Rheumatoid pleurisy confirmed by biopsy of a chest wall nodule by thoracoscopy under local anaesthesia.

Rheumatoid pleurisy is common in patients with rheumatoid arthritis, but distinguishing it from other diseases, such as heart failure and tuberculous pleurisy, is often difficult. A man in his 70s with stable rheumatoid arthritis presented with cardiac enlargement and bilateral pleural effusion on chest radiography. Pleural fluid studies showed lymphocytosis, adenosine deaminase level of 51.6 U/L and rheumatoid factor level of 2245.3 IU/mL, suggestive of rheumatoid pleurisy and tuberculous pleurisy. Thoracoscopy under local anaesthesia revealed erythema of the parietal pleura, small papillary projections and fibrin deposits. H&E-stained biopsy specimens showed inflammatory granulomas with strong lymphocytic infiltration and non-caseating granulomas. He was diagnosed with rheumatoid pleurisy. His symptoms improved with 30 mg of prednisolone. This study highlights that biopsy using thoracoscopy under local anaesthesia effectively diagnoses rheumatoid pleurisy, which may be challenging to diagnose.

Pathological analysis and etiological assessment of pulmonary lesions and its association with pleurisy in slaughtered pigs.

The intensification of pig farming has posed significant challenges in managing and preventing sanitary problems, particularly diseases of the respiratory complex. Monitoring at slaughter is an important control tool and cannot be overstated. Hence, this study aimed at characterizing both macroscopical and microscopical lesions and identifying the Actinobacillus pleuropneumoniae (APP), Mycoplasma hyopneumoniae (Mhyo), and Pasteurella multocida (PM) associated with pleurisy in swine. For this, a selected slaughterhouse in São Paulo State underwent a thorough examination of carcasses on the slaughter line, followed by lung sampling. The carcasses and lungs underwent macroscopical examination and were classified according to the score of pleurisy and lung samples were allocated into five groups, being: G0: score 0 - no lesions; G1: score 1; G2: score 2; G3: score 3; and G4: score 4. In total, 217 lung fragments were collected, for the histopathological evaluation and detection of the following respiratory pathogens: APP, Mhyo, and PM by qPCR. The results demonstrated that Mhyo and APP were the most prevalent etiological agents (single and co-identification) in lung samples, in different scores of pleurisies, while bronchopneumonia and bronchus-associated lymphoid tissue (BALT) hyperplasia lesions were the most frequent histopathological findings. Positive correlations were found between the quantification of APP DNA with 1) the score of pleurisy (R=0.254); 2) with the score of lung consolidation in all lung lobes (R=0.181 to R=0.329); and 3) with the score of lung consolidation in the entire lung (R=0.389). The study brings relevant information regarding the main bacterial pathogens associated with pleurisy in pigs and helps with understanding the relationship between the abovementioned pathogens and their impact on the respiratory health of pigs.

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.

Effects of Acylhydrazone Derivatives on Experimental Pulmonary Inflammation by Chemical Sensitization.

BACKGROUND: Chronic lung diseases are characterized by airway inflammation and remodelling of the lung parenchyma that triggers considerable impairment of respiratory function. OBJECTIVE: In this study, two compounds belonging to the N-acylhydrazone class were evaluated, aiming to identify new therapeutic agents for pulmonary inflammatory diseases. MATERIALS AND METHODS: The acute toxicity of 2-cyano-N'-(3-ethoxy-4-hydroxybenzylidene)- acetohydrazide (JR-12) and N'-benzylidene-2-cyano-3-phenylacrylohydrazide (JR09-Bz) was evaluated. Afterwards, they were tested in models of ovalbumin (OVA)-induced allergic asthma and pleurisy, bleomycin-induced pulmonary fibrosis, in addition to mucolytic activity. RESULTS AND DISCUSSION: The compounds did not show toxicity at the dose of 2,000 mg/kg, and no animal died. On OVA-induced pleurisy, animals treated with JR-12 or JR09-Bz at a dose of 10 mg/kg (orally) showed significant inhibition of the leukocyte infiltrate in the bronchoalveolar lavage by 62.5% and 61.5%, respectively, compared to the control group. The compounds JR-12 and JR09-Bz were also active in blocking the allergic asthmatic response triggered by OVA, reducing the leukocyte infiltrate by 73.1% and 69.8%, respectively. Histopathological changes and mast cell migration in treated animals with JR-12 or JR09-Bz were similar to treatment with the reference drugs dexamethasone and montelukast. JR-12 and JR09-Bz also reversed airway remodeling in animals on the bleomycin-induced fibrosis model compared to the control group. Furthermore, it was observed that N-arylhydrazone derivatives showed expectorant and mucolytic activities, increasing mucus secretion by 45.6% and 63.8% for JR-12 and JR09-Bz, respectively. CONCLUSION: Together, the results show that JR-12 and JR09-Bz showed promising activity against airway inflammation, as well as low toxicity.

