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.

Shunt Catheter Migration Due to Negative Thoracic Pressure.

Permanent cerebrospinal fluid diversion has a lengthy list of complications. We present an unusual clinical image of shunt catheter migration. A 54-year-old female had a history of subarachnoid hemorrhage that resulted in communicating hydrocephalus, which needed a ventriculoperitoneal shunt placement. On outpatient follow-up, she was found to have a sunken skin flap that was resistant to raising the shunt valve setting. A radiograph of the shunt system revealed that the peritoneal catheter had migrated into the thoracic cavity. On review of the patient's previous imaging, an area indicative of a minor pleural breach was identified that exposed the catheter to the negative thoracic pressure, which resulted in progressive catheter migration. The patient then underwent removal of the shunt system since her hydrocephalus had resolved. A pleural breach during shunt placement can result in the migration of the shunt catheter into the thoracic cavity under the effect of negative thoracic pressure.

Experience harvesting costal cartilage under IV sedation.

IMPORTANCE: While numerous techniques for costal cartilage harvesting have been described, one consistency in the published literature is that the procedure is performed under general anesthesia. This is the first report to offer IV sedation as a safe alternative to general inhalational anesthesia in cases involving costal cartilage harvesting. OBJECTIVE: To determine the feasibility and safety of costal cartilage harvest with IV sedation. DESIGN: A retrospective chart review was performed of 116 rhinoplasty patients who underwent harvest of costal cartilage grafts under IV sedation from 2005 to 2019. SETTING: Private practice of senior author (AF) at Lasky Clinical Surgical Center. PARTICIPANTS: Consecutive patients who underwent cosmetic and/or functional rhinoplasty. MAIN OUTCOME & MEASURES: The number of cases involving a pneumothorax, size of the pleural injury, radiographic findings, repair technique and treatment for pneumothorax were all recorded. RESULTS: There were 7 cases involving a pleural tear (size range 3-8 mm) during costal cartilage harvest and each of these was repaired intra-operatively. All 7 patients remained clinically stable in recovery room on 2 L of oxygen. Although clinically stable, one patient had radiologic evidence of a pneumothorax of 50%, and thus she was transferred to a hospital for placement of a Heimlich tube with overnight observation. CONCLUSIONS AND RELEVANCE: Although plenural tears can be attributed to surgical technique rather than the type of anesthesia, these cases do provide valuable insight to the fact that successful management of such complications can be accomplished without the need for general anesthesia.

Comparative Study Between Endoscopic Thyroid Surgery via the Oral Vestibular Approach and the Areola Approach.

Objective: To investigate the clinical efficacy and safety of endoscopic thyroidectomy through the oral vestibular approach and the breast approach. Methods: Retrospective analysis was done on clinical data of 80 patients who received an endoscopic thyroidectomy from April 2018 to March 2019. The research group had endoscopic thyroidectomy through the oral vestibular approach, whereas the control group had endoscopic thyroidectomy through the areola breast approach. Comparison between the two groups including intraoperative bleeding, operation time, total postoperative drainage, drainage time, postoperative sustained pain time, recovery feeding time, postoperative hospitalization duration, satisfactory esthetic outcomes of incision, central lymph node clearance, skin injury, infection incidence, and complications such as facial hematoma, subcutaneous emphysema, abnormal feeling of the neck and chest, and pleural injury was recorded. Results: There was no significant difference between the two groups in the amount of intraoperative bleeding, operation time, total postoperative drainage, drainage time, postoperative sustained pain time, recovery feeding time, and postoperative hospitalization time (P > .05). The incidence of complications such as skin injury, infection, wound hematoma, subcutaneous emphysema, abnormal feeling of the neck and chest, and pleural injury was not statistically different between the two groups (P > .05). There was no significant difference in the number of lymph nodes cleaned in the central area between the two groups (P > .05). The overall satisfaction of the patients with the cosmetic effects of the incision (100.00%) was higher than that of the control group (90.00%). Conclusions: The clinical treatment effect and safety in the two groups were similar, but the transoral group had better cosmetic effects.

[Occurrence of a lethal outcome due to iatrogenic damage of an intercostal vessel during a pleural puncture procedure]. / Nastuplenie letal'nogo iskhoda vsledstvie iatrogennogo povrezhdeniia vetvi mezhrebernoi arterii pri provedenii plevral'noi punktsii.

