Maximal Oxygen Uptake--Risk Predictor of NSCLC Resection in Patients With Comorbid Emphysema: Lessons From NETT.

We compared VO2 max values from ACCP Guidelines and from NETT's homogenous NULPD surrogate for predicting operative mortalities. Estimated mid and long-term non-cancer related survival in NETT's subset was also obtained. NETT and ACCP Guideline VO2 max values were similar in the "low" and "mid" risk operative mortality categories but NETT's "high" risk subset showed lower mortality (14% vs. 26%). Estimated non-cancer related survival in NETT "low", "mid" and "high" risk VO2 max categories at two and eight years were 100%, 74%, 59% and 48%, 26%, 14%, respectively. The lower predicted risk in NETT's "high- risk" subset raises the possibility of extending indications for potential curative resection in selected patients. The NETT surrogate also provides hitherto unavailable estimate on long-term non-cancer related survival after potential curative resection of NSCLC and suggests that the operation does not shorten eight-year longevity.

Regional deposition of mometasone furoate nasal spray suspension in humans.

Nasal deposition studies can demonstrate whether nasal sprays treating allergic rhinitis and polyposis reach the ciliated posterior nasal cavity, where turbinate inflammation and other pathology occurs. However, quantifying nasal deposition is challenging, because in vitro tests do not correlate to human nasal deposition; gamma scintigraphy studies are thus used. For valid data, the radiolabel must distribute, as the drug, into different-sized droplets, remain associated with the drug in the formulation after administration, and not alter its deposition. Some nasal deposition studies have demonstrated this using homogenous solutions. However, most commercial nasal sprays are heterogeneous suspensions. Using mometasone furoate nasal suspension (MFS), we developed a technique to validate radiolabel deposition as a surrogate for nasal cavity drug deposition and characterized regional deposition and nasal clearance in humans. Mometasone furoate (MF) formulation was spiked with diethylene triamine pentacaetic acid. Both unlabeled and radiolabeled formulations (n = 3) were sprayed into a regionally divided nasal cast. Drug deposition was quantified by high pressure liquid chromatography within each region; radiolabel deposition was determined by gamma camera. Healthy subjects (n = 12) were dosed and imaged for six hours. Scintigraphic images were coregistered with magnetic resonance imaging scans to quantify anterior and posterior nasal cavity deposition and mucociliary clearance. The ratio of radiolabel to unlabeled drug was 1.05 in the nasal cast and regionally appeared to match, indicating that in vivo radiolabel deposition could represent drug deposition. In humans, MFS delivered 86% (9.2) of metered dose to the nasal cavity, approximately 60% (9.1) of metered dose to the posterior nasal cavity. After 15 minutes, mucociliary clearance removed 59% of the initial radiolabel in the nasal cavity, consistent with clearance rates from the ciliated posterior surface. MFS deposited significant drug into the posterior nasal cavity. Both nasal cast validation and mucociliary clearance confirm the radiolabel deposition distribution method accurately represented corticosteroid nasal deposition.

Evaluation of tracheobronchomalacia by dynamic flexible bronchoscopy. A pilot study.

OBJECTIVES: Dynamic flexible bronchoscopy is the "gold standard" for assessing changes in airway luminal size associated with tracheobronchomalacia, but the procedure has not been adequately validated. The present study was designed to test the validity of diagnosing tracheobronchomalacia by dynamic flexible bronchoscopy through assessing inter- and intraobserver agreements in estimating degree of central airway collapse associated with tracheobronchomalacia. METHODS: This prospective observational pilot study enrolled consecutive patients with suspected tracheobronchomalacia scheduled for dynamic flexible bronchoscopy. Images of the airway lumen were obtained at five different sites in the tracheobronchial tree during forced inspiration and expiration and were evaluated by 23 pulmonologists (not involved in the care of study patients) with different levels of training and experience at baseline (interobserver agreement) and 8 days later (intraobserver agreement). The degree of airway collapse was visually estimated by each examiner and expressed as a percentage of narrowing. A multirater generalized kappa-type statistical method was used to calculate the correlation coefficients and to assess reliability of the measurements obtained during dynamic flexible bronchoscopy. MEASUREMENTS AND MAIN RESULTS: Between September 1 and 30, 2009, 10 patients (median age, 65 yr) underwent dynamic flexible bronchoscopy. The correlation coefficients for inter- and intraobserver agreement were favorable and ranged for the five airway sites from 0.68 to 0.92 and from 0.80 to 0.96, respectively. CONCLUSIONS: The favorable inter- and intraobserver agreements among 23 pulmonologists using dynamic flexible bronchoscopy to estimate the degree of dynamic central airway collapse provide additional evidence that dynamic flexible bronchoscopy is a reliable diagnostic tool for tracheobronchomalacia.

