Recognizing the pleura in asbestos-related pleuropulmonary disease: Known and new manifestations of pleural fibrosis.

Pleural thickening (PT) is a major consequence of exposure to all fiber types of asbestos. In recent decades, it is more prevalent than parenchymal asbestosis. Its manifestations occupy a full clinical and radiographic spectrum. Six major manifestations can be identified: (a) acute pleuritis generally with effusion; (b) diffuse PT or fibrous pleuritis; (c) rounded atelectasis; (d) circumscribed PT or plaques; (e) chronic pleuritic pain; and (f) mesothelioma. Review of the experience of workers and community members in Libby, MT to asbestiform fibers in vermiculite has confirmed the appearance of these previously known benign and malignant asbestos-related diseases as well as a unique pleuropulmonary disease characterized as lamellar PT and associated with progressive decline in pulmonary function and pleuritic pain. Despite previous literature asserting that PT represents a marker for asbestos exposure without significant effect on pulmonary function and physiology, the experience of Libby amphibole (LA) disease, along with other studies, indicates that PT plays a role in declining vital capacity in those with prolonged or unusual exposures such as those arising from LA.

Anatomy and function of the lymphatic vessels in the parietal pleura and their plasticity under inflammation in mice.

Inflammatory pleuritis often causes pleural effusions, which are drained through lymphatic vessels (lymphatics) in the parietal pleura. The distribution of button- and zipper-like endothelial junctions can identify the subtypes of lymphatics, the initial, pre-collecting, and collecting lymphatics. Vascular endothelial growth factor receptor (VEGFR)-3 and its ligands VEGF-C/D are crucial lymphangiogenic factors. Currently, in the pleura covering the chest walls, the anatomy of the lymphatics and connecting networks of blood vessels are incompletely understood. Moreover, their pathological and functional plasticity under inflammation and the effects of VEGFR inhibition are unclear. This study aimed to learn the above-unanswered questions and immunostained mouse chest walls as whole-mount specimens. Confocal microscopic images and their 3-dimensional reconstruction analyzed the vasculatures. Repeated intra-pleural cavity lipopolysaccharide challenge induced pleuritis, which was also treated with VEGFR inhibition. Levels of vascular-related factors were evaluated by quantitative real-time polymerase chain reaction. We observed the initial lymphatics in the intercostals, collecting lymphatics under the ribs, and pre-collecting lymphatics connecting both. Arteries branched into capillaries and gathered into veins from the cranial to the caudal side. Lymphatics and blood vessels were in different layers with an adjacent distribution of the lymphatic layer to the pleural cavity. Inflammatory pleuritis elevated expression levels of VEGF-C/D and angiopoietin-2, induced lymphangiogenesis and blood vessel remodeling, and disorganized the lymphatic structures and subtypes. The disorganized lymphatics showed large sheet-like structures with many branches and holes inside. Such lymphatics were abundant in zipper-like endothelial junctions with some button-like junctions. The blood vessels were tortuous and had various diameters and complex networks. Stratified layers of lymphatics and blood vessels were disorganized, with impaired drainage function. VEGFR inhibition partially maintained their structures and drainage function. These findings demonstrate anatomy and pathological changes of the vasculatures in the parietal pleura and their potential as a novel therapeutic target.

Review on the methodology to assess respiratory tract lesions in pigs and their production impact.

Porcine respiratory disease is one of the most important health problems in pig production worldwide. Cranioventral pulmonary consolidation (CVPC) and pleurisy are the two most common lesions in the respiratory tract of slaughtered pigs. The present review paper discusses pathogens involved in the lesions, lesion prevalence, scoring systems, advantages and disadvantages of slaughterhouse examination, and the impact of CVPC and pleurisy on performance, carcass, and meat quality. Cranioventral pulmonary consolidation and pleurisy in slaughter pigs are characteristic for infections with Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae, respectively, although other pathogens may cause similar lesions and/or be involved in their development. The overall prevalence of CVPC and pleurisy in slaughter pigs are still high, being the prevalence of CVPC generally higher than that of chronic pleurisy. The advantages and disadvantages of slaughterhouse examination are discussed in relation to practical aspects, the assessment of lesions, the number and representativeness of the examined animals and the interpretation and value of the results for the stakeholders. The main scoring methods for CVPC and pleurisy are shortly reviewed. In general, scoring methods can be applied rapidly and easily, although significant variation due to abattoir and observer remains. Artificial intelligence-based technologies that automatically score lesions and facilitate processing of data may aid solving these problems. Cranioventral pulmonary consolidation and pleurisy have a major negative impact on pig performance, and the effects increase the extension of the lesions and/or presence of multiple lesions. The performance losses caused by these lesions, however, vary significantly between studies and farms, possibly due to differences in study population and used methodology. Both lesions also have a negative impact on different carcass and meat quality parameters, leading to increased risk for poor processing and storage of the carcasses. Monitoring lung lesions of slaughter pigs should be optimized and implemented routinely; however, it is recommended to complement this information with farm data and laboratory results for specific pathogens.

