Lung Entrapment Research Articles

MiR-4739 mediates pleural fibrosis by targeting bone morphogenetic protein 7.

BackgroundPleural fibrosis is defined as excessive depositions of matrix components that result in pleural tissue architecture destruction and dysfunction. In severe cases, the progression of pleural fibrosis leads to lung entrapment, resulting in dyspnea and respiratory failure. However, the mechanism of pleural fibrosis is poorly understood.MethodsmiR-4739 levels were detected by miRNA array and real-time PCR. Real-time PCR, western blotting and immunofluorescence were used to identify the expression profile of indicators related to fibrosis. Target gene of miR-4739 and promoter activity assay was measured by using dual-luciferase reporter assay system. In vivo, pleural fibrosis was evaluated by Masson staining and miR-4739 level was detected by In situ hybridization histochemistry.FindingsWe found that bleomycin induced up-regulation of miR-4739 in pleural mesothelial cells (PMCs). Over-regulated miR-4739 mediated mesothelial-mesenchymal transition and increased collagen-I synthesis in PMCs. Investigation on the clinical specimens revealed that high levels of miR-4739 and low levels of bone morphogenetic protein 7 (BMP-7) associated with pleural fibrosis in patients. Then we next identified that miR-4739 targeted and down-regulated BMP-7 which further resulted in unbalance between Smad1/5/9 and Smad2/3 signaling. Lastly, in vivo studies revealed that miR-4739 over-expression induced pleural fibrosis, and exogenous BMP-7 prevented pleural fibrosis in mice.InterpretationOur data indicated that miR-4739 targets BMP-7 which mediates pleural fibrosis. The miR-4739/BMP-7 axis is a promising therapeutic target for the disease.FundThe National Natural Science Foundation of China.

Outpatient Talc Administration by Indwelling Pleural Catheter for Malignant Effusion

BackgroundMalignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone.MethodsOver a period of 4 years, we recruited patients with malignant pleural effusion at 18 centers in the United Kingdom. After the insertion of an indwelling pleural catheter, patients underwent drainage regularly on an outpatient basis. If there was no evidence of substantial lung entrapment (nonexpandable lung, in which lung expansion and pleural apposition are not possible because of visceral fibrosis or bronchial obstruction) at 10 days, patients were randomly assigned to receive either 4 g of talc slurry or placebo through the indwelling pleural catheter on an outpatient basis. Talc or placebo was administered on a single-blind basis. Follow-up lasted for 70 days. The primary outcome was successful pleurodesis at day 35 after randomization.ResultsThe target of 154 patients undergoing randomization was reached after 584 patients were approached. At day 35, a total of 30 of 69 patients (43%) in the talc group had successful pleurodesis, as compared with 16 of 70 (23%) in the placebo group (hazard ratio, 2.20; 95% confidence interval, 1.23 to 3.92; P=0.008). No significant between-group differences in effusion size and complexity, number of inpatient days, mortality, or number of adverse events were identified. No significant excess of blockages of the indwelling pleural catheter was noted in the talc group.ConclusionsAmong patients without substantial lung entrapment, the outpatient administration of talc through an indwelling pleural catheter for the treatment of malignant pleural effusion resulted in a significantly higher chance of pleurodesis at 35 days than an indwelling catheter alone, with no deleterious effects. (Funded by Becton Dickinson; EudraCT number, 2012-000599-40.)

Pleural manometry in patients with pleural diseases - the usefulness in clinical practice.

