OPTN/SRTR 2015 Annual Data Report: Lung.

In 2015, 2409 active candidates aged 12 years or older were added to the lung transplant waiting list; 2072 transplants were performed, the most of any year. The median waiting time for candidates listed in 2015 was 3.4 months; the shortest waiting time was for diagnosis group D. Despite the highest recorded transplant rate of 157 per 100 waitlist years, waitlist mortality continued a steady decade-long rise to a high of 16.5 deaths per 100 waitlist years. Measures of short- and long-term survival showed no trend toward improved overall survival in the past 5 years, except that 6-month death rates decreased from 9.4% in 2005 to 7.9% in 2014. At 5 years posttransplant, 55.5% of recipients remained alive. In 2015, 23 new child (ages 0-11 years) candidates were added to the list; 17 transplants were performed. Incidence of death was 6.1% at 6 months and 8.2% at 1 year for transplants in 2013-2014. Important policy changes will affect access to transplant. In February 2015, OPTN implemented a comprehensive revision of the lung allocation score to better reflect mortality risk. Broader geographic sharing of donor lungs for pediatric candidates and allowance for selected transplants across blood types for candidates aged younger than 2 years have been approved and are expected to improve pediatric access to transplant. The impact of these changes on lung transplant trends will be observed in the coming years.

OPTN/SRTR 2015 Annual Data Report: Heart.

The number of heart transplant candidates and transplants performed continued to rise each year. In 2015, 2819 heart transplants were performed. In addition, the number of new adult candidates on the waiting list increased 51% since 2004. The number of adult heart transplant survivors continued to increase, and in 2015, 29,172 recipients were living with heart transplants. Patient mortality following transplant has declined. The number of pediatric candidates and transplants performed also increased. New listings for pediatric heart transplants increased from 451 in 2004 to 644 in 2015. The number of pediatric heart transplants performed each year increased from 297 in 2004 to 460 in 2015. Among pediatric patients who underwent transplant in 2014, death occurred in 7.2% at 6 months and 9.6% at 1 year.

The OPTN Deceased Donor Potential Study: Implications for Policy and Practice.

The Organ Procurement and Transplantation Network (OPTN) Deceased Donor Potential Study, funded by the Health Resources and Services Administration, characterized the current pool of potential deceased donors and estimated changes through 2020. The goal was to inform policy development and suggest practice changes designed to increase the number of donors and organ transplants. Donor estimates used filtering methodologies applied to datasets from the OPTN, the National Center for Health Statistics, and the Agency for Healthcare Research and Quality and used these estimates with the number of actual donors to estimate the potential donor pool through 2020. Projected growth of the donor pool was 0.5% per year through 2020. Potential donor estimates suggested unrealized donor potential across all demographic groups, with the most significant unrealized potential (70%) in the 50-75-year-old age group and potential Donation after Circulatory Death (DCD) donors. Actual transplants that may be realized from potential donors in these categories are constrained by confounding medical comorbidities not identified in administrative databases and by limiting utilization practices for organs from DCD donors. Policy, regulatory, and practice changes encouraging organ procurement and transplantation of a broader population of potential donors may be required to increase transplant numbers in the United States.

Heart.

As the number of candidates listed for heart transplant continues to rise, it is encouraging that the number of heart transplants also continues to rise steadily each year. Evaluation of waitlist activity demonstrates a growing number of adult candidates removed from the list due to undergoing transplant, but also growing numbers of adult candidates added to the list over the past 3 years. In 2014, 2679 heart transplants were performed, an increase of 28.4% since 2003, and the number of people living with a transplanted heart continued to increase. The number of new pediatric candidates added to the heart transplant waiting list increased to 593 in 2014. The number of pediatric heart transplants performed each year increased from 293 in 2003 to 410 in 2014. Almost 60% of pediatric candidates waiting on December 31, 2014, had been waiting for less than 1 year, compared with 43.0% in 2004. Among pediatric patients who underwent transplant in 2008-2012, overall cumulative incidence of death at 1, 3, and 5 years was 9.2%, 14.7%, and 18.3%, respectively.

Lung.

