Genomic profiling of tissue and blood predicts survival outcomes in patients with resected pleural mesothelioma.

Purpose: Pleural mesothelioma (PM) is an aggressive tumor still considered incurable, in part due to the lack of predictive biomarkers. Little is known about the clinical implications of molecular alterations in resectable PM tissues and blood. Here, we characterized genetic alterations to identify prognostic and predictive biomarkers in patients with resected PM.

Prophylactic epinephrine attenuates severe bleeding in lung transplantation patients undergoing transbronchial lung biopsy: Results of the PROPHET randomized trial.

Background: Severe hemorrhage is an uncommon yet potentially life-threatening complication of transbronchial lung biopsy. Lung transplantation recipients undergo multiple bronchoscopies with biopsy and are considered to be at an increased risk for bleeding from transbronchial biopsy, independent of traditional risk factors. We aimed to evaluate the efficacy and safety of endobronchial administration of prophylactic topical epinephrine in attenuating transbronchial biopsy-related hemorrhage in lung transplant recipients.

Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection: An International, Multicenter, Retrospective Cohort Study.

Background: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined.

Liquid biopsy from research to clinical practice: focus on non-small cell lung cancer.

Introduction: In the current era of personalized medicine, liquid biopsy has acquired a relevant importance in patient management of advanced stage non-small cell lung cancer (NSCLC). As a matter of fact, liquid biopsy may supplant the problem of inadequate tissue for molecular testing. The term 'liquid biopsy' refers to a number of different biological fluids, but is most clearly associated with plasma-related platforms.

Management of life-threatening hemoptysis in the ICU.

Life-threatening hemoptysis is commonly encountered in the ICU and its management can be challenging even for experienced clinicians. Depending on the etiology and severity, one can tailor the treatment modality and therapeutic intervention(s). The grading of severity of hemoptysis varies greatly in the literature; however, unlike hemorrhage in other scenarios, small amounts of blood can significantly impair oxygenation and ventilation leading to cardiovascular collapse.

Cryptococcal empyema treated with tube thoracostomy and intrapleural fibrinolysis.

A 55-year old woman with a history of relapsed T-cell ALL presented with right pleuritic chest pain and decreased breath sounds over the right hemithorax. Imaging of the chest showed loculated effusions. Tube thoracostomy was performed with intrapleural application of alteplase and dornase alpha over a 3-day period.

Electrocautery Snare Resection and Argon Plasma Coagulation of Endobronchial Kaposi Sarcoma Presenting as an Obstructing Tumor.

Kaposi sarcoma (KS) is the most common neoplasm associated with Acquired Immune Deficiency Syndrome (AIDS), but antiretroviral therapy has reduced its incidence dramatically. Endobronchial KS is usually associated with concurrent mucocutaneous lesions and is highly vascular; so biopsy generally is not recommended. The use of advanced bronchoscopic techniques for evaluation of endobronchial KS may mitigate the bleeding risks but has not been described previously.

Intrapleural Alteplase and Dornase in a Pregnant Woman With Complicated Parapneumonic Effusion.

The use of intrapleural alteplase and dornase in pregnant patients remains an uncertain practice because bleeding complications in these cases could be devastating. We present a case in which we successfully used a modified protocol safely.

Acute eosinophilic pneumonia triggered by secondhand cigarette smoke exposure in an elderly man.

The spectrum of eosinophilic lung diseases comprises a diverse group of pulmonary disorders associated with tissue or peripheral eosinophilia. [Acute eosinophilic pneumonia (AEP)] is an uncommon eosinophilic lung disease that can be idiopathic, but identifiable causes include medications, inhalational exposures and infections. Most cases in the literature are associated with first-time cigarette smoking or resuming smoking.

Prophylactic epinephrine for the prevention of transbronchial lung biopsy-related bleeding in lung transplant recipients (PROPHET) study: a protocol for a multicentre randomised, double-blind, placebo-controlled trial.

Introduction: Transbronchial lung biopsy (TBLB) is frequently performed in single-lung and double-lung transplant recipients for evaluation of clinical and radiological findings as well as routine surveillance for acute cellular rejection. While rates of clinically significant TBLB-related haemorrhage are <1% for all comers, the incidence in lung transplant recipients is reported to be higher, presumably due to persistent allograft inflammation and alterations in allograft blood flow. While routinely performed by some bronchoscopists, the efficacy and safety profile of prophylactic administration of topical intrabronchial diluted epinephrine for the prevention of TBLB-related haemorrhage has not been explored in a prospective manner.

Tissue Acquisition During EBUS-TBNA: Comparison of Cell Blocks Obtained From a 19G Versus 21G Needle.

