Excretion of excess nitrogen and increased survival by loss of SLC6A19 in a mouse model of ornithine transcarbamylase deficiency.

Protein catabolism ultimately yields toxic ammonia, which must be converted to urea by the liver for renal excretion. In extrahepatic tissues, ammonia is temporarily converted primarily to glutamine for subsequent hepatic extraction. Urea cycle disorders (UCDs) are inborn errors of metabolism causing impaired ureagenesis, leading to neurotoxic accumulation of ammonia and brain glutamine.

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.

Feasibility of a prototype carbon nanotube enabled stationary digital chest tomosynthesis system for identification of pulmonary nodules by pulmonologists.

Background: Screen detected and incidental pulmonary nodules are increasingly common. Current guidelines recommend tissue sampling of solid nodules >8 mm. Bronchoscopic biopsy poses the lowest risk but is paired with the lowest diagnostic yield when compared to CT-guided biopsy or surgery.

Comparison of Microflow and Analytical Flow Liquid Chromatography Coupled to Mass Spectrometry Global Metabolomics Methods Using a Urea Cycle Disorder Mouse Model.

Microscale-based separations are increasingly being applied in the field of metabolomics for the analysis of small-molecule metabolites. These methods have the potential to provide improved sensitivity, less solvent waste, and reduced sample-size requirements. Ion-pair free microflow-based global metabolomics methods, which we recently reported, were further compared to analytical flow ion-pairing reagent containing methods using a sample set from a urea cycle disorder (UCD) mouse model.

AABIP Evidence-informed Guidelines and Expert Panel Report for the Management of Indwelling Pleural Catheters.

Background: While the efficacy of Indwelling pleural catheters for palliation of malignant pleural effusions is supported by relatively robust evidence, there is less clarity surrounding the postinsertion management.

Methods: The Trustworthy Consensus-Based Statement approach was utilized to develop unbiased, scientifically valid guidance for the management of patients with malignant effusions treated with indwelling pleural catheters. A comprehensive electronic database search of PubMed was performed based on a priori crafted PICO questions (Population/Intervention/Comparator/Outcomes paradigm).

Incidence and clinical relevance of non-small cell lung cancer lymph node micro-metastasis detected by staging endobronchial ultrasound-guided transbronchial needle aspiration.

Background: Approximately twenty percent of lymph node (LN) negative non-small cell lung cancer (NSCLC) patients who undergo curative intent surgery have pan-cytokeratin immunohistochemistry (IHC)-detectable occult micro-metastases (MMs) in resected LNs. The presence of the MMs in NSCLC is associated worsened outcomes. As a substantial proportion of NSCLC LN staging is conducted using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), we sought to determine the frequency of detection of occult MMs in EBUS-TBNA specimens and to evaluate the impact of MMs on progression-free and overall survival.

Electromagnetic Transthoracic Nodule Localization for Minimally Invasive Pulmonary Resection.

Background: Increased use of chest computed tomography and the institution of lung cancer screening have increased the detection of ground-glass and small pulmonary nodules. Intraoperative localization of these lesions via a minimally invasive thoracoscopic approach can be challenging. We present the feasibility of perioperative transthoracic percutaneous nodule localization using a novel electromagnetic navigation platform.

Quaking orchestrates a post-transcriptional regulatory network of endothelial cell cycle progression critical to angiogenesis and metastasis.

Angiogenesis is critical to cancer development and metastasis. However, anti-angiogenic agents have only had modest therapeutic success, partly due to an incomplete understanding of tumor endothelial cell (EC) biology. We previously reported that the microRNA (miR)-200 family inhibits metastasis through regulation of tumor angiogenesis, but the underlying molecular mechanisms are poorly characterized.

Peripheral Lung Nodule Diagnosis and Fiducial Marker Placement Using a Novel Tip-Tracked Electromagnetic Navigation Bronchoscopy System.

Background: Electromagnetic navigation (EMN) has improved bronchoscopic access to peripheral pulmonary nodules. A novel EMN system utilizing novel tip-tracked instruments for endobronchial [electromagnetic navigation bronchoscopy (ENB)] as well as transthoracic lung biopsy [electromagnetic-guided transthoracic needle aspiration (EMTTNA)] has become available. The system provides real-time feedback as well as the ability to biopsy lesions outside of the airway.