Lungs are allocated to adult and adolescent transplant candidates (aged ≥ 12 years) on the basis of age, geography, blood type compatibility, and the lung allocation score (LAS), which reflects risk of waitlist mortality and probability of posttransplant survival. In 2014, 2458 active candidates aged 12 years or older, the most of any year, were added to the list; 1949 transplants were performed. Overall median waiting time to transplant for candidates listed in 2014 was 3.7 months. Candidates undergoing lung transplant in 2014 were sicker than ever before with median LAS 44.4. Measures of short-term survival continue to improve; however, long-term survival has plateaued since the implementation of the LAS in 2005; at 5 years posttransplant, 42.4% of recipients had died. In 2014, 30 new active child (ages 0-11) candidates were added to the list; 19 transplants were performed. Incidence of patient death was 7.1% at 6 months and 10.8% at 1 year for transplants in 2013, 29.7% at 3 years for transplants in 2009-2010, and 42.7% at 5 years for transplants in 2007-2008. By age, 5-year patient survival was poorest for recipients aged younger than 1 year.

Retransplant and Medical Therapy for Cardiac Allograft Vasculopathy: International Society for Heart and Lung Transplantation Registry Analysis.

Cardiac retransplantation for heart transplant recipients with advanced cardiac allograft vasculopathy (CAV) remains controversial. The International Society for Heart and Lung Transplantation Registry was used to examine survival in adult heart recipients with CAV who were retransplanted (ReTx) or managed medically (MM). Recipients transplanted between 1995 and 2010 who developed CAV and were either retransplanted within 2 years of CAV diagnosis (ReTx) or alive at ≥2 years after CAV diagnosis, managed medically (MM), without retransplant, constituted the study groups. Donor, recipient, transplant characteristics and long-term survival were compared. The population included 65 patients in ReTx and 4530 in MM. During a median follow-up of 4 years, there were 24 deaths in ReTx, and 1466 in MM. Survival was comparable at 9 years (55% in ReTx and 51% in MM; p = 0.88). Subgroup comparison suggested survival benefit for retransplant versus MM in patients who developed systolic graft dysfunction. Adjusted predictors for 2-year mortality were diagnosis of CAV in the early era and longer time since CAV diagnosis following primary transplant. Retransplant was not an independent predictor in the model. Challenges associated with retransplantation as well as improved CAV treatment options support the current consensus recommendation limiting retransplant to highly selected patients with CAV.

Risk factors for specific causes of death following pediatric heart transplant: An analysis of the registry of the International Society of Heart and Lung Transplantation.

We sought to determine temporal changes in COD and identify COD-specific risk factors in pediatric primary HTx recipients. Using the ISHLT registry, time-dependent hazard of death after pediatric HTx, stratified by COD, was analyzed by multiphasic parametric hazard modeling with multivariable regression models for risk factor analysis. The proportion of pediatric HTx deaths from each of cardiovascular cause, allograft vasculopathy, and malignancy increased over time, while all other COD decreased post-HTx. Pre-HTx ECMO was associated with increased risk of death from graft failure (HR 2.43; p < 0.001), infection (HR 2.85; p < 0.001), and MOF (HR 2.22; p = 0.001), while post-HTx ECMO was associated with death from cerebrovascular events/bleed (HR 2.55; p = 0.001). CHD was associated with deaths due to pulmonary causes (HR 1.78; p = 0.007) or infection (HR 1.72; p < 0.001). Non-adherence was a significant risk factor for all cardiac COD, notably graft failure (HR 1.66; p = 0.001) and rejection (HR 1.89; p < 0.001). Risk factors related to specific COD are varied across different temporal phases post-HTx. Increased understanding of these factors will assist in risk stratification, guide anticipatory clinical decisions, and potentially improve patient survival.

OPTN/SRTR 2013 Annual Data Report: lung.

Lungs are allocated to adult and adolescent transplant candidates (aged ⩾ 12 years) on the basis of age, geography, blood type compatibility, and the lung allocation score (LAS), which reflects risk of waitlist mortality and probability of posttransplant survival. In 2013, the most adult candidates, 2394, of any year were added to the list. Overall median waiting time for candidates listed in 2013 was 4.0 months. The preferred procedure remained bilateral lung transplant, representing approximately 70% of lung transplants in 2013. Measures of short-term and longterm survival have plateaued since the implementation of the LAS in 2005. The number of new child candidates (aged 0-11 years) added to the lung transplant waiting list increased to 39 in 2013. A total of 28 lung transplants were performed in child recipients, 3 for ages younger than 1 year, 9 for ages 1 to 5 years, and 16 for ages 6 to 11 years. The diagnosis of pulmonary hypertension was associated with higher survival rates than cystic fibrosis or other diagnosis (pulmonary fibrosis, bronchiolitis obliterans, bronchopulmonary dysplasia). For child candidates, infection was the leading cause of death in year 1 posttransplant and graft failure in years 2 to 5.