Although pleural manometry is a relatively simple medical procedure it is only occasionally used to follow pleural pressure (Ppl) changes during a therapeutic thoracentesis and pneumothorax drainage. As some studies showed that pleural pressure monitoring might be associated with significant advantages, pleural manometry has been increasingly evaluated in the last decade. The major clinical applications of pleural pressure measurements include: the prevention of complications associated with large volume thoracentesis, diagnosis and differentiation between various types of an unexpandable lung and a possible prediction of the efficacy of chest tube drainage in patients with spontaneous pneumothorax. It is well known that the therapeutic thoracentesis might be complicated by cough, chest discomfort, and rarely, by a life threatening condition called reexpansion pulmonary edema (RPE). The serious adverse events of thoracentesis are related to pleural pressure drop rather than to the volume of removed pleural effusion. The use of pleural manometry during pleural fluid withdrawal enables the evaluation of the relationship between withdrawn pleural fluid volume, pleural pressure changes and procedure related complications. Pleural pressure measurement is also an important tool to study the different mechanism of pneumothorax complicating the thoracentesis. Pleural manometry is critical for measurement of pleural elastance, diagnosis of an unexpandable lung and differentiation between trapped lung and lung entrapment. This usually has significant clinical implications in terms of further management of patients with pleural effusion. The paper is a comprehensive review presenting different aspects of pleural pressure measurement in clinical practice.

Unexpandable lung from pleural disease.

Unexpandable lung is a common complication of malignant pleural effusions and inflammatory pleural diseases, such as pleural infection (e.g. empyema and complicated parapneumonic effusion) and noninfectious fibrinous pleuritis. Unexpandable lung due to pleural disease may be because of an active pleural process, and is referred to as malignant or inflammatory lung entrapment. An unexpandable lung may also be encountered in the setting of remote pleural inflammation resulting in a mature fibrous membrane overlying the visceral pleura preventing full expansion of the lung. This condition is termed trapped lung and may be understood as a form of defective healing of the pleural space. Trapped lung typically presents as a chronic, stable pleural effusion without evidence of active pleural disease. An unexpandable lung most often manifests itself as an inability of fully expanding the lung with pleural space drainage. Patients will either develop chest pain preventing complete drainage of the pleural space or develop a post-procedure pneumothorax. Pleural manometry and radiological imaging are useful in the assessment of an unexpandable lung. Pleural manometry can demonstrate abnormal lung expansion during drainage and imaging will demonstrate abnormal visceral pleural thickening found in trapped lung or malignant and inflammatory lung entrapment.

Minimal Invasive Surgical Experience in Pleural Pathology: The Basis of Good Treatment is a Good Diagnosis