Inhibiting neutral amino acid transport for the treatment of phenylketonuria.

The neuropathological effects of phenylketonuria (PKU) stem from the inability of the body to metabolize excess phenylalanine (Phe), resulting in accumulation of Phe in the blood and brain. Since the kidney normally reabsorbs circulating amino acids with high efficiency, we hypothesized that preventing the renal uptake of Phe might provide a disposal pathway that could lower systemic Phe levels. SLC6A19 is a neutral amino acid transporter responsible for absorption of the majority of free Phe in the small intestine and reuptake of Phe by renal proximal tubule cells.

An update on the role of advanced diagnostic bronchoscopy in the evaluation and staging of lung cancer.

Lung cancer remains a common and deadly disease. Many modalities are available to the bronchoscopist to evaluate and stage lung cancer. We review the role of bronchoscopy in the staging of the mediastinum with convex endobronchial ultrasound (EBUS) and discuss emerging role of esophageal ultrasonography as a complementary modality.

Pleural effusions in non-transplanted cystic fibrosis patients.

Background: Pleural effusions are considered rare in cystic fibrosis (CF) patients. There is a paucity of available information in the literature concerning the nature and significance of pleural effusions in non-transplanted CF patients.

Methods: We conducted a multicenter retrospective evaluation of non-transplanted adult CF patients.

Convex Endobronchial Ultrasound-Guided Fiducial Placement for Malignant Central Lung Lesions: A Case Series.

Background: Stereotactic radiotherapy is a useful therapeutic modality in patients with lung cancer and patients with pulmonary metastases who cannot tolerate, are not candidates for, or do not want surgery. Successful use of radial endobronchial ultrasound (EBUS) and navigation bronchoscopy to guide the placement of the fiducials required for stereotactic radiotherapy in peripheral lung lesions has been previously reported. We present the first series of patients in which convex-probe EBUS was used to deliver fiducials to hilar and mediastinal lymph nodes as well as central thoracic lesions.

Interventional pulmonology in the intensive care unit: percutaneous tracheostomy and gastrostomy.

Bedside percutaneous tracheostomy and gastrostomy tube placement are cost-effective and safe techniques employed in the management of critically ill patients requiring prolonged mechanical ventilation. Both procedures have been well characterized and studied in the surgical and gastroenterology literature. Recently the performance of these procedures by interventional pulmonologists have been reported.

Inhibition of osteoclastogenesis by prolyl hydroxylase inhibitor dimethyloxallyl glycine.

Studies examining the effects of hypoxia upon osteoclast biology have consistently revealed a stimulatory effect; both osteoclast differentiation and resorption activity have been shown to be enhanced in the presence of hypoxia. In the present study we examined the effects of the hypoxia mimetics dimethyloxallyl glycine (DMOG) and desferrioxamine (DFO) upon osteoclastogenesis. In contrast to hypoxia, our studies revealed a dose-dependent inhibition of osteoclast formation from macrophages treated with DMOG and DFO.

Intra-arterial methylprednisolone infusion in treatment-resistant graft-versus-host disease.

Acute graft-versus-host disease (GVHD) is a potentially fatal complication following allogeneic hematopoietic stem cell transplant. Standard primary therapy for acute GVHD includes systemic steroids, often in combination with other agents. Unfortunately, primary treatment failure is common and carries a high mortality.

A hypoxic inducible factor-1 alpha hybrid enhances collateral development and reduces vascular leakage in diabetic rats.

Background: Diabetes mellitus is a common comorbidity of atherosclerosis. Hypoxia-inducible factor-1 (HIF-1) is the master regulator of the angiogenic response to hypoxia.

Methods: We studied the effects of adenoviral vectors expressing a constitutively active HIF-1 alpha hybrid (Ad2/HIF-1 alpha/VP16) or vascular endothelial growth factor (Ad2/VEGF) on collateral development and vascular leakiness in a diabetic rat model of hindlimb ischemia.