OPTN/SRTR 2013 Annual Data Report: heart.

The number of heart transplants performed annually continues to increase gradually, and the number of adult candidates on the waiting list increased by 34.2% from 2003 to 2013. The heart transplant rate among active adult candidates peaked at 149.0 per 100 waitlist years in 2007 and has been declining since then; in 2013, the rate was 87.4 heart transplants per 100 active waitlist years. Increased waiting times do not appear to be correlated with an overall increase in waitlist mortality. Since 2008, the proportion of patients on life support before transplant increased from 53.4% to 65.8% in 2013. Medical urgency categories have become less distinct, with most patients listed in higher urgency categories. Approximately 500 pediatric candidates are added to the waiting list each year; the number of pediatric transplants performed each year increased from 293 in 2003 to 411 in 2013. Patient survival among pediatric recipients continues to improve; 5-year patient survival for transplants performed from 2001 through 2008 was 70% to 80%. Medicare paid for some or all of the care for 42.2% of all heart transplant recipients in 2012.

The future direction of the adult heart allocation system in the United States.

Ensuring equitable and fair organ allocation is a central charge of the United Network for Organ Sharing (UNOS) as the Organ Procurement and Transplantation Network (OPTN) through its contract with the Department of Health and Human Services (DHHS). The OPTN/UNOS Board initiated a reassessment of the current allocation system. This paper describes the efforts of the OPTN/UNOS Heart Subcommittee, acting on behalf of the OPTN/UNOS Thoracic Organ Transplantation Committee, to modify the current allocation system. The Subcommittee assessed the limitations of the current three-tiered system, outcomes of patients with status exceptions, emerging ventricular assist device (VAD) population, options for improved geographic sharing and status of potentially disenfranchised groups. They analyzed waiting list and posttransplant mortality rates of a contemporary cohort of patient groups at risk, in collaboration with the Scientific Registry of Transplant Recipients to develop a proposed multi-tiered allocation scheme. This proposal provides a framework for simulation modeling to project whether candidates would have better waitlist survival in the revised allocation system, and whether posttransplant survival would remain stable. The tiers are subject to change, based on further analysis by the Heart Subcommittee and will lead to the development of a more effective and equitable heart allocation system.

OPTN/SRTR 2012 Annual Data Report: heart.

The number of heart transplants performed annually continues to increase gradually, and the number of adult candidates on the waiting list increased by 25% from 2004 to 2012. The heart transplant rate among active adult candidates peaked at 149 per 100 wait-list years in 2007 and has been declining since; in 2012, the rate was 93 heart transplants per 100 active wait-list years. Increased waiting times do not appear to be correlated with an overall increase in wait-list mortality. Since 2007, the proportion of patients on life support before transplant increased from 48.6% to 62.7% in 2012. Medical urgency categories have become less distinct, with most patients listed in higher urgency categories. Approximately 500 pediatric candidates are added to the waiting list each year; the number of transplants performed each year increased from 274 in 1998 to 372 in 2012. Graft survival in pediatric recipients continues to improve; 5-year graft survival for transplants performed in 2007 was 78.5%. Medicare paid for some or all of the care for nearly 40% of heart transplant recipients in 2010. Heart transplant appears to be more expensive than ventricular assist devices for managing end-stage heart failure, but is more effective and likely more cost-effective.

OPTN/SRTR 2012 Annual Data Report: lung.

Lung transplants are increasingly used as treatment for end-stage lung diseases not amenable to other medical and surgical therapies. Lungs are allocated to adult and adolescent transplant candidates on the basis of age, geography, blood type compatibility, and the Lung Allocation Score, which reflects risk of wait-list mortality and probability of posttransplant survival. The overall median waiting time in 2012 was 4 months, and 65.3% of candidates underwent transplant within 1 year of listing; however, this proportion varied greatly by donation service area. Unadjusted median survival of lung transplant recipients was 5.3 years in 2012, and median survival conditional on living for 1 year posttransplant was 6.7 years. Among pediatric lung candidates in 2012, 32.1% were wait-listed for less than 1 year, 17.9% for 1 to less than 2 years, 16.7% for 2 to less than 4 years, and 33.3% for 4 or more years. Both graft and patient survival have continued to improve; survival rates for recipients aged 6-11 years are better than for younger recipients. Compared with recipients of other solid organ transplants, lung transplant recipients experienced the highest rates of rehospitalization for transplant complications: 43.7 per 100 patients in year 1 and 36.0 in year 2.