Background: Previous studies have shown that needle gauge size has no significant impact on diagnostic yield during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Our objective was to determine whether cell blocks obtained via the new Flex 19G EBUS-TBNA needle would contain more cellular material based on cell area compared with those obtained from a 21G needle.

Methods: A prospective analysis of patients undergoing EBUS-TBNA at our institutions was performed.

Intrapleural Therapy for Empyema in the Setting of a Bronchopleural Fistula: A Novel Use of an Intrabronchial Valve.

Postsurgical empyema with bronchopleural fistula can be difficult to manage. We present a patient with postoperative empyema with bronchopleural fistula who was successfully treated nonoperatively by placing an intrabronchial valve to address the bronchopleural fistula, which allowed for safe administration of intrapleural fibrinolytics and antibiotics for definitive treatment of the empyema. Although the presence of a bronchopleural fistula is considered a contraindication to the administration of intrapleural tissue plasminogen activator and deoxyribonuclease, this case demonstrates a novel use of the intrabronchial valve that allowed these medications to be used.

Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer.

Purpose: To determine, in a retrospective analysis of a large cohort of stage III non-small cell lung cancer patients treated with curative intent at our institution, whether having a pathologic complete response (pCR) influenced overall survival (OS) or freedom from recurrence (FFR) in patients who underwent definitive (≥60 Gy) neoadjuvant doses of chemoradiation (CRT).

Methods And Materials: At our institution, 355 patients with locally advanced non-small cell lung cancer were treated with curative intent with definitive CRT (January 2000-December 2013), of whom 111 underwent mediastinal reassessment for possible surgical resection. Ultimately 88 patients received trimodality therapy.

From electrocautery, balloon dilatation, neodymium-doped:yttrium-aluminum-garnet (Nd:YAG) laser to argon plasma coagulation and cryotherapy.

Over the past decade, there has been significant advancement in the development/application of therapeutics in thoracic diseases. Ablation methods using heat or cold energy in the airway is safe and effective for treating complex airway disorders including malignant and non-malignant central airway obstruction (CAO) without limiting the impact of future definitive therapy. Timely and efficient use of endobronchial ablative therapies combined with mechanical debridement or stent placement results in immediate relief of dyspnea for CAO.

IFN-γ directly controls IL-33 protein level through a STAT1- and LMP2-dependent mechanism.

IL-33 contributes to disease processes in association with Th1 and Th2 phenotypes. IL-33 mRNA is rapidly regulated, but the fate of synthesized IL-33 protein is unknown. To understand the interplay among IL-33, IFN-γ, and IL-4 proteins, recombinant replication-deficient adenoviruses were produced and used for dual expression of IL-33 and IFN-γ or IL-33 and IL-4.

Full-length IL-33 promotes inflammation but not Th2 response in vivo in an ST2-independent fashion.

Expression of IL-33 is elevated in patients with pulmonary diseases, and full-length (not proteolytically processed) IL-33 is the predominant form in the lungs in health and disease. To determine whether activation of IL-33 is needed for functional effects, activities of full-length mouse and mature mouse (mm) forms of IL-33 were compared in vivo. Replication-deficient adenoviral constructs were used for gene delivery.

Natural production and functional effects of alternatively spliced interleukin-4 protein in asthma.

We have previously described an alternatively spliced isoform of IL-4 mRNA that omits exon 2 and is termed IL-4δ2. However, the natural production of IL-4δ2 protein and its association with disease have not been previously assessed due to unavailability of an antibody that interacts with IL-4δ2 without cross-reactivity with full length IL-4. We used a unique monoclonal antibody (mAb) that reacts with IL-4δ2, but not with IL-4, and observed that IL-4δ2 is naturally produced by T cells from patients with asthma, but not from healthy controls.

A novel assay for monitoring internalization of nanocarrier coupled antibodies.

Background: Discovery of tumor-selective antibodies or antibody fragments is a promising approach for delivering therapeutic agents to antigen over-expressing cancers. Therefore it is important to develop methods for the identification of target- and function specific antibodies for effective drug delivery. Here we describe a highly selective and sensitive method for characterizing the internalizing potential of multivalently displayed antibodies or ligands conjugated to liposomes into tumor cells.

Therapeutic efficacy of anti-ErbB2 immunoliposomes targeted by a phage antibody selected for cellular endocytosis.

Many targeted cancer therapies require endocytosis of the targeting molecule and delivery of the therapeutic agent to the interior of the tumor cell. To generate single chain Fv (scFv) antibodies capable of triggering receptor-mediated endocytosis, we previously developed a method to directly select phage antibodies for internalization by recovering infectious phage from the cytoplasm of the target cell. Using this methodology, we reported the selection of a panel of scFv that were internalized into breast cancer cells from a nonimmune phage library.