Shu S Lin

Duke University Medical Center, Durham, North Carolina, United States

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Publications (64)213.54 Total impact

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    ABSTRACT: Despite improving outcomes following lung transplantation, chronic rejection continues to limit survival. The predominant form of chronic rejection, bronchiolitis obliterans syndrome, has been associated with multiple etiologies including aspiration from gastroduodenal reflux. This article reviews the current literature with regards to the incidence of reflux following lung transplantation, the association of reflux with allograft dysfunction and survival, and the success of prevention and treatment of reflux in this patient population. Although antireflux surgery has been demonstrated to be safe in this population and leads to a stabilization of lung function in patients with reflux, there have not been definitive data that it improves survival.
    Thoracic Surgery Clinics 02/2015; 25(1):97-105. DOI:10.1016/j.thorsurg.2014.09.006 · 0.77 Impact Factor
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    ABSTRACT: The standard of care for chronic gastro-esophageal reflux disease (GERD), which affects up to 40% of the population, is the use of drugs such as proton pump inhibitors (PPIs) that block the production of stomach acid. Despite widespread use, the effects of PPIs on gastric fluid remain poorly characterized. In this study, gastric fluid was collected from patients undergoing cardiac surgery who were not (n = 40) or were (n = 25) actively taking PPIs. Various enzymatic and immunoassays as well as mass spectrometry were utilized to analyze the concentrations of bile, gastricsin, trypsin, and pepsin in the gastric fluid. Proteomic analyses by mass spectrometry suggested that degradation of trypsin at low pH might account, at least in part, for the observation that patients taking PPIs have a greater likelihood of having high concentrations of trypsin in their gastric fluid. In general, the concentrations of all analytes evaluated varied over several orders of magnitude, covering a minimum of a 2000-fold range (gastricsin) and a maximum of a 1 × 10(6) -fold range (trypsin). Furthermore, the concentrations of various analytes were poorly correlated with one another in the samples. For example, trypsin and bile concentrations showed a significant (P < 0.0001) but not strong correlation (r = 0.54). Finally, direct assessment of bacterial concentrations by flow cytometry revealed that PPIs did not cause a profound increase in microbial load in the gastric fluid. These results further delineate the profound effects that PPI usage has on the physiology of the stomach. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
    01/2015; 3(1). DOI:10.14814/phy2.12269
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    ABSTRACT: Previous studies have compared the immune systems of wild and of laboratory rodents in an effort to determine how laboratory rodents differ from their naturally occurring relatives. This comparison serves as an indicator of what sorts of changes might exist between modern humans living in Western culture compared to our hunter-gatherer ancestors. However, immunological experiments on wild-caught animals are difficult and potentially confounded by increased levels of stress in the captive animals. In this study, the humoral immune responses of laboratory rats in a traditional laboratory environment and in an environment with enriched biodiversity were examined following immunization with a panel of antigens. Biodiversity enrichment included colonization of the laboratory animals with helminths and co-housing the laboratory animals with wild-caught rats. Increased biodiversity did not apparently affect the IgE response to peanut antigens following immunization with those antigens. However, animals housed in the enriched biodiversity setting demonstrated an increased mean humoral response to T-independent and T-dependent antigens and increased levels of "natural" antibodies directed at a xenogeneic protein and at an autologous tissue extract that were not used as immunogens.