Sternal fracture: isolated lesion versus polytrauma from associated extrasternal injuries--analysis of 1,867 cases.

BACKGROUND: Sternal fractures fall into two distinct categories as follows: (1) isolated sternal fracture (ISF) without associated injury and (2) polytrauma sternal fracture (PSF) with associated extrasternal injury. PSF can be sufficiently severe to require hospitalization, while ISF is usually a mild insult manageable in an ambulatory setting. Nonetheless, most patients with ISF are hospitalized. The disconnect between treatment based on existing evidence and actual clinical practice may be caused in large part by the small patient cohorts in published studies conducive to inaccurate conclusions. This article addresses the issue by analyzing prospectively collected data on a far larger population than hitherto available. METHODS: The Israeli National Trauma Registry (INTR) collects data prospectively on patients admitted to trauma centers in Israel. We analyzed the INTR database on sternal fractures for demographics, mechanisms and severity of injury, diagnostic evaluation, treatment, and outcomes. RESULTS: Between 1997 and 2008, the INTR received data on 1,867 consecutive patients hospitalized with sternal fractures. The injury was sustained most often during motor vehicle accidents (84.1%), followed by falls (10.3%) and other blunt or penetrating mechanisms (5.6%). ISF was sustained in 26.4%, and PSF was sustained in 73.6%. Associated injuries involved most parts of the body. Cardiac contusions or lacerations were diagnosed in 1.8% of the 1,867 patients. ISF was associated with a lower incidence of cardiorespiratory compromise, more favorable trauma scores (Glasgow Coma Scale [GCS] score > 14, Revised Trauma Score > 11), and use of fewer intensive care facilities or operations compared with PSF. Endotracheal intubation, chest tube insertion, or thoracotomy was not performed in any ISF patient but was performed in 16.9% of the PSF cohort. The differences between ISF and PSF were statistically significant in all analyzed indices of injury severity. CONCLUSION: This study produced compelling evidence that ISF is an identifiable and mild injury. Consequently, pain, the major clinical manifestation of ISF, can usually be treated in outpatient settings. To avoid the inconvenience, risk of complications, and cost associated with hospitalization, discharge from the emergency department merits serious consideration. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level II.

Cryotechnology for staged removal of self-expandable metallic airway stents.

Self-expandable covered metallic airway stents (SEMAS) deployed for relieving inoperable central airway obstruction frequently develop complications that require removal of the device. Current techniques for SEMAS removal also involve serious complications. We are reporting a novel two-staged endoscopic approach using cryotechnology for removal of SEMAS obstructed by exuberant granulation tissue in two patients. During the first stage, the obstructing intraluminal granulation tissue was removed with cryodebridement and residual extraluminal deposits were lysed with cryotherapy. During the second stage, performed two days later, the SEMAS was liberated by mechanical means and removed in one piece. The staged approach with cryotechnology was successful and without complications.

An evidence-based estimate on the size of the potential patient pool for lung volume reduction surgery.

BACKGROUND: Observational and randomized studies have demonstrated that lung volume reduction surgery (LVRS) improves symptoms, lung function, and survival in selected patients with emphysema. In spite of an approximately 3.8 million patient prevalence of the disease in the US, only 119 LVRS procedures were performed nationwide under Medicare during 2008. In order to obtain evidence-based estimate on the size of the patient pool potentially suitable for LVRS, we analyzed the database from our clinical practice that is representative of a substantial segment of the general emphysema population. METHODS: Our pulmonary function test laboratory database between 1996 and 2006 was searched for patients with stage III and IV global initiative for chronic obstructive lung disease (GOLD) who also had lung volumes and carbon monoxide diffusing capacity data. Patients without available chest computed tomographic scans (CT) or with primary diagnoses other than emphysema were excluded. The resultant emphysema cohort was screened using clinical inclusion and exclusion criteria adopted from the National Emphysema Treatment Trial. A suitable clinical profile combined with CT scan evidence of 40% or greater involvement of the lungs and predominantly upper lobe distribution of emphysema were regarded as favorable markers for LVRS. RESULTS: Pulmonary function test criteria were met by 959 patients and CT scans were available in 588 patients, but 175 patients were excluded because of primary diagnoses other than emphysema. In the remaining 413 patients, 61 or 15% exhibited favorable clinical profiles and anatomy for LVRS. CONCLUSIONS: In a subset of patients that resembles a substantial segment of the general population with advanced emphysema, up to 15% appeared potential candidates for LVRS. Formation of a task force by relevant medical specialty and patient advocate organizations to address the apparent underutilization of LVRS is recommended.

Lung volume reduction therapies for advanced emphysema: an update.

