Biomedical subjects

David R Jones

Publications and source records attributed to David R Jones.

At least 19 recordsLinked to original sources

PubMed2007

Evidence-based sample size calculations based upon updated meta-analysis.

Meta-analyses of randomized controlled trials (RCTs) provide the highest level of evidence regarding the effectiveness of interventions and as such underpin much of evidence-based medicine. Despite this, meta-analyses are usually produced as observational by-products of the existing literature, with no formal consideration of future meta-analyses when individual trials are being designed. Basing the sample size of a new trial on the results of an updated meta-analysis which will include it, may sometimes make more sense than powering the trial in isolation. A framework for sample size calculation for a future RCT based on the results of a meta-analysis of the existing evidence is presented. Both fixed and random effect approaches are explored through an example. Bayesian Markov Chain Monte Carlo simulation modelling is used for the random effects model since it has computational advantages over the classical approach. Several criteria on which to base inference and hence power are considered. The prior expectation of the power is averaged over the prior distribution for the unknown true treatment effect. An extension to the framework allowing for consideration of the design for a series of new trials is also presented. Results suggest that power can be highly dependent on the statistical model used to meta-analyse the data and even very large studies may have little impact on a meta-analysis when there is considerable between study heterogeneity. This raises issues regarding the appropriateness of the use of random effect models when designing and drawing inferences across a series of studies.

Anti-Bacterial Agents↗

PubMed2006

The quantification of erlotinib (OSI-774) and OSI-420 in human plasma by liquid chromatography-tandem mass spectrometry.

An accurate and precise method was developed using HPLC-MS/MS to quantify erlotinib (OSI-774) and its O-desmethyl metabolite, OSI-420, in plasma. The advantages of this method include the use of a small sample volume, liquid-liquid extraction with high extraction efficiency and short chromatographic run times. The analytes were extracted from 100 microL plasma volume using hexane:ethyl acetate after midazolam was added to the sample for internal standardization. The compounds were separated on a Phenomenex C-18 Luna analytical column with acetonitrile:5 mM ammonium acetate as the mobile phase. All compounds were monitored by tandem mass spectrometry with electrospray positive ionization. The intra-day accuracy and precision (% coefficient of variation, % CV) estimates for erlotinib at 10 ng/mL were 90% and 9%, respectively. The intra-day accuracy and precision estimates for OSI-420 at 5 ng/mL were 80% and 4%, respectively. This method was used to quantify erlotinib and OSI-420 in plasma of patients (n=21) administered 150 mg erlotinib per day for non-small cell lung cancer.

Chromatography, High Pressure Liquid↗

PubMed2006

Exercise warms adult leatherback turtles.

Leatherback sea turtles (Dermochelys coriacea) can maintain body temperature (T(B)) up to 18 degrees C above that of the surrounding sea water (T(W)) which allows leatherbacks to enter cold temperate waters and have the largest global range of any reptile. Using a cylindrical model of a leatherback we investigated the extent to which heat production through variation of swim speed could be used in a leatherback's thermal strategy. Drag force of a full scale cast of a leatherback was measured in a low velocity wind tunnel to obtain an estimate of the metabolic cost needed to offset drag. Heat released in the core of a turtle as a byproduct of the metabolic cost of locomotion is conducted from the core of the turtle to the surrounding water through its insulation layer. By keeping insulation thickness constant, we highlight the effectiveness of swim speed in maintaining T(B)-T(W). Our model, when tested against published data at a given T(W), showed a close correlation between predicted and measured swimming speed at a given T(B). We conclude that the ability to maintain a large T(B)-T(W) is an interplay between mass, insulation thickness and water temperature selection but behavioural control of swimming speed predominates.

Animals↗

PubMed2006

Breast cancer metastasis suppressor 1 functions as a corepressor by enhancing histone deacetylase 1-mediated deacetylation of RelA/p65 and promoting apoptosis.

