This article highlights trends and changes in lung and heart–lung transplantation in the United States from 1999 to 2008. While adult lung transplantation grew significantly over the past decade, ...rates of heart–lung and pediatric lung transplantation have remained low. Since implementation of the lung allocation score (LAS) donor allocation system in 2005, decreases in the number of active waiting list patients, waiting times for lung transplantation and death rates on the waiting list have occurred. However, characteristics of recipients transplanted in the LAS era differed from those transplanted earlier. The proportion of candidates undergoing lung transplantation for chronic obstructive pulmonary disease decreased, while increasing for those with pulmonary fibrosis. In the LAS era, older, sicker and previously transplanted candidates underwent transplantation more frequently compared with the previous era. Despite these changes, when compared with the pre‐LAS era, 1‐year survival after lung transplantation did not significantly change after LAS inception. The long‐term effects of the change in the characteristics of lung transplant recipients on overall outcomes for lung transplantation remain unknown. Continued surveillance and refinements to the LAS system will affect the distribution and types of candidates transplanted and hopefully lead to improved system efficiency and outcomes.
Since implementation of the Lung Allocation Score (LAS), decreases in the number of active waiting list patients, waiting times to transplant, and death rates on the waiting list have occurred, and one‐year survival has not significantly changed.
While EBV PCR is used in the management of PTLD, the optimal primer set, relative importance of intracellular versus free plasma EBV, and the baseline profile in an organ transplant population ...remains unclear. We performed a prospective 2‐arm trial utilizing an EBV PCR panel measuring LMP‐1, EBER‐1 and EBNA‐1 in both free plasma as well as intracellular whole blood. Control Arm A consisted of 31 lung transplant patients and Arm B consisted of 35 transplant patients being evaluated for possible PTLD. In Arm A, 1/31 (3%) patients developed a transient plasma EBV load. Thirteen of 31 (42%) had detectable intracellular EBV. In Arm B, 17 (49%) patients were diagnosed with PTLD. Thirteen (76%) had EBV‐positive PTLD with 12/13 (92%) having detectable EBV by PCR. The EBV PCR panel had a high sensitivity (92%), specificity (72%), positive predictive value (PPV) (71%) and negative predictive value (NPV) (93%) for diagnosing EBV‐positive PTLD and followed patients' clinical course well (p < 0.001). Comparing the individual PCR assays, plasma EBNA PCR was superior with high sensitivity (77%), specificity (100%), PPV (100%) and NPV (86%). We conclude that EBV PCR is a useful test for managing PTLD patients. While plasma EBNA PCR is the best single assay for diagnosing and monitoring PTLD, the complete PCR panel is superior for ruling out its presence.
This study determined that utilizing plasma as a specimen source and gene targets EBNA and EBER in EBV quantitative real‐time PCR assays provided the highest sensitivity and specificity for diagnosing and monitoring PTLD. Therefore an assay that incorporates both gene targets would be the most successful in the management of PTLD patients.
Lymphangioleiomyomatosis (LAM) is a slowly progressive, low grade, metastasizing neoplasm, associated with cellular invasion and cystic destruction of the pulmonary parenchyma. Although the source of ...LAM cells that infiltrate the lung is unknown, available evidence indicates that the disease spreads primarily through lymphatic channels, often involving abdominal, axial, and retroperitoneal nodes, suggestive of an origin in the pelvis. LAM cells harbor mutations in tuberous sclerosis genes and produce lymphangiogenic growth factors, which facilitate access to and movement through the lymphatic system and likely play an important role in destructive tissue remodeling in the lung. Lymphatic manifestations of LAM include thoracic duct wall invasion, lymphangioleiomyoma formation, chylous fluid collections in the peritoneal, pleural, and pericardial spaces, chyloptysis, chylocolporrheal chylometrorrhea, chyle leak from the umbilicus, chylous pulmonary congestion, and lower extremity lymphedema. LAM lesions express lymphangiogenic growth factors VEGF-C and VEGF-D; growth factor receptors, VEGFR-2 and VEGFR-3; and markers LYVE-1 and podoplanin, and are laced with chaotic lymphatic channels. Serum VEGF-D is elevated in 70% of patients with LAM and is a clinically useful diagnostic and prognostic biomarker. Molecular targeted therapy with sirolimus stabilizes lung function, is anti-lymphangiogenic, and is highly effective for the lymphatic and chylous complications of LAM. Future trials in patients with LAM who have lymphatic manifestations or elevated serum VEGF-D will likely focus on the VEGF-C/VEGF-D/VEGFR-3 axis.
Medical complications of lung transplantation Kotloff, R.M; Ahya, V.N
European respiratory journal/The European respiratory journal,
02/2004, Letnik:
23, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Surgical advances, in conjunction with more effective immunosuppressive strategies, have propelled the field of lung transplantation forward and have made intermediate-term survival an achievable ...goal. Nonetheless, the post-transplant course is often marked by complications that threaten both the quality and duration of the recipient's life. Many of the medical complications that arise are the direct consequence of the need to administer potent immunosuppressive agents, with their attendant risks of infection, malignancy and drug toxicity. This article will review the major medical complications, excluding allograft rejection, which may be encountered in the lung transplant recipient. Familiarity with, and vigilance for, these problems should facilitate earlier recognition, more expeditious intervention and more favourable outcomes.
