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Changing treatment and outcome of children with hepatoblastoma: analysis of a single center experience over the last 20 years.

Fri, 08/10/2012 - 19:10
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Changing treatment and outcome of children with hepatoblastoma: analysis of a single center experience over the last 20 years.

J Pediatr Surg. 2012 Jul;47(7):1331-9

Authors: Ismail H, Broniszczak D, Kaliciński P, Dembowska-Bagińska B, Perek D, Teisseyre J, Kluge P, Kościesza A, Lembas A, Markiewicz M

Abstract
BACKGROUND/PURPOSE: The aim of the study was to analyze changing management and survival of children with hepatoblastoma (HBL) treated in one center.
MATERIALS AND METHODS: Over the last 20 years, 51 children with HBL were treated. Surgery was performed in 48 children (94.1%), conventional liver resection in 38 (of those, 2 received a rescue liver transplantation [LTx] for relapse), and total hepatectomy and primary LTx in 10 patients. The remaining 3 patients received only palliative treatment. Patient data were analyzed for survival with respect to PRETreatment EXTent of disease (PRETEXT), metastases, histopathology, conventional resection, and LTx.
RESULTS: Survival of children with HBL treated with liver resection is 71% and 80% for primary LTx. Favorable prognostic factors for patient survival was tumor histology as epithelial-fetal subtype and mixed epithelial and mesenchymal type, without teratoid features, and good response to chemotherapy (necrosis, fibrosis). Unfavorable prognostic factors were small cells undifferentiated, transitional liver cell tumor, α-fetoprotein level above 1,000,000 IU/mL and below 100 IU/mL at diagnosis, lung metastases, and local recurrence after initial resection. Survival was related to PRETEXT stage. However, among patients with PRETEXT III and IV, LTx resulted in better survival.
CONCLUSION: Liver transplantation is a good option for children with advanced HBL. Early referral of children with potentially unresectable tumors to centers where combined treatment (chemotherapy, surgery including LTx) is available is crucial.

PMID: 22813792 [PubMed - in process]

[The lung].

Fri, 08/10/2012 - 19:10
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[The lung].

Bull Acad Natl Med. 2011 Oct;195(7):1677-85

Authors: Martinod E, Uzunhan Y, Radu DM, Seguin A, Boddaert G, Valeyre D, Planès C, Carpentier A

Abstract
Lung transplantation is still the only curative treatment for end-stage pulmonary diseases. The results remain poor, however, because of the limited availability of lung donors, chronic rejection, and complications related to immunosuppressive therapy. The use of a bioartificial lung generated from autologous cells could offer a solution. We have demonstrated that in vivo epithelial and cartilage regeneration of the airways is feasible with the use of an aortic tissue matrix. Other studies show that in vitro and in vivo airway regeneration, respectively, can be obtained by using bio-engineering and heterotopic allograft implantation. A more complex challenge is the creation of an artificial lung Indeed, this would require the use of an elastic matrix that can promote regeneration of the different lung components (airways, alveoli, vessels) over a large surface area, thus allowing ventilation, blood perfusion and gas exchanges. Recent studies have demonstrated the possibility of in vitro and in vivo regeneration of lung tissue from autologous cells, and especially stem cells. This emerging research field is currently dominated by the use of decellularized lung matrices and autologous epithelial and endothelial cells. Implantation of such a recellularized matrix in animals has proved the feasibility of a functional bio-artificial lung. The first human transplantation of a bio-artificial lung should be possible within 10-20 years.

PMID: 22812170 [PubMed - in process]

The human fetal lung Xenograft: Validation as model of microvascular remodeling in the postglandular lung.

Fri, 08/10/2012 - 19:10
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The human fetal lung Xenograft: Validation as model of microvascular remodeling in the postglandular lung.