OPTN/SRTR 2011 Annual Data Report: heart.

Since 2005, the number of new active adult candidates on the heart transplant waiting list increased by 19.2%. The transplant rate peaked at 78.6 per 100 wait-list years in 2007, and declined to 67.8 in 2011. Wait-list mortality declined over the past decade, including among patients with a ventricular assist device at listing; in 2010 and 2011, the mortality rate for these patients was comparable to the rate for patients without a device. Median time to transplant was lowest for candidates listed in 2006-2007, and increased by 3.8 months for patients listed in 2010-2011. Graft survival has gradually improved over the past two decades, though acute rejection is common. Hospitalizations are frequent and increase in frequency over the life of the graft. In 2011, the rate of pediatric heart transplants was 124.6 per 100 patient-years on the waiting list; the highest rate was for patients aged less than 1 year. The pre-transplant mortality rate was also highest for patients aged less than 1 year. Short- and long-term graft survival has continued to improve. The effect on wait-list outcomes of a new pediatric heart allocation policy implemented in 2009 to reduce pediatric deaths on the waiting list cannot yet be determined.

OPTN/SRTR 2011 Annual Data Report: lung.

Lungs are allocated in part based on the Lung Allocation Score (LAS), which considers risk of death without transplant and posttransplant. Wait-list additions have been increasing steadily after an initial decline following LAS implementation. In 2011, the largest number of adult candidates were added to the waiting list in a single year since 1998; donation and transplant rates have been unable to keep pace with wait-list additions. Candidates aged 65 years or older have been added faster than candidates in other age groups. After an initial decline following LAS implementation, wait-list mortality increased to 15.7 per 100 wait-list years in 2011. Short- and long-term graft survival improved in 2011; 10-year graft failure fell to an all-time low. Since 1998, the number of new pediatric (aged 0-11 years) candidates added yearly to the waiting list has declined. In 2011, 19 pediatric lung transplants were performed, a transplant rate of 34.7 per 100 wait-list years. The percentage of patients hospitalized before transplant has not changed. Both graft and patient survival have continued to improve over the past decade. Posttransplant complications for pediatric lung transplant recipients, similar to complications for adult recipients, include hypertension, renal dysfunction, diabetes, bronchiolitis obliterans syndrome, and malignancy.

Lung transplantation in the United States, 1998-2007.

This article highlights trends and changes in lung and heart-lung transplantation in the United States from 1998 to 2007. The most significant change over the last decade was implementation of the Lung Allocation Score (LAS) allocation system in May 2005. Subsequently, the number of active wait-listed lung candidates declined 54% from pre-LAS (2004) levels to the end of 2007; there was also a reduction in median waiting time, from 792 days in 2004 to 141 days in 2007. The number of lung transplants performed yearly increased through the decade to a peak of 1 465 in 2007; the greatest single year increase occurred in 2005. Despite candidates with increasingly higher LAS scores being transplanted in the LAS era, recipient death rates have remained relatively stable since 2003 and better than in previous years. Idiopathic pulmonary fibrosis became the most common diagnosis group to receive a lung transplant in 2007 while emphysema was the most common diagnosis in previous years. The number of retransplants and transplants in those aged > or =65 performed yearly have increased significantly since 1998, up 295% and 643%, respectively. A decreasing percentage of lung transplant recipients are children (3.5% in 2007, n = 51). With LAS refinement ongoing, monitoring of future impact is warranted.

Development of the new lung allocation system in the United States.

This article reviews the development of the new U.S. lung allocation system that took effect in spring 2005. In 1998, the Health Resources and Services Administration of the U.S. Department of Health and Human Services published the Organ Procurement and Transplantation Network (OPTN) Final Rule. Under the rule, which became effective in 2000, the OPTN had to demonstrate that existing allocation policies met certain conditions or change the policies to meet a range of criteria, including broader geographic sharing of organs, reducing the use of waiting time as an allocation criterion and creating equitable organ allocation systems using objective medical criteria and medical urgency to allocate donor organs for transplant. This mandate resulted in reviews of all organ allocation policies, and led to the creation of the Lung Allocation Subcommittee of the OPTN Thoracic Organ Transplantation Committee. This paper reviews the deliberations of the Subcommittee in identifying priorities for a new lung allocation system, the analyses undertaken by the OPTN and the Scientific Registry for Transplant Recipients and the evolution of a new lung allocation system that ranks candidates for lungs based on a Lung Allocation Score, incorporating waiting list and posttransplant survival probabilities.