Posttransplant lymphoproliferative disorder (PTLD) is an Epstein-Barr virus-associated malignancy that occurs in the setting of pharmacologic immunosuppression after organ transplantation. With the ...increased use of organ transplantation and intensive immunosuppression, this disease is becoming more common. We explore reduction in immunosuppression as an initial therapy for PTLD.
We analyzed our organ transplant patient database to identify patients with biopsy-proven PTLD who were initially treated with reduction of their immunosuppressive medications with or without surgical resection of all known disease.
Forty-two adult patients were included in this study. Thirty patients were treated with reduction in immunosuppression alone. Twelve patients were treated with both reduction in immunosuppression and surgical resection of all known disease. Thirty-one of 42 patients (73.8%) achieved a complete remission. Of those patients who were treated with reduction in immunosuppression alone, 19 of 30 (63%) responded with a median time to documentation of response of 3.6 weeks. Multivariable analysis showed that elevated lactate dehydrogenase (LDH) ratio, organ dysfunction, and multi-organ involvement by PTLD were independent prognostic factors for lack of response to reduction in immunosuppression. In patients with none of these poor prognostic factors, 16 of 18 (89%) responded to reduction in immunosuppression in contrast to three of five (60%) with one risk factor and zero of seven (0%) with two to three factors present. The analysis also showed that increased age, elevated LDH ratio, severe organ dysfunction, presence of B symptoms (fever, night sweats, and weight loss), and multi-organ involvement by PTLD at the time of diagnosis are independent prognostic indicators for poor survival. With median follow-up of 147 weeks, 55% of patients are alive with 50% in complete remission.
Reduction in immunosuppression is an effective initial therapy for PTLD. Clinical prognostic factors may allow clinicians to identify which patients are likely to respond to reduction in immunosuppression.
To characterize the course of patients with advanced sarcoidosis who have been listed for lung transplantation and to identify prognostic factors for death while they are on the waiting list.
...Retrospective cohort study.
Tertiary-care university hospital.
Forty-three patients with sarcoidosis who have been listed for lung transplantation at the University of Pennsylvania Medical Center.
A multivariable explanatory analysis using a Cox proportional hazards model was performed to determine risk factors that are independently associated with mortality while patients await transplantation.
Twenty-three of the 43 patients (53%) died while awaiting transplantation. The survival rate of listed patients (as determined by the Kaplan-Meier method) was 66% at 1 year, 40% at 2 years, and 31% at 3 years. In a univariate analysis, the following factors were significantly associated with death on the waiting list: Pao2 ≤ 60 mm Hg (relative risk RR, 3.4; 95% confidence interval CI, 1.2 to 9.3); mean pulmonary artery pressure ≥ 35 mm Hg (RR, 3.2; 95% CI, 1.1 to 9.5); cardiac index≤ 2 L/min/m2 (RR, 2.8; 95% CI, 1.2 to 6.6), and right atrial pressure (RAP) ≥ 15 mm Hg (RR, 7.6; 95% CI, 3.0 to 19.3). Multivariable analysis revealed that RAP ≥ 15 mm Hg was the only independent prognostic variable (RR, 5.2; 95% CI, 1.6 to 16.7; p = 0.006). Twelve patients underwent lung transplantation. Survival after transplantation determined by the Kaplan-Meier method was 62% at both 1 and 2 years, and 50% at 3 years.
Patients with advanced sarcoidosis awaiting lung transplantation have a high mortality rate with a median survival of < 2 years. Mortality is most closely linked to elevated RAP. While earlier referral may diminish the mortality rate of patients on the waiting list for transplantation, further improvements in posttransplantation outcomes will be necessary to ensure that this procedure truly bestows a survival benefit.
A fundamental goal of lung transplantation is the regaining of functional capacity, yet little is known about what factors are associated with the achievement of this goal. The aim of this study is ...to test the association of clinical risk factors with functional status 1 year following lung transplantation. We conducted a cohort study of 321 lung transplants and assessed functionality by the distance achieved during a standard 6‐min walk test (6MWT). Preoperative recipient risk factors were evaluated for association with functional status and adjusted for confounding using multivariable linear regression models. In these multivariable analyses, recipient female gender (p < 0.001), recipient pretransplant body mass index (BMI) of greater than 27 kg/m2 (p = 0.017) and shorter pretransplant 6MWT distances (p = 0.006) were independently associated with shorter distances achieved during 6MWT after lung transplant, while cystic fibrosis (CF) (p = 0.003), and bilateral lung transplant (p = 0.014) were independently associated with longer distances achieved. Approximately 51% of the variance in 6MWT distance was explained by these risk factors in the linear regression models (R2= 0.51). These findings may have implications in patient counseling, selection, procedure choice, and may lead to interventions aimed at improving the functional outcomes of lung transplantation.