DOCK2 Promotes Pleural Fibrosis by Modulating Mesothelial to Mesenchymal Transition.

Mesothelial to mesenchymal transition (MesoMT) is one of the crucial mechanisms underlying pleural fibrosis, which results in restrictive lung disease. DOCK2 (dedicator of cytokinesis 2) plays important roles in immune functions; however, its role in pleural fibrosis, particularly MesoMT, remains unknown. We found that amounts of DOCK2 and the MesoMT marker α-SMA (α-smooth muscle actin) were significantly elevated and colocalized in the thickened pleura of patients with nonspecific pleuritis, suggesting the involvement of DOCK2 in the pathogenesis of MesoMT and pleural fibrosis. Likewise, data from three different pleural fibrosis models (TGF-ß [transforming growth factor-ß], carbon black/bleomycin, and streptococcal empyema) consistently demonstrated DOCK2 upregulation and its colocalization with α-SMA in the pleura. In addition, induced DOCK2 colocalized with the mesothelial marker calretinin, implicating DOCK2 in the regulation of MesoMT. Our in vivo data also showed that DOCK2-knockout mice were protected from Streptococcus pneumoniae-induced pleural fibrosis, impaired lung compliance, and collagen deposition. To determine the involvement of DOCK2 in MesoMT, we treated primary human pleural mesothelial cells with the potent MesoMT inducer TGF-ß. TGF-ß significantly induced DOCK2 expression in a time-dependent manner, together with α-SMA, collagen 1, and fibronectin. Furthermore, DOCK2 knockdown significantly attenuated TGF-ß-induced α-SMA, collagen 1, and fibronectin expression, suggesting the importance of DOCK2 in TGF-ß-induced MesoMT. DOCK2 knockdown also inhibited TGF-ß-induced Snail upregulation, which may account for its role in regulating MesoMT. Taken together, the current study provides evidence that DOCK2 contributes to the pathogenesis of pleural fibrosis by mediating MesoMT and deposition of neomatrix and may represent a novel target for its prevention or treatment.

Endothelial Cell Protein C Receptor Deficiency Attenuates Streptococcus pneumoniae-induced Pleural Fibrosis.

Streptococcus pneumoniae is the leading cause of hospital community-acquired pneumonia. Patients with pneumococcal pneumonia may develop complicated parapneumonic effusions or empyema that can lead to pleural organization and subsequent fibrosis. The pathogenesis of pleural organization and scarification involves complex interactions between the components of the immune system, coagulation, and fibrinolysis. EPCR (endothelial protein C receptor) is a critical component of the protein C anticoagulant pathway. The present study was performed to evaluate the role of EPCR in the pathogenesis of S. pneumoniae infection-induced pleural thickening and fibrosis. Our studies show that the pleural mesothelium expresses EPCR. Intrapleural instillation of S. pneumoniae impairs lung compliance and lung volume in wild-type and EPCR-overexpressing mice but not in EPCR-deficient mice. Intrapleural S. pneumoniae infection induces pleural thickening in wild-type mice. Pleural thickening is more pronounced in EPCR-overexpressing mice, whereas it is reduced in EPCR-deficient mice. Markers of mesomesenchymal transition are increased in the visceral pleura of S. pneumoniae-infected wild-type and EPCR-overexpressing mice but not in EPCR-deficient mice. The lungs of wild-type and EPCR-overexpressing mice administered intrapleural S. pneumoniae showed increased infiltration of macrophages and neutrophils, which was significantly reduced in EPCR-deficient mice. An analysis of bacterial burden in the pleural lavage, the lungs, and blood revealed a significantly lower bacterial burden in EPCR-deficient mice compared with wild-type and EPCR-overexpressing mice. Overall, our data provide strong evidence that EPCR deficiency protects against S. pneumoniae infection-induced impairment of lung function and pleural remodeling.

