Surgery versus intrapleural fibrinolysis for management of complicated pleural infections: a systematic review and meta-analysis.

BACKGROUND: Complicated pleural infection comprises of complex effusions and empyema. When tube thoracostomy is ineffective, treatment options include surgical drainage, deloculation and decortication or intrapleural fibrinolysis. We performed a systematic review and meta-analysis to examine which technique is superior in treating complicated pleural infections. METHODS: PubMed, MEDLINE and EMBASE databases were searched for studies published between January 2000 to July 2023 comparing surgery and intrapleural fibrinolysis for treatment of complicated pleural infection. The primary outcome was treatment success. Secondary outcomes included hospital length of stay, chest drain duration and in-hospital mortality. RESULTS: Surgical management of complicated pleural infections was more likely to be successful than intrapleural fibrinolysis (RR 1.18; 95% CI 1.02, 1.38). Surgical intervention group benefited from statistically significant shorter hospital length of stay (MD: 3.85; 95% CI 1.09, 6.62) and chest drain duration (MD: 3.42; 95% CI 1.36, 5.48). There was no observed difference between in-hospital mortality (RR: 1.00; 95% CI 0.99, 1.02). CONCLUSION: Surgical management of complicated pleural infections results in increased likelihood of treatment success, shorter chest drain duration and hospital length of stay in the adult population compared with intrapleural fibrinolysis. In-hospital mortality did not differ. Large cohort and randomized research need to be conducted to confirm these findings.

Management of patient with Fusobacterim nucletum related pleural empyema: intrapleural antibiotic therapy can be considered for salvage therapy.

Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.

Development of a multivariable prediction model for prolonged air leak after lung resection.

OBJECTIVES: Prolonged air leak (PAL) is a common complication of lung resection. Research on predictors of PAL using a digital drainage system (DDS) remains insufficient. In this study, we investigated the predictive factors of PAL to establish a novel early postoperative prediction model for PAL. METHODS: A retrospective cohort study and validation study were conducted. We examined patients who underwent lung resection with DDS at our institute. The relationship between the clinical factors and measurements of the DDS, including the difference between the set and measured intrapleural pressure (named: additional negative pressure [ANP]) at postoperative hour (POH) 3, with PAL was analyzed. RESULTS: A total of 494 patients were enrolled, 29 of whom had PAL. Percent forced expiratory volume in 1 s <60%, ANP <1 cmH2O, air leak flow >20 mL/min and pleural adhesion findings at surgery were independent predictors of PAL according to a multivariable analysis. The PAL rate was clearly stratified according to our novel risk scoring system, which simply notes the presence of the above four factors, that is, the rate increases when the score increases. The area under the curve (AUC) of the receiver operating characteristic (ROC) analysis for this scoring system was 0.818. Analysis of the validation cohort (n = 133) revealed that this scoring system showed a sufficient ability to predict PAL. CONCLUSIONS: ANP at POH 3 is an independent predictor of PAL. Thus, the risk-scoring system proposed in this study is useful for predicting PAL in the early postoperative period.

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).

Intrapleural Fibrinolytic Interventions for Retained Hemothoraces in Rabbits.

Bleeding within the pleural space may result in persistent clot formation called retained hemothorax (RH). RH is prone to organization, which compromises effective drainage, leading to lung restriction and dyspnea. Intrapleural fibrinolytic therapy is used to clear the persistent organizing clot in lieu of surgery, but fibrinolysin selection, delivery strategies, and dosing have yet to be identified. We used a recently established rabbit model of RH to test whether intrapleural delivery of single-chain urokinase (scuPA) can most effectively clear RH. scuPA, or single-chain tissue plasminogen activator (sctPA), was delivered via thoracostomy tube on day 7 as either one or two doses 8 h apart. Pleural clot dissolution was assessed using transthoracic ultrasonography, chest computed tomography, two-dimensional and clot displacement measurements, and gross analysis. Two doses of scuPA (1 mg/kg) were more effective than a bolus dose of 2 mg/kg in resolving RH and facilitating drainage of pleural fluids (PF). Red blood cell counts in the PF of scuPA, or sctPA-treated rabbits were comparable, and no gross intrapleural hemorrhage was observed. Both fibrinolysins were equally effective in clearing clots and promoting pleural drainage. Biomarkers of inflammation and organization were likewise comparable in PF from both groups. The findings suggest that single-agent therapy may be effective in clearing RH; however, the clinical advantage of intrapleural scuPA remains to be established by future clinical trials.