The antiapoptotic transcription factor NF-kappaB is constitutively activated in many cancers and is important for cytokine-mediated progression and metastatic movement of tumors. Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene whose mechanisms of action are poorly understood. In this report, we demonstrate that BRMS1 decreases the transactivation potential of RelA/p65 and ameliorates the expression of NF-kappaB-regulated antiapoptotic gene products. BRMS1 immunoprecipitates with the RelA/p65 subunit of NF-kappaB with protein-protein interactions occurring at the C terminus region of the rel homology domain but not at its known transactivation domains. Moreover, BRMS1 functions as a corepressor by promoting binding of HDAC1 to RelA/p65, where it deacetylates lysine K310 on RelA/p65, which suppresses RelA/p65 transcriptional activity. Selective small interfering RNA knockdown of BRMS1 confirms that chromatin-bound BRMS1 is required for deacetylation of RelA/p65, while enhancing chromatin occupancy of HDAC1 onto the NF-kappaB-regulated promoters cIAP2 and Bfl-1/A1. We observed in cells lacking BRMS1 a dramatic increase in cell viability after the loss of attachment from the extracellular matrix. Collectively, these results suggest that BRMS1 suppresses metastasis through its ability to function as a transcriptional corepressor of antiapoptotic genes regulated by NF-kappaB.

Acetylation↗

PubMed2006

Nuclear PtdIns5P as a transducer of stress signaling: an in vivo role for PIP4Kbeta.

Inhibitor of growth protein-2 (ING2) is a nuclear adaptor protein that can regulate p53 and histone acetylation in response to cellular stress and contains a PHD (plant homeodomain) finger that can interact with phosphatidylinositol-5-phosphate (PtdIns5P). However, whether or how nuclear PtdIns5P levels are regulated in response to cellular stress or whether ING2 can sense these changes has not been demonstrated. We show that UV irradiation increases nuclear PtdIns5P levels via inhibition of the activity of the beta isoform of PtdIns5P 4-kinase (PIP4Kbeta), an enzyme that can phosphorylate and remove PtdIns5P. Inhibition of PIP4Kbeta activity occurs through the direct phosphorylation of PIP4Kbeta at Ser326 by the p38 stress-activated protein kinase. Finally, we show that changes in nuclear PtdIns5P are translated into changes in the association of ING2 with chromatin. Our data define a pathway connecting cellular stressors with changes in nuclear PtdIns5P levels and the regulation of PHD motif-containing proteins.

1-Phosphatidylinositol 4-Kinase↗

PubMed2006

Suberoylanilide hydroxamic acid induces Akt-mediated phosphorylation of p300, which promotes acetylation and transcriptional activation of RelA/p65.

We have previously demonstrated that the transcription factor NF-kappaB is activated by histone deacetylase inhibitors in a PI3K/Akt-dependent manner. The molecular mechanisms governing this process have not been well described. By virtue of their inhibitory action, it is unclear whether the addition of histone deacetylase inhibitors simply preserves the acetylation status of RelA/p65 or whether they actively stimulate signaling cascades that result in increased acetylation and transcription of NF-kappaB. Here we provide evidence that suberoylanilide hydroxamic acid stimulates NF-kappaB transcription through a signaling cascade that involves activation of both the serine/threonine kinase Akt and the p300 acetyltransferase. Using newly developed phosphospecific antibodies to p300 (pSer(1834)), and site-directed mutant proteins, we find that suberoylanilide hydroxamic acid stimulates Akt activity, which is required to phosphorylate p300 at Ser(1834). Akt-mediated phosphorylation of p300 dramatically increases its acetyltransferase activity as measured by an increased acetylation of RelA/p65 at Lys(310), a modification that is required for full NF-kappaB transcription. Importantly, coordinate activation of Akt/p300 pathway by suberoylanilide hydroxamic acid occurs at the chromatin level, resulting in recruitment of activated Akt (pSer(473)), p300 (pSer(1834)), acetylated RelA/p65 (Lys(310)), and RNA polymerase II to the NF-kappaB-dependent cIAP-2 and Bfl-1/A1 promoters. These studies provide evidence that histone deacetylase inhibitors, such as suberoylanilide hydroxamic acid, not only inhibit deacetylase activity but also stimulate active NF-kappaB transcription and cell survival through signaling pathways involving Akt and increased p300 acetyltransferase activity.

Apoptosis↗

PubMed2006

Could cholesterol bound to haemoglobin be a missing link for the occasional inverse relationship between superoxide dismutase and glutathione peroxidase activities?

The concept of an anti-oxidant defence system as a means to prevent oxidative cell damage implies balanced activities of anti-oxidant defence enzymes. As well as positive correlations between anti-oxidant enzyme activities in human erythrocytes, it has been observed that sometimes when glutathione peroxidase activity is increased, CuZn-superoxide dismutase activity is decreased. In our current study we have examined the plasma lipid profile and the anti-oxidant defence enzymes in erythrocytes from humans, pigs, and bulls. We found that a negative correlation existed between CuZn-superoxide dismutase and glutathione peroxidase activities in human erythrocytes when the concentrations of both plasma triglycerides and total cholesterol were high. This correlation was also found in pig erythrocytes, but not in bull erythrocytes. We propose that cholesterol could affect membrane lipid peroxidation and superoxide generation in erythrocytes via the recently found fraction of cholesterol bound to haemoglobin, termed haemoglobin-cholesterol.