NOX1 Promotes Mesothelial-Mesenchymal Transition through Modulation of Reactive Oxygen Species-mediated Signaling.

Pleural organization may occur after empyema or complicated parapneumonic effusion and can result in restrictive lung disease with pleural fibrosis (PF). Pleural mesothelial cells (PMCs) may contribute to PF through acquisition of a profibrotic phenotype, mesothelial-mesenchymal transition (MesoMT), which is characterized by increased expression of α-SMA (α-smooth muscle actin) and other myofibroblast markers. Although MesoMT has been implicated in the pathogenesis of PF, the role of the reactive oxygen species and the NOX (nicotinamide adenine dinucleotide phosphate oxidase) family in pleural remodeling remains unclear. Here, we show that NOX1 expression is enhanced in nonspecific human pleuritis and is induced in PMCs by THB (thrombin). 4-Hydroxy-2-nonenal, an indicator of reactive oxygen species damage, was likewise increased in our mouse model of pleural injury. NOX1 downregulation blocked THB- and Xa (factor Xa)-mediated MesoMT, as did pharmacologic inhibition of NOX1 with ML-171. NOX1 inhibition also reduced phosphorylation of Akt, p65, and tyrosine 216-GSK-3ß, signaling molecules previously shown to be implicated in MesoMT. Conversely, ML-171 did not reverse established MesoMT. NOX4 downregulation attenuated TGF-ß- and THB-mediated MesoMT. However, NOX1 downregulation did not affect NOX4 expression. NOX1- and NOX4-deficient mice were also protected in our mouse model of Streptococcus pneumoniae-mediated PF. These data show that NOX1 and NOX4 are critical determinants of MesoMT.

An update of the long-term outcome of patients with nonspecific pleurisy at medical thoracoscopy.

BACKGROUND: Medical thoracoscopy (MT) is recommended in patients with undiagnosed exudative pleural effusion and offers a degree of diagnostic sensitivity for pleural malignancy. However, not all patients who undergo MT receive an exact diagnosis. Our previous investigation from 2014 summarized the long-term outcomes of these patients with nonspecific pleurisy (NSP); now, we offer updated data with the goal of refining our conclusions. METHODS: Between July 2005 and August 2018, MT with pleural biopsies were performed in a total of 1,254 patients with undiagnosed pleural effusions. One hundred fifty-four patients diagnosed with NSP with available follow-up data were included in the present study, and their medical records were reviewed. RESULTS: A total of 154 patients were included in this study with a mean follow-up duration of 61.5 ± 43.7 months (range: 1-180 months). No specific diagnosis was established in 67 (43.5%) of the patients. Nineteen patients (12.3%) were subsequently diagnosed with pleural malignancies. Sixty-eight patients (44.2%) were diagnosed with benign diseases. Findings of pleural nodules or plaques during MT and the recurrence of pleural effusion were associated with malignant disease. CONCLUSIONS: Although most NSP patients received a diagnosis of a benign disease, malignant disease was still a possibility, especially in those patients with nodules or plaques as noted on the MT and a recurrence of pleural effusion. One year of clinical follow-up for NSP patients is likely sufficient. These updated results further confirm our previous study's conclusions.

Non-necrotizing granulomatous pneumonitis and chronic pleuritis in soldiers deployed to Southwest Asia.