Observational and randomized studies provide convincing evidence that lung volume reduction surgery (LVRS) improves symptoms, lung function, exercise tolerance, and life span in well-defined subsets of patients with emphysema. Yet, in the face of an estimated 3 million patients with emphysema in the United States, < 15 LVRS operations are performed monthly under the aegis of Medicare, in part because of misleading reporting in lay and medical publications suggesting that the operation is associated with prohibitive risks and offers minimal benefits. Thus, a treatment with proven potential for palliating and prolonging life may be underutilized. In an attempt to lower risks and cost, several bronchoscopic strategies (bronchoscopic emphysema treatment [BET]) to reduce lung volume have been introduced. The following three methods have been tested in some depth: (1) unidirectional valves that allow exit but bar entry of gas to collapse targeted hyperinflated portions of the lung and reduce overall volume; (2) biologic lung volume reduction (BioLVR) that involves intrabronchial administration of a biocompatible complex to collapse, inflame, scar, and shrink the targeted emphysematous lung; and (3) airway bypass tract (ABT) or creation of stented nonanatomic pathways between hyperinflated pulmonary parenchyma and bronchial tree to decompress and reduce the volume of oversized lung. The results of pilot and randomized pivotal clinical trials suggest that the bronchoscopic strategies are associated with lower mortality and morbidity but are also less efficient than LVRS. Most bronchoscopic approaches improve quality-of-life measures without supportive physiologic or exercise tolerance benefits. Although there is promise of limited therapeutic influence, the available information is not sufficient to recommend use of bronchoscopic strategies for treating emphysema.

Clinical experience with a novel thermosensitive temporary coronary artery occluder (LeGoo).

BACKGROUND: A bloodless field is important for visualizing relevant anatomical structures and facilitating construction of high-quality coronary anastomoses during off-pump coronary artery bypass graft surgery (OPCABG). Currently employed devices can damage target arteries as well as myocardium and are not uniformly effective, especially with diseased arteries. METHODS: LeGoo (Pluromed, Woburn, MA) is a thermosensitive polymer that is a viscous liquid at room temperatures and changes into a firm occlusive plug instantaneously when exposed to body temperatures. The polymer is nontoxic and neither metabolized nor absorbed. It dissolves spontaneously or can be dissolved at will by cooling. LeGoo was instilled through the arteriotomy of 99 coronaries in 50 patients during construction of OPCABG anastomoses. RESULTS: LeGoo formed an occlusive endoluminal plug instantaneously and blocked blood flow into the surgical field. In 89 vessels with available information, the quality of bloodless field was satisfactory, without need for substantial use of blood removal systems or application of another device in 81 vessels (91%). Resort to other means was prompted by serious arrhythmia (1 case) epicardial bleeding (1 vessel), bleeding from collateral branches (3 vessels), and shortcomings in design of the injecting catheter (3 vessels) that has been corrected. Intraoperative and perioperative profiles of these patients were similar to those reported from other OPCABG series. Abnormal bleeding, coagulopathy, metabolic derangements, and evidence of LeGoo embolization were not observed. CONCLUSIONS: In this first large-scale human experience, LeGoo had been an atraumatic, safe, and effective temporary coronary artery occluder. It produced a bloodless field during OPCABG in 91% of target vessels. Improvements on these results with further experience is anticipated.

Lung volume reduction surgery: a meta-analysis of randomized clinical trials.

BACKGROUND: Observational studies have suggested that lung volume reduction surgery (LVRS) is superior to optimal medical therapy for selected subsets of patients with advanced emphysema. Randomized clinical trials (RCTs) with the exception of the National Emphysema Treatment Trial (NETT), failed to enroll a sufficient number of patients to provide clinicians and patients with convincing outcome data on the usefulness of LVRS. It was postulated that a meta-analysis of these RCTs (3-12 months' follow up) may provide more compelling information on the value of LVRS in patients with emphysema. METHODS: A comprehensive search of the MEDLINE database between January 1994 and January 2004 for RCTs on LVRS was performed. RESULTS: From a total of eight RCTs on record, six studies (306 patients) with 3- to 12-month follow up were deemed suitable for meta-analysis. Key baseline features of these RCT populations included heterogeneous emphysema, comparable inclusion/exclusion criteria and, in retrospect, low walking capacity as measured by the 6-minute walk distance (6MWD). This profile closely resembles NETT's 'predominantly upper lobe--low exercise tolerance emphysema' cohort. The LVRS arm of the meta-analysis population showed better results than the medical cohort in terms of pulmonary function (FEV(1) p < 0.0001, FVC p < 0.0001, residual volume p < 0.0001, total lung capacity p = 0.004), gas exchange (arterial partial pressure of oxygen p < 0.0001) and exercise capacity (6MWD p = 0.0002). Although information on quality-of-life measures was not sufficiently uniform to qualify for meta-analysis, a survey of available data revealed better results in the surgical than in the medical arms of each RCT. Mortality 6-12 months after random assignment to treatment was similar in the two study arms, suggesting that the operative mortality from LVRS was offset, within months, by deaths in the medical arm. CONCLUSIONS: This meta-analysis showed that a selected subset of patients with advanced, heterogeneous emphysema and low exercise tolerance (6MWD) experienced better outcomes from LVRS than from medical therapy.

