Imaging of pleural disease.

The pleural space is a "potential" anatomical space which is formed of two layers: visceral and parietal. It normally contains a trace of fluid (∼10 mL in each hemithorax). Diseases of the pleura can manifest with thickening of the pleural membranes or by abnormal accumulation of air or liquid. Chest radiographs are often the first imaging tests to point to a pleural pathology. With the exception of pneumothorax, and due to the inherent limitations of chest radiographs, ultrasound and/or computed tomography are usually required to further characterise the pleural pathology and guide management. This review summarises the utility of different imaging tools in the management of pleural disease and discusses new and evolving tools in imaging of the pleura.

Transbronchial Lung Cryobiopsy for Diagnosing Interstitial Lung Diseases and Peripheral Pulmonary Lesions - A Stepwise Approach.

Transbronchial lung cryobiopsy (TBLC) is an invasive procedure increasingly implemented during the last decade as an alternative to video-assisted thoracic surgery lung biopsy (SLB) for diagnosing interstitial lung diseases (ILDs). The indication for TBLC has primarily been to sub-classify a specific ILD subtype when this cannot be achieved on the basis of a preceding multidisciplinary team discussion. Although SLB is considered the gold standard for establishing a histological diagnosis, TBLC has been gradually suggested as the first-choice histological diagnostic modality in patients with unclassified ILDs due to a comparable diagnostic yield with SLB, but superior to SLB in terms of complications, including mortality. During recent years, radial endobronchial ultrasound (R-EBUS) and electromagnetic navigation bronchoscopy (ENB)-guided TBLC for peripheral pulmonary lesions have also been described as safe procedures, which may improve the diagnostic yield compared to forceps biopsies. Still, the diagnostic properties of TBLC rely on the quality of the procedure's performance. This article aims to describe the stepwise approach to conducting TBLC with a flexible bronchoscope for the different indications mentioned, which might be helpful for novice bronchoscopists performing TBLC.

The CRISPR/Cas9 Minipig-A Transgenic Minipig to Produce Specific Mutations in Designated Tissues.

The generation of large transgenic animals is impeded by complex cloning, long maturation and gastrulation times. An introduction of multiple gene alterations increases the complexity. We have cloned a transgenic Cas9 minipig to introduce multiple mutations by CRISPR in somatic cells. Transgenic Cas9 pigs were generated by somatic cell nuclear transfer and were backcrossed to Göttingen Minipigs for two generations. Cas9 expression was controlled by FlpO-mediated recombination and was visualized by translation from red to yellow fluorescent protein. In vitro analyses in primary fibroblasts, keratinocytes and lung epithelial cells confirmed the genetic alterations executed by the viral delivery of single guide RNAs (sgRNA) to the target cells. Moreover, multiple gene alterations could be introduced simultaneously in a cell by viral delivery of sgRNAs. Cells with loss of TP53, PTEN and gain-of-function mutation in KRASG12D showed increased proliferation, confirming a transformation of the primary cells. An in vivo activation of Cas9 expression could be induced by viral delivery to the skin. Overall, we have generated a minipig with conditional expression of Cas9, where multiple gene alterations can be introduced to somatic cells by viral delivery of sgRNA. The development of a transgenic Cas9 minipig facilitates the creation of complex pre-clinical models for cancer research.

[Malignant pleural effusion].

Malignant pleural effusion (MPE) is a common condition, often associated with a high level of symptoms. In this review, several palliative treatments for symptomatic MPE are summarised, including repeated thoracentesis, pleurodesis and insertion of indwelling pleural catheters. Choice of treatment depends on patient symptoms, life expectancy, pleural fluid production, expected effect of oncological treatment, whether trapped lung is suspected or not, and patient preferences. Treatment should be discussed with a pulmonary specialist with knowledge of pleural diseases.

Ultrasound Evaluation of Hemidiaphragm Function Following Thoracentesis: A Study on Mechanisms of Dyspnea Related to Pleural Effusion.

BACKGROUND: Dyspnea is the major symptom caused by pleural effusion. The pathophysiological pathways leading to dyspnea are poorly understood. Dysfunction of respiratory mechanics may be a factor. We aimed to study the change in diaphragmatic function following thoracentesis. METHODS: Patients undergoing thoracentesis at a highly specialized pleural center, underwent ultrasound evaluation of hemidiaphragm movement, before and after thoracentesis was performed. The change was compared to the reduction of dyspnea measured at the modified Borg scale. RESULTS: Thirty-two patients were included. Dyspnea was reduced from 5.01 [95% confidence interval (CI): 4.12-6.04] to 2.6 (95% CI: 1.87-3.4, P<0.0001). Low hemidiaphragmatic movement before thoracentesis on the side of pleural effusion was improved by 17.4 cm (95% CI: 13.04-21.08), equalizing movement to the side without pleural effusion. On average, 1283 mL (SD: 469) fluid was drained. Multiple linear regression analysis showed that prethoracentesis ultrasound evaluation of hemidiaphragmatic function was correlated with successful thoracentesis. CONCLUSION: Hemidiaphragm function is reduced on the side of pleural effusion, and thoracentesis restores function. Improvement in diaphragm movement is related to a reduction in dyspnea.

Intralymphatic Immunotherapy: Update and Unmet Needs.

Allergen-specific immunotherapy (AIT) is the only allergy treatment that confers long-term symptom amelioration for patients suffering from allergy. The most frequently used allergen application route is subcutaneous injection (SCIT), commonly taken as the gold standard, followed by sublingual (SLIT) or oral (OIT) application of allergen preparations. This is an up-to-date review of the clinical evidence for a novel route of allergen application, i.e., directly into lymph nodes - intralymphatic immunotherapy (ILIT). The major advantages of ILIT over the current AIT approaches are its short duration and the low allergen doses administered. The whole treatment consists of merely 3 ultrasound-guided injections into inguinal lymph nodes 1 month apart. While the number of patients included in randomised controlled trials is still limited, the clinical results for ILIT are encouraging, but more clinical trials are needed, as well as more preclinical work for optimising formulations.