Pediatr Pulmonol. 2012 Jul 18;

Authors: De Paepe ME, Chu S, Hall S, Heger NE, Thanos C, Mao Q

Abstract
BACKGROUND: Coordinated remodeling of epithelium and vasculature is essential for normal postglandular lung development. The value of the human-to-rodent lung xenograft as model of fetal microvascular development remains poorly defined. AIM: The aim of this study was to determine the fate of the endogenous (human-derived) microvasculature in fetal lung xenografts. METHODS: Lung tissues were obtained from spontaneous pregnancy losses (14-22 weeks' gestation) and implanted in the renal subcapsular or dorsal subcutaneous space of SCID-beige mice (T, B, and NK-cell-deficient) and/or nude rats (T-cell-deficient). Informed parental consent was obtained. Lung morphogenesis, microvascular angiogenesis, and epithelial differentiation were assessed at 2 and 4 weeks post-transplantation by light microscopy, immunohistochemical, and gene expression studies. Archival age-matched postmortem lungs served as control. RESULTS: The vascular morphology, density, and proliferation of renal subcapsular grafts in SCID-beige mice were similar to age-matched control lungs, with preservation of the physiologic association between epithelium and vasculature. The microvasculature of subcutaneous grafts in SCID-beige mice was underdeveloped and dysmorphic, associated with significantly lower VEGF, endoglin, and angiopoietin-2 mRNA expression than renal grafts. Grafts at both sites displayed mild airspace dysplasia. Renal subcapsular grafts in nude rats showed frequent infiltration by host lymphocytes and obliterating bronchiolitis-like changes, associated with markedly decreased endogenous angiogenesis. CONCLUSION: This study demonstrates the critical importance of host and site selection to ensure optimal xenograft development. When transplanted to severely immune suppressed, NK-cell-deficient hosts and engrafted in the renal subcapsular site, the human-to-rodent fetal lung xenograft provides a valid model of postglandular microvascular lung remodeling. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

PMID: 22811288 [PubMed - as supplied by publisher]

Physical therapy management of a patient on portable extracorporeal membrane oxygenation as a bridge to lung transplantation: a case report.

Fri, 08/10/2012 - 19:10
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Physical therapy management of a patient on portable extracorporeal membrane oxygenation as a bridge to lung transplantation: a case report.

Cardiopulm Phys Ther J. 2012 Mar;23(1):30-5

Authors: Lowman JD, Kirk TK, Clark DE

Abstract
INTRODUCTION: Although the life expectancy for patients with cystic fibrosis (CF) has increased dramatically in the preceding decades, often the final therapeutic option for patients with end-stage CF is lung transplantation. Prior to transplantation, patients with severe disease may require mechanical ventilation. Those refractory to mechanical ventilation may require extracorporeal membrane oxygenation (ECMO). The purpose of this case report is to describe the physical therapy management of a patient who received ECMO as a bridge to lung transplantation.
CASE PRESENTATION: A 16-year-old girl with severe acute respiratory failure due to a CF exacerbation eventually required ECMO to maintain adequate gas exchange. While on ECMO, she received physical therapy interventions ranging from therapeutic exercise, manual therapy, and integumentary protection techniques in addition to airway clearance techniques. Prior to her transplant, she was standing multiple times per day with moderate assistance, was sitting on the edge-of-bed, as well as taking steps to transfer to/from a chair. She successfully received a bilateral lung transplant after 8 days on ECMO.
CONCLUSION: Physical therapy interventions, including out-of-bed mobility, can be safely provided to patients on portable ECMO as a bridge to lung transplantation. These interventions were focused on preventing the negative sequelae of bed rest, increasing her strength and endurance, as well as improving her level of consciousness and psychological well being in preparation for lung transplantation.

PMID: 22807653 [PubMed - in process]

Development of obliterative bronchiolitis in a murine model of orthotopic lung transplantation.

Fri, 08/10/2012 - 19:10
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Development of obliterative bronchiolitis in a murine model of orthotopic lung transplantation.