Animals↗

PubMed2006

Visualization of PtdIns3P dynamics in living plant cells.

To investigate PtdIns3P localization and function in plants, a fluorescent PtdIns3P-specific biosensor (YFP-2xFYVE) was created. On lipid dot blots it bound specifically and with high affinity to PtdIns3P. Transient expression in cowpea protoplasts labelled vacuolar membranes and highly motile structures undergoing fusion and fission. Stable expression in tobacco BY-2 cells labelled similar motile structures, but labelled vacuolar membranes hardly at all. YFP-2xFYVE fluorescence strongly co-localized with the pre-vacuolar marker AtRABF2b, partially co-localized with the endosomal tracer FM4-64, but showed no overlap with the Golgi marker STtmd-CFP. Treatment of cells with wortmannin, a PI3 kinase inhibitor, caused the YFP-2xFYVE fluorescence to redistribute into the cytosol and nucleus within 15 min. BY-2 cells expressing YFP-2xFYVE contained twice as much PtdIns3P as YFP-transformed cells, but this had no effect on cell-growth or stress-induced phospholipid signalling responses. Upon treatment with wortmannin, PtdIns3P levels were reduced by approximately 40% within 15 min in both cell lines. Stable expression of YFP-2xFYVE in Arabidopsis plants labelled different subcellular structures in root compared with shoot tissues. In addition labelling the motile structures common to all cells, YFP-2xFYVE strongly labelled the vacuolar membrane in leaf epidermal and guard cells, suggesting that cell differentiation alters the distribution of PtdIns3P. In dividing BY-2 cells, YFP-2xFYVE-labelled vesicles surrounded the newly formed cell plate, suggesting a role for PtdIns3P in cytokinesis. Together, these data show that YFP-2xFYVE may be used as a biosensor to specifically visualize PtdIns3P in living plant cells.

Androstadienes↗

PubMed2006

Characterisation of insulin-like growth factor receptors and insulin receptors in the human placenta using lectin affinity methods.

Insulin and insulin-like growth factor receptors (IR, IGF-IR, IGF-IIR) from human placental cell membranes were solubilised and their glycoprotein properties were studied in terms of their interaction with five lectins: wheat germ agglutinin (WGA), banana lectin (BanLec), phytohaemagglutinin (PHA), concanavalin A (Con A), and Sambucus nigra agglutinin (SNA). The pattern of binding to the immobilised lectins indicated that the glycosylation of the IGF-IR, IGF-IIR and IR differed. We found several populations of receptors in placental cell membranes, differing with respect to their oligosaccharide moieties. IGF-IIR populations bore highly branched complex type N-glycans with a very high content of oligosaccharides terminating with Sia, high-mannose type N-glycans and hybrid type N-glycans. All these glycans seemed to be attached to the same IGF-II receptor molecules. Two major glycoforms of IR were detected, one having multiple highly branched N-glycans with a low content of terminal Sia and the other, having high-mannose type glycans attached to multiple N-glycosylation sites. As for the IGF-IR, multiple glycoforms were detected, bearing complex type N-glycans with various content of Sia-terminating branches, hybrid type N-glycans or high-mannose type N-glycans. The specific binding of (125)I-IGF-II to its receptor increased in the presence of immobilised WGA and SNA, which might imply the existence of a mammalian lectin counterpart whose potential physiological significance may lie in different targeting to various membrane compartments, thereby potentially modifying their cell signalling pathways.

Binding, Competitive↗

PubMed2006

Wave reflection effects in the central circulation of American alligators (Alligator mississippiensis): what the heart sees.