SESSION TITLE: Unusual Pulmonary Infections SESSION TYPE: Global Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: The pleural pathology is intimately associated with many local, regional and sistemic diseases condition, its embryonic derivation generate different pathology manifestations of many conditions that primarily or secundarily affects the pleura, a wide spectrum ranging from minimal inflamatory changes to highly malignant neoplasms. The clinical setting and radiologic picture is relevant to make a surgical decision, knowledge of the normal anatomical consierations and familiarity with the pleural histopathology will make a correct diagnosis providing optimal treatment. CASE PRESENTATION: Since february 2012 to february 2017, was recabate a total of 101 patients for pleural surgical protocol in a thoracic reference hospital center, in Mexico, evaluated by a single thoracic surgical team. The surgical aproache was thoracoscopic with a single port incision and complete surgical protocol, including radiologic images and clinical consensus between the oncological thoracic team (pathologist, clinical oncologist, pneumologist and thoracic surgeon ). The patient history includes exposure to cement, lime, metals, tabacco and asbestos. Our indication for surgical managment includes: pleural thickening, macro and micro nodulos, pleural effusion, lung entrapment and radiologic aspect of the mediastinum. As to clinical data dyspnoea, pain, weight lost and sirs. All liquid samples and surgical specimens where analyze in microbiology and pathology laboratory, the sample of pleural effusions for histopatologic study include 100 ml for cell block. Based on this finding we decided to do or not to do surgical pleurodesis. All pactients where managed whith pleural drainage and was retired until microbiology and histopatology laboratory reports were given to confirm the need of antibiotics or repeat chemical pleurodesis. Based on clinical evolution and repotrs were managed whith oncological and infectology group. The following was in the ambulatory medical consultation. DISCUSSION: Taking in account that in a considerable number of cases , evaluation of specimens obteined by less invasive modalities are inconclusive, the vats is the prefered method for surgical diagnosis. Vats allows larges tissue samples and important considerations given the heterogeneity of the phatology. Multiple separated biopsies increases the likelihood of accurately determining histologic subtype. Pathologists frequently receive pleural specimens showing evidence of inflammation, repair, or neoplasm. Knowledge of the clinical setting and radiological picture is often of great value to the pathologist in arriving at a correct diagnosis. Similarly, knowledge of the normal anatomical considerations and familiarity with the expected pleural histopathology for the most clinically relevant pleural diseases are critical assets for pulmonary physicians in providing optimal care for their patients. Between 1994 and 2008, 92 253 mesothelioma deaths, in 83 countries, were reported to the who. The mean age at death was 70 years. The male-to-female ratio was 3.6:1. by anatomical site, the age-adjusted mortality rate was 2.3, 2.3 and 0.3 per million for the pleura in Mexico, between 1998 and 2005 there were 3459 mesothelioma deaths reported, 2306 (66.7%) occurring in males and 1153 (33.3%) in females. Anatomical site of presentation is pleura 18.5%. CONCLUSIONS: Our primary goal is to detect patients at an early satge of pleuropulmonary cancer and in those whith inflamatory and infectious disease, decortication and recovery of the lung through and utility incision. Or to mantain the mis approach a 2nd and 3rd incision to performe lavage and decortication. All of our 101 patients get 100% diagnosis and specific treatment, our patologic report includes inflamatory and infectious disease in 70 patients (69.3%), neoplasic disease including metastasis 31 (30.6%). Average length of stay one week whith specific antimicrobial treatment, in oncologic cases whith and input of fluid more than 400ml per day a heimlich valve was put on and dischage home. Reference #1: Delgermaa V, Takahashi K, Park E, Vinh Le G, Hara T,& Sorahan T. Global mesothelioma deaths reported to the world health organization between 1994 and 2008. Bulletin of the world health organization 2011;89:716-724C. Doi: 10.2471/blt.11.086678 Reference #2: Clin Chest Med. 2006 Jun;27(2):157-80. Pathology of the pleura. English JC1, Leslie KO. Reference #3: Semin Respir Crit Care Med. 2010 Dec;31(6):649-73. doi: 10.1055/s-0030-1269826. Epub 2011 Jan 6. The pleura in health and disease. Murali R1, Park K, Leslie KO. DISCLOSURE: The following authors have nothing to disclose: Emmanuel Peña Gomez Portugal, Ivan Orlando Lopez Vargas, Ricardo Villa Sierra, Alma Leticia Solano Nieto, Sonia Omaña Hernandez No Product/Research Disclosure Information

Safety and Efficacy of Tissue Plasminogen Activator and DNase for Complicated Pleural Effusions Secondary to Abdominal Pathology.