    PLoS ONE 01/2015; 10(4):e0120255. DOI:10.1371/journal.pone.0120255 · 3.53 Impact Factor
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    ABSTRACT: Background Methods for direct GFR measurement are expensive and inconsistently applied across transplant centers. The Modified Diet in Renal Disease (MDRD) equation is commonly used for GFR estimation, but is inaccurate for GFR above 60ml/min per 1.73m2. The CKDEPI and Wright equations have shown improved predictive capabilities in some patient populations. We compare these equations to determine which correlates best with direct GFR measurement in lung transplant candidates. Methods We conducted a retrospective cohort analysis of 274 lung transplant recipients. Preoperative GFR was directly measured using a radionuclide GFR assay. Results from the following equations were compared to direct measurement: MDRD, CKDEPI, Wright and Cockroft-Gault. Findings were validated using logistic regression models and ROC analyses looking at GFR as a predictor of mortality and renal function outcomes post-transplant. Results Assessed against the radionuclide GFR measurement, CKDEPI provided the most consistent results with low values for bias (0.78), relative standard error (0.03) and mean absolute percentage error (15.02). Greater deviation from radionuclide GFR was observed for all other equations. Pearson correlation between radionuclide and calculated GFR was significant for all equations. Regression and ROC analyses revealed equivalent utility of the radionuclide assay and GFR equations for predicting post-transplant acute kidney injury and chronic kidney disease (p < 0.05). Conclusions In patients being evaluated for lung transplantation, CKDEPI correlates closely with direct radionuclide GFR measurement and equivalently predicts post-operative renal outcomes. Transplant centers could consider replacing or supplementing direct GFR measurement with cheaper, more convenient estimation using the CKDEPI equation.
    The Journal of Heart and Lung Transplantation 12/2014; DOI:10.1016/j.healun.2014.06.011 · 5.61 Impact Factor
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    ABSTRACT: Rates of repeat lung transplantation have increased since implementation of the lung allocation score (LAS). The purpose of this study is to compare survival between repeat (ReTx) and primary (LTx) lung transplant recipients in the LAS era. We extracted data from 9,270 LTx and 456 ReTx recipients since LAS implementation, from the United Network for Organ Sharing registry. Propensity scoring was used to match ReTx and LTx recipients. Kaplan-Meier analysis compared survival between LTx and ReTx groups, with and without stratification based on time between first and second transplant. Multivariable Cox models estimated predictors of survival in lung recipients. Comparing all ReTx to LTx demonstrates a survival advantage for LTx that is diminished with propensity score matching (p = 0.174). Considering LTx against ReTx greater than 90 days after the initial procedure, there are similar survival results (p < 0.067). In contrast, ReTx within 90 days was associated with a survival disadvantage that persisted despite matching (p = 0.011). In ReTx populations, factors conferring worse outcomes include intensive care unit admission, unilateral transplantation, poor functional status, and primary graft dysfunction as the indication for retransplantation (p < 0.05). Late lung retransplantation appears to be as beneficial as primary transplantation in propensity-matched patients. However, survival is severely diminished in those retransplanted less than 90 days after primary transplantation. The utility of early retransplantation needs to be carefully weighed in light of risks. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    The Annals of Thoracic Surgery 12/2014; 98(6):1914-21. DOI:10.1016/j.athoracsur.2014.06.036 · 3.63 Impact Factor
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    ABSTRACT: Background Preprocedural multidetector computed tomography (MDCT) may identify patients at risk for mechanical complications during lead extraction. Methods To describe the use and feasibility of computed tomography scanning for preprocedural planning of lead extraction, we conducted a retrospective study of high-risk patients, who underwent electrocardiogram (ECG)-gated MDCT before planned lead extraction between January 1, 2012, and March 30, 2013. ResultsAmong 30 patients the mean age was 63 15 years, 60% were male, and 20% had prior sternotomy. Most devices were left sided (93%) and 24 had implantable defibrillators (80%). Indications for extraction included lead malfunction (n = 15; 50%), class I lead advisories (n = 11; 37%), and infection (n = 10; 33%). Overall, there were 65 leads extracted (mean 2.1 leads per patient). One extraction procedure was deferred due to MDCT evidence of significant myocardial perforation with the lead tip > 1 cm beyond the epicardium (n = 1, 3%). MDCT suggestion of lead adherence to central venous structures (n = 13, 43%) was associated with significantly longer laser times (88 +/- 71 seconds vs 30 +/- 37 seconds, P = 0.02) and larger sheath size (14.9 +/- 1.3 vs 13.5 +/- 1.2 French, P = 0.02). MDCT evidence of central venous occlusion or stenosis was not associated with increased laser times. Excluding the patient with MDCT evidence of significant perforation, clinical success was achieved in all patients (n = 29/29). ConclusionsECG-gated MDCT scanning before lead extraction may facilitate the identification of significant perforation and patients at high risk for mechanical complication.