Effect of preoperative pulmonary artery pressure on early survival after lung transplantation for idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the second largest indication for lung transplantation worldwide. Average 90-day mortality rates for this procedure are 22%. It is unclear what factors predispose patients with IPF to this increased early posttransplant mortality. Pulmonary hypertension may increase the risk of development of early posttransplant complications through several mechanisms. We examined the effect of secondary pulmonary hypertension on 90-day mortality after lung transplantation for IPF. METHODS: An International Society for Heart and Lung Transplant Registry cohort study of 830 patients with IPF transplanted from January 1995 to June 2002 was undertaken. Risk factors were assessed individually and adjusted for confounding by a multivariable logistic regression model. RESULTS: In the univariate analysis, pulmonary hypertension and bilateral-lung transplantation were significant risk factors for increased 90-day mortality. Multivariate analysis confirmed that mean pulmonary artery pressure and bilateral procedure remain independent risk factors after adjustment for potential confounders. Recipient age, ischemia time, cytomegalovirus status mismatch, and donor age were not independent risk factors for early mortality. CONCLUSIONS: Bilateral-lung transplantation carries a greater risk of early mortality than single-lung transplantation for IPF. Increasing pulmonary artery pressure is a risk factor for death after single-lung transplantation in IPF. Mean pulmonary artery pressure should be included in the overall risk assessment of patients with IPF evaluated for lung transplantation.

Effect of topical fosfomycin on polymyxin B ototoxicity.

Fosfomycin is an antibiotic that has been found to reduce the ototoxicity of aminoglycoside antibiotics and cisplatin when systemically coadministered. Polymyxin B, an antibiotic frequently used in ototopical preparations, has been shown to be ototoxic in experimental studies. To investigate the effect of fosfomycin on polymyxin B ototoxicity, topical administration of the two agents into the middle ear cavity was performed. Two groups of chinchillas were used. One group received applications of polymyxin B alone, and the second group received polymyxin B combined with fosfomycin. It was found that application of polymyxin B produces severe damage to the cochlea. However, when polymyxin B was given in combination with fosfomycin, cochlear damage was dramatically reduced. It is likely that in clinical use, a combination of polymyxin B and fosfomycin would demonstrate reduced risk of ototoxicity.

The ototoxicity of ceftazidime in the chinchilla middle ear.

Ceftazidime (Tazicef) is a broad-spectrum cephalosporin antibiotic that may be useful as a topical agent in the treatment of otorrhea. To test the potential ototoxicity of the drug, 0.5 mL of a 10% solution of ceftazidime was introduced into the bullae of 22 chinchillas. The organ of Corti was normal in 20 temporal bones examined at 1 week after administration of the ceftazidime solution. Only 2 of 24 temporal bones examined after 4 weeks showed minor outer hair cell loss of the basal turn of the organ of Corti. Focal hemorrhage and occasional serous effusions were found in the middle ears of all animals after 1 week; these findings had mostly cleared after 4 weeks. Our results indicate that ceftazidime causes reversible middle ear inflammation, and may have some minor ototoxic potential under these experimental conditions.

Cell volume density alterations within the stria vascularis after administration of a hyperosmotic agent.

The purpose of this study was to determine the effects of an intravenous injection of a hyperosmotic agent (mannitol) on the volume density (Vv) of the primary components of the stria vascularis (SV). Chinchillas received either a 2.0 g/kg injection of mannitol or an equal volume of saline as a control. At 1, 10 and 60 min after the injection, the right cochleas were fixed with osmium tetroxide and prepared for transmission electron microscopy. At a distance of 70% from the cochlear apex, the complete radial area of the SV was photographed and stereologically analyzed. Additional animals received mannitol or bumetanide for the purpose of measuring serum osmolality and the endocochlear potential (EP). The present results showed elevation of serum osmolality after mannitol but not after bumetanide and depression of the +EP after bumetanide but not after mannitol. Vv alterations of SV components after mannitol were similar to those Vv changes observed in a previous study, after bumetanide. After treatment with either diuretic, the Vv of the marginal cells decreased and the Vv of the intermediate cells and intercellular spaces increased. We conclude that since the Vv alterations of the SV components are so similar after both diuretics, none of these alterations is a morphological correlate of a depressed +EP which was observed after bumetanide. A model of the action of mannitol on the SV is proposed.