UHRF1 Immunohistochemical Staining Separates Benign Reactive Spindle Cell Mesothelial Proliferations From Sarcomatoid Mesotheliomas.

The separation of benign from malignant mesothelial proliferations is often a difficult pathologic problem. UHRF1 (ubiquitin-like with plant homeodomain and ring finger domains-1) is a regulator of DNA methylation and an epigenetic driver of various human cancers. It has recently been reported that UHRF1 is overexpressed in mesotheliomas. We asked whether UHRF1 immunohistochemistry could be used to separate benign from malignant mesothelial proliferations. Initial studies showed that UHRF1 stained mesothelial cells but also endothelial and other non-neoplastic cells, so that accurate counting of positive mesothelial cells was difficult. Therefore, we ran dual UHRF1-AE1/AE3 stains on 2 tissue microarrays containing 40 reactive mesothelial proliferations and 61 mesotheliomas and only counted UHRF1 staining in keratin-positive cells. On average 10.3±8.6% (mean±SD; range: 0% to 36, median: 6.8%) of epithelioid mesothelioma cells stained compared with 5.3±4.8% (range: 0% to 15%, median: 4.1%) of reactive epithelial mesothelial cells. This difference was statistically significant but there was too much overlap to use diagnostically. In contrast, 37±26% (range: 2.5% to 95%, median: 31%) of cells in sarcomatoid mesotheliomas compared with 1.2±1.2% (range: 0% to 3.0%, median: 1.0%) of cells in reactive spindle cell mesothelial proliferations stained. To confirm this difference we stained whole sections of 21 sarcomatoid mesotheliomas and 19 cases of organizing pleuritis. Staining of mesothelial cells was seen in 2.1±2.4% (range: 0% to 6.8%, median: 1.0%) of organizing pleuritis cases and 44±22% (range: 14% to 90%, median: 41%) of sarcomatoid mesotheliomas. We conclude that dual UHRF1-AE1/AE3 immunohistochemistry is very useful for separating benign spindle cell mesothelial proliferations from sarcomatoid mesotheliomas.

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.

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.

Acute toxicity, antinociceptive, and anti-inflammatory activities of the orally administered crotamine in mice.

Crotamine is a polypeptide toxin isolated from rattlesnake venom. Although several studies have been developed identifying many biological effects of isolated crotamine, none of them evaluated its acute toxicity, antinociceptive, and anti-inflammatory activities through oral administration. All in vivo experiments from this study were performed in mice. The up-and-down procedure and hippocratic screening were carried out to evaluate possible pharmacological and toxic effects. Antinociceptive and anti-inflammatory activities of this toxin were evaluated using acetic acid-induced abdominal writhing, formalin-induced pain assays, croton oil-induced ear edema, and carrageenan-induced pleurisy. Crotamine did not cause lethality or signs of intoxication up to the maximum dose tested (10.88 mg/kg). The number of contortions was reduced significantly by 34, 57, and 74% at the oral doses of 0.08, 0.16, and 0.32 mg/kg, respectively. At the dose of 0.16 mg/kg, crotamine decreases pain time-reactivity at neurogenic phase by 45% and at inflammatory phase by 60%. Also, crotamine elicited antiedematogenic activity through the attenuation of the croton oil-induced ear edema by 77%. In the carrageenan-induced pleurisy, the leukocyte, neutrophil, and mononuclear cell migration to the lesion site were reduced by 52%, 46%, and 59%, respectively. Altogether, crotamine demonstrated in vivo antinociceptive and anti-inflammatory effect through acute oral administration, generating an anti-migratory mechanism of action at non-toxic doses.

GATA3 is a useful immunohistochemical marker for distinguishing sarcomatoid malignant mesothelioma from lung sarcomatoid carcinoma and organizing pleuritis.

Sarcomatoid malignant mesothelioma (SMM) tends to occur in the pleura and is morphologically similar to lung sarcomatoid carcinoma (LSC) and organizing pleuritis (OP). Because SMM often does not express mesothelial markers, it is very difficult to distinguish from LSC and OP. GATA-binding protein 3 (GATA3) is a specific immunohistochemical (IHC) marker of breast and urothelial carcinoma. We routinely find that GATA is expressed in MM; however, GATA3 expression in SMM and its reference value for distinguishing SMM from LSC and OP remain unclear. Here, we used IHC methods to detect the expression of GATA3 and classic mesothelial markers in 17 SMM, 12 LSC, and 7 OP cases. We detected the following expression rates in SMM versus LSC cases: GATA3 (70.6% vs. 16.7%, p = 0.008), calretinin (52.9% vs. 8.3%, p = 0.019), Wilms tumor (WT)-1 (64.7% vs. 0%, p = 0.000), D2-40 (47.1% vs. 16.7%, p = 0.126), CK5/6 (35.3% vs. 25.0%, p = 0.694), and pan-cytokeratin (CKpan) (88.2% vs. 100.0%, p = 0.498). The specificities of calretinin, WT-1, and GATA3 in distinguishing SMM from LSC were 91.7%, 100%, and 83.3%, respectively, and combinations of any two of these three markers exhibited 100% specificity for SMM. Notably, the sensitivity of calretinin+/WT1+ staining for SMM was only 23.5%, which increased to 64.7% after including GATA3. Furthermore, all OP cases showed partial or diffuse expression of CKpan, WT-1, and D2-40 but no GATA3 and calretinin expression. In conclusion, GATA3 is an IHC marker with excellent sensitivity and specificity for SMM, and the combined consideration of GATA3, calretinin, and WT-1 was best for distinguishing SMM from LSC. Moreover, CKpan, WT-1, and D2-40 had no value for distinguishing SMM from OP, and GATA3 and calretinin were the most specific markers for distinguishing these two lesions.