J Vis Exp. 2012;(65)

Authors: Suzuki H, Fan L, Wilkes DS

Abstract
Orthotopic lung transplantation in rats was first reported by Asimacopoulos and colleagues in 1971 (1). Currently, this method is well accepted and standardized not only for the study of allo-rejection but also between syngeneic strains for examining mechanisms of ischemia-reperfusion injury after lung transplantation. Although the application of the rat and other large animal model (2) contributed significantly to the elucidation of these studies, the scope of those investigations is limited by the scarcity of knockout and transgenic rats. Due to no effective therapies for obliterative bronchiolitis, the leading cause of death in lung transplant patients, there has been an intensive search for pre-clinical models that replicate obliterative bronchiolitis. The tracheal allograft model is the most widely used and may reproduce some of the histopathologic features of obliterative bronchiolitis (3). However, the lack of an intact vasculature with no connection to the recipient's conducting airways, and incomplete pathologic features of obliterative bronchiolitis limit the utility of this model (4). Unlike transplantation of other solid organs, vascularized mouse lung transplants have only recently been reported by Okazaki and colleagues for the first time in 2007 (5). Applying the basic principles of the rat lung transplant, our lab initiated the obliterative bronchiolitis model using minor histoincompatible antigen murine orthotopic single-left lung transplants which allows the further study of obliterative bronchiolitis immunopathogenesis(6).

PMID: 22805894 [PubMed - in process]

Organizing Pneumonia in Recipients of Hematopoietic Stem Cell Transplantation: CT Features in 16 Patients.

Fri, 08/10/2012 - 19:10
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Organizing Pneumonia in Recipients of Hematopoietic Stem Cell Transplantation: CT Features in 16 Patients.

J Comput Assist Tomogr. 2012 Jul;36(4):431-6

Authors: Pipavath SN, Chung JH, Chien JW, Godwin JD

Abstract
PURPOSE: To evaluate computed tomographic (CT) scans of patients with organizing pneumonia (OP) complicating hematopoietic stem cell transplantation (HSCT).
MATERIALS AND METHODS: A review of patients who underwent HSCT at our institution identified 16 patients who had documented OP on biopsy. Computed tomographic scans were reviewed by 2 thoracic radiologists.
RESULTS: Ground glass opacities (GGO) were seen in 15 patients, consolidation in 8 patients, linear opacities in 8 patients, traction bronchiectasis in 2 patients, and septal thickening in 2 patients. Ground glass opacity was the dominant abnormality in 7 patients, consolidation in 4 patients, and linear opacities in 5 patients. Peribronchovascular distribution was found in 4 patients, peripheral in 2 patients, diffuse in 3 patients; upper lung predominance was found in 10 patients, and lower lung predominance in 5 patients.
CONCLUSION: The principal computed tomographic features of OP after HSCT are ground glass opacities, consolidation and linear opacities, with upper lung predominance. Allowing for a possible sampling bias, these findings differ from those reported in cryptogenic OP and OP from other causes.

PMID: 22805673 [PubMed - in process]

Emergence of Aspergillus calidoustus Infection in the Era of Posttransplantation Azole Prophylaxis.

Fri, 08/10/2012 - 19:10
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Emergence of Aspergillus calidoustus Infection in the Era of Posttransplantation Azole Prophylaxis.

Transplantation. 2012 Jul 16;

Authors: Egli A, Fuller J, Humar A, Lien D, Weinkauf J, Nador R, Kapasi A, Kumar D

Abstract
BACKGROUND: Universal antifungal prophylaxis with azoles is commonly used after lung transplantation. We noted an increase in isolates of Aspergillus calidoustus in our transplant population and hypothesized that increasing azole use (universal prophylaxis since 2008) may be promoting this infection. METHODS: Clinical and microbiologic data for A. calidoustus cases from 2008 to 2011 were extracted from chart review. For lung transplant patients, a case-control study was performed to determine risk factors, and incidence rates were calculated. RESULTS: From 2008 to 2011, we identified seven organ transplant recipients and one hematopoietic stem-cell transplant patient with positive A. calidoustus culture results in bronchoalveolar lavage at a median of 13 months after transplantation (interquartile range, 4-39 months). Chest computed tomographic scan was consistent with fungal infection in six of eight patients, and the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria classified these as "probable" invasive aspergillosis. In the case-control study, there were no differences in immunosuppression, number of respiratory samples taken, length of intensive care unit stay, or rejection rates. Of controls, 33.3% received third-generation azole prophylaxis compared with 83.3% of cases (P=0.13). However, median duration of exposure was greater in cases than in controls (3 vs. 0 months, P=0.045). Fungal minimum inhibitory concentration for voriconazole was 4 µg/mL or greater for six of eight cases. Incidence rates in lung transplants showed an increase of A. calidoustus (0/1000 vs. 11.3/1000 patient-years in 2006-2007 and 2008-2011, respectively; P=0.018), whereas Aspergillus fumigatus cases decreased (73.9/1000 vs. 49.0/1000 patient-years, P=0.0066). CONCLUSIONS: Pulmonary A. calidoustus seems to be an emerging pathogen mainly in lung transplants. We suggest that third-generation azole use reduced the incidence of A. fumigatus, but the incidence of A. calidoustus, an azole-resistant fungus, was increased.