Exudative pleural effusions may arise secondary to inflammation of intra-abdominal structures. Pleural space loculations can complicate these effusions, preventing adequate chest tube drainage and leading to consideration of surgical intervention. Previous studies have demonstrated that intrapleural administration of tissue plasminogen activator (tPA) combined with human recombinant DNase can improve fluid drainage and reduce surgery for patients with loculated parapneumonic effusions; however, the efficacy of this treatment has not been evaluated for complicated pleural effusions attributed to intra-abdominal inflammation. We assessed the safety and efficacy of tPA/DNase for 17 pleural effusions associated with nonmalignant intra-abdominal pathology that did not drain adequately after placement of one or more chest tubes. Efficacy was measured by comparing post- to pretreatment fluid drainage rates, volumetric assessment of pleural fluid on radiographic images before and after treatment, and clinical improvement, including the need for surgical intervention. Symptomatic relief was assessed using the Borg scale for breathlessness. After a median of two doses of tPA/DNase, 23.5% of patients had chest pain and none had pleural bleeding. The volume of pleural fluid drained increased from a median of 325 ml to 890 ml per 24 hours after therapy (P = 0.018). The area of pleural space opacity on chest radiographs decreased from a median of 42.8-17.8% of the hemithorax (P = 0.001). tPA/DNase reduced the pleural fluid volume on chest computed tomographic imaging from a median of 294.4 ml to 116.1 ml. Borg scores improved from a median of 3 (interquartile range = 1-6) to 0 (interquartile range = 0-2) after therapy (P = 0.001). The median duration of chest tube placement and hospital stay were 4 and 11 days, respectively. Two patients required surgical intervention for lung entrapment. Overall, treatment was considered successful for 88.2% of patients. This retrospective case series suggests that intrapleural tPA/DNase can be safe and effective for patients with complicated pleural effusions attributed to abdominal pathology that do not drain adequately after chest tube placement. Additional studies are needed to determine whether the combination of tPA and DNase is more effective than tPA for this indication.

Medical image of the week: lung entrapment

Medical image of the week: lung entrapment

Suction evacuation of hemothorax: A prospective study.

Although tube thoracostomy is a common procedure after thoracic trauma, incomplete evacuation of fluid places the patient at risk for retained hemothorax. As little as 300 to 500 cm of blood may result in the need for an additional thoracostomy tube or, in more severe cases, lung entrapment and empyema. We hypothesized that suction evacuation of the thoracic cavity before tube placement would decrease the incidence of late complications. Patients requiring tube thoracostomy within 96 hours of admission were prospectively identified and underwent suction evacuation of the pleural space (SEPS) before tube placement. These patients were compared to historical controls without suction evacuation. Demographics, admission vital signs, laboratory values, details of chest tube placement, and outcomes were collected on all patients. Multivariable logistic regression was used to compare outcomes between groups. A total of 199 patients were identified, consisting of 100 retrospective controls and 99 SEPS patients. There were no differences in age, sex, admission injury severity score or chest abbreviated injury score, admission laboratory values or vital signs, or hospital length of stay. Mean (SD) volume of hemothorax in SEPS patients was 220 (297) cm; with only 48% having a volume greater than 100 cm at the time of tube placement. Three patients developed empyema, and 19 demonstrated retained blood; there was no difference between SEPS and control patients. Suction evacuation of the pleural space was significantly protective against recurrent pneumothorax after chest tube removal (odds ratio, 0.332; 95% confidence interval, 0.148-0.745). Preemptive suction evacuation of the thoracic cavity did not have a significant impact on subsequent development of retained hemothorax or empyema. Suction evacuation of the pleural space significantly decreased incidence of recurrent pneumothorax after thoracostomy removal. Although the mechanism is unclear, such a benefit may make this simple procedure worthwhile. A larger sample size is required for validation and to determine if preemptive thoracic evacuation has a clinical benefit. Therapeutic/care management study, level IV.

Root Cause of Analysis of Peculiar Response of Pneumothorax to Chest Tube Drainage

Chest tube drainage is a simple system to manage pneumothorax. It is inserted at the safety triangle after local anesthesia. Due to the positive intrapulmonary pressure and the negative intrapleural pressure during inspiration, air in the pleural space will be forced out into the chest drain bottle with underwater seal. The resorption of pneumothorax is further enhanced by oxygen therapy, which displaces the nitrogen inside the pneumothorax. Out of our expectation, there are cases with peculiar response to chest tube drainage. We should consider the following in the root cause analysis. 1. Chest drain system integrity: The chest drain should be placed in the pleural cavity, rather than sub-cutaneous or intra-abdominal cavity. The tubing should not be kinked or disconnected and the connection site should not be masked by dressing. 2. Anatomy of the pneumothorax: The anatomy of the pneumothorax should be on CXR or preferably contrast CT thorax. Any loculation, endobronchial obstruction, trapped lung due to old inflammatory process, lung entrapment due to persistent active inflammatory process should be noted. 3. Clinical assessment: It includes pleural fluid analysis, if present, and pleural manometry with air aspiration. In case of persistent air-leak seen in the chest drain bottle, suspect alveolopleural or bronchopleural fistula especially when patient is on positive pressure ventilation. Alternating or persistent bilateral pneumothorax without air-leak suggests interpleural communication (Simultaneous Bilateral Spontaneous Pneumothorax). The observed phenomena can be explained by considering the pressure change between various intra-thoracic compartments accounts for the observed phenomena, although confirmation of the communication during thoracoscopy is preferred.

