trial of adults with empyema recently demonstrated decreased length of stay in hospital in patients treated with intrapleurally administered dornase alfa and fibrinolytics compared to fibrinolytics alone. Whether this treatment strategy is safe and effective in children remains unknown. Methods/design This study protocol is for a superiority, placebo-controlled, parallel-design, multicenter randomized controlled trial. The participants are previously well children admitted to a children’s hospital with a diagnosis of empyema requiring chest tube insertion and fibrinolytics administered intrapleurally. Children will be randomized after the treating physician has decided that pleural drainage is required but prior to chest tube insertion. After chest tube insertion, participants in the treatment group will receive intrapleurally administered tissue plasminogen activator (tPA) 4 mg followed by dornase alfa 5 mg. Participants in the placebo group will receive tPA 4 mg followed by normal saline. Study treatments will be administered once daily for 3 days. All participants, parents or caregivers, clinicians, and research personnel will remain blinded. The primary outcome is length of stay from chest tube insertion to discharge from hospital. Secondary outcomes include time to meeting discharge criteria, chest tube duration, fever duration, need for additional procedures, adverse events, hospital readmission, cost of hospitalization, and mortality. Discussion This multicenter randomized controlled trial will assess the safety, effectiveness, and cost-effectiveness of combined treatment with dornase alfa and fibrinolytics compared to fibrinolytics alone for the treatment of empyema in children. Trial registration ClinicalTrials.gov: NCT01717742 . Registered on 8 October 2012.

Despite increasing incidence and morbidity, little evidence exists to inform the best management approach in childhood empyema. To compare chest drain with intrapleural urokinase and primary video-assisted thoracoscopic surgery (VATS) for the treatment of childhood empyema. Children were prospectively randomized to receive either percutaneous chest drain with intrapleural urokinase or primary VATS. The primary outcome was the number of hospital days after intervention. Secondary end points were number of chest drain days, total hospital stay, failure rate, radiologic outcome at 6 mo, and total treatment costs. Sixty children were recruited. The two groups were well matched for demographics; baseline characteristics; and hematologic, biochemical, and bacteriologic parameters. No significant difference was found in length of hospital stay after intervention between the two groups: VATS (median [range], 6 [3-16] d) versus urokinase (6 [4-25] d) (p = 0.311; 95% confidence interval, -2 to 1). No difference was demonstrated in total hospital stay: VATS versus urokinase (8 [4-17] d and 7 [4-25] d) (p = 0.645); failure rate: 5 (16.6%); and radiologic outcome at 6 mo after intervention in both groups. The mean (median) treatment costs of patients in the urokinase arm US dollars 9,127 (US dollars 6,914) were significantly lower than those for the VATS arm US dollars 11,379 (US dollars 10,146) (p < 0.001). There is no difference in clinical outcome between intrapleural urokinase and VATS for the treatment of childhood empyema. Urokinase is a more economic treatment option compared with VATS and should be the primary treatment of choice. This study provides an evidence base to guide the management of childhood empyema.