PMID: 22805441 [PubMed - as supplied by publisher]

[Bilateral lung transplantation for pulmonary destruction after concentrated sulfuric acid inhalation: report of one case].

Fri, 08/10/2012 - 19:10
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[Bilateral lung transplantation for pulmonary destruction after concentrated sulfuric acid inhalation: report of one case].

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2012 Apr;30(4):312-3

Authors: Mao WJ, Xia W, Chen JY

PMID: 22804948 [PubMed - in process]

Use of prophylactic voriconazole for three months after lung transplantation does not reduce infection with Aspergillus: a retrospective study of 147 patients.

Fri, 08/10/2012 - 19:10
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Use of prophylactic voriconazole for three months after lung transplantation does not reduce infection with Aspergillus: a retrospective study of 147 patients.

Scand J Infect Dis. 2012 Jul 17;

Authors: Tofte N, Jensen C, Tvede M, Andersen CB, Carlsen J, Iversen M

Abstract
Background: This was a retrospective study analyzing the mortality and incidence of Aspergillus infection and invasive disease, comparing patients given voriconazole for 3 months following transplantation to patients not given prophylaxis. Methods: All consecutive patients (n = 147) transplanted at Copenhagen University Hospital, Rigshospitalet from 2002 to 2006 were included in the study; the study period included the 2 years before the initiation of fungal prophylaxis (88 patients) and the 2 years after (59 patients). Eight patients transplanted in this period were excluded leaving 139 patients in the study. Results: No effect of voriconazole on the incidence of Aspergillus infection (colonization, or superficial or invasive infection) or on the time from transplantation to the first sign of infection was seen when the 2 groups of patients were compared. The cumulated incidence of infection was 45% without and 49% with prophylaxis, and in both groups approximately half of the infections occurred in the first 3 months, the time during which prophylaxis was given. There were significantly more cystic fibrosis (CF) patients among the Aspergillus-infected patients compared to other diagnoses, and the effect of prophylaxis was the same as in non-CF patients. There was a significantly lower mortality in the voriconazole-treated group compared to the non-prophylaxis group, but in an isolated analysis of Aspergillus-infected patients this difference no longer existed; hence, the difference in mortality must be attributable to a time effect and not to voriconazole prophylaxis. Conclusions: Routine use of voriconazole treatment for prophylaxis against Aspergillus infection in lung transplant recipients does not appear to be warranted.

PMID: 22803836 [PubMed - as supplied by publisher]

[Study on the mechanism of polypeptide extract from scorpion venom to promote the restraint of cyclophosphamide on Lewis lung cancer].

Fri, 08/10/2012 - 19:10
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[Study on the mechanism of polypeptide extract from scorpion venom to promote the restraint of cyclophosphamide on Lewis lung cancer].