    Pacing and Clinical Electrophysiology 09/2014; 37(10). DOI:10.1111/pace.12485 · 1.25 Impact Factor
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    ABSTRACT: The evidence behind the widely used pre-lung transplant glomerular filtration rate (GFR) cutoff of 50 mL/min per 1.73 m(2) is limited. This study reviews data from a large cohort to assess outcomes associated with this historical cutoff and to estimate other possible cutoffs that might be appropriate in lung transplantation. We conducted a retrospective cohort analysis of lung recipients at a single center. Recursive partitioning and receiver operating characteristics analysis were used to estimate other potential GFR cutoffs with 1-year mortality as the outcome. Postoperative outcomes around the various cutoffs, including survival, acute kidney injury, and dialysis, were assessed using χ(2), Kaplan-Meier, and Cox regression methods. A total of 794 lung recipients met study inclusion criteria. Compared with 778 patients with GFR 50 mL/min per 1.73 m(2) or greater at time of transplant, 16 patients with GFR below this cutoff were older and more likely to have restrictive disease. One-year mortality below the cutoff was 31.3% compared with 15.1% above the cutoff (p = 0.021). Recursive partitioning estimated potential GFR cutoff values between 46 and 61 mL/min per 1.73 m(2). Patients with GFR below these cutoffs were at significantly higher risk for adverse outcomes (p < 0.05). Receiver operating characteristics analysis was less successful at identifying meaningful cutoff values with areas under the curve approximately 0.5. Study results support the practice of requiring candidate GFR 50 mL/min per 1.73 m(2) or greater for lung transplantation. Future work should focus on reproducing the analysis in a larger cohort of patients including more individuals with low GFR.
    The Annals of thoracic surgery 04/2014; 98(1). DOI:10.1016/j.athoracsur.2014.03.010 · 3.65 Impact Factor
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    ABSTRACT: Mast cells have been associated with obliterative bronchiolitis (OB) in human pulmonary allografts, although their role in the development of OB remains unknown. In this study, we evaluated the role of mast cells in pulmonary allograft rejection using an orthotopic rat pulmonary allograft model that utilizes chronic aspiration of gastric fluid to reliably obtain OB. Pulmonary allograft recipients (n = 35) received chronic aspiration of gastric fluid with (n = 10) and without (n = 16) treatment with a mast cell membrane stabilizer, cromolyn sodium, or chronic aspiration with normal saline (n = 9) as a control. The acute graft injury associated with long ischemic time in the model (6 hours total ischemic time; typical acute graft injury rate ~30%) was apparently blocked by cromolyn, because peri-operative mortality associated with the acute graft injury was not observed in any of the animals receiving cromolyn (p = 0.045). Further, the rats receiving cromolyn developed significantly fewer OB lesions than those treated with gastric fluid alone (p < 0.001), with a mean reduction of 46% of the airways affected. These findings provide impetus for further studies aimed at elucidating the effects of cromolyn and the role of mast cells in pulmonary allotransplantation.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 03/2014; DOI:10.1016/j.healun.2014.03.004 · 5.61 Impact Factor
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    ABSTRACT: Coronary artery disease has a high prevalence among lung transplant recipients and has historically been a contraindication to transplant at many institutions. In patients with mild-to-moderate coronary artery disease (Mod-CAD) undergoing lung transplant, outcomes are not well defined. All patients who underwent pulmonary transplantation from January 1996 through November 2010 with pretransplant coronary angiogram were included in our study. Recipients of multivisceral, redo, and lobar lung transplants and those who underwent pretransplant coronary revascularization were excluded. Patients were grouped into Mod-CAD or no-coronary artery disease group (No-CAD). Primary end point was overall survival. Secondary end points were 30-day events and the need for posttransplant coronary revascularization. Approximately 539 patients were included in the study: 362 in the No-CAD, 177 in the Mod-CAD group. Patients with Mod-CAD were predominantly male, older, and had a higher body mass index. No difference in either perioperative morbidity and mortality (Mod-CAD, 4.2% vs. No-CAD 3.3%, P=0.705) or late overall mortality was shown between groups. Mod-CAD patients had a shorter hospitalization (median: 12 days vs. 14 days, P=0.009) and required a higher rate of late coronary revascularization procedures (PCI: Mod-CAD vs. No-CAD, 0.3% vs. 4.0%, P=0.0035; CABG: Mod-CAD vs. No-CAD, 0.3% vs. 2.3%, P=0.0411). Mod-CAD does not appear to be associated with increased perioperative morbidity or decreased survival after transplant. Coronary artery disease may worsen and require coronary revascularization in patients with risk factors for disease progression. In these patients, close follow-up and screening for progression of coronary artery disease may help prevent late cardiac morbidity.