Targeting drug or gene delivery to the phrenic motoneuron pool.

Phrenic motoneurons (PhrMNs) innervate diaphragm myofibers. Located in the ventral gray matter (lamina IX), PhrMNs form a column extending from approximately the third to sixth cervical spinal segment. Phrenic motor output and diaphragm activation are impaired in many neuromuscular diseases, and targeted delivery of drugs and/or genetic material to PhrMNs may have therapeutic application. Studies of phrenic motor control and/or neuroplasticity mechanisms also typically require targeting of PhrMNs with drugs, viral vectors, or tracers. The location of the phrenic motoneuron pool, however, poses a challenge. Selective PhrMN targeting is possible with molecules that move retrogradely upon uptake into phrenic axons subsequent to diaphragm or phrenic nerve delivery. However, nonspecific approaches that use intrathecal or intravenous delivery have considerably advanced the understanding of PhrMN control. New opportunities for targeted PhrMN gene expression may be possible with intersectional genetic methods. This article provides an overview of methods for targeting the phrenic motoneuron pool for studies of PhrMNs in health and disease.

Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) Study-2: Use of 2.5 mg alteplase as a starting intrapleural dose.

BACKGROUND AND OBJECTIVE: Intrapleural tissue plasminogen activator/deoxyribonuclease (tPA/DNase) therapy is increasingly used in pleural infection. Bleeding risks and costs associated with tPA remain the clinical concerns. Our dose de-escalation series aims to establish the lowest effective dosing regimen for tPA/DNase. This study assesses the intrapleural use of 2.5 mg tPA/5 mg DNase for pleural infection. METHODS: Consecutive patients with pleural infection treated with a starting regime of 2.5 mg tPA/5 mg DNase were included from two centres in Australia and UK. Escalation of tPA dose was permitted if clinical response was inadequate. RESULTS: Sixty-nine patients (mean age 61.0 years) received intrapleural 2.5 mg tPA/5 mg DNase. Most (88.4%) were treated successfully and discharged from hospital without surgery by 90 days. Patients received a median of 5 [interquartile range [IQR] = 3-6] doses of tPA/DNase. Total amount of tPA used per patient was 12.5 mg [median, IQR = 7.5-15.0]. Seventeen patients required dose escalation of tPA; most (n = 12) for attempted drainage of distant non-communicating locule(s). Treatment success was corroborated by clearance of pleural opacities on radiographs (from median 27.0% [IQR = 17.1-44.5] to 11.0% [IQR = 6.4-23.3] of hemithorax, p < 0.0001), increased pleural fluid drainage (1.98 L [median, IQR = 1.38-2.68] over 72 h following commencement of tPA/DNase) and reduction of serum C-reactive protein level (by 45.0% [IQR = 39.3-77.0] from baseline at day 5, p < 0.0001). Two patients required surgery. Six patients with significant comorbidities (e.g., advanced cancer) had ongoing infection when palliated and died. Two patients experienced self-limiting pleural bleeding and received blood transfusion. CONCLUSION: A starting intrapleural regime of 2.5 mg tPA/5 mg DNase, with up-titration if needed, can be effective and deserves further exploration.

Modified regimen intrapleural alteplase with pulmozyme in pleural infection management: a tertiary teaching hospital experience.