A rare case of a lethal outcome due to iatrogenic damage to the intercostal vessel, a collateral branch of the posterior intercostal artery, is described. The little-known features of the topography of this vessel (location on the upper edge of the underlying rib), which requires further study in the context of variable anatomy, are given. The risks associated with deviations from the traditionally recommended sites of pleural puncture (below the eighth intercostal space to the scapular line) are substantiated. An analysis of the characteristics of bleeding arising from the intercostal vessels (from two ends, under high pressure, etc.) is given, which implies the extreme importance of a timely diagnosis. Differing points of view on the legal assessment of malpractice when care is delivered by a series of doctors, and the legal necessity of determining the 'point of no return' (the latest moment after the onset of bleeding, in which medical aid can still prevent an unfavorable outcome), are considered. An opinion is expressed on the need for the active participation (initiative) of an expert in the provision of expertise.

Upper Pole Access for Prone Percutaneous Nephrolithotomy: Advantage or Risk?

OBJECTIVE: To analyze the outcomes of upper pole access during percutaneous nephrolithotomy (PCNL), an option pole often avoided due to the concern for pleural injury. METHODS: We retrospectively collected data on patients undergoing PCNL at our institution. Patients were divided into 3 groups according to access: supracostal upper calyx (group 1), subcostal upper calyx (group 2), and nonupper calyx (group 3). Preoperative imaging was reviewed to assess stone burden, Hounsfield units (HU), location, and Guy's Stone Score. Patients were considered stone-free if residual fragments were 3 mm or smaller on CT scan. RESULTS: We analyzed 329 PCNLs (left: 174; right: 155). Stones had a median size of 32 mm, 800 HU, and Guy's Stone Score of 2. Groups 1, 2, and 3 had 119, 108, and 102 patients, respectively. The 90-day complication rate was 20.4% (7.9% Clavien 3-4). Group 1 patients, with higher BMI and larger stones, had higher SFR than group 3 (89.9% vs 79.4%, P = .038), but with a significantly higher risk of complications (P = .001). Within group 1, left PCNL (7.0% vs 24.2%, P = .016) and BMI ≥30 (6.9% vs 25.0%, P = .013) carried a lower risk of chest tube insertion. There was no difference in complications between groups 2 and 3 (1.9% vs 2.9%). CONCLUSION: Upper pole access is safe and effective, particularly if done below the ribs. Supracostal access is an effective option to achieve higher stone-free rates in complex stones, while carrying a risk of significant hydrothorax, particularly on the right side and in nonobese patients.

Massive subcutaneous emphysema mimicking anaphylaxis - pathological and radiological correlations.

This report details the pathological and radiological findings in a rare case of massive subcutaneous emphysema. A 74-year-old male presented with sudden onset dyspnea and facial swelling following a fall. His symptoms were refractory to treatments for anaphylaxis, which was suspected clinically, and he quickly succumbed. Autopsy, including post mortem CT scan revealed the underlying etiology to be multiple rib fractures with rupture of the parietal pleura, bilateral pneumothoraxes and massive subcutaneous emphysema involving the face, torso and upper limbs. Multiple frothy air bubbles were observed throughout the mediastinal adipose tissues on internal examination. Our findings echo those of rare previous reports and show how subcutaneous emphysema may, in rare circumstances, mimic anaphylaxis.

Off-the-Shelf Cell Sheets as a Pleural Substitute for Closing Visceral Pleural Injuries.

During pulmonary resections, removal of visceral pleura is frequently required, resulting in lung air leakage (LAL) and bleeding. Especially persistent LAL after pulmonary surgery has negative consequences. Current surgical procedures are ineffective in closing these visceral pleural injuries. Previously, the authors' laboratory has developed a novel and effective LAL sealant using tissue-engineered cell sheets harvested from temperature-responsive culture dishes. The clinical application of fresh fibroblast sheets (FSs) is limited by several problems related to the cell culture period, mass production, preservation, and transportation. Therefore, cryopreservation of FSs and feasibility of off-the-shelf FSs for repairing visceral pleural defects were investigated. Over 3 to 6 months, harvested skin-derived FSs in Dulbecco's modified Eagle's medium supplemented with 10% dimethyl sulfoxide were stored in an atmosphere of liquid nitrogen. The amounts of cytokines (basic fibroblast growth factor [bFGF] and vascular endothelial growth factor) released from frozen-thawed FSs were determined. bFGF levels were significantly elevated in frozen-thawed FSs compared with fresh FSs. After a visceral pleural injury model was created, a frozen-thawed skin-derived FS was transplanted directly to the defect. One month after transplantation, the frozen-thawed FS remained on the pleural surface, resulting in permanent closure, suggesting that cells in the off-the-shelf FS had the ability to proliferate and release various cytokines. Frozen-thawed FSs were useful for closing LALs during pulmonary surgery as an off-the-shelf technique and would be used as a pleural substitute.