Excess Integrins Cause Lung Entrapment of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are largely entrapped in the lungs after intravenous delivery. The underlying mechanisms have been poorly understood. Flow cytometry and Western blot analysis showed that the expression levels of many integrins such as β1, α5, and αVβ3 in MSCs increased markedly upon cultured expansion in 2D monolayers, whose ligands fibronectin and vitronectin were detected on the surface of vascular endothelial cells in the lungs by immunostaining and flow cytometry. Blockade of integrin β1, integrin α5, or integrins αVβ3 with functional blocking antibodies significantly decreased the amount of MSCs entrapped in the lungs following intravenous infusion as determined by real-time PCR and histological analysis; meanwhile, corresponding increases in the levels of circulating MSCs in the blood and MSCs homed to the ischemic myocardium and inflamed ear were found. Intriguingly, a short period of 3D spheroid culture of MSCs, which had been expanded for several passages in monolayers, substantially reduced the expression levels of many integrins and the number of MSCs entrapped in the lungs. Our results indicate that the excess expression and activation of integrins is a significant cause of lung entrapment of MSCs.

Year in review 2014: Lung cancer, pleural diseases, respiratory infections and tuberculosis, bronchoscopic intervention and imaging.

Year in review 2014: Lung cancer, pleural diseases, respiratory infections and tuberculosis, bronchoscopic intervention and imaging.

A Case of Lung Entrapment; Mesothelioma

72 y/o Caucasian male with a past medical history of hypertension, non-ischemic cardiomyopathy, dyslipidemia and CVA presents with worsening shortness of breath over past one month. Our patient also has a long standing history of tobacco abuse and an employment history of working ship broiler rooms. Chest examination revealed no breath sounds on left side. Chest radiography revealed complete opacification of the left hemithorax with a mediastinal shift from left to right (Figure 1). A computed tomographic scan of the chest showed a large left hydropneumothorax with complete collapse of the left lung. Also noted was a mediastinal shift towards the right associated with a small right pleural effusion with right lower lobe atelectasis and small pericardial effusion (Figure 2). The management of this collapsed lung is surgical, with removal of the fibrosed visceral pleura to allow for the expansion of the underlying lung. In this patient, video-assisted thoracoscopic surgery and decortication was performed. Bronchial washings showed benign bronchial epithelial cells mixed with alveolar macrophages. Pleural biopsy revealed a poorly differentiated neoplasm carcinoma versus mesothelioma. Fragments of fibrous soft tissue and clusters of pleomorphic neoplastic cells were negative for adenocarcinoma markers (CEA-m, EpCam, and BerEP4). They instead expressed mesothelial markers including Calretinin and GLUT-1, favoring a diagnosis of mesothelioma.

Optimization of mesenchymal stem cells (MSCs) delivery dose and route in mice with acute liver injury by bioluminescence imaging.