BACKGROUND: Current management of poorly draining complex effusions favours less invasive image-guided placement of smaller tubes and adjunctive intrapleural fibrinolysis therapy (IPFT). In MIST-2 trial, intrapleural 10 mg alteplase (t-PA) with 5 mg of pulmozyme (DNase) twice daily for 72 h were used. We aimed to assess the effectiveness and safety of a modified regimen 16 mg t-PA with 5 mg of DNase administered over 24 h in the management of complex pleural infection. METHODS: This was a single centre, prospective study involving patients with poorly drained pleural infection. Primary outcome was the change of pleural opacity on chest radiograph at day 7 compared to baseline. Secondary outcomes include volume of fluid drained, inflammatory markers improvement, surgical referral, length of hospitalisation, and adverse events. RESULTS: Thirty patients were recruited. Majority, 27 (90%) patients were successfully treated. Improvement of pleural opacity on chest radiograph was observed from 36.9% [Interquartile range (IQR 21.8-54.9%)] to 18.1% (IQR 8.8-32.7%) of hemithorax (P < 0.05). T-PA/DNase increased fluid drainage from median of 45 mls (IQR 0-100) 24 h prior to intrapleural treatment to 1442 mls (IQR 905-2360) after 72 h; (P < 0.05) and reduction of C-reactive protein (P < 0.05). Pain requiring escalation of analgesia affected 20% patients and 9.9% experienced major adverse events. None required surgical intervention. CONCLUSION: This study suggests that a modified regimen 16 mg t-PA with 5 mg DNase can be safe and effective for patients with poorly drained complex pleural infection. Trial registration The study was registered retrospectively on 07/06/2021 with ClinicalTrials number NCT04915586 ( https://clinicaltrials.gov/ct2/show/NCT04915586 ).

Safety and efficacy of vacuum bottle plus catheter for drainage of iatrogenic pneumothorax.

BACKGROUND: Iatrogenic pneumothorax is common after thoracic procedures. For patients with pneumothorax larger than 15%, simple aspiration is suggested. Although vacuum bottle plus non-tunneled catheter drainage has been performed in many institutions, its safety and efficacy remain to be assessed. METHODS: Through this prospective cohort study (NCT03724721), we evaluated the safety and efficacy of vacuum bottle plus non-tunneled catheter drainage. Patients older than 20 years old who developed post-procedural pneumothorax were enrolled. A non-tunneled catheter was placed at the intersection of the midclavicular line and the second intercostal space. A 3-way stopcock, a drainage set, and a digital pressure gauge were connected. The stopcock was manipulated to connect the pleural space to the pressure gauge for measurement of end-expiration intrapleural pressure or to the vacuum bottle for air drainage. The rate of successful drainage, the end-expiration intrapleural pressure before, during, and after the procedure and the duration of hospitalization were recorded. RESULTS: From August 2018 to February 2020, 21 patients underwent vacuum bottle plus catheter drainage (intervention group) and 31 patients received conservative treatment (control group). The end-expiration intrapleural pressure of all patients remained less than - 20 cmH2O during drainage. No procedure related complication was observed. Large pneumothorax (≥ 15%) was associated with higher risk of persistent air leak (Odds ratio 12, 95% CI 1.2-569.7). Vacuum bottle assisted air drainage yielded shorter event-free duration than that of conservative treatment (2 days vs 5 days [interquartile range 1-4 days vs 3-7 days], p < .05). Vacuum bottle assisted air drainage also help identifying patients with persistent pneumothorax and necessitate the subsequent management. The event-free duration of persistent air leak in the intervention group was also comparable with that of conservative treatment (5 days vs 5 days [interquartile range 5-8 days vs 3-7 days], p = .45). CONCLUSIONS: Vacuum bottle plus catheter drainage of iatrogenic pneumothorax is a safe and efficient procedure. It may be considered as an alternative management of stable post-procedural pneumothorax with size larger than 15%. Trial registration The study protocol was approved by the Research Ethics Committee of National Taiwan University Hospital (No. 201805105DINA) on 6th August, 2018. The first participant was enrolled on 23rd August, 2018 after Research Ethics Committee approval. This clinical trial complete registration at U.S. National Library of Medicine clinicaltrials.gov with identifier NCT03724721 and URL: https://clinicaltrials.gov/ct2/show/NCT03724721 on 30th October, 2018.