    Transplantation 03/2014; 97(10). DOI:10.1097/01.TP.0000438619.96933.02 · 3.78 Impact Factor
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    ABSTRACT: Risk factors and outcomes of bronchial stricture after lung transplantation are not well defined. An association between acute rejection and development of stricture has been suggested in small case series. We evaluated this relationship using a large national registry. All lung transplantations between April 1994 and December 2008 per the United Network for Organ Sharing (UNOS) database were analyzed. Generalized linear models were used to determine the association between early rejection and development of stricture after adjusting for potential confounders. The association of stricture with postoperative lung function and overall survival was also evaluated. Nine thousand three hundred thirty-five patients were included for analysis. The incidence of stricture was 11.5% (1,077/9,335), with no significant change in incidence during the study period (P = 0.13). Early rejection was associated with a significantly greater incidence of stricture (adjusted odds ratio [AOR], 1.40; 95% confidence interval [CI], 1.22-1.61; p < 0.0001). Male sex, restrictive lung disease, and pretransplantation requirement for hospitalization were also associated with stricture. Those who experienced stricture had a lower postoperative peak percent predicted forced expiratory volume at 1 second (FEV1) (median 74% versus 86% for bilateral transplants only; p < 0.0001), shorter unadjusted survival (median 6.09 versus 6.82 years; p < 0.001) and increased risk of death after adjusting for potential confounders (adjusted hazard ratio 1.13; 95% CI, 1.03-1.23; p = 0.007). Early rejection is associated with an increased incidence of stricture. Recipients with stricture demonstrate worse postoperative lung function and survival. Prospective studies may be warranted to further assess causality and the potential for coordinated rejection and stricture surveillance strategies to improve postoperative outcomes.
    The Annals of thoracic surgery 07/2013; DOI:10.1016/j.athoracsur.2013.01.104 · 3.65 Impact Factor
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    ABSTRACT: BACKGROUND: Chronic aspiration of gastric fluid potentially plays a central role in the pathogenesis of obliterative bronchiolitis, which is often associated with chronic pulmonary allograft failure. It remains unknown whether pharmaceutical-induced increases in gastric pH might effectively prevent any putative pulmonary injury associated with chronic aspiration. MATERIALS AND METHODS: To test the hypothesis that neutralization of gastric fluid would affect the development of aspiration-associated obliterative bronchiolitis, an established rat lung transplant model (WKY-to-F344) was utilized. Pulmonary allograft recipients were subjected to eight weekly aspirations of gastric fluid at pH 2.5 (low-pH), gastric fluid at pH 7.4 (neutralized-pH), or saline as a control. RESULTS: Histologic analysis revealed that the fraction of airways affected with lesions consistent with obliterative bronchiolitis was 0.55 ± 0.08 (mean ± SEM) in rats receiving aspiration with low-pH gastric fluid, 0.49 ± 0.07 in animals receiving neutralized-pH gastric fluid, and 0.07 ± 0.05 in rats receiving normal saline only. The difference between groups receiving gastric fluid, regardless of pH, was significantly different from the saline control (P < 0.0001), whereas the difference between the groups receiving low-pH gastric fluid and neutralized-pH gastric fluid was not significant (P = 0.75). CONCLUSIONS: Effective management of gastroesophageal reflux disease in lung transplant recipients should probably include more than neutralization of gastric fluid.