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.

Latent class analysis identifies multimorbidity patterns in pigs with respiratory disease.

Respiratory disease is one of the major causes of losses to the pig industry worldwide. The pig subsector is the largest component of the livestock sector in the Philippines. Using lung scoring, this study aimed to estimate the prevalence of thoracic lesions in slaughter-age pigs in two provinces in the Philippines (Batangas and Albay) and define classes for respiratory health of pigs characterised by different patterns of thoracic lesions. A total of 260 pigs from Batangas and 300 pigs from Albay from either commercial or backyard farm types were included in this cross-sectional study. Lungs were scored for cranio-ventral pneumonia (0-55) and pleurisy (0-3). Presence or absence of pericarditis as well as focal dorso-caudal pneumonia were recorded. Latent class analyses considering four indicator variables, and province and farm type as covariates were used to explore different patterns of thoracic lesions across the study populations. Using a threshold of ≥7, the prevalence of a high lung score was 51.9% (95% confidence interval [CI]: 42.3-61.4%) and 13.7% (95% CI: 8.1-22.2%) in Batangas and Albay, respectively. Similarly, the prevalence of a pleurisy score of ≥1 was 56.9% (95% CI: 37.5-74.4%) and 5.0% (95% CI: 2.9-8.4%), pericarditis 24.6% (95%CI: 10.1-48.6%) and 1.7% (95%CI: 0.3-6.7%) and focal dorso-caudal pneumonia lesions 7.7% (95% CI: 3.7-15.5%) and 0% (97.5% one-sided CI: 0-1.2%), respectively. Latent class analyses identified four classes based on lung score, pleurisy score and the presence/absence of pericarditis: "healthy", "mild respiratory disease", "moderate pneumonia", and "multi-lesion". The relative frequency of these classes differed with province and farm type. Most pigs from Albay were "healthy", whereas in Batangas most pigs from commercial farms were "multi-lesion" and those from backyard farms were in the "mild respiratory disease" class. This study has provided baseline data on thoracic lesions in slaughter-age pigs for the provinces of Batangas and Albay in the Philippines. Targeting farms and areas where "multi-lesion pigs" are most common and further research to identify risk factors for particular classes should maximize impact of future control measures. The latent class analysis approach used could be applied more widely and could add value to analysis of multi-morbidity data collected routinely as part of ongoing monitoring schemes.

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.

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.

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.

Use of Programmed Death Ligand-1 (PD-L1) Staining to Separate Sarcomatoid Malignant Mesotheliomas From Benign Mesothelial Reactions.

CONTEXT.­: The separation of benign from malignant mesothelial proliferations is a difficult morphologic problem. Some mesotheliomas stain for programmed death ligand-1 (PD-L1). OBJECTIVE.­: To determine whether PD-L1 staining can separate mesotheliomas from reactive mesothelial proliferations (RMPs). DESIGN.­: We stained 2 tissue microarrays containing in toto 62 malignant mesotheliomas and 88 RMPs, using anti-PD-L1 antibody 22C3. Staining was graded by using an immunoreactive score encompassing intensity/distribution and was divided into negative, weak, moderate, and strong. Because PD-L1 staining can be heterogeneous, we also stained 10 whole sections of sarcomatoid/desmoplastic mesotheliomas (SMMs) and 10 whole sections of spindled RMPs in the form of organizing pleuritis, the major morphologic differential of SMM. These 20 cases were not on the tissue microarrays. RESULTS.­: RMPs showed generally negative, or occasionally weak staining in either the epithelioid or spindle cell compartments, whereas moderate to strong staining was seen in 10 of 14 SMMs but only in 6 of 48 epithelioid mesotheliomas (EMMs). The difference between SMM and RMP staining was statistically significant (P < .001), but between EMM and RMP was not significant. Whole section cases of organizing pleuritis showed no staining (N = 8) or weak staining (N = 2), whereas moderate/strong staining was seen in 9 of 10 whole sections of SMMs, a statistically significant difference (P = .02). There were no "hot spots" of RMP staining, suggesting that heterogeneous staining of RMPs is not a confounder. CONCLUSIONS.­: Strong diffuse PD-L1 staining using antibody 22C3 supports a diagnosis of SMM when the differential diagnosis is RMPs, but PD-L1 staining is not useful for separating EMMs from RMPs.

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.