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2012 Apr;32(4):537-42

Authors: Ning YN, Zhang WD, Wu LC

Abstract
OBJECTIVE: To explore the mechanism of polypeptide extract from scorpion venom (PESV) on promoting anti-tumor effects of cyclophosphamide (CTX).
METHODS: The Lewis lung tumor model was established by subcutaneously implanting Lewis lung cells into C57BL/6 mice. The tumor-bearing mice were randomly divided into 4 groups, i. e., the model group, the cyclophosphamide (CTX) group, the polypeptide extract from scorpion venom (PESV) group, and the combination group (CTX + PESV), 10 mice in each group. The tumor growth curve was recorded. Changes of vascular endothelial growth factor-A (VEGF-A) and transfroming growth factor-beta1 (TGF-beta1) expressions in the tumor microenvironment were detected using reverse transcription PCR and immunohistochemical assay. Changes of dendritic cells (DCs) phenotype CD80 and CD86 expressions in the tumor tissue were detected using immunofluorescence chemical assay.
RESULTS: After 21 successive days of treatment, the growth of Lewis lung cancer transplantation tumor in the combination group was obviously inhibited (P<0.05). Compared with the model group,the expressions of CD80 and CD86 in the PESV group was somewhat enhanced, while those in the CTX group was somewhat lowered. Compared with the CTX group, the fluorescent signal strength and expressions in the combination group somewhat increased. Compared with the model group, the expressions of TGF-beta1 and VEGF-A mRNA decreased in the PESV group and the CTX group (both P<0.05). Compared with the PESV group and the CTX group, the expressions of TGF-beta1 and VEGF-A in the combination group both decreased (both P<0.05).
CONCLUSION: PESV could inhibit the expressions of VEGF and TGF-beta1, promote the maturation of DCs, recover its antigen uptake presentation function, and reverse the immune injury to the body by CTX, thus playing a role in inducing the tumor cell apoptosis.

PMID: 22803439 [PubMed - in process]

Modulating the alveolar milieu to enhance resolution of fibrotic lung injury.

Fri, 08/10/2012 - 19:10
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Modulating the alveolar milieu to enhance resolution of fibrotic lung injury.

Proc Am Thorac Soc. 2012 Jul;9(3):117-9

Authors: Garcia O, Buckley S, Navarro S, Driscoll B, Warburton D

Abstract
Fibrotic lung injury is often attributed to a myriad of factors, including environmental exposure, age, genetic predisposition, epigenetics, coexisting conditions, acute lung injury, and viral infection. No effective therapies, other than lung transplantation, have proven effective against lung fibrosis. Loss of cellular homeostasis mechanisms in alveolar epithelial type I cells and any inability of type II progenitor cells to resist and repair epithelial injury are indicators that impaired response to injury and regeneration is a critical component of this disorder. The alveolar epithelium has a limited repertoire of responses to injury, which are dictated by the alveolar milieu, a repository of cytokines and growth factors that affect recruitment of other cells to the site of injury, or the proliferation of resident cells at the site of injury. The identification and characterization of the cytokines, growth factors, and other biomarkers that dictate the response to disease is key to understanding, diagnosing, treating, and determining the trajectory of various lung disorders. Corrective therapy of the alveolar milieu may therefore prove to be beneficial in many presently serious and incurable lung diseases that likely begin and progress with injury to the alveolar epithelium.

PMID: 22802284 [PubMed - in process]

Failure of chimerism formation and tolerance induction from Fas ligand mutant bone marrow donors after nonmyeloablative conditioning.

Fri, 08/10/2012 - 19:10
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Failure of chimerism formation and tolerance induction from Fas ligand mutant bone marrow donors after nonmyeloablative conditioning.

Transpl Immunol. 2012 Jul 16;

Authors: Nusair S, Gincberg G, Almogi-Hazan O, Breuer R, Or R, Wallach-Dayan SB

Abstract
Formation of donor-recipient mixed chimerism after nonmyeloablative conditioning allows co-existence of donor and recipient hematopoietic stem cells, with solid organ allograft tolerance and less likeliness of graft versus host development. Using a post-transplant bronchiolitis obliterans murine model, we aimed to test the hypothesis that allograft preservation after mixed chimerism formation is dependent on the presence of a functional Fas ligand (FasL) on donor hematopoietic cells. To form mixed chimerism, two aliquots of 30×10(6) whole bone marrow cells (BMC) from either wild-type C57BL/6 in one group, or transgenic gld mice with mutant FasL (d=0 and 2+) in the other were used, with both groups receiving intravenous busulfan (10mg/kg) on d-1 and intraperitoneal cyclophosphamide (200mg/kg) on d+1. Tracheal allografts obtained from C57BL/6 mice were implanted into recipient BALB/c mice subcutaneously on d=0. Tracheal allografts were harvested at d+28 post-transplant and were evaluated by histopathology. Mixed chimerism formation was detected in wild type C57BL/6 whole BMC recipients, which was accompanied by tracheal allograft acceptance with near normal structure at d+28 post implantation. However, in recipients of FasL mutant whole BMC, neither mixed chimerism formation nor tracheal allograft acceptance was obtained. We thus conclude that bone marrow cells lacking functional FasL molecules could not be engrafted in allogeneic recipients to form stable mixed chimerism after nonmyeloablative conditioning, thus not allowing tracheal allograft acceptance.