    Journal of Surgical Research 06/2012; 181(1). DOI:10.1016/j.jss.2012.06.036 · 2.12 Impact Factor
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    The Annals of thoracic surgery 06/2012; 93(6):1773-9. DOI:10.1016/j.athoracsur.2012.03.003 · 3.65 Impact Factor
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    ABSTRACT: The hypothesis that aspiration of gastric fluid drives the anti-ovalbumin response toward a Th2 reaction even in animals not prone to Th2 responses was evaluated. Forty-eight male C57BL/6 mice were used. Mice were sensitized and challenged with ovalbumin starting 5 weeks prior to the initiation of weekly aspirations of either gastric fluid or normal saline as a control. Weekly aspiration continued during the course of exposure to ovalbumin. Aspiration consisted of 50 μl of gastric fluid with 50 μl of 0.9 % normal saline used as a control. Antigen exposure consisted of sensitization to ovalbumin via intraperitoneal injection on days 0 and 14 and challenge on day 21 with aerosolized antigen for 30 min. No evidence of a shift toward a Th2 response as a result of gastric fluid aspiration was seen in the Th1-prone strain utilized, although a profound down-regulation of a broad array of T cell-associated cytokines and chemokines and up-regulation of macrophage-associated markers was observed as a result of aspiration. These data provide support for the hypothesis that the clinical association between asthma and gastroesophageal reflux disease (GERD) does not involve an exacerbation of asthma by GERD-associated aspiration of gastric fluid, but may cause immune reactions unrelated to the asthma pathology.
    Agents and Actions 05/2012; 61(8):863-73. DOI:10.1007/s00011-012-0479-x · 2.14 Impact Factor
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    ABSTRACT: The immune systems of wild rats and of laboratory rats can been utilized as models of the human immune system in pre-industrial and post-industrial societies, respectively. In this study, lymphocyte phenotypes in wild rats were broadly characterized, and the results were compared to those obtained by us and by others using cells derived from various strains of laboratory rats. Although not expected, the production of regulatory T cells was not apparently different in wild rats compared to laboratory rats. On the other hand, differences in expression of markers involved in complement regulation, adhesion, signaling and maturation suggest increased complement regulation and decreased sensitivity in wild-caught rats compared to laboratory rats, and point toward complex differences between the maturation of T cells. The results potentially lend insight into the pathogenesis of post-industrial epidemics of allergy and autoimmune disease.
    Cellular & molecular immunology 03/2012; 9(2):163-74. DOI:10.1038/cmi.2011.61 · 4.19 Impact Factor
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    ABSTRACT: The accurate diagnosis of idiopathic pulmonary fibrosis (IPF) is a major clinical challenge. We developed a model to diagnose IPF by applying Bayesian probit regression (BPR) modelling to gene expression profiles of whole lung tissue. Whole lung tissue was obtained from patients with idiopathic pulmonary fibrosis (IPF) undergoing surgical lung biopsy or lung transplantation. Controls were obtained from normal organ donors. We performed cluster analyses to explore differences in our dataset. No significant difference was found between samples obtained from different lobes of the same patient. A significant difference was found between samples obtained at biopsy versus explant. Following preliminary analysis of the complete dataset, we selected three subsets for the development of diagnostic gene signatures: the first signature was developed from all IPF samples (as compared to controls); the second signature was developed from the subset of IPF samples obtained at biopsy; the third signature was developed from IPF explants. To assess the validity of each signature, we used an independent cohort of IPF and normal samples. Each signature was used to predict phenotype (IPF versus normal) in samples from the validation cohort. We compared the models' predictions to the true phenotype of each validation sample, and then calculated sensitivity, specificity and accuracy. Surprisingly, we found that all three signatures were reasonably valid predictors of diagnosis, with small differences in test sensitivity, specificity and overall accuracy. This study represents the first use of BPR on whole lung tissue; previously, BPR was primarily used to develop predictive models for cancer. This also represents the first report of an independently validated IPF gene expression signature. In summary, BPR is a promising tool for the development of gene expression signatures from non-neoplastic lung tissue. In the future, BPR might be used to develop definitive diagnostic gene signatures for IPF, prognostic gene signatures for IPF or gene signatures for other non-neoplastic lung disorders such as bronchiolitis obliterans.