A large central compliance is thought to dominate the hemodynamics of all vertebrates except birds and mammals. Yet large crocodilians may adumbrate the avian and mammalian condition and set the stage for significant wave transmission (reflection) effects, with potentially detrimental impacts on cardiac performance. To investigate whether crocodilians exhibit wave reflection effects, pressures and flows were recorded from the right aorta, carotid artery, and femoral artery of six adult, anesthetized American alligators (Alligator mississippiensis) during control conditions and after experimentally induced vasodilation and constriction. Hallmarks of wave reflection phenomena were observed, including marked differences between the measured profiles for flow and pressure, peaking of the femoral pressure pulse, and a diastolic wave in the right aortic pressure profile. Pulse wave velocity and peripheral input impedance increased with progressive constriction, and thus changes in both the timing and magnitude of reflections accounted for the altered reflection effects. Resolution of pressure and flow waves into incident and reflected components showed substantial reflection effects within the right aorta, with reflection coefficients at the first harmonic approaching 0.3 when constricted. Material properties measured from isolated segments of blood vessels revealed a major reflection site at the periphery and, surprisingly, at the junction of the truncus and right aorta. Thus, while our results clearly show that significant wave reflection phenomena are not restricted to birds and mammals, they also suggest that rather than cope with potential negative impacts of reflections, the crocodilian heart simply avoids them because of a large impedance mismatch at the truncus.

Alligators and Crocodiles↗

PubMed2006

Comparison of two methods to detect publication bias in meta-analysis.

CONTEXT: Egger's regression test is often used to help detect publication bias in meta-analyses. However, the performance of this test and the usual funnel plot have been challenged particularly when the summary estimate is the natural log of the odds ratio (lnOR). OBJECTIVE: To compare the performance of Egger's regression test with a regression test based on sample size (a modification of Macaskill's test) with lnOR as the summary estimate. DESIGN: Simulation of meta-analyses under a number of scenarios in the presence and absence of publication bias and between-study heterogeneity. MAIN OUTCOME MEASURES: Type I error rates (the proportion of false-positive results) for each regression test and their power to detect publication bias when it is present (the proportion of true-positive results). RESULTS: Type I error rates for Egger's regression test are higher than those for the alternative regression test. The alternative regression test has the appropriate type I error rates regardless of the size of the underlying OR, the number of primary studies in the meta-analysis, and the level of between-study heterogeneity. The alternative regression test has comparable power to Egger's regression test to detect publication bias under conditions of low between-study heterogeneity. CONCLUSION: Because of appropriate type I error rates and reduction in the correlation between the lnOR and its variance, the alternative regression test can be used in place of Egger's regression test when the summary estimates are lnORs.

Meta-Analysis as Topic↗

PubMed2006

Deep diving mammals: Dive behavior and circulatory adjustments contribute to bends avoidance.

A mathematical model was created that predicted blood and tissue N(2) tension (P(N2)) during breath-hold diving. Measured muscle P(N2) from the bottlenose dolphin after diving repeatedly to 100 m (Tursiops truncatus [Ridgway and Howard, 1979, Science, 4423, 1182-1183]) was compared with predictions from the model. Lung collapse was modelled as a 100% pulmonary shunt which yielded tissue P(N2) similar to those reported for the dolphin. On the other hand, predicted muscle P(N2) for an animal with a dive response, reducing cardiac output by 66% from surface values (20.5 to 6.8l x min(-1)), also agreed well with observed values in the absence of lung collapse. In fact, modelling indicated that both cardiovascular adjustments and dive behaviour are important in reducing N2 uptake during diving and enhancing safe transfer of tissue and blood N2 back to the lung immediately before coming to the surface. In particular, diving bradycardia during the descent and bottom phase together with a reduced ascent rate and increase in heart rate reduced mixed venous P(N2) upon return to the surface by as much as 45%. This has important implications as small reductions in inert gas load (approximately 5%) can substantially reduce decompression sickness (DCS) risk by as much as 50% (Fahlman et al., 2001, J. Appl. Physiol. 91, 2720-2729).

Acclimatization↗

PubMed2006

Endogenous S-nitrosoglutathione modifies 5-lipoxygenase expression in airway epithelial cells.

S-Nitrosoglutathione (GSNO) is an endogenous bronchodilator with several beneficial pulmonary effects. Levels are decreased in the asthmatic airway, and GSNO inhalation has been proposed as an asthma therapy. 5-lipoxygenase (5-LO) is the rate-limiting enzyme in the synthetic pathway for cysteinyl leukotrienes (CysLTs), bronchoconstricting agents that are overproduced in asthma. Here, we have studied the effect of GSNO on the expression of 5-LO in human airway A549 cell lines and in primary normal human tracheobronchial epithelial (NHBE) cells in vitro. GSNO at concentrations of 0.5-1 microM caused a 3- to 6-fold increase in 5-LO expression. However, GSNO at>5 microM significantly inhibited both 5-LO expression and LT production. We also found that airway epithelial cells had gamma-glutamyl transpeptidase (gamma-GT) activity. The effect of 1 microM GSNO on 5-LO expression was prevented by the gamma-GT inhibitor, acivicin, suggesting a convergence of GSNO and CysLT metabolic pathway that may be relevant to asthma. Our data demonstrate that GSNO levels 5microM suppresses 5-LO expression. These data suggest that GSNO might inhibit 5-LO expression in the clinical setting.