Structural heteropolysaccharides as air-tight sealants of the human pleura.

Pulmonary "air leaks," typically the result of pleural injury caused by lung surgery or chest trauma, result in the accumulation of air in the pleural space (pneumothorax). Air leaks are a major source of morbidity and prolonged hospitalization after pulmonary surgery. Previous work has demonstrated structural heteropolysaccharide (pectin) binding to the mouse pleural glycocalyx. The similar lectin-binding characteristics and ultrastructural features of the human and mouse pleural glycocalyx suggested the potential application of these polymers in humans. To investigate the utility of pectin-based polymers, we developed a simulacrum using freshly obtained human pleura. Pressure-decay leak testing was performed with an inflation maneuver that involved a 3 s ramp to a 3 s plateau pressure; the inflation was completely abrogated after needle perforation of the pleura. Using nonbiologic materials, pressure-decay leak testing demonstrated an exponential decay with a plateau phase in materials with a Young's modulus less than 5. In human pleural testing, the simulacrum was used to test the sealant function of four mixtures of pectin-based polymers. A 50% high-methoxyl pectin and 50% carboxymethylcellulose mixture demonstrated no sealant failures at transpleural pressures of 60 cmH2 O. In contrast, pectin mixtures containing 50% low-methoxyl pectin, 50% amidated low-methoxyl pectins, or 100% carboxymethylcellulose demonstrated frequent sealant failures at transpleural pressures of 40-50 cmH2 O (p < 0.001). Inhibition of sealant adhesion with enzyme treatment, dessication and 4°C cooling suggested an adhesion mechanism dependent upon polysaccharide interpenetration. We conclude that pectin-based heteropolysaccharides are a promising air-tight sealant of human pleural injuries. © 2018 Wiley Periodicals, Inc. J. Biomed. Mater. Res. Part B, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 799-806, 2019.

Pressure-decay testing of pleural air leaks in intact murine lungs: evidence for peripheral airway regulation.

The critical care management of pleural air leaks can be challenging in all patients, but particularly in patients on mechanical ventilation. To investigate the effect of central airway pressure and pleural pressure on pulmonary air leaks, we studied orotracheally intubated mice with pleural injuries. We used clinically relevant variables - namely, airway pressure and pleural pressure - to investigate flow through peripheral air leaks. The model studied the pleural injuries using a pressure-decay maneuver. The pressure-decay maneuver involved a 3 sec ramp to 30 cmH2 0 followed by a 3 sec breath hold. After pleural injury, the pressure-decay maneuver demonstrated a distinctive airway pressure time history. Peak inflation was followed by a rapid decrease to a lower plateau phase. The decay phase of the inflation maneuver was influenced by the injury area. The rate of pressure decline with multiple injuries (28 ± 8 cmH2 0/sec) was significantly greater than a single injury (12 ± 3 cmH2 O/sec) (P < 0.05). In contrast, the plateau phase pressure was independent of injury surface area, but dependent upon transpulmonary pressure. The mean plateau transpulmonary pressure was 18 ± 0.7 cm H2 O. Finally, analysis of the inflation ramp demonstrated that nearly all volume loss occurred at the end of inflation (P < 0.001). We conclude that the air flow through peripheral lung injuries was greatest at increased lung volumes and limited by peripheral airway closure. In addition to suggesting an intrinsic mechanism for limiting flow through peripheral air leaks, these findings suggest the utility of positive end-expiratory pressure and negative pleural pressure to maintain lung volumes in patients with pleural injuries.

Hidatidosis pulmonar complicada con apertura a vía aérea y cavidad pleural / Complicated pulmonary hydatid cyst with pleural and airway communication

No disponible

Efficacy of a sheet combined with fibrin glue in repair of pleural defect at the early phase after lung surgery in a canine model.