Modified application of vacuum-assisted closure in thoracic surgery patients.

OBJECTIVE: Surgical site infection (SSI), ranging from superficial, deep and to organ space, is one of the major predictors for morbidity and mortality in patients undergoing thoracic surgery. Care to accelerate SSI healing is taken to shorten hospital stay and reduce costs. The deep application of vacuum-assisted closure (VAC) in thoracic patients is not well established in the literature. In this study, the deep application and safety of VAC therapy in patients with various thoracic pathologies was evaluated. METHOD: A retrospective chart review of all patients who were admitted to the thoracic surgery service between July 2014 and July 2018 and who developed deep SSI was carried out. RESULTS: A total of 12 patients were included, and their demographic data analysed. There were various thoracic pathologies complicated with postoperative deep SSI treated with VAC. The duration of VAC application ranged from 4-40 days with an average hospital stay of 37.6 days. All patients showed clinical, radiological and microbiological improvement rather than developing complications except for one case of mortality due to septicaemia. CONCLUSION: In this study, partial intrapleural VAC therapy was safe for use in patients who underwent thoracic surgery, regardless of the underling pathology, with caution (i.e., with continued monitoring of the patient's tolerance to the treatment). The overall hospital stay may be reduced with the use of VAC. It also decreased perioperative morbidity, secondary to wound infection.

Update on Novel Targeted Therapy for Pleural Organization and Fibrosis.

Pleural injury and subsequent loculation is characterized by acute injury, sustained inflammation and, when severe, pathologic tissue reorganization. While fibrin deposition is a normal part of the injury response, disordered fibrin turnover can promote pleural loculation and, when unresolved, fibrosis of the affected area. Within this review, we present a brief discussion of the current IPFT therapies, including scuPA, for the treatment of pathologic fibrin deposition and empyema. We also discuss endogenously expressed PAI-1 and how it may affect the efficacy of IPFT therapies. We further delineate the role of pleural mesothelial cells in the progression of pleural injury and subsequent pleural remodeling resulting from matrix deposition. We also describe how pleural mesothelial cells promote pleural fibrosis as myofibroblasts via mesomesenchymal transition. Finally, we discuss novel therapeutic targets which focus on blocking and/or reversing the myofibroblast differentiation of pleural mesothelial cells for the treatment of pleural fibrosis.

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

BACKGROUND: Multiple studies describing the benefits of intrapleural fibrinolytic over placebo and DNase therapy have been published, but few have been published on intrapleural fibrinolytic and DNase therapy. OBJECTIVE: Our meta-analysis aims to compare the outcomes of surgical intervention, mortality, and hospital length of stay between intrapleural fibrinolytic and DNase therapy with either intrapleural fibrinolytic or DNase therapy alone in patients with pleural space infections. METHODS: We searched Pubmed, EMBASE, Web of Science, and Cochrane library databases for observational studies and randomized controlled trials (RCTs) containing comparative data for hospitalized adults and children with pleural infections receiving intrapleural therapy of fibrinolytic and DNase versus those receiving intrapleural fibrinolytic or DNase alone. Meta-analysis was performed using the Review Manager software, and heterogeneity was tested using I2 statistics. RESULTS: A total of 2 cohorts and 2 RCTs involving 362 adult and children was included. There was significant reduction in surgical intervention requirement among patients who received intrapleural fibrinolytic and DNase (OR 0.30; 95% CI 0.11-0.83; I2 = 31%; P = 0.02) than those receiving either intrapleural fibrinolytic or DNase alone. No difference was observed for mortality (OR 0.72; 95% CI 0.31-1.71; I2 = 0%; P = 0.46) and complication rates (OR 3.09; 95% CI 0.75-12,74; I2 = 54%; P = 0.12). The hospital length of stay (mean 13.70 vs. 16.67 days; P = 0.19) and duration of chest tube drainage (mean 6.47 vs. 6.30 days; P = 0.58) was similar between the two groups. CONCLUSION: Combination of intrapleural fibrinolytic and DNase, compared to single-agent intrapleural therapy alone, is associated with a lesser need for surgical interventions. However, no difference was found in mortality, hospital length of stay, and chest tube drainage duration.

