Novel bronchoscopic strategies for the diagnosis of peripheral lung lesions: Present techniques and future directions

The diagnosis of the peripheral lung lesion has been a long‐standing clinical challenge—balancing accuracy with patient safety. With recent data revealing mortality benefits with lung cancer screening via low‐dose computed tomography, now more than ever, clinicians will be challenged with the task of providing the means to provide a safe and minimally invasive method of obtaining accurate tissue diagnostics for the pulmonary nodule. In this review, we present available technologies to aid clinicians in attempts at minimally invasive techniques and the data supporting their use. In addition, we review novel tools under investigation that may further increase yield and provide additional benefit in obtaining an early diagnosis of lung cancer.     

Safety and efficiency of interventional pulmonologists performing percutaneous tracheostomy

Background: The steady rise in the number of critically ill patients in the USA has led to an increase in the need for tracheostomies in patients requiring chronic ventilatory support. There is a matched need for experienced operators to safely and efficiently perform these procedures. Objectives: We evaluated the effects on procedural outcomes and efficiency of percutaneous dilatational tracheostomy (PDT) placement in the medical intensive care unit (MICU) by the surgical team (ST) or interventional pulmonologists (IP). The IP team joined the PDT team in September 2007 and became primarily responsible for all PDT in the MICU. Methods: A retrospective analysis of prospectively collected data of patients who received PDT in the MICU by ST and IP from September 2007 to August 2010 was made. Outcomes including safety, efficacy, and procedural efficiency were compared. Results: One hundred seven patients underwent bedside PDT in the MICU during this period. Forty-three procedures (40.2%) were performed by the ST and 64 procedures (59.8%) were performed by IP. There was no statistical difference between the incidence of airway injury and infection between the two procedural groups. There were no deaths related to the performance of PDT in our series. PDT was completed within 48 h of request in 100% of IP patients and 95% of ST patients (p = 0.08). Conclusions: There were no statistical differences in PDT between the ST and IP groups when comparing complications. There was a trend towards an increased efficiency in time to PDT after consultation within the IP PDT group. Trained IP can safely and effectively perform PDT.     

Clean intermittent catheterization rates after initial and subsequent treatments with onabotulinumtoxinA for non-neurogenic overactive bladder in real-world clinical settings

Objective: Previous randomized controlled trials have reported a 6.1–6.9% incidence of clean intermittent catheterization (CIC) following treatment with onabotulinumtoxinA in non-neurogenic overactive bladder (OAB) patients who were inadequately managed by ≥1 anticholinergic. A multi-center retrospective chart review assessed the real-world rate of voiding dysfunction requiring catheterization.

Methods: Patients received onabotulinumtoxinA 100?U (approved dose) administered by experienced injectors between January 2013 and June 2015. Patients using CIC or an indwelling catheter for ≥24?hours for voiding dysfunction prior to onabotulinumtoxinA injections were excluded. The primary outcome was post-treatment CIC (lasting >24?hours; per individual physician’s clinical judgment considering patient’s voiding symptoms, post-void residual [PVR] urine volumes and patient bother). Potential baseline predictors of CIC (history of pelvic prolapse, cystocele, diabetes, PVR urine volume and age) were assessed using multivariable logistic regression.

Results: Overall, 299 patients received their first treatment with onabotulinumtoxinA 100?U. Mean age was 66.4 years; 98.3% were female. The incidence of CIC was 2.7% in the total study population after the first treatment with onabotulinumtoxinA. The de novo CIC rate in treatments 2 and 3 combined was similarly low (3.2%). None of the evaluated baseline characteristics were significant predictors of CIC initiation due to the low CIC incidence.

Conclusions: This real-world study of non-neurogenic OAB patients treated with onabotulinumtoxinA suggests that the CIC rate is lower than the rates reported in previous studies. There were no significant correlations between baseline predictors and CIC initiation, although statistical significance may not have been reached because of the low incidence of CIC.     

Calcium-sensing soluble adenylyl cyclase mediates TNF signal transduction in human neutrophils

Through chemical screening, we identified a pyrazolone that reversibly blocked the activation of phagocyte oxidase (phox) in human neutrophils in response to tumor necrosis factor (TNF) or formylated peptide. The pyrazolone spared activation of phox by phorbol ester or bacteria, bacterial killing, TNF-induced granule exocytosis and phox assembly, and endothelial transmigration. We traced the pyrazolone's mechanism of action to inhibition of TNF-induced intracellular Ca2+ elevations, and identified a nontransmembrane ("soluble") adenylyl cyclase (sAC) in neutrophils as a Ca2+-sensing source of cAMP. A sAC inhibitor mimicked the pyrazolone's effect on phox. Both compounds blocked TNF-induced activation of Rap1A, a phox-associated guanosine triphosphatase that is regulated by cAMP. Thus, TNF turns on phox through a Ca2+-triggered, sAC-dependent process that may involve activation of Rap1A. This pathway may offer opportunities to suppress oxidative damage during inflammation without blocking antimicrobial function.