Arachidonate 5-Lipoxygenase↗

PubMed2006

Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial.

BACKGROUND: Little prospective, multiinstitutional data exist regarding the morbidity and mortality after major pulmonary resections for lung cancer or whether a mediastinal lymph node dissection increases morbidity and mortality. METHODS: Prospectively collected 30-day postoperative data was analyzed from 1,111 patients undergoing pulmonary resection who were enrolled from July 1999 to February 2004 in a randomized trial comparing lymph node sampling versus mediastinal lymph node dissection for early stage lung cancer. RESULTS: Of the 1,111 patients randomized, 1,023 were included in the analysis. Median age was 68 years (range, 23 to 89 years); 52% were men. Lobectomy was performed in 766 (75%) and pneumonectomy in 42 (4%). Pathologic stage was IA in 424 (42%), IB in 418 (41%), IIA in 37 (4%), IIB in 97 (9%), and III in 45 (5%). Lymph node sampling was performed in 498 patients and lymph node dissection in 525. Operative mortality was 2.0% (10 of 498) for lymph node sampling and 0.76% (4 of 525) for lymph node dissection. Complications occurred in 38% of patients in each group. Lymph node dissection had a longer median operative time and greater total chest tube drainage (15 minutes, 121 mL, respectively). There was no difference in the median hospitalization, which was 6 days in each group (p = 0.404). CONCLUSIONS: Complete mediastinal lymphadenectomy adds little morbidity to a pulmonary resection for lung cancer. These data from a current, multiinstitutional cohort of patients who underwent a major pulmonary resection constitute a new baseline with which to compare results in the future.

Adult↗

PubMed2006

Stage IB nonsmall cell lung cancers: are they all the same?

BACKGROUND: There is renewed interest in adjuvant chemotherapy after complete resection of nonsmall cell lung cancer, including stage IB (T2N0) cancers. Given the heterogeneity of the T2 classification, we hypothesize that there are survival differences in patients with stage IB NSCLC based on specific histopathologic tumor characteristics. METHODS: A retrospective evaluation of 119 consecutive patients from 1999 to 2004 with a pathologic diagnosis of T2N0 nonsmall cell lung cancer was performed. Patient follow-up was 97%. Overall survival and disease-free survival rates were calculated by the Kaplan-Meier method. Univariate analysis was performed using the log rank test and multivariate analysis by Cox's proportional hazard model. Data were significant if p < 0.05. RESULTS: The 4-year overall survival and disease-free survival rates were 62% and 60%, respectively. The local and distant recurrence rates were 5% and 18%, respectively. Tumor size (p = 0.001), histologic grade (p = 0.002), the Eastern Cooperative Oncology Group performance status (p = 0.002), angioinvasion (p = 0.03), and visceral pleural involvement (p = 0.02) were predictors of overall survival by univariate analysis. Multivariate analysis demonstrated increasing tumor size (1.26 [95% confidence intervals 1.12, 1.64]) and histologic grade (4.05 [95% confidence intervals 1.38, 11.90]) to be significant independent predictors of a worse overall survival. The 4-year survival of patients without any of these variables was 89% compared with 56% if one or more of these factors were present (p = 0.03). CONCLUSIONS: There is significant heterogeneity in the T2N0 class of nonsmall cell lung cancer. Risk stratification using specific histopathologic variables may help determine which patients will benefit most from adjuvant therapy.

Adult↗

PubMed2006

Economic assessment of the general thoracic surgery outpatient service.