AIMS: Reports of respiratory illnesses among soldiers returning from Southwest Asia have been described. During deployment to Southwest Asia, soldiers are exposed to various respiratory hazards, including dust storms, smoke from burn pits and industrial air pollutants. A few studies have reported increased rates of constrictive bronchiolitis and asthma in these patients. We sought to expand upon the pathological findings in this cohort. METHODS AND RESULTS: Lung biopsies from veterans of Southwest Asia were identified and re-reviewed. All patients had undergone pulmonary function tests and chest high-resolution CT imaging with no significant findings. Overall, 59 patients with a history of inhalational exposure to at least one of the following were identified: smoke from burn pit, dust storm and sulphur plant fire. Samples included video-assisted thoracoscopic lung biopsies (57 of 59, 96.6%) and cryobiopsies (two of 59, 3.4%). Patients were predominantly male (54 of 59, 91.5%) with an age range of 24-55 years (mean and median = 35). Non-necrotising, poorly formed granulomas were identified in 22 cases (22 of 59, 37.2%). The granulomas were mainly bronchiolocentric and were associated with chronic lymphoplasmacytic bronchiolitis, similar to hypersensitivity pneumonitis (HP). Pleural reaction in the form of focal chronic lymphocytic pleuritis and/or focal pleural adhesions were seen in 43 of 57 (75.4%) biopsies. CONCLUSIONS: To our knowledge, this is the first study to report pleural reaction as well as features of HP in this population, suggesting that pleural reaction and HP may be part of the spectrum of Southwest Asia deployment-related lung diseases.

Scoring pleurisy in slaughtered pigs using convolutional neural networks.

Diseases of the respiratory system are known to negatively impact the profitability of the pig industry, worldwide. Considering the relatively short lifespan of pigs, lesions can be still evident at slaughter, where they can be usefully recorded and scored. Therefore, the slaughterhouse represents a key check-point to assess the health status of pigs, providing unique and valuable feedback to the farm, as well as an important source of data for epidemiological studies. Although relevant, scoring lesions in slaughtered pigs represents a very time-consuming and costly activity, thus making difficult their systematic recording. The present study has been carried out to train a convolutional neural network-based system to automatically score pleurisy in slaughtered pigs. The automation of such a process would be extremely helpful to enable a systematic examination of all slaughtered livestock. Overall, our data indicate that the proposed system is well able to differentiate half carcasses affected with pleurisy from healthy ones, with an overall accuracy of 85.5%. The system was better able to recognize severely affected half carcasses as compared with those showing less severe lesions. The training of convolutional neural networks to identify and score pneumonia, on the one hand, and the achievement of trials in large capacity slaughterhouses, on the other, represent the natural pursuance of the present study. As a result, convolutional neural network-based technologies could provide a fast and cheap tool to systematically record lesions in slaughtered pigs, thus supplying an enormous amount of useful data to all stakeholders in the pig industry.

Thoracic Involvement in IgG4-Related Disease.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that has been recognized to involve virtually any organ in the body and typically manifests mass-like lesions (tumefactive). Although initial reports of this disease (autoimmune pancreatitis [AIP]) were described in the Japanese population, it has since been reported worldwide. It is most commonly seen in adults of middle age or older, more often men than women. The pathogenesis of IgG4-RD is largely unknown, but genetic factors, microorganisms, and autoimmunity are thought to play important roles. Serum IgG4 concentration is elevated in the majority of patients with IgG4-RD but is a nonspecific finding. Characteristic histopathologic features include dense lymphoplasmacytic infiltrate, fibrosis (often in storiform pattern), and obliterative phlebitis. Lung involvement in IgG4-RD was first reported in 2004 in two patients with AIP and coexisting interstitial lung disease. Since then, a wide spectrum of intrathoracic involvement has been reported and includes not only parenchymal lung diseases but also pleural, airway, vascular, and mediastinal lesions. Thoracic involvement in IgG4-RD is often found incidentally during the workup of extrathoracic lesions but can sometimes be the presenting abnormality. The diagnosis of IgG4-RD requires correlation of clinical, laboratory, imaging, and histopathologic features. Glucocorticoids are the first-line therapy but other options including B cell depletion are being investigated. IgG4-RD is generally associated with an indolent clinical course and most patients improve with glucocorticoid therapy.

Oridonin attenuates carrageenan-induced pleurisy via activation of the KEAP-1/Nrf2 pathway and inhibition of the TXNIP/NLRP3 and NF-κB pathway in mice.