Both experimental and initial clinical studies have shown the therapeutic potential of mesenchymal stem cells (MSCs) in liver disease. Noninvasive tracking of MSCs could facilitate its clinical translation. The purpose of this study was to optimize MSCs delivery dose and route in mice with acute liver injury using bioluminescence imaging (BLI) to track the cells. MSCs were labeled with the Luc2-mKate2 dual-fusion reporter gene (MSCs-R). The fate of MSCs-R was tracked through in vivo BLI after administration of different doses or delivery through different routes. When delivered via the superior mesenteric vein (SMV), the high-dose (1.0 × 10(6) and 5.0 × 10(5)) group mice demonstrated high liver BLI signal but also had lethal portal vein embolization (PVE). By contrast, no PVE and its related death occurred in the low-dose (2.5 × 10(5)) group mice. Thus, 2.5 × 10(5) is the optimal delivery dose. Three delivery routes, i.e., inferior vena cava (IVC), SMV, and intrahepatic (IH) injection, were also systematically compared. After IVC infusion, MSCs-R were quickly trapped inside the lungs, and no detectable homing to the liver and other organs was observed. By IH injection, lung entrapment was bypassed, but MSCs-R distribution was only localized in the injection region of the liver. By contrast, after SMV infusion, MSCs-R were dispersedly distributed and stayed as long as 7-day posttransplantation in the liver. The in vivo imaging results were further validated by ex vivo imaging, digital subtraction angiography (DSA), and tissue analysis. Therefore, SMV is the optimal MSCs delivery route for liver disease. Collectively, BLI, which could dynamically and quantitatively track cellular location and survival, is useful in determining MSCs transplantation parameters.

Unexpandable Lung

Unexpandable lung is a mechanical complication by which the lung does not expand to the chest wall, impeding a normal apposition between the two pleural layers. The main mechanism involved is the restriction of the visceral pleura due to the formation of a fibrous layer along this pleural membrane. This happens because of the presence of an active pleural disease (lung entrapment), which can be resolved if proper therapeutic measures are taken, or a remote disease (trapped lung), in which an irreversible fibrous pleural layer has been formed. The clinical suspicion arises with the presence of post-thoracocentesis hydropneumothorax or a pleural effusion that cannot be drained due to the appearance of thoracic pain. The diagnosis is based on the analysis of the pleural liquid, the determination of pleural pressures as we drain the effusion and on air-contrast chest CT. As both represent the continuity of one same process, the results will depend on the time at which these procedures are done. If, when given a lung that is becoming entrapped, the necessary therapeutic measures are not taken, the final result will be a trapped lung. In this instance, most patients are asymptomatic or have mild exertional dyspnea and therefore they do not require treatment. Nevertheless, in cases of incapacitating dyspnea, it may be necessary to use pleural decortication in order to resolve the symptoms.

Cell Surface Structures Influence Lung Clearance Rate of Systemically Infused Mesenchymal Stromal Cells

The promising clinical effects of mesenchymal stromal/stem cells (MSCs) rely especially on paracrine and nonimmunogenic mechanisms. Delivery routes are essential for the efficacy of cell therapy and systemic delivery by infusion is the obvious goal for many forms of MSC therapy. Lung adhesion of MSCs might, however, be a major obstacle yet to overcome. Current knowledge does not allow us to make sound conclusions whether MSC lung entrapment is harmful or beneficial, and thus we wanted to explore MSC lung adhesion in greater detail. We found a striking difference in the lung clearance rate of systemically infused MSCs derived from two different clinical sources, namely bone marrow (BM-MSCs) and umbilical cord blood (UCB-MSCs). The BM-MSCs and UCB-MSCs used in this study differed in cell size, but our results also indicated other mechanisms behind the lung adherence. A detailed analysis of the cell surface profiles revealed differences in the expression of relevant adhesion molecules. The UCB-MSCs had higher expression levels of α4 integrin (CD49d, VLA-4), α6 integrin (CD49f, VLA-6), and the hepatocyte growth factor receptor (c-Met) and a higher general fucosylation level. Strikingly, the level of CD49d and CD49f expression could be functionally linked with the lung clearance rate. Additionally, we saw a possible link between MSC lung adherence and higher fibronectin expression and we show that the expression of fibronectin increases with MSC culture confluence. Future studies should aim at developing methods of transiently modifying the cell surface structures in order to improve the delivery of therapeutic cells.

