Survival after lung transplantation of cystic fibrosis patients infected with Burkholderia dolosa (genomovar VI).

Cystic fibrosis (CF) with severe lung disease is a well-recognized indication for lung transplantation. Colonization with various organisms in CF patients may impact post-transplant morbidity and mortality. Burkholderia cepacia complex (BCC) is made up of distinct genomovars with significant morbidity and mortality associated with B.

Economic Outcomes of Extracorporeal Membrane Oxygenation With and Without Ambulation as a Bridge to Lung Transplantation.

Background: An increasing number of centers are using active rehabilitation and ambulation for critically ill patients on extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation. This investigation assessed the economic impact at a single center of ambulatory versus non-ambulatory ECMO strategies as a bridge to lung transplantation.

Methods: We conducted a single-center retrospective cohort analysis of all subjects supported with ECMO as a bridge to lung transplantation (N = 9) from 2007 to 2012.

Ambulatory extracorporeal membrane oxygenation as a bridge to lung transplantation: walking while waiting.

The proportion of critically ill patients awaiting lung transplantation has increased since the implementation of the Lung Allocation Score (LAS) in 2005. Critically ill patients comprise a sizable proportion of wait-list mortality and are known to experience increased posttransplant complications. These critically ill patients have been successfully bridged to lung transplantation with extracorporeal membrane oxygenation (ECMO), but historically these patients have required excessive sedation, been immobile, and have had difficult functional recovery in the posttransplant period and high mortality.

Candidacy for lung transplant and lung allocation.

This article provides a summary of the changes in lung transplantation after implementation of the Lung Allocation Score in 2005. Specific issues that are addressed include impact of diagnosis group, age, critical illness, and geographic disparities in transplant.

Ambulatory ECMO as a bridge to lung transplant in a previously well pediatric patient with ARDS.

Extracorporeal membrane oxygenation (ECMO) is increasingly implemented in patients with end-stage pulmonary disease as a bridge to lung transplant. Several centers have instituted an approach that involves physical rehabilitation and ambulation for patients supported with ECMO. Recent reports describe the successful use of ambulatory ECMO in patients with chronic respiratory illnesses being bridged to lung transplant.

An official American Thoracic Society/International Society for Heart and Lung Transplantation/Society of Critical Care Medicine/Association of Organ and Procurement Organizations/United Network of Organ Sharing Statement: ethical and policy considerations in organ donation after circulatory determination of death.

Rationale: Donation after circulatory determination of death (DCDD) has the potential to increase the number of organs available for transplantation. Because consent and management of potential donors must occur before death, DCDD raises unique ethical and policy issues.

Objectives: To develop an ethics and health policy statement on adult and pediatric DCDD relevant to critical care and transplantation stakeholders.

Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients.

Background: Long-term survival after lung transplant is limited by the development of chronic and progressive airflow obstruction, a condition known as bronchiolitis obliterans syndrome (BOS). While prior studies strongly implicate cellular rejection as a strong risk factor for BOS, less is known about the clinical significance of human leukocyte antigen (HLA) antibodies and donor HLA-specific antibodies in long-term outcomes.

Methods: A single-center cohort of 441 lung transplant recipients, spanning a 10-year period, was prospectively screened for HLA antibodies after transplant using flow cytometry-based methods.

Active rehabilitation during extracorporeal membrane oxygenation as a bridge to lung transplantation.

Background: Patients with end-stage lung disease often progress to critical illness, which dramatically reduces their chance of survival following lung transplantation. Pre-transplant deconditioning has a significant impact on outcomes for all lung transplant patients, and is likely a major contributor to increased mortality in critically ill lung transplant recipients. The aim of this report is to describe a series of patients bridged to lung transplant with extracorporeal membrane oxygenation (ECMO) and to examine the potential impact of active rehabilitation and ambulation during pre-transplant ECMO.

Rationing in urologic oncology: lessons from sipuleucel-T for advanced prostate cancer.

Objectives: As complex novel cancer drugs are developed, supply may transiently fail to meet demand as production capacity established for research purposes is scaled up to meet anticipated clinical volume. There are no clear guidelines for how clinicians and medical centers should allocate scarce cancer care resources among patients who may benefit from the intervention.

Materials And Methods: We describe a recent scenario in which demand exceeded supply for a novel immunotherapy, sipuleucel-T, that was newly approved by the FDA for castration-resistant prostate cancer.

Increased Nitric Oxide Production Prevents Airway Hyperresponsiveness in Caveolin-1 Deficient Mice Following Endotoxin Exposure.

Background: Caveolin-1, the hallmark protein of caveolae, is highly expressed within the lung in the epithelium, endothelium, and in immune cells. In addition to its classical roles in cholesterol metabolism and endocytosis, caveolin-1 has also been shown to be important in inflammatory signaling pathways. In particular, caveolin-1 is known to associate with the nitric oxide synthase enzymes, downregulating their activity.

Active rehabilitation and physical therapy during extracorporeal membrane oxygenation while awaiting lung transplantation: a practical approach.

Objective: Extracorporeal membrane oxygenation as a bridge to lung transplantation has traditionally been associated with substantial morbidity and mortality. A major contributor to these complications may be weakness and overall deconditioning secondary to pretransplant critical illness and immobility. In an attempt to address this issue, we developed a collaborative program to allow for active rehabilitation and physical therapy for patients requiring life support with extracorporeal membrane oxygenation before lung transplantation.