The classic NLRP3 inflammasome and NF-κB molecular pathways are activated in many inflammatory-related diseases, such as pleurisy. Because oridonin (Ori) has been indicated as a covalent NLRP3 inhibitor with strong anti-inflammasome activity, we herein aimed to assess the effects of Ori in a mouse model of carrageenan (CAR)-induced pleurisy. The results showed that CAR caused hemorrhaging and exudation of lung tissues and the release of inflammatory factors (TNF-α, IL-6 and IL-1ß), effects that were significantly reduced by treatment with Ori. In addition, increased neutrophil infiltration, protein concentrations and volumes were found in the exudates of the CAR group, and these phenomena were suppressed by Ori treatment. Regarding cellular pathways, Ori could alleviate the CAR-activated NF-κB and TXNIP/NLRP3 pathways. Additionally, oxidative stress was shown to be involved in the pathogenesis of pleurisy, but possible mechanisms remain to be explored. Herein, Ori reversed the CAR-induced depletion of GSH and SOD and the CAR-induced increases in ROS, MPO and MDA levels. Furthermore, Ori inhibited NOX-4 levels, initiated the dissociation of KEAP-1 from Nrf2, activated the downstream genes HO-1 and exerted antioxidative effects on CAR-induced pleurisy. In conclusion, Ori conferred protection against CAR-induced pleurisy via Nrf2-dependent antioxidative and NLRP3-dependent anti-inflammatory properties.

Effects of Aliskiren, an RAAS inhibitor, on a carrageenan-induced pleurisy model of rats.

Our aim is to investigate the potentially preventive effects of Aliskiren in a carrageenan-induced lung pleurisy model and to compare the standard anti-inflammatory agents, indomethacin and dexamethasone. The pleurisy model was induced through the injection of carrageenan (0.2 ml-%2) into the pleural cavity. After the experiment, serum and lung tissues were collected and biochemical, molecular and pathological examinations were performed. In our study, pleural inflammation decreased superoxide dismutase activity and the glutathione level and increased the malondialdehyde level in the lung of rats, while Aliskiren increased the superoxide dismutase activity and glutathione level and decreased the malondialdehyde level. In addition, carrageenan-induced pleurisy caused a significant increase in pro-inflammatory cytokines mRNA expressions (TNF-α, IL-1ß, and NF-KB), while Aliskiren administration decreased their expressions as well as the standard treatments, indomethacin and dexamethasone, did. Aliskiren administration at the 200 mg/kg dose protected the lungs in the pathological evaluation, especially against inflammatory cell infiltration and edematous lesions. It appears that Aliskiren protects the lung from carrageenan-induced pleurisy damage by regulating inflammation and antioxidant-oxidant balance via Renin Angiotensin Aldosterone System inhibition.

The diagnostic role of video-assisted thoracoscopic surgery in exudative pleural effusion and follow-up results in patients with nonspecific pleuritis.

OBJECTIVE: To assess the diagnostic value of video-assisted thoracoscopic surgery in exudative pleural effusions, and to evaluated the frequency of malignancy development with long term follow-up of patients defined as nonspecific pleuritis after surgery. . METHODS: The retrospective study was conducted at Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey, and comprised data of patients with undiagnosed exudative pleural effusions seen between January 2008 and December 2013. Data related to clinical, radiological, thoracoscopical, histopathological and follow-up periods were obtained from the hospital records. SPSS 15 was used for data analysis. RESULTS: Of the 229 patients, 145(63.3%) were males and 84(36.7%) were females. The overall mean age was 54.5 }15.1 years. Malignancy was found in 84 (36.6%) patients, and tuberculosis in 26(11.4%). The remaining 119(52%) patients had nonspecific pleuritis and their mean follow-up period was 29.2}27.1 months (range: 1-103 months). Video-assisted thoracoscopic surgery was repeated in 3(2.52%) patients in the 1st, 4th and 16th months of followup period due to the recurrence of pleural effusion. Tuberculosis and mesothelioma were diagnosed in 1(0.8%) and 2(1.7%) cases, respectively. CONCLUSIONS: Video-assisted thoracoscopic surgery was found to be a valuable diagnostic procedure in patients with undiagnosed exudative pleural effusion.

The resolution of acute inflammation induced by cyclic AMP is dependent on annexin A1.