Are cultured mesenchymal stromal cells an option for immunomodulation in transplantation?

Are cultured mesenchymal stromal cells an option for immunomodulation in transplantation?

Cultivation in Human Serum Reduces Adipose Tissue-Derived Mesenchymal Stromal Cell Adhesion to Laminin and Endothelium and Reduces Capillary Entrapment

The increasing use of mesenchymal stromal cells (MSC) in clinical cellular therapy requires a safe and controlled production process compliant with Good Manufacturing Practice guidelines. Pooled blood group AB human serum (HS) has been used to replace fetal bovine serum (FBS), critically rated by the regulatory agencies, since it can support the expansion of adipose tissue-derived mesenchymal stromal cells (ASC). However, it remains unknown whether the choice of serum affects application-relevant characteristics of ASC. A microarray-based screen has revealed differentially expressed adhesion and extracellular matrix-associated molecules in HS- and FBS-ASC. Since cell therapy relies on the cells' efficacy to home and engraft, HS- and FBS-ASC were compared by analyzing adhesion, migration, and transmigration as well as short-term homing in vivo. HS-cultivated ASC demonstrated a higher adhesion to plastic, but reduced adhesion to extracellular matrix molecules, that is, laminin, and to endothelial cells both under static and flow conditions. Migration and transmigration assays confirmed the attraction of ASC by the tumor conditioned medium irrespective of the supplement. Coinjecting differently labeled HS- and FBS-ASC into nonobese diabetic, severe combined immunodeficiency mice revealed reduced numbers of HS-ASC in lungs and liver. This has been interpreted as reduced capillary entrapment. Our data indicate that varying the serum supplement may alter application-relevant characteristics of ASC, such as adhesion, as well as lung entrapment after infusion. Appropriate injury models and further molecular analyses are required to provide mechanistic insight into the differential effects of HS versus FBS on ASC cultures.

Adenocarcinoma of Lung Presenting as Diffuse Nodular Pleural Thickening With Lung Entrapment Mimicking Mesothelioma: A Case Report

SESSION TYPE: Cancer Student/Resident Cases

IgG4-Related Systemic Disease Presenting With Lung Entrapment and Constrictive Pericarditis

We describe a 29-year-old woman who presented with chronic pleuropericarditis complicated by lung entrapment and constrictive pericarditis. Pleural biopsy performed during the decortication procedure revealed fibrinous pleuritis with lymphoplasmacytic inflammation including IgG4-positive plasma cells. The patient responded favorably to corticosteroid therapy with resolution of pleural effusion and constrictive physiology. To our knowledge, this is the first reported case of IgG4-related systemic disease manifesting as lung entrapment and constrictive pericarditis.

Mesenchymal Stem Cells Home to Sites of Injury and Inflammation

Mesenchymal stem cells (MSCs) have shown significant therapeutic potential in preclinical animal models of wound healing. However, the translation of MSC-based therapeutics to clinical practice has been delayed by questions including the mechanisms of MSC homing, engraftment, and ultimate function. Experimental models of MSC-based wound therapies often involve intravenous injection of cells followed by sacrifice of animals at various time points and detection of MSCs in wounds by histological methods. However, this methodology is limited by its sampling of only specific tissue at a single time point and provides no information about how exogenously transplanted MSCs home to the wound environment. Most systemically injected MSCs initially become entrapped within the lungs before migrating out to the liver and spleen in the normal state. When an injury is present, after the initial lung entrapment, MSCs migrate in response to inflammatory mediators and home to sites of wounding. As MSC-based wound therapies continue to advance toward clinical trials, the availability of noninvasive methods to track cells after injection into patients affords the opportunity to monitor stem cell behavior post-transplantation. MSCs have demonstrated great promise as an emerging therapeutic for wound management. However, further preclinical studies will be needed to elucidate the reparative mechanisms of these cells and to determine how to optimize their regenerative potential.