Recipient female gender, high BMI, and poor exercise performance before transplant were independently associated with poor exercise performance post‐transplant, while cystic fibrosis and bilateral lung transplants were associated with better post‐transplant exercise performance.
Abstract Background Tuberous sclerosis complex is highly variable in clinical presentation and findings. Disease manifestations continue to develop over the lifetime of an affected individual. ...Accurate diagnosis is fundamental to implementation of appropriate medical surveillance and treatment. Although significant advances have been made in the past 15 years in the understanding and treatment of tuberous sclerosis complex, current clinical diagnostic criteria have not been critically evaluated or updated since the last clinical consensus conference in 1998. Methods The 2012 International Tuberous Sclerosis Complex Consensus Group, comprising 79 specialists from 14 countries, was organized into 12 subcommittees, each led by a clinician with advanced expertise in tuberous sclerosis complex and the relevant medical subspecialty. Each subcommittee focused on a specific disease area with important diagnostic implications and was charged with reviewing prevalence and specificity of disease-associated clinical findings and their impact on suspecting and confirming the diagnosis of tuberous sclerosis complex. Results Clinical features of tuberous sclerosis complex continue to be a principal means of diagnosis. Key changes compared with 1998 criteria are the new inclusion of genetic testing results and reducing diagnostic classes from three (possible, probable, and definite) to two (possible, definite). Additional minor changes to specific criterion were made for additional clarification and simplification. Conclusions The 2012 International Tuberous Sclerosis Complex Diagnostic Criteria provide current, updated means using best available evidence to establish diagnosis of tuberous sclerosis complex in affected individuals.
Abstract Background Tuberous sclerosis complex is a genetic disorder affecting every organ system, but disease manifestations vary significantly among affected individuals. The diverse and varied ...presentations and progression can be life-threatening with significant impact on cost and quality of life. Current surveillance and management practices are highly variable among region and country, reflective of the fact that last consensus recommendations occurred in 1998 and an updated, comprehensive standard is lacking that incorporates the latest scientific evidence and current best clinical practices. Methods The 2012 International Tuberous Sclerosis Complex Consensus Group, comprising 79 specialists from 14 countries, was organized into 12 separate subcommittees, each led by a clinician with advanced expertise in tuberous sclerosis complex and the relevant medical subspecialty. Each subcommittee focused on a specific disease area with important clinical management implications and was charged with formulating key clinical questions to address within its focus area, reviewing relevant literature, evaluating the strength of data, and providing a recommendation accordingly. Results The updated consensus recommendations for clinical surveillance and management in tuberous sclerosis complex are summarized here. The recommendations are relevant to the entire lifespan of the patient, from infancy to adulthood, including both individuals where the diagnosis is newly made as well as individuals where the diagnosis already is established. Conclusions The 2012 International Tuberous Sclerosis Complex Consensus Recommendations provide an evidence-based, standardized approach for optimal clinical care provided for individuals with tuberous sclerosis complex.
To compare short-term outcomes following bilateral lung volume reduction surgery performed by median sternotomy (MS) and video-assisted thoracoscopic surgery (VATS).
Bilateral lung volume reduction ...surgery was performed by MS in 80 patients and by VATS in 40. All patients underwent preoperative assessment with pulmonary function testing, arterial blood gas determination, and 6-min walk test (6MWT). Pulmonary function testing and 6MWT were repeated at 3 to 6 months postoperatively.
The mean age of the VATS group was lower than that of the MS group (59.3 +/- 9.4 vs 62.4 +/- 6.9 years; p = 0.001), but there were no differences in baseline functional parameters of disease severity (FEV1, FVC, residual volume RV, arterial PCO2, or 6MWT). All patients in both groups were extubated at the completion of surgery, but 17.5% of patients in the MS group and 2.5% in the VATS group (p = 0.02) subsequently required reintubation at some point during the postoperative course. Thirty-day operative mortality was 4.2% for the MS group and 2.5% for the VATS group (p = not significant). However, total in-hospital mortality was 13.8% for the MS group, while it remained 2.5% for the VATS group (p = 0.05). Mortality was largely confined to patients 65 years of age or older. There was no significant difference in duration of air leaks or length of hospital stay between the two groups. Functional outcomes achieved with the two techniques were similar. Specifically, there was no difference between the two groups in mean postoperative FEV1, FVC, RV, or 6MWT, or in the magnitude of change in these parameters over preoperative values.
Bilateral lung volume reduction surgery performed by either MS and VATS approaches leads to similar improvements in pulmonary function and exercise tolerance. VATS is associated with a significantly lower incidence of respiratory failure and a trend toward decreased in-hospital mortality and may be the preferred technique, particularly for high-risk patients.
PDF