PMID: 22801052 [PubMed - as supplied by publisher]

A lifetime markov model for the economic evaluation of chronic obstructive pulmonary disease.

Fri, 08/10/2012 - 19:10
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A lifetime markov model for the economic evaluation of chronic obstructive pulmonary disease.

Pharmacoeconomics. 2012 Sep 1;30(9):825-40

Authors: Menn P, Leidl R, Holle R

Abstract
Background: Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death worldwide. It has serious health effects and causes substantial costs for society. Objectives: The aim of the present paper was to develop a state-of-the-art decision-analytic model of COPD whereby the cost effectiveness of interventions in Germany can be estimated. To demonstrate the applicability of the model, a smoking cessation programme was evaluated against usual care. Methods: A seven-stage Markov model (disease stages I to IV according to the GOLD [Global Initiative for Chronic Obstructive Lung Disease] classification, states after lung-volume reduction surgery and lung transplantation, death) was developed to conduct a cost-utility analysis from the societal perspective over a time horizon of 10, 40 and 60 years. Patients entered the cohort model at the age of 45 with mild COPD. Exacerbations were classified into three levels: mild, moderate and severe. Estimation of stage-specific probabilities (for smokers and quitters), utilities and costs was based on German data where possible. Data on effectiveness of the intervention was retrieved from the literature. A discount rate of 3% was applied to costs and effects. Probabilistic sensitivity analysis was used to assess the robustness of the results. Results: The smoking cessation programme was the dominant strategy compared with usual care, and the intervention resulted in an increase in health effects of 0.54 QALYs and a cost reduction of &U20AC;1115 per patient (year 2007 prices) after 60 years. In the probabilistic analysis, the intervention dominated in about 95% of the simulations. Sensitivity analyses showed that uncertainty primarily originated from data on disease progression and treatment cost in the early stages of disease. Conclusions: The model developed allows the long-term cost effectiveness of interventions to be estimated, and has been adapted to Germany. The model suggests that the smoking cessation programme evaluated was more effective than usual care as well as being cost-saving. Most patients had mild or moderate COPD, stages for which parameter uncertainty was found to be high. This raises the need to improve data on the early stages of COPD.

PMID: 22799876 [PubMed - in process]

Lung-enriched Organisms and Aberrant Bacterial and Fungal Respiratory Microbiota following Lung Transplant.

Fri, 08/10/2012 - 19:10
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Lung-enriched Organisms and Aberrant Bacterial and Fungal Respiratory Microbiota following Lung Transplant.

Am J Respir Crit Care Med. 2012 Jul 12;

Authors: Charlson ES, Diamond JM, Bittinger K, Fitzgerald AS, Yadav A, Haas AR, Bushman FD, Collman RG

Abstract
RATIONALE: Long-term survival after lung transplantation is limited both by infectious complications and by bronchiolitis obliterans syndrome (BOS), a form of chronic rejection linked in part to microbial triggers. OBJECTIVE: To define microbial populations in the respiratory tract of transplant patients comprehensively using unbiased high-density sequencing. METHODS: Lung was sampled by bronchoalveolar lavage (BAL) and upper respiratory tract by oropharyngeal wash (OW). Bacterial 16S rDNA and fungal ITS sequencing was used to profile organisms present. Outlier analysis plots defining taxa enriched in lung relative to OW were used to identify bacteria enriched in lung against a background of oropharyngeal carryover. MEASUREMENTS AND MAIN RESULTS: Lung transplant recipients had higher bacterial burden in BAL than controls, frequent appearance of dominant organisms, greater distance between communities in BAL and OW indicating more distinct populations, and decreased respiratory tract microbial richness and diversity. Fungal populations were typically dominated by Candida in both sites, or Aspergillus in BAL but not OW. 16S outlier analysis identified lung-enriched taxa indicating bacteria replicating in the lower respiratory tract. In some cases this confirmed respiratory cultures but in others revealed enrichment by anaerobic organisms or mixed outgrowth of upper respiratory flora, and provided quantitative data on relative abundances of bacteria found by culture. CONCLUSIONS: Respiratory tract microbial communities in lung transplant recipients differ in structure and composition from healthy subjects. Outlier analysis can identify specific bacteria replicating in lung. These findings provide novel approaches to address the relationship between microbial communities and transplant outcome, and aid in assessing lung infections.