Medical thoracoscopy treatment for pleural infections: a systematic review and meta-analysis.

BACKGROUND: Complicated parapneumonic effusions and empyema represent advanced stages of pleural infections and are characterized by a high mortality. Medical thoracoscopy is a safe and minimally invasive endoscopic technique prescribed to treat severe pleural infections. However, only a few studies evaluated its success rate. A systematic review of observational studies was performed to assess the efficacy of medical thoracoscopy in patients with complicated parapneumonic effusions and empyema, as well as its predictive factors. METHODS: A search of the scientific evidence was carried out using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials. Articles describing observational studies on medical thoracoscopy in patients with parapneumonic effusions and empyema were selected. RESULTS: Eight studies met the inclusion criteria. The pooled treatment success rate of thoracoscopy was 85% (95% CI 80.0-90.0%; I2: 61.8%) when used as first-line intervention or after failure of chest tube. The pooled complication rate was 9.0% (95% CI 6.0-14.0%; I2: 58.8%). A pooled difference of treatment success of 9.0% (95% CI 1.0-18.0%) was found when post-thoracoscopy intra-pleural fibrinolysis was prescribed. Pooled success rate was higher in cases with pleural fluid culture negativity (pooled difference: 14.0%; 95% CI 4.0-24.0%). CONCLUSIONS: Medical thoracoscopy is effective and safe when prescribed for complicated parapneumonic effusions and empyema. Bacteriological negativity of pleural effusion specimens and administration of adjuvant intra-pleural fibrinolysis after the procedure are associated with a higher success rate.

[Laparothoracoscopic Ivor Lewis esophagectomy with esophageal-gastric intrapleural anastomosis]. / Metodika laparotorakoskopicheskoi ezofagektomii po tipu Ivor Lewis s neapparatnym pishchevodno-zheludochnym vnutriplevral'nym anastomozom.

OBJECTIVE: To describe the methodology of laparothoracoscopic Ivor Lewis esophagectomy in surgical treatment of esophageal cancer and compare early outcomes of this procedure with conventional Ivor Lewis surgery. MATERIAL AND METHODS: There were 30 laparothoracoscopic Ivor Lewis esophagectomies followed by non-hardware esophageal-gastric intrapleural anastomosis for esophageal cancer. All procedures have been performed for the period 2016-2019 at the Moscow Regional Research and Clinical Institute (suturing of anastomosis was based on the method of professor A.S. Allakhverdyan). RESULTS: Laparothoracoscopic esophagectomy is characterized by higher surgery time by 136.57 min (p=0.012), less duration of anesthesia and mechanical ventilation by 77.5 min (p=0.042), postoperative ICU-stay by 2.25 hours (p=0.021), blood loss by 550 ml (p=0,000), duration of postoperative fasting by 2 days (p=0.034), hospital-stay by 8 days (p=0.021) compared to open esophagectomy. There were no significant between-group differences in the number of resected lymph nodes (p=0.142). Incidence of esophageal-gastric anastomosis failure is insignificantly higher in the OE group (χ2=1.89; p=0.075). Incidence of pulmonary complications (pneumonia, chylothorax, paresis of the vocal cords, pleural empyema) is less in the LTSE group (p<0.05). Cardiovascular morbidity is significantly lower in the LTSE group (p<0.05). A 30-day mortality rate was similar in both groups (χ2=2.56; p=0.0253). CONCLUSION: Early results of laparothoracoscopic Ivor Lewis esophagectomy are superior to the results of conventional Ivor Lewis surgery in surgical treatment of esophageal cancer.