OBJECTIVE: Polyglycolic acid and oxidized regenerated cellulose have been widely used as a sealant for repairing pulmonary air leakage during respiratory surgery. However, fundamental research of these materials has not been sufficiently conducted. Therefore, we conducted studies to assess the pressure resistance ability of these materials using a canine visceral pleural defect model at the early phase. METHOD: The 6-mm circular defect and the 12-mm square defect were created on the visceral pleura of anesthetized beagles. These defects were then repaired using one of four methods: method A using polyglycolic acid and fibrin glue; method B using oxidized regenerated cellulose and fibrin glue; method C using oxidized regenerated cellulose; method D using fibrin glue. Airway pressure was measured as bursting pressure when air leakage from the repaired areas occurred at 5 min, 3 h, and 24 h after repair. RESULTS: For the 6-mm circle defect, method A showed higher bursting pressures than the other methods at 5 min and 3 h (p < 0.05); method B showed higher than methods C and D at 5 min and 3 h (p < 0.05). For the 12-mm square defect, method A showed higher bursting pressures than the other methods at all time points (p < 0.05). Moreover, method B showed higher than method C at 24 h (p < 0.05). CONCLUSION: Visceral pleural repairs using polyglycolic acid combined with fibrin glue showed the highest bursting pressure. Oxidized regenerated cellulose combined with fibrin glue showed sufficiently high bursting pressure in repair of small 6-mm circular defects.

Is Traditional Closed Thoracic Drainage Necessary to Treat Pleural Tears After Posterior Approach Thoracic Spine Surgery?

STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to evaluate the outcomes and efficacy of using a 10Fr elastic tube with a regular negative pressure ball to treat the operative pleural tear in the complicated single-stage posterior approach thoracic spine surgeries. SUMMARY OF BACKGROUND DATA: In some complicated single-stage posterior approach thoracic spine surgeries, such as total en bloc spondylectomy, pleural tear is quite inevitable. Traditional chest tube with a water-sealed bottle has many shortcomings, as pain, inconvenience, and other complications. In many thoracic surgeries, a smaller-caliber elastic tube has been used to avoid such complications and achieve quick recovery. However, there are concerns about the efficacy and safety of the smaller-caliber elastic tube. METHODS: A prospective trial was performed in 72 patients between April 2008 and March 2012. Pleural tear occurred in 19 patients, among whom 10 patients were inserted a 10Fr elastic tube with a regular negative pressure ball (Group I), and nine were inserted a 28Fr chest tube with a water-sealed bottle (Group II). Comparative evaluation of the clinical and radiographic data was carried out. RESULTS: The basic condition of two groups did not differ significantly. The oxygen saturation monitor, hospital length of stay, average volume, and failure rate of drainage between two groups were not statistically significant. The difference of the visual analog score was significant (1.10 ±â€Š0.35 vs. 3.89 ±â€Š0.59, P < 0.001). CONCLUSION: Patients who received a 10Fr elastic tube with a regular negative pressure ball experienced less pain and a tendency of quicker recovery than those who received a 28Fr chest tube with a water-sealed bottle. The complication rate in Group I was not higher than Group II, indicating an equally good drainage efficacy. LEVEL OF EVIDENCE: 2.

Inhibition of Glycogen Synthase Kinase 3ß Blocks Mesomesenchymal Transition and Attenuates Streptococcus pneumonia-Mediated Pleural Injury in Mice.

Pleural loculation affects about 30,000 patients annually in the United States and in severe cases can resolve with restrictive lung disease and pleural fibrosis. Pleural mesothelial cells contribute to pleural rind formation by undergoing mesothelial mesenchymal transition (MesoMT), whereby they acquire a profibrotic phenotype characterized by increased expression of α-smooth muscle actin and collagen 1. Components of the fibrinolytic pathway (urokinase plasminogen activator and plasmin) are elaborated in pleural injury and strongly induce MesoMT in vitro. These same stimuli enhance glycogen synthase kinase (GSK)-3ß activity through increased phosphorylation of Tyr-216 in pleural mesothelial cells and GSK-3ß mobilization from the cytoplasm to the nucleus. GSK-3ß down-regulation blocked induction of MesoMT. Likewise, GSK-3ß inhibitor 9ING41 blocked induction of MesoMT and reversed established MesoMT. Similar results were demonstrated in a mouse model of Streptococcus pneumoniae-induced empyema. Intraperitoneal administration of 9ING41, after the induction of pleural injury, attenuated injury progression and improved lung function (lung volume and compliance; P < 0.05 compared with untreated and vehicle controls). MesoMT marker α-smooth muscle actin was reduced in 9ING41-treated mice. Pleural thickening was also notably reduced in 9ING41-treated mice (P < 0.05). Collectively, these studies identify GSK-3ß as a newly identified target for amelioration of empyema-related pleural fibrosis and provide a strong rationale for further investigation of GSK-3ß signaling in the control of MesoMT and pleural injury.