PMID: 22798321 [PubMed - as supplied by publisher]

Transition of PH Patients from Sildenafil to Tadalafil: Feasibility and Practical Considerations.

Fri, 08/10/2012 - 19:10
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Transition of PH Patients from Sildenafil to Tadalafil: Feasibility and Practical Considerations.

Lung. 2012 Jul 15;

Authors: Shlobin OA, Whitney Brown A, Weir N, Ahmad S, Lemma M, Nathan SD

Abstract
BACKGROUND: Sildenafil was the only phosphodiesterase-5 inhibitor available for the treatment of pulmonary arterial hypertension (PAH) until the approval and availability of once-daily tadalafil. Since no direct comparative study is likely to be performed between these agents, we sought to evaluate the feasibility of transitioning stable PAH patients from sildenafil to tadalafil. METHODS: The primary end point was continuation on tadalafil without clinical deterioration. A functional outcome through an evaluation of serial change in the 6-min walk test distance (6MWD) was also performed. RESULTS: Thirty-five patients on sildenafil qualified for the analysis, of which 85.7 % (30/35) were successfully transitioned. The remaining 14.3 % (5/30) (failure group) were switched back to sildenafil due to worsening symptoms. The mean pretransition 6MWD was 363 m, with an average change in the success group of +16.4 m (range = -64 to +140 m) compared to -45 m (range = -123 to +32 m) in the failure group at 1-3 months post switch (p = 0.02). All 30 patients in the success group remained on tadalafil, with an average improvement in the 6MWD of +37.04 m (range = -36.5 to +236.5 m) at 12 months post switch. The failure group had a higher daily sildenafil dose (180 vs. 115.5 mg; p = 0.06), with 42.8 % of patients at the highest sildenafil dose failing the transition. CONCLUSION: The transition from sildenafil to tadalafil is safe and generally well tolerated. Patients with more severe disease and those on higher doses of sildenafil are more likely to fail the transition and should be monitored closely post switch.

PMID: 22797830 [PubMed - as supplied by publisher]

Dynamic Patient Counseling: A Novel Concept in IPF.

Fri, 08/10/2012 - 19:10
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Dynamic Patient Counseling: A Novel Concept in IPF.

Chest. 2012 Jul 10;

Authors: Brown AW, Shlobin OA, Weir N, Albano MC, Ahmad S, Smith M, Leslie K, Nathan SD

Abstract
ABSTRACT BACKGROUND: The characteristics of long-term IPF survivors have never been fully elucidated. We sought to illustrate the attenuated mortality and describe the characteristics of IPF patients who survived at least five years beyond their initial presentation. METHODS: IPF patients evaluated between 1997 and 2006 were identified through the clinic database. Patients who survived beyond five years from the time of their evaluation were compared to those who died or underwent lung transplantation within five years. Survival analyses were performed from the time of initial evaluation as well as contingent on annualized survival thereafter. RESULTS: Eighty-seven patients who survived at least five years formed the comparator group to whom other patients were contrasted. These patients had a higher body mass index, FVC%, FEV1%, TLC%, and DLco% predicted, but a lower FEV1/FVC ratio and lower mean pulmonary artery pressures. More than half of these patients had moderate or severe disease at the time of presentation. Our annualized contingent survival analyses revealed a progressively increasing median survival dependent on the duration of the disease. CONCLUSIONS: While we were able to demonstrate differences in our five year survivors, rather than being a distinct group, these patients appear to exist within a continuum of improving survival dependent on prior disease duration. This progressively improving time-dependent prognosis mandates the serial re-evaluation of