Annexin A1 (AnxA1) is a glucocorticoid-regulated protein known for its anti-inflammatory and pro-resolving effects. We have shown previously that the cAMP-enhancing compounds rolipram (ROL; a PDE4 inhibitor) and Bt2cAMP (a cAMP mimetic) drive caspase-dependent resolution of neutrophilic inflammation. In this follow-up study, we investigated whether AnxA1 could be involved in the pro-resolving properties of these compounds using a model of LPS-induced inflammation in BALB/c mice. The treatment with ROL or Bt2cAMP at the peak of inflammation shortened resolution intervals, improved resolution indices, and increased AnxA1 expression. In vitro studies showed that ROL and Bt2cAMP induced AnxA1 expression and phosphorylation, and this effect was prevented by PKA inhibitors, suggesting the involvement of PKA in ROL-induced AnxA1 expression. Akin to these in vitro findings, H89 prevented ROL- and Bt2cAMP-induced resolution of inflammation, and it was associated with decreased levels of intact AnxA1. Moreover, two different strategies to block the AnxA1 pathway (by using N-t-Boc-Met-Leu-Phe, a nonselective AnxA1 receptor antagonist, or by using an anti-AnxA1 neutralizing antiserum) prevented ROL- and Bt2cAMP-induced resolution and neutrophil apoptosis. Likewise, the ability of ROL or Bt2cAMP to induce neutrophil apoptosis was impaired in AnxA-knock-out mice. Finally, in in vitro settings, ROL and Bt2cAMP overrode the survival-inducing effect of LPS in human neutrophils in an AnxA1-dependent manner. Our results show that AnxA1 is at least one of the endogenous determinants mediating the pro-resolving properties of cAMP-elevating agents and cAMP-mimetic drugs.

Non-specific pleuritis in patients with active malignancy.

BACKGROUND AND OBJECTIVE: Pleuroscopy is the test of choice for patients with suspected malignant pleural effusion and negative cytology. Biopsies negative for malignancy are frequently attributed to non-specific pleuritis, which poses a dilemma in patients with a known active malignancy, raising concern for a false-negative result. Our primary objective was to determine the outcomes of patients with active malignancy who had a non-malignant diagnosis on pleuroscopy. METHODS: Retrospective review of all pleuroscopy cases from January 2005 to January 2015 at our institution was conducted. Biopsies were categorized by histopathology as malignant, eosinophilic or non-specific pleuritis. Malignant histopathology was considered a true positive. Eosinophilic or non-specific pleuritis was categorized as malignant, if malignancy was later identified during follow-up, or chemotherapy induced, possible radiation induced, other paramalignant, other benign or idiopathic. RESULTS: Of the 199 pleuroscopy cases reviewed, 172 (86%) had a history of active malignancy. On histopathology, 73 (42%) had malignancy, 9 (5%) had eosinophilic pleuritis and 90 (52%) had non-specific pleuritis. Three patients with non-specific pleuritis were diagnosed with malignancy at follow-up. Pleuritis in 24 patients was chemotherapy induced, 27 were possibly radiation induced, 11 were other paramalignant and 3 were other benign. Idiopathic pleuritis was diagnosed in 31 patients. Patients were monitored for a mean of 23 ± 11 months. CONCLUSION: The prevalence of malignant pleural disease was lower than expected for our patient population. Patients with no malignancy on histopathology were most likely to have non-specific pleuritis, a cause for which was identified in a majority of patients after clinical review.

Clinical Features and Prognosis of Nontuberculous Mycobacterial Pleuritis.

BACKGROUND: While nontuberculous mycobacterial (NTM) pleuritis rarely complicates pulmonary NTM infection, high mortality has been reported in case reports and small studies. OBJECTIVES: The purpose of this study was to clarify the clinical features and treatment outcomes of pulmonary NTM infection cases accompanied by NTM pleuritis. METHODS: Medical records of 1,044 patients with pulmonary NTM disease were retrospectively reviewed to select patients complicated by NTM-proven pleuritis. We investigated clinical characteristics, pathogens, pleural effusion examinations, radiographic findings, treatments, and clinical course of the NTM pleuritis patients. RESULTS: Among 1,044 cases with pulmonary NTM, NTM pleuritis occurred in 15 cases (1.4%). The mean age was 69 years with a performance status of mostly 2 or better (80.0%), and 6 cases (40.0%) were complicated by pneumothorax. Subpleural cavities were radiologically detected in 11 cases (73.3%), and extrapulmonary air-fluid level was detected in 14 cases (93.3%). Eleven patients were treated with combinations of 2-4 antimycobacterial drugs, including clarithromycin, and 2 patients were treated with isoniazid, rifampicin, and ethambutol. Chest tube drainage was performed in 11 cases, and surgical approach was added in 6 cases. The pleural effusion of 2 patients treated with only antimycobacterial medications gradually deteriorated. Two patients died from NTM pleuritis, and 1 patient died from pneumonitis during a mean of 1.8 years of follow-up. CONCLUSIONS: Comorbid NTM pleuritis was difficult to treat by medical therapy alone and resulted in a poor prognosis. In addition to antimycobacterial agents, chest tube drainage and surgical procedures in the early stages should be considered to treat NTM pleuritis.

