Various reports have demonstrated the importance of small airway inflammation in the development of airflow limitation and progression of COPD. This hypothesis proposes that the pathogenesis of COPD mirrors a chronic inhalational dust-induced disease. The putative inorganic dust in cigarette smoke is aluminum silicate or kaolinite, a common component of clay soils. Kaolinite has been recovered in the alveolar macrophages of smokers and has been reported as a constituent of tobacco products. The origin of kaolinite in tobacco products remains unknown, and possible potential sources are proposed. On inhalation, kaolinite deposition in the distal lung may promote macrophage accumulation within the terminal airways leading to a respiratory bronchiolitis. In the susceptible smoker, important genetic, environmental, immunologic, and mechanical factors interact and modulate this small airway inflammation, ultimately leading to the pathologic lesion of emphysema. Further studies into the effects of kaolinite on macrophage function and the subsequent development of respiratory bronchiolitis could lead to prevention of COPD at its precursor lesion.

Despite the widespread use of inhaled corticosteroids, many asthmatic patients experience persistent symptoms. In such individuals, the addition of a long-acting beta2-agonist (LABA) is frequently more effective than doubling the dose of inhaled corticosteroid. However, the role of additional therapy with a leukotriene receptor antagonist (LTRA) as an alternative to an LABA has been the focus of attention in recent studies. In order to determine the overall efficacy of the pharmacologic armamentarium used in asthma, it is imperative that a combination of end points, including lung function, airway hyperresponsiveness, effects on underlying inflammation, symptoms, and more long-term sequelae such as exacerbations, are assessed. This evidence-based systematic review outlines the pharmacologic properties of LABAs and LTRAs and the importance of evaluating end points in addition to lung function when assessing these drugs. We also highlight the results of all published studies that have performed direct comparisons of both LABAs and LTRAs as add-on therapy to inhaled corticosteroids.

Current medicine has displayed a trend toward less interfering techniques but more invasive surgical approaches in older patients with more comorbidities. In this population, the prevalence of symptomatic cardiac disease including aortic stenosis is increased. More than 25 years have elapsed since severe aortic stenosis was identified as an independent, important risk factor for patients undergoing general anesthesia for noncardiac surgery. Despite impressive advances in anesthesiologic and surgical techniques, morbidity and mortality in patients with severe aortic stenosis remains high. Published study results clearly show that adverse perioperative risk in patients with aortic stenosis depends on the interaction of factors such as the severity of valve disease, concomitant coronary artery disease, and the severity and/or urgency of the surgical procedures. The mainstay of preoperative evaluation remains the obtaining of a comprehensive preoperative medical history and a physical examination, while transthoracic echocardiography is necessary to establish or exclude hemodynamically relevant aortic stenosis in selected patients. Perioperative care is established in patients with asymptomatic aortic stenosis and/or those undergoing low-risk surgery. However, further preoperative testing or aortic valve replacement prior to noncardiac surgery should be discussed individually with the patients awaiting urgent surgical procedures who are at medium or high risk. At this point, decisions should be made in an interdisciplinary manner, including the opinions/wishes of the patient and the patient's family.

Lung cancer is the leading cause of cancer-related mortality in the developed world. Non-small cell lung cancer (NSCLC) represents 85% of cases of lung cancer, and patients have a poor 5-year survival rate. Approximately one third of NSCLC patients present with early-stage disease that is amenable to potentially curative resection and multimodality therapy. Several randomized trials now have confirmed the survival benefit with adjuvant platinum-based chemotherapy, as seen in the 1995 meta-analysis from the NSCLC Collaborative Group. The International Adjuvant Lung Cancer Collaborative Group Trial demonstrated a 4.5% improvement in survival for patients with stage I to III NSCLC. Studies from Japan have reported an improvement of 15.4% in the 5-year survival rate among patients with T1N0 disease after they had received adjuvant therapy with a combination of platinum and uracil-tegafur, and an improvement in the 5-year survival of 11% rate favoring chemotherapy with uracil-tegafur in a subgroup analysis of patients with T2N0 disease. Two recently published meta-analyses have estimated a relative risk reduction in mortality of 11 to 13% at 5 years. Significant improvement in the long-term survival rate has been demonstrated for patients with stage IB and II disease by the Cancer and Leukemia Group B 9633 trial (4-year survival rate, 12%) and the The National Cancer Institute of Canada Clinical Trials Group BR.10 trial (5-year survival rate, 15%; risk reduction for recurrence, 40%). Thus, there is compelling evidence to now recommend adjuvant platinum-based combination chemotherapy for patients after resection of early-stage NSCLC.

Gas embolism is a known complication of various invasive procedures, and its management is well established. The consequence of gas microemboli, microbubbles, is underrecognized and usually overlooked in daily practice. We present the current data regarding the pathophysiology of microemboli and their clinical consequences. Microbubbles originate mainly in extracorporeal lines and devices, such as cardiopulmonary bypass and dialysis machines, but may be endogenous in cases of decompression sickness or mechanical heart valves. Circulating in the blood stream, microbubbles lodge in the capillary bed of various organs, mainly the lungs. The microbubble obstructs blood flow in the capillary, thus causing tissue ischemia, followed by inflammatory response and complement activation. Aggregation of platelets and clot formation occurs as well, leading to further obstruction of microcirculation and tissue damage. In this review, we present evidence of the biological and clinical detrimental effects of microbubbles as demonstrated by studies in animal models and humans, and discuss management of the microbubble problem with regard to detection, prevention, and treatment.

Tumors of the mediastinum represent a wide diversity of disease states. The location and composition of a mass is critical to narrowing the differential diagnosis. The most common causes of an anterior mediastinal mass include the following: thymoma; teratoma; thyroid disease; and lymphoma. Masses of the middle mediastinum are typically congenital cysts, including foregut and pericardial cysts, while those that arise in the posterior mediastinum are often neurogenic tumors. The clinical sequelae of mediastinal masses can range from being asymptomatic to producing symptoms of cough, chest pain, and dyspnea. This article will review the anatomy of the mediastinum as well as the different clinical, radiographic, and prognostic features, and therapeutic options of the most commonly encountered masses.

Hepatitis C virus (HCV) infection is a chronic blood-borne disease that affects > 4,000,000 individuals in the United States. The majority of individuals with HVC infection acquire a chronic hepatitis that predisposes them to the complications of cirrhosis and hepatoma. Chronic HCV infection is, however, associated with multiple extrahepatic manifestations as well, including recently recognized effects on the lung. These include primary effects on lung function, as well as secondary effects in the settings of progressive liver disease and drug treatment for HCV. In this article, we discuss the emerging clinical data that support a role for HCV infection in lung disease, describe the multiple pulmonary manifestations of this viral infection, and outline the therapies available for specific pulmonary complications of chronic HCV infection.

Laser microdissection (LMD) is an accurate and fast method to procure pure populations of cells from complex, heterogeneous tissues under direct microscopic visualization. It can be applied to a wide range of cell preparation, including paraffin-embedded material. The morphology of the captured cells is retained, and DNA, RNA, and proteins can be extracted for molecular analysis. The potential applications of LMD to human cardiovascular research are multiple, including viral/autoimmune myocarditis and arteritis, atherosclerotic lesions, and myocardial and vascular cell proliferation and death. Molecular and genetic analysis of LMD-procured cells in cardiac and vascular tissues may provide a better understanding of several cardiac diseases.

Disseminated intravascular coagulation is a frequent complication of sepsis. Coagulation activation, inhibition of fibrinolysis, and consumption of coagulation inhibitors lead to a procoagulant state resulting in inadequate fibrin removal and fibrin deposition in the microvasculature. As a consequence, microvascular thrombosis contributes to promotion of organ dysfunction. Recently, three randomized, double-blind, placebo-controlled trials investigated the efficacy of antithrombin, activated protein C (APC), and tissue factor pathway inhibitor, respectively, in sepsis patients. A significant reduction in mortality was demonstrated in the APC trial. In this article, we first discuss the physiology of coagulation and fibrinolysis activation. Then, the pathophysiology of coagulation activation, consumption of coagulation inhibitors, and the inhibition of fibrinolysis leading to a procoagulant state are described in more detail. Moreover, therapeutic concepts as well as the three randomized, double-blind, placebo-controlled studies are discussed.

Acute tubular necrosis (ATN) is a form of acute renal failure (ARF) that is common in hospitalized patients. In critical care units, it accounts for about 76% of cases of ARF. Despite the introduction of hemodialysis > 30 years ago, the mortality rates from ATN in hospitalized and ICU patients are about 37.1% and 78.6%, respectively. The purpose of this review is to discuss briefly the cause, diagnosis, and epidemiology of ARF, and to review in depth the clinical trials performed to date that have examined the influence of growth factors, hormones, antioxidants, diuretics, and dialysis. In particular, the role of the dialysis modality, dialyzer characteristics, and dosing strategies are discussed.

Postresuscitation syndrome is a state of myocardial dysfunction after the restoration of circulation by successful resuscitation. Despite several advances in the field of resuscitation, the management of out-of-hospital cardiac arrest is still suboptimal. The high fatality rate shortly after successful resuscitation is mainly related to postresuscitation myocardial dysfunction. Postresuscitation myocardial stunning is reversible, while stony heart is irreversible due to prolonged unsuccessful resuscitation. This article reviews most of the published articles concerning the causes, mechanism, pathophysiology, and the updated trials for management of postresuscitation myocardial dysfunction. Further studies are warranted to highlight postresuscitation disease and its hemodynamic sequences and then to intervene according to the different phases of cardiac arrest. By modifying the conventional modalities of resuscitation together with new promising agents, the rescuers will be able to salvage the jeopardized postresuscitation myocardium and prevent its progression to the dismal stony heart. Community awareness and staff education are crucial to shorten resuscitation time and improve short-term and long-term outcomes. There is an urgent need to revise the guidelines for cardiopulmonary resuscitation in community setting, but how? It is a matter of where and when it is of enough value to be efficacious and cost-effective.

Low-molecular-weight heparins have been compared with unfractionated heparin (UFH) for treatment of deep vein thrombosis (DVT). However, a comparison of their efficacy in the presence or absence of pulmonary embolism (PE) has not been studied. We estimated the efficacy and safety of enoxaparin vs UFH in patients with proximal DVT with/without symptomatic PE using a meta-analysis of individual data from randomized controlled trials.

Of the 128 articles evaluated on the overall topic of atrial fibrillation (AF) after cardiac surgery, only 19 studies dealing with pharmacologic heart rhythm control were relevant for inclusion in this analysis, indicating the relative paucity of evidence-based studies addressing this topic. We found limited data on guiding treatment for the rhythm control of AF following cardiac surgery in patients who do not require urgent cardioversion; therefore, the choice of an antiarrhythmic drug needs to be guided by patient characteristics. Based on limited available evidence, amiodarone is recommended for pharmacologic conversion of postoperative AF and AFL in patients with depressed left ventricular function who do not need urgent electrical cardioversion. This recommendation is made largely because of the effectiveness of amiodarone and also because of its relatively favorable side-effects profile. Sotalol and class 1A antiarrhythmic drugs are reasonable choices for patients with coronary artery disease who do not have congestive heart failure. There are currently no definitive data to guide the decision about the duration of antiarrhythmic drug therapy for patients with AF following cardiac surgery. Most protocols continue therapy with the antiarrhythmic drug for 4 to 6 weeks following surgery, but evidence from randomized studies is lacking.

New-onset atrial fibrillation (AF) occurs frequently in patients after cardiac surgery. The purpose of this study was to review the published trials and to provide clinical practice guidelines for pharmacologic prophylaxis against postoperative AF. Trials of pharmacologic prophylaxis against AF after heart surgery were identified by searching MEDLINE, the Cochrane Controlled Trials Register, and the bibliographies of published reports. Evidence grades and clinical recommendation scores were assigned to each prophylactic drug based on published evidence. Ninety-one trials were identified. The primary study design was a randomized, controlled trial of one drug vs placebo/usual care. Pharmacologic therapies that are reviewed include Vaughan-Williams class II agents (ie, beta-receptor antagonists) [29 trials; 2,901 patients], Vaughan-Williams class III agents (ie, sotalol and amiodarone) [18 trials; 2,978 patients], Vaughan-Williams class IV agents (ie, verapamil and diltiazem) [5 trials; 601 patients], and Vaughan-Williams class I agents (ie, quinidine and procainamide) [3 trials; 246 patients], as well as digitalis (10 trials; 1,401 patients), magnesium (14 trials; 1,853 patients), dexamethasone (1 trial; 216 patients), glucose-insulin-potassium (3 trials; 102 patients), insulin (1 trial; 501 patients), triiodothyronine (2 trials; 301 patients), and aniline (1 trial; 32 patients). A consistent finding in this review is that antiarrhythmic drugs with beta-adrenergic receptor-blocking effects (ie, class II beta-blockers, sotalol, and amiodarone) demonstrated successful prophylaxis. Furthermore, those therapies that did not inhibit beta-receptors generally failed to demonstrate a decreased incidence in postoperative AF. While sotalol and amiodarone have been shown in some studies to be effective, their safety and the incremental prophylactic advantage in comparison with beta-blockers has not been conclusively demonstrated. On the basis of evidence that has been reviewed and graded for quality, it is recommended that strong consideration should be given to the prophylactic administration of Vaughan-Williams class II beta-blocking drugs as a means of lowering the incidence of new-onset post-cardiac surgery AF.

New-onset atrial fibrillation (AF) occurs frequently after cardiac surgery. The utility of prophylactic atrial pacing to prevent AF following cardiac surgery has been investigated in a number of trials, but clinical guidelines for its use are lacking. Trials of prophylactic atrial pacing to prevent AF following cardiac surgery were identified by searching PubMed, the Cochrane database, selected medical journals, and references in selected articles. Nine randomized controlled trials were identified that addressed prophylactic atrial pacing after cardiac surgery to prevent AF. Prophylactic right atrial pacing and prophylactic left atrial pacing have yielded inconclusive results. Prophylactic biatrial pacing (BAP) reduced the incidence of AF significantly in four studies, reduced it nonsignificantly in one study, and had no effect in one study. On the basis of the literature that was reviewed and graded for quality, it was concluded that prophylactic atrial pacing to prevent AF after cardiac surgery is safe. We recommend that BAP be considered, particularly in patients who are at high risk for the development of postoperative AF.

A comprehensive evidence review was conducted of the medical literature regarding the relationship between intraoperative interventions and the incidence of postoperative atrial arrhythmias, including, most commonly, atrial fibrillation (AF). Fifteen randomized, controlled studies and one large-scale concurrent cohort study were identified that reported on the following issues: systemic temperature during surgery (one report); "beating heart" surgery vs conventional bypass surgery (three reports); type of myocardial protection (five reports); the use of adjunctive posterior pericardiotomy (one report); the use of thoracic epidural anesthesia (TEA) [two reports]; the use of glucose-insulin-potassium (GIK) solutions (two reports); and the use of heparin-coated circuits for cardiopulmonary bypass (CPB) [two reports]. Based on a systematic review of the reported data and an analysis of the quality of the reported data, we recommend the following: (1) that mild hypothermia, rather than moderate hypothermia, may be effective in reducing the frequency of postoperative AF; (2) the use of posterior pericardiotomy may be a useful adjunct to reduce the frequency of postoperative AF; and (3) the use of heparin-coated CPB circuits is associated with less postoperative AF. Because of conflicting or inadequate data, we cannot conclude that the frequency of postoperative AF is affected by (1) the use of beating-heart techniques, (2) the type of myocardial protection strategy used, (3) the use of TEA, or (4) the use of GIK solutions perioperatively.

Post-cardiac surgery atrial fibrillation (AF) places patients at risk for thromboembolism and stroke, while the surgery and cardiopulmonary bypass alter the multiple factors of coagulation and may increase the tendency to bleed. It is in the context of this complex clinical picture that the physician must make decisions regarding the risks and benefits of anticoagulation therapy to lower the risk for thromboembolism and stroke associated with postoperative AF. Physicians must also weigh the usually transient and self-limited duration of new-onset postoperative AF against the potential for postoperative bleeding if anticoagulation therapy is started. No randomized, controlled clinical trials are available that specifically address the problem of anticoagulation therapy for the postoperative AF. In that context, recommendations are based on the established therapy for nonsurgical situations modified by the potential risk of bleeding in the postoperative patient.

Atrial fibrillation (AF) is one of the most frequent complications of cardiac surgery, affecting more than one third of patients. The mechanism of this arrhythmia is believed to be reentry. The electrophysiologic substrate may be preexisting or may develop due to heterogeneity of refractoriness after surgery. Multiple perioperative factors have been proposed to contribute to the latter, including operative trauma, inflammation, elevations in atrial pressure (including that due to left ventricular diastolic dysfunction), autonomic nervous system imbalance, metabolic and electrolyte imbalances, or myocardial ischemic damage incurred during the operation. Whether ectopic beats originating in the pulmonary veins explain at least some episodes of postoperative AF, as has been shown for nonsurgical patients with the arrhythmia, is of current interest as such sites could easily be isolated at the time of surgery. The development of postoperative AF is associated with a higher risk of operative morbidity, prolonged hospitalization, and increased hospital cost compared with that in patients remaining in sinus rhythm. Many factors have been identified as being associated with postoperative AF, but the most consistent variable across studies is increasing patient age. It is speculated that age-related pathologic changes in the atrium contribute to arrhythmia susceptibility. An important modifiable risk factor for postoperative AF is the failure to resume therapy with beta-adrenergic receptor blockers after surgery. The stratification of patients who are at higher risk for AF would focus preventative strategies on patients who are most likely to benefit from such therapy. Nonetheless, since postoperative AF often develops in patients with comorbidities who are predisposed to other complications and prolonged hospitalization, it is presently unclear whether the prevention of postoperative AF will result in improved patient outcomes, particularly shorter hospitalizations.