[A mysterious pleural lesion: A case report]. / Une mystérieuse lésion pleurale : observation anatomoclinique.

A computed tomography scanner first, then a magnetic resonance imaging were performed for chest pain in a 24-year-old woman allowed to find out a 5-cm long and 2-cm large right pleural tumour close to the rachis (T9 and T10) and spindle-shaped. This patient was a smoker and reported a fall down the stairs a few weeks ago. A scan-guided biopsy was decided and microscopic examination revealed a fibrous tissue in which were entrapped regular and non-suspicious alveolar glands. After elimination of differential diagnosis, the most probable hypothesis was that this lesion was due to the traumatism reported by the patient.

CT-guided core needle biopsy of mediastinal nodes through a transpulmonary approach: retrospective analysis of the procedures conducted over six years.

PURPOSE: To retrospectively evaluate the diagnostic performance and complications of a CT-guided core needle cutting biopsy of mediastinal nodes through a transpulmonary approach. MATERIALS AND METHODS: From January 2009 to December 2014, we used a coaxial positioning system and an 18G cutting-type biopsy device to perform CT-guided percutaneous transpulmonary needle biopsies of mediastinal nodes for 127 patients. The diagnostic performance, complication rate, influencing factors, distribution of mediastinal nodes and pathological diagnoses were investigated. RESULTS: Among 127 patients, pathologic analyses showed that all of the biopsies were technically successful. The sensitivity, specificity, positive predictive value, and negative predictive value were all 100%. As for complications, the ratios for pneumothorax and hemoptysis were 33.9% and 4.7%, respectively. Multivariate analyses revealed that the distance from the pleura to the target lesion (P = 0.008) and the numbers of visceral pleura injuries (P = 0.006) were the two most significant risk factors for pneumothorax, and that the distance from the pleura to the target lesion (P = 0.004) was the most significant risk factor for hemoptysis. CONCLUSIONS: CT-guided core needle cutting biopsy of mediastinal nodes through a transpulmonary approach is a safe and efficient diagnostic method. KEY POINTS: • CT-guided core needle biopsy is an accurate technique for diagnosing mediastinal nodes. • The rates of complications are similar to those for pulmonary lesion biopsy. • Pneumothorax risk factors include distance from pleura to target lesion and number of visceral pleura. • Distance from pleura to target lesion is the risk factor for hemoptysis. • CT-guided core needle biopsy is an important diagnostic method for mediastinal nodes.

[The benefits of digital chest drainage in pleural decortication in thoracic empyema. Prospective, randomized, control trial]. / Beneficios del drenaje torácico digital en pleurodecorticación por empiema. Estudio prospectivo, comparativo aleatorizado.

BACKGROUND: Prolonged air leak after pleural decortication is one of the most frequent complications. OBJECTIVE: The aim of this study is to compare the effects of prolonged air leak between the digital chest drainage (DCD) system and the classic drainage system in patients with empyema class IIB or III (American Thoracic Society classification) in pleural decortication patients. MATERIAL AND METHODS: A total of 37 patients were enrolled in a prospective randomized control trial over one year, consisting of 2blinded groups, comparing prolonged air leak as a main outcome, the number of days until removal of chest drain, length of hospital stay and complications as secondary outcomes. RESULTS: The percentage of prolonged air leak was 11% in the DCD group and 5% in the classic group (P=0.581); the mean number of days of air leak was 2.5±1.8 and 2.4±2.2, respectively (P=0.966). The mean number of days until chest tube removal was 4.5±1.8 and 5.1±2.5 (P=0.41), the length of hospital stay was 7.8±3.7 and 8.9±4.0 (P=0.441) and the complication percentages were 4 (22%) and 7 (36%), respectively (P=0.227). DISCUSSION: In this study, no significant difference was observed when the DCD was compared with the classic system. This was the first randomized clinical trial for this indication; thus, future complementing studies are warranted.