    BMC Medical Genomics 10/2011; 4:70. DOI:10.1186/1755-8794-4-70 · 3.91 Impact Factor
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    ABSTRACT: Previous reports demonstrate that 1-year survival is severely compromised in patients with severe primary graft dysfunction (PGD) after lung transplantation. We examined if advances in extracorporeal membrane oxygenation (ECMO) support, including polymethylpentene oxygenators and reliance on venovenous (VV) ECMO have improved outcomes in patients with severe PGD after lung transplantation. The analysis included data prospectively collected on all single-lung or double-lung transplants between November 2001 and December 2009. Heart-lung transplants were excluded. Comparisons were made between recipients who did and did not require ECMO for PGD after transplant. Since November 2001, when VV ECMO became the routine treatment for severe PGD after transplant at our center, 28 of 498 patients (6%) have required VV ECMO support. Successful weaning occurred in 27 of 28 (96%). Support was withdrawn for 1 patient with irreversible neurologic injury. Survival was substantially better than in previous reports: 30 days, 82%; 1 year, 64%; and 5 years, 49%. Freedom from bronchiolitis obliterans syndrome was 88% in the ECMO survivors at 3 years, but maximum allograft function was considerably worse than in transplant recipients not requiring ECMO (peak forced expiratory volume in 1 second: 58% in ECMO vs 83% in non-ECMO, p=0.001). Advances in ECMO technology, particularly VV ECMO, have greatly improved the ability to support patients with severe PGD after lung transplantation. VV ECMO is an important tool in the armamentarium of any lung transplant program to optimize patient outcomes; however, strategies to improve lung allograft function in patients experiencing severe PGD are still needed.
    The Annals of thoracic surgery 09/2011; 93(2):366-71. DOI:10.1016/j.athoracsur.2011.05.017 · 3.65 Impact Factor
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    ABSTRACT: Gastroesophageal reflux disease (GERD) in lung recipients is associated with decreased survival and attenuated allograft function. This study evaluates fundoplication in preventing GERD-related allograft dysfunction. Prospectively collected data on patients who underwent transplantation between January 2001 and August 2009 were included. Lung transplant candidates underwent esophageal pH probe testing before transplantation and surveillance spirometry evaluation after transplantation. Bilateral lung transplant recipients who had pretransplant pH probe testing and posttransplant 1-year forced expiratory volume in the first second of expiration (FEV1) data were included for analysis. Of 297 patients who met study criteria, 222 (75%) had an abnormal pH probe study before or early after transplantation and 157 (53%) had a fundoplication performed within the first year after transplantation. Patients with total proximal acid contact times greater than 1.2% or total distal acid contact times greater than 7.0% demonstrated an absolute decrease of 9.4% (±4.6) or 12.0% (±5.4) in their respective mean 1-year FEV1 values. Patients with abnormal acid contact times who did not undergo fundoplication had considerably worse predicted peak and 1-year FEV1 results compared with recipients receiving fundoplication (peak percent predicted=75% vs. 84%; p=0.004 and 1-year percent predicted=68% vs. 77%; p=0.003, respectively). Lung transplant recipients with abnormal esophageal pH studies attain a lower peak allograft function as well as a diminished 1-year FEV1 after transplantation. However a strategy of early fundoplication in these recipients appears to preserve lung allograft function.