Fritz Rohrer (1888-1926), a pioneer in pulmonary mechanics whose work was inexplicably ignored for about 30 years.

Fritz Rohrer (1888-1926) has a special place in the history of respiratory physiology for two reasons. The first is that he laid the foundations of modern pulmonary mechanics in the early 1900s. For example, his seminal paper on pulmonary dynamics, that is, the pressure-flow relationships in the airways, was published in 1915 in one of the top journals in the field. It included extensive measurements of airway dimensions in postmortem human lungs and a sophisticated analysis of the modes of airflow. This was closely followed by a very original analysis of lung statics, which included studies of airway pressures at normal, maximal, and minimal lung volumes in relaxed normal volunteers, and was published in 1916. Remarkably, both papers were essentially ignored at the time. Fortunately, in 1925 he was able to summarize his major findings in a chapter in an important handbook of physiology. However, he tragically died from pulmonary tuberculosis in the following year at the early age of 37. The second reason for his importance in the history of pulmonary mechanics is that inexplicably his very innovative research was essentially ignored for about 30 years. It was not until the 1940s that his work was rediscovered, although not in time to save investigators from duplicating his very original studies. Possible reasons why his work was ignored for so long are discussed. Even today it is not easy to recover some important features of his career, and some aspects of his very original research are still almost unknown.

Phase I Study of Intrapleural Gene-Mediated Cytotoxic Immunotherapy in Patients with Malignant Pleural Effusion.

Gene-mediated cytotoxic immunotherapy (GMCI) is an immune strategy implemented through local delivery of an adenovirus-based vector expressing the thymidine kinase gene (aglatimagene besadenovec, AdV-tk) followed by anti-herpetic prodrug valacyclovir. A phase I dose escalation trial of GMCI followed by chemotherapy was conducted in patients with malignant pleural effusion (MPE). AdV-tk was administered intrapleurally (IP) in three cohorts at a dose of 1 × 1012 to 1013 vector particles. Primary endpoint was safety; secondary endpoints included response rate, progression-free survival, and overall survival. Nineteen patients were enrolled: median age 67 years; 14 with malignant mesothelioma, 4 non-small-cell lung cancer (NSCLC), and 1 breast cancer. There were no dose limiting toxicities. All 3 patients in cohort 2 experienced transient cytokine release syndrome (CRS). Addition of celecoxib in cohort 3 reduced the incidence and severity of CRS (none > grade 2). Three patients are alive (23-33 months after GMCI), and 3 of 4 NSCLC patients had prolonged disease stabilization; one is alive 29 months after GMCI, 3.6 years after initial diagnosis. GMCI was safe and well tolerated in combination with chemotherapy in patients with MPE and showed encouraging response. Further studies are warranted to determine efficacy.

Fluid Balance Is Associated with Clinical Outcomes and Extravascular Lung Water in Children with Acute Asthma Exacerbation.

RATIONALE: The effects of fluid administration during acute asthma exacerbation are likely unique in this patient population: highly negative inspiratory intrapleural pressure resulting from increased airway resistance may interact with excess fluid administration to favor the accumulation of extravascular lung water, leading to worse clinical outcomes. OBJECTIVES: Investigate how fluid balance influences clinical outcomes in children hospitalized for asthma exacerbation. METHODS: We analyzed the association between fluid overload and clinical outcomes in a retrospective cohort of children admitted to an urban children's hospital with acute asthma exacerbation. These findings were validated in two cohorts: a matched retrospective and a prospective observational cohort. Finally, ultrasound imaging was used to identify extravascular lung water and investigate the physiological basis for the inferential findings. MEASUREMENTS AND MAIN RESULTS: In the retrospective cohort, peak fluid overload [(fluid input - output)/weight] is associated with longer hospital length of stay, longer treatment duration, and increased risk of supplemental oxygen use (P values < 0.001). Similar results were obtained in the validation cohorts. There was a strong interaction between fluid balance and intrapleural pressure: the combination of positive fluid balance and highly negative inspiratory intrapleural pressures is associated with signs of increased extravascular lung water (P < 0.001), longer length of stay (P = 0.01), longer treatment duration (P = 0.03), and increased risk of supplemental oxygen use (P = 0.02). CONCLUSIONS: Excess volume administration leading to fluid overload in children with acute asthma exacerbation is associated with increased extravascular lung water and worse clinical outcomes.