BACKGROUND: One aspect of the definition of institutional value for any program is based on the return on investment (ROI) for that program. Program requests for future resource allocations depend, in part, on that information. The purpose of this project was to determine the ROI for initial outpatient visits only for our General Thoracic Surgery (GTS) program. METHODS: The number of GTS outpatient visits, studies, and requested consultations ordered by GTS surgeons only was determined after review of the hospital database and office records for the calendar year 2003. Only charges associated with the initial outpatient visits (no inpatient or physician charges) were included. Charges were based on hospital finance department data. The ROI for GTS outpatient services was calculated using total hospital costs and hospital collections. RESULTS: There were 689 initial outpatient GTS visits. The majority were for lung cancer (48%), benign lung diseases (21%), and esophageal diseases (14%). Total outpatient charges were 1.25M dollars and by disease process were lung cancer (644,000 dollars), benign lung disease (90,000 dollars), esophageal disease (159,000 dollars), and other (357,000 dollars). The most significant hospital charges were the following: radiology (850,000 dollars), laboratory studies (82,000 dollars), gastrointestinal medicine studies (59,000 dollars), and cardiology (42,000 dollars). Total operational costs for the GTS clinic were 415,000 dollars and hospital collections were 513,000 dollars, yielding an ROI of 98,000 dollars or an operating margin of 19%. CONCLUSIONS: An operating margin of 19% for GTS outpatient services is better than most Fortune 500 companies. Acquisition of this type of information by GTS surgeons may be helpful for future program development and institutional resource allocation.

Clinical Laboratory Techniques↗

PubMed2006

Clinical experience with radiotracer-guided thoracoscopic biopsy of small, indeterminate lung nodules.

BACKGROUND: Although computed tomography lung-screening programs report a 31% to 51% incidence of subcentimeter pulmonary nodules, 85% are too small to biopsy or interrogate with positron emission spectroscopy scans. We developed a technique using transthoracic percutaneous radiotracer injection with thoracoscopic radioprobe localization and excision for small pulmonary nodules. This report describes our series of the first 46 patients evaluated with this technique. METHODS: Forty-six patients (79% smokers; 52% males; median age, 64 years) were evaluated. Patient selection was based on the surgeon's anticipated difficulty in thoracoscopically locating small nodules because of lesion size or location. Computed tomographic-guided injection of radiotracer solution was made into or adjacent to the nodule the day of surgery. Intraoperative gamma probe localization, followed by thoracoscopic excision of the lesion, was subsequently performed. RESULTS: Median nodule size was 9 mm (range, 3 to 22 mm), and median depth was 5 mm (range, 0 to 50 mm). Forty-four (96%) of the lesions were successfully localized and excised. Median time from injection to surgery was 270 minutes. Failures were the result of inadvertent pleural or chest wall radiotracer placement. Forty-six percent (21 of 46) of the lesions were malignant, of which 71% (15 of 21) were primary lung cancers. Patients with lung cancer underwent lobectomy or segmentectomy. Fourteen of 15 were stage IA, whereas 1 was stage IIIB (6 mm primary with 4 mm intralobar metastasis). Complications were three pneumothoraces at the time of radiotracer injection. CONCLUSIONS: Computed tomography-guided radiotracer localization of small pulmonary nodules combined with thoracoscopic excisional biopsy is feasible and safe. This technique successfully localized and excised the nodule in 96% of cases.

Biopsy↗

PubMed2006

Lung transplantation in patients 60 years and older: results, complications, and outcomes.

BACKGROUND: Advanced recipient age is reported to negatively affect survival after lung transplantation (LTX). We hypothesized that LTX in patients aged > or = 60 years could be performed with acceptable outcomes. METHODS: We identified 182 consecutive LTX recipients from 1995 to 2005. Outcomes were analyzed and survival compared with results in recipients aged < 60, as well as with United Network for Organ Sharing (UNOS) registry outcomes for the same age and study period. Actuarial survivals were calculated by the Kaplan-Meier method. RESULTS: During the study period, 29% (52/182) of LTX recipients were > or = 60 years old (range, 60 to 69 years). Median follow-up was 2.9 years (range, 0 to 10 years). All patients but one received a single lung. Indications included chronic obstructive pulmonary disease in 63% (33/52), idiopathic pulmonary fibrosis in 27% (14/52), and other in 10% (5/52). In-hospital mortality was 12% (6/52) for those aged > or = 60 compared with 7% (9/130) for those aged < 60 (p = NS). Complications included reoperation in 10% (5/52), requirement for extracorporeal membrane oxygenation in 6% (3/52), renal failure in 12% (6/52), and stroke in 4% (2/52). Actuarial survivals at 30 days, and 1, 3, and 5 years were 90% (82, 98), 86% (76, 96), 71% (56, 85), and 55% (37, 73), respectively. No significant difference in survival was observed between age cohorts for our institutional data by Kaplan-Meier analysis (p = 0.34) or by Cox proportional hazard model (p = 0.15). A significant survival advantage was noted for our institution compared with UNOS for this cohort (p = 0.018). CONCLUSIONS: In carefully selected recipients > or = 60 years of age, LTX offers acceptable outcomes and survival.

Adolescent↗