    The Annals of thoracic surgery 08/2011; 92(2):462-8; discussion; 468-9. DOI:10.1016/j.athoracsur.2011.04.035 · 3.65 Impact Factor
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    ABSTRACT: 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. An interdisciplinary team responded to an acute need to develop a mechanism for active rehabilitation and physical therapy for patients awaiting lung transplantation while being managed with extracorporeal membrane oxygenation. We describe a series of three patients who benefited from this new approach. A quaternary care pediatric intensive care unit in a children's hospital set within an 800-bed university academic hospital with an active lung transplantation program for adolescent and adult patients. PATIENTS, INTERVENTIONS, AND MAIN RESULTS: Three patients (ages 16, 20, and 24 yrs) with end-stage respiratory failure were rehabilitated while on extracorporeal membrane oxygenation awaiting lung transplantation. These patients were involved in active rehabilitation and physical therapy and, ultimately, were ambulatory on extracorporeal membrane oxygenation before successful transplantation. Following lung transplantation, the patients were liberated from mechanical ventilation, weaned to room air, transitioned out of the intensive care unit, and ambulatory less than 1 wk posttransplant. A comprehensive, multidisciplinary system can be developed to safely allow for active rehabilitation, physical therapy, and ambulation of patients being managed with extracorporeal membrane oxygenation. Such programs may lead to a decreased threshold for the utilization of extracorporeal membrane oxygenation before transplant and have the potential to improve conditioning, decrease resource utilization, and lead to better outcomes in patients who require extracorporeal membrane oxygenation before lung transplantation.
    Critical care medicine 07/2011; 39(12):2593-8. DOI:10.1097/CCM.0b013e3182282bbe · 6.15 Impact Factor
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    ABSTRACT: A wide range of techniques, including high-throughput DNA sequencing methods, have been applied to the evaluation of the normal intestinal flora. However, the inability to grow many of those species in culture imposes substantial constraints on the techniques used to evaluate this important community. The presence of biofilms in the normal gut adds further complexity to the issue. In this study, a flow cytometric analysis was used to separate intact bacterial cells, cell debris, and other particulate matter based on bacteria-specific staining and particle size. In addition, an analysis of biofilm formation using fluorescent light microscopy was conducted. Using these approaches, the ratio of bacterial cell debris to intact bacterial cells as a measure of spontaneous lysis of bacterial cells in the gut of the Cape dune mole-rat (Bathyergus suillus) and the laboratory rabbit (Oryctolagus cuniculus) was examined, and the degree of biofilm formation was semi-quantitatively assessed. The results suggest that the degree of spontaneous cell lysis was greater in the appendix than in the cecum in both the mole-rat and the rabbit. Further, the results point toward extensive epithelial-associated biofilm formation in the proximal mole-rat and rabbit large bowel, although the biofilms may be less structured than those found in laboratory rodents and in humans.
    Applied Microbiology and Biotechnology 06/2011; 90(5):1773-83. DOI:10.1007/s00253-011-3207-5 · 3.81 Impact Factor
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    ABSTRACT: After substantial progress on many fronts, one of the remaining barriers still opposing the clinical application of xenotransplantation is a disseminated intravascular coagulopathy (DIC) that is observed in the pre-clinical model of porcine-to-primate transplantation. The onset of DIC is particularly rapid in recipients of pulmonary xenografts, usually occurring within the first days or even hours of reperfusion. In this study, we describe the results of two porcine-to-baboon transplants utilizing porcine lungs depleted of macrophages, deficient in the α-1,3-galactosyltransferase gene, and with the expression of human decay-accelerating factor, a complement regulatory protein. In both cases, evidence of DIC was observed within 48 h of reperfusion, with thrombocytopenia and increases in levels of thrombin-antithrombin complex evident in both cases. Depletion of fibrinogen was observed in one graft, whereas elevation of D-dimer levels was observed in the other. One graft, which showed focal lymphocytic infiltrates pre-operatively, failed within 3 h. The results indicate that further efforts to address the coagulopathy associated with pulmonary xenotransplantation are needed. Further, evidence suggests that resident porcine immune cells can play an important role in the coagulopathy associated with xenotransplantation.
    Xenotransplantation 01/2011; 18(1):6-13. DOI:10.1111/j.1399-3089.2011.00621.x · 1.78 Impact Factor