Lung volume reduction surgery vs medical treatment: for patients with advanced emphysema.

OBJECTIVE: To contribute to the knowledge on the therapeutic value of lung volume reduction surgery (LVRS). DESIGN: Two similar, independently conceived and conducted, multicenter, randomized clinical trials. SETTING: The Canadian Lung Volume Reduction (CLVR) study and the Overholt-Blue Cross Emphysema Surgery Trial (OBEST). METHODS: Using a fixed-effects meta-analysis, the 6-month results produced by the addition of LVRS to optimal medical therapy were compared to those obtained from optimal medical therapy alone. Patients were required to have severe emphysema, marked airflow limitation (ie, FEV(1), 15 to 40% predicted), hyperinflation (total lung capacity [TLC], > 120% predicted), CO(2), < 55 mm Hg, and measurable dyspnea (chronic respiratory disease questionnaire [CRDQ] scores /= 1 for the OBEST). Optimal medical therapy included pulmonary rehabilitation in both arms of both studies. RESULTS: The CLVR study randomized 58 patients and the OBEST randomized 35 patients for a total of 93 patients. Of these, 54 patients were randomized to undergo surgery, and 39 patients were randomized to receive medical treatment. The 6-month mortality rate (including operative mortality) in the surgical and medical cohorts was similar (5.6% vs 5.1%, respectively). A comparison of the medical and surgical arms of the combined CLVR study/OBEST population showed that LVRS was associated with a higher FEV(1) (167 mL or 24% predicted; 95% confidence interval [CI], 29 to 304; p = 0.017), lower residual volume (-1,342 mL or 24.5% predicted; 95% CI, -1,844 to -840; p < 0.001), lower TLC (-1,044 mL or 13% predicted; 95% CI, -1483 to -605; p < 0.001), and higher 6-min walk distance (148.8 feet; 95% CI, 24.3 to 273.2; p = 0.019). Each domain of the CRDQ showed statistically significant improvement in the surgical arm of the study, but not in the medical arm. The summary physical component scale of the Medical Outcomes Study 36-item short form (SF-36) was also more favorable in the LVRS cohort (6.9; 95% CI, 2.86 to 10.90; p < 0.001). The summary mental component scale of the SF-36 did not show a statistically significant difference between the two groups. CONCLUSION: Six months after randomization, LVRS produced better palliation than optimal medical therapy in patients with advanced emphysema.

Bronchoscopic lung volume reduction using tissue engineering principles.

Bronchoscopic lung volume reduction (BLVR), a minimally invasive procedure based on tissue engineering principles, was performed in six sheep with papain-induced experimental emphysema (EMPH). Physiologic measurements, at baseline, after generation of EMPH, and at 3 and 9 weeks after BLVR, included lung volumes, diffusing capacity (DL(CO)), pressure-volume relationships for the lung and chest wall, pleural pressures generated during active respiratory muscle contraction, lung resistance and dynamic elastance. The animal model displayed hyperinflation (change in total lung capacity +8%; change in residual volume +66%), reduced DL(CO) (-21%), and elevated airway resistance (+76%) that resembled advanced human EMPH. BLVR was well tolerated without complications, and it reduced lung volumes (change in total lung capacity -16%; change in residual volume -55%) in a pattern that resulted in significant improvements in vital capacity (10%). At autopsy, well-organized, peripheral scars associated with tissue contraction were observed at 33 of the 36 (91%) treated sites. There was no evidence of infection, abscess, or granuloma formation, or allergic reaction. Scar tissue, generated by BLVR, replaced hyperinflated lung, reduced overall lung volume, and improved respiratory function safely and consistently. The BLVR technology employed in this study addresses the limitations identified in our prior attempt at BLVR therapy and appears safe and effective enough to justify a trial in humans.

DISC VARIANCE OF THE HARKEN MITRAL PROSTHESIS: THE CONTRIBUTION OF ASSOCIATED AORTIC REGURGITATION.

Four cases of severe mitral regurgitation due to disc variance of the Harken disc prosthesis in the mitral position are described. The valve occluder actually escaped into the left atrium in two patients, and neither survived despite emergency valve replacement. In the other two, disc malfunction was identified by flouroscopy, the prosthesis was replaced, and both patients survived. All four patients had associated aortic regurgitation, which most likely contributed to erosion of the disc edges. It is suggested that patients with the Harken disc prosthesis undergo periodic evaluation to detect abnormal disc motion.