Antiinflammatory properties of betulinic acid and xylopic acid in the carrageenan-induced pleurisy model of lung inflammation in mice.

This study investigated the antiinflammatory properties of betulinic acid (BA) and xylopic acid (XA) extracted from Margaritaria discoidea and Xylopia aethiopica, respectively. M. discoidea and X. aethiopica are plants native in Ghana and the West-African region and used traditionally to treat different pathologies including inflammatory conditions. The antiinflammatory effect of BA and XA was established by an in vivo assay using the carrageenan-induced pleural inflammation model in mice. Also, the ability of BA and XA to increase catalase, superoxide dismutase, glutathione levels and decrease lipid peroxidation level in reactive oxidative assays was assessed. In addition, the ability of XA and BA to prevent potential lung tissue damage was quantified. Pretreatment with BA and XA reduced significantly, signs of inflammation: neutrophil infiltration, oedema, and alveoli septal thickening in carrageenan-treated lung tissue. Additionally, BA or XA pretreatment lowered the degree of lipid peroxidation in the lung tissue while increasing the levels of catalase, superoxide dismutase, and glutathione in vivo. Comparatively, XA was more efficacious than BA in the prevention of lung tissue damage. BA and XA derived from X. aethiopica and M. discoidea possess antiinflammatory and in vivo antioxidant activities in mice pleurisy model. The effect of these compounds gives credence to the traditional use in the management of inflammatory conditions of the airway.

[Lupus-like syndrome in patients treated with anti-TNF-α factors]. / Anti-TNF tedavi ile iliskili lupus like sendromu.

A 56-year-old male patient presented with history of complaints of night sweats, short ness of breath, cough and yellow sputum, fever. There was a history of tumor neurosis factor-alpha (etanercept) due to ankylosing spondylitis. Postero-anterior chest X-ray; the right sinus was blunt, the right diaphragm had linear opacity compatible with atelectasis extending from the diaphragm to the periphery, left pleural effusion, left middle basal paracardiac opacity. In thorax tomography; pleural effusion and pericardial effusion and compressive atelectasis in the adjacent lung parenchyma were detected. Lymphocyte dominance had in cytological examination. Active chronic pleuritis and fibrinous exudate as benign cytology were reported in pleural biopsy. We are thought to develop pleurisy due to anti TNF-induced lupus like syndrome. 100 mg prednol was applied for three days. One month later the control was found toregress in the filter.

[Role of surgery in Saprochaete capitata (S. capitata) sepsis in a patient with acute myeloid leukemia]. / Rol de la cirugía en el manejo de la infección invasora por Saprochaete capitata.

Saprochaete capitata (S. capitata) fungal sepsis is a severe condition with a clinical presentation that is similar to other yeast originated fungal sepsis. It is observed in patients with hematological malignancies such as acute myeloid leukemia and neutropenia. We report a 23 year old male presenting with cough, fever and malaise. A bone marrow biopsy led to the diagnosis of acute myeloid leukemia. During the first cycle of chemotherapy the patient presented fever: blood cultures were positive for Klebsiella pneumoniae. Despite antimicrobial treatment, fever persisted; a computed tomography showed a focal splenic lesion; a left exudative pleural effusion appeared. A Matrix Assisted Laser Desorption Ionization-Time of Flight mass spectrometry identified the presence of S. capitata. After multiple antifungal treatments and pleural cavity cleansing by means of videothoracoscopy and laparoscopic splenectomy, the infection resolved and the patient completed his chemotherapy.

[ЕNDOSCOPIC METHODS OF TREATMENT OF SUBACUTE AND CHRONIC INFLAMMATORY PLEURAL DISEASES].

Own experience of the endoscopic methods usage in diagnosis and treatment of chronic pleural diseases in 343 patients, оperated, using videothoracoscopy and video-assisted thoracoscopy, was presented. Postoperative lethality have constituted 0.29%. Application of endoscopic methods in treatment of chronic pleural diseases was highly effective and miniinvasive.