Measurement of intrapleural pressure in patients with spontaneous pneumothorax: a pilot study.

BACKGROUND: The initial management of pneumothorax remains controversial, and we speculated that this might be because there is no method available for evaluation of air leak during initial management. We have developed a system for measurement of intrapleural pressure in pneumothorax to address air leak without the need for chest drainage. The aim of this clinical study was to confirm the ability of this measurement system and to determine the clinical impact of management of air leak. METHODS: Patients in whom need aspiration was indicated for spontaneous pneumothorax were enrolled in the study. The intrapleural pressure was measured during stable breathing and data recorded when patients were coughing were excluded. RESULTS: Eleven patients were enrolled in the study between December 2016 to July 2017. The patterns in change of intrapleural pressure varied widely depending on the state of the pneumothorax. The mean intrapleural pressure values on end-inspiration and end-expiration in patients with persistent air leak was significantly lower than those in patients without persistent air leak (p = 0.020). The number of negative mean pressure recordings in end-inspiration and end-expiration was significantly lower in patients with persistent air leak than in those without persistent air leak (p = 0.0060). CONCLUSIONS: In this study, we demonstrated that intrapleural pressure could be successfully measured and visualized in patients with pneumothorax. Whether or not the pressure value is a predictor of persistent air leak needs to be confirmed in the future.

Intrapleural alteplase therapy: what are the knowns and unknowns?

In pneumology, enzymatic properties of plasmin are used to disrupt fibrin adhesions and septations formed during pathological conditions of the pleural cavity. In that case, fibrinolytics are administrated locally via a chest tube in the pleural cavity to evacuate pathological effusion. Although the first intrapleural administration of fibrinolytic occurred seventy years ago, there has been no consensus on dosing or a uniform procedure of their application. The aim of the article is to summarize current knowledge of alteplase usage in pneumology and discuss practical aspects of its intrapleural application regarding specific possibilities in the Czech Republic.

Comparative evaluation of effects of intrapleural block with adjuvants on analgesia and pulmonary function after intercostal drainage: A pilot study.

BACKGROUND: Inter-costal chest drain (ICD) used for varied thoracic pathologies causes continuous pain and irritation of the pleura, which limits respiratory efforts and impairs ventilatory function. Intrapleural block deposits local anaesthetic between the layers of pleura and may improve ventilatory function especially in non surgical patients. METHODS: Twenty eight ASA I-III patients treated with ICD, who could perform incentive spirometry, were included for study. They were randomized to 'Group C' (control group); 'Group B' (Bupivacaine); 'Group M' (Bupivacaine + Morphine) and 'Group D' (Bupivacaine + Dexmedetomidine). The drugs were administered via the ICD itself and clamped thereafter for 15 min. The success of the block was assessed by time for first analgesic demand, maximum inspiratory volume generated and Numerical Rating Scale score for pain; by patients. RESULTS: Effective analgesia was observed in Group B, M and D. Addition of an adjuvant significantly prolonged time for rescue analgesic demand. Patients who received local anaesthetic alone or with an adjuvant had significantly improved maximal inspiratory volume and required lesser rescue analgesics. No significant complications were observed in any group. Pain relief in post-surgical patients using intraplural block is masked by systemic analgesics. However its application in patients with ICD for non surgical indications was explored in this study and was found to improve patient comfort and ventilation. CONCLUSION: Intra-pleural blockade is safe and effective in relieving the constant pleural irritation and pain of ICD, thus enabling the patient to improve ventilatory effort and faster recovery of respiratory function.