SLC4A11 mediates ammonia import and promotes cancer stemness in hepatocellular carcinoma.

End stage liver disease is marked by portal hypertension, systemic elevations in ammonia, and development of hepatocellular carcinoma (HCC). While these clinical consequences of cirrhosis are well described, it remains poorly understood whether hepatic insufficiency and the accompanying elevations in ammonia contribute to HCC carcinogenesis. Using preclinical models, we discovered that ammonia entered the cell through the transporter SLC4A11 and served as a nitrogen source for amino acid and nucleotide biosynthesis. Elevated ammonia promoted cancer stem cell properties in vitro and tumor initiation in vivo. Enhancing ammonia clearance reduced HCC stemness and tumor growth. In patients, elevations in serum ammonia were associated with an increased incidence of HCC. Taken together, this study forms the foundation for clinical investigations using ammonia lowering agents as potential therapies to mitigate HCC incidence and aggressiveness.

Routine Chest Radiography for the Evaluation of Pneumothorax Following Bronchoscopy.

RATIONALE AND OBJECTIVES: To determine the utility of routine postbronchoscopy chest radiography to detect pneumothorax. MATERIALS AND METHODS: This retrospective quality improvement cohort study was approved by the Institutional Review Board. All outpatients (n = 1443) who underwent protocol-driven postbronchoscopy chest radiography in one health system from January 2010 to July 2017 were identified by electronic medical record query. The prevalence of pneumothorax (with 95% confidence intervals [CI]) and clinical outcome were determined following coded review of chest radiography reports and review of the electronic medical record. The effect of smoking and lung disease on risk of pneumothorax was determined with Chi Square tests. RESULTS: Of 1443 subjects undergoing interventional bronchoscopy, 6% (93/1443) were current smokers, 35% (505/1442) were former smokers, and 35% (540/1443) had known lung disease. Pneumothorax prevalence was 3.4% (49/1443; 95% CI: 2.6%-4.5%) following any intervention and 4.1% (42/1032; 95% CI: 3.9%-5.5%) following transbronchial intervention. In those without known pre-existing pneumothorax or a confirmed false positive diagnosis, the real overall pneumothorax rate was 2.9% (42/1443; 95% CI: 2.1%-3.9%). The risk of pneumothorax did not differ based on smoking history (p = 0.99) or history of lung disease (p = 0.19). Of 49 subjects with pneumothorax, 13 were symptomatic, and 10 had a change in management including chest tube placement (N = 2), inpatient admission (N = 3), and/or observation (N = 7). No pneumothorax-related intervention was performed in asymptomatic patients. CONCLUSION: Pneumothorax following interventional outpatient bronchoscopy is uncommon, usually asymptomatic, and often clinically insignificant. Asymptomatic postbronchoscopy patients are very low risk and may not need routine imaging.

Advanced Quality Training in Radiology: Inaugural Report of a 2-Year Program.

OBJECTIVE. The purpose of this study is to describe and analyze the outcomes of a 2-year advanced quality training program for radiology residents. MATERIALS AND METHODS. In 2016, the radiology quality committee of a quaternary health system created a hands-on 2-year advanced quality training curriculum for diagnostic and interventional radiology residents. Internal candidates with the following prerequisites submitted competitive applications: registration for a 2-day lean health care management course, completion of four or more Radiological Society of North America (RSNA) quality essentials certificates, identification of faculty mentor(s), selection of one quality improvement project to champion, and completion of a two-page essay summarizing interest in quality improvement, the proposed project, and its potential impact. Residents were required to attend monthly quality meetings, pursue their project and its derivatives, submit completed work for consideration to a national meeting and for publication, and present at departmental grand rounds. Outcomes were summarized using descriptive statistics. RESULTS. Five residents submitted four projects for consideration, and all five were selected. In addition to the four submitted projects, seven additional projects were pursued. Participants worked on nine local and three multicenter process improvements, gave one to two grand rounds each, presented three oral and five poster presentations, generated eight publications, received three awards, formed 14 mentor-mentee relationships, and influenced local and multisite practice patterns. Participants reported gaining firsthand experience in quality improvement principles and developing real-world leadership skills. CONCLUSION. A targeted 2-year curriculum emphasizing hands-on quality improvement experience with rich mentor-mentee relationships can produce meaningful results.

Routine Postprocedure Chest Radiography Is Not Warranted After Right-Heart Catheterization.

PURPOSE: To determine whether routine postprocedure chest radiography is indicated to exclude pneumothorax after outpatient right heart catheterization with or without endomyocardial biopsy. METHODS: This HIPAA-compliant retrospective quality improvement cohort study was approved by the institutional review board. All outpatients from January 1, 2010, to July 1, 2017, who underwent routine postprocedure chest radiography after right heart catheterization with or without endomyocardial biopsy formed the study population (n = 6,036). Subjects were identified by electronic medical record query using Current Procedural Terminology codes. Pneumothorax prevalence was calculated by coded review of chest radiography reports. Size of pneumothorax (if present) and clinical outcome were determined, and 95% confidence intervals (CIs) were calculated. RESULTS: Most (99%) right heart catheterizations were performed using an internal jugular vein approach, as determined by a random sample of 100 subjects. The prevalence of pneumothorax on postprocedure chest radiography reports was 0.1% (7 of 6,036; 95% CI: 0.05%-0.24%). Three of these seven pneumothoraces were confirmed by repeat imaging within 1 hour to be false-positives (ie, no pneumothorax), resulting in a corrected pneumothorax rate of 0.07% (4 of 6,036; 95% CI: 0.00%-0.2%). The remaining four that reported pneumothoraces were less than 1 cm. No chest tubes were placed, and all subjects were discharged home without an unexpected escalation in the level of care. CONCLUSION: In a large cohort of over 6,000 subjects, pneumothorax after right heart catheterization utilizing an internal jugular vein approach was rare and when found was clinically insignificant. False-positives were common. Routine postprocedure chest radiography in this setting is not warranted and is being discontinued at the study institution.

EPR spin trapping of an oxalate-derived free radical in the oxalate decarboxylase reaction.

EPR spin trapping experiments on bacterial oxalate decarboxylase from Bacillus subtilis under turn-over conditions are described. The use of doubly (13)C-labeled oxalate leads to a characteristic splitting of the observed radical adducts using the spin trap N-tert-butyl-α-phenylnitrone linking them directly to the substrate. The radical was identified as the carbon dioxide radical anion which is a key intermediate in the hypothetical reaction mechanism of both decarboxylase and oxidase activities. X-ray crystallography had identified a flexible loop, SENS161-4, which acts as a lid to the putative active site. Site directed mutagenesis of the hinge amino acids, S161 and T165 was explored and showed increased radical trapping yields compared to the wild type. In particular, T165V shows approximately ten times higher radical yields while at the same time its decarboxylase activity was reduced by about a factor of ten. This mutant lacks a critical H-bond between T165 and R92 resulting in compromised control over its radical chemistry allowing the radical intermediate to leak into the surrounding solution.