Update on infectious complications following lung transplantation.

Purpose Of Review: Lung transplantation is an important therapeutic treatment for many patients with life-threatening pulmonary diseases; however, long-term survival is still relatively limited compared with other solid organ transplants. Over the last year, several articles have been published helping to increase our knowledge of infections in lung transplant recipients. In particular, important new information has been published recently regarding cytomegalovirus (CMV) and fungal infections following lung transplantation.

Survival after bronchiolitis obliterans syndrome among bilateral lung transplant recipients.

Rationale: Despite the importance of bronchiolitis obliterans syndrome (BOS) in lung transplantation, little is known regarding the factors that influence survival after the onset of this condition, particularly among bilateral transplant recipients.

Objectives: To identify factors that influence survival after the onset of BOS among bilateral lung transplant recipients.

Methods: The effect of demographic or clinical factors, occurring before BOS, upon survival after the onset of BOS was studied in 95 bilateral lung transplant recipient using Cox proportional hazards models.

Complex bacterial infections pre- and posttransplant.

Infections complications following lung transplantation are associated with significant morbidity and mortality. Management of infections is most challenging in patients with cystic fibrosis (CF), but all lung transplant recipients are at heightened risk for opportunistic infections. Particularly in CF, pretransplant infections with PSEUDOMONAS AERUGINOSA, other highly resistant bacteria (e.

The expanding roles of caveolin proteins in microbial pathogenesis.

Caveolin proteins have been implicated in a wide range of cellular functions including lipid raft mediated endocytosis and regulation of cell signaling cascades. Recent discoveries have shown that these proteins are involved not only in regulating these homeostatic cellular functions, but also in the host response to a wide range of different infections. Both caveolin-1 and 2 have been shown to play important roles in pathogen uptake.

Update on medical complications involving the lungs.

Purpose Of Review: Lung transplant is now an accepted treatment for end-stage lung disease with improving survival and an increasing number of transplants being performed every year. Recognition of the common medical complications after lung transplant is important for timely diagnosis and treatment. This review will highlight the clinical presentation, diagnosis, and treatment of several noninfectious pulmonary complications that are encountered in lung transplant recipients.

Counteracting signaling activities in lipid rafts associated with the invasion of lung epithelial cells by Pseudomonas aeruginosa.

Pseudomonas aeruginosa has the capacity to invade lung epithelial cells by co-opting the intrinsic endocytic properties of lipid rafts, which are rich in cholesterol, sphingolipids, and proteins, such as caveolin-1 and -2. We compared intratracheal Pseudomonas infection in wild type and caveolin-deficient mice to investigate the role of caveolin proteins in the pathogenesis of Pseudomonas pneumonia. Unlike wild type mice, which succumb to pneumonia, caveolin-deficient mice are resistant to Pseudomonas.

Lung transplantation at Duke University.

Clinical lung transplantation continues to grow worldwide. Advances in donor selection and management have been critical to support the expanded growth of lung transplant as a therapeutic option for patients with advanced lung disease. In recent years, allocation in the US has changed to a disease severity based system that has led to a dramatic reduction of deaths on the waiting list with concomitant increases in transplantation of recipients who are now sicker, older, and more likely to have interstitial lung disease.

An unusual case of cardiac amyloidosis.

Cardiac amyloidosis can result from any of the systemic amyloidoses. The disease is often characterized by a restrictive cardiomyopathy although the particular signs and symptoms depend in part on the underlying cause. In addition to managing the symptoms of heart failure, treatment options vary depending on the etiology of amyloid deposition.

Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells.

The superficial bladder epithelium is a powerful barrier to urine and also serves as a regulator of bladder volume, which is achieved by apical exocytosis of specialized fusiform vesicles during distension of the bladder. We report that type 1 fimbriated uropathogenic Escherichia coli (UPEC) circumvents the bladder barrier by harboring in these Rab27b/CD63-positive and cAMP-regulatable fusiform vesicles within bladder epithelial cells (BECs). Incorporation of UPEC into BEC fusiform compartments enabled bacteria to escape elimination during voiding and to re-emerge in the urine as the bladder distended.

The role of lipid rafts in the pathogenesis of bacterial infections.

Numerous pathogens have evolved mechanisms of co-opting normal host endocytic machinery as a means of invading host cells. While numerous pathogens have been known to enter cells via traditional clathrin-coated pit endocytosis, a growing number of viral and bacterial pathogens have been recognized to invade host cells via clustered lipid rafts. This review focuses on several bacterial pathogens that have evolved several different mechanisms of co-opting clustered lipid rafts to invade host cells.

Bacterial penetration of the mucosal barrier by targeting lipid rafts.

Several traditionally extracellular pathogens not known to possess invasive capacity have been shown to invade various mucosal epithelial cells. The mucosal epithelium performs an important barrier function and is not typically amenable to bacterial invasion. Valuable clues to the underlying basis for bacterial invasion have emerged from recent studies examining the invasion of bladder epithelial cells by uropathogenic Escherichia coli and alveolar epithelial cells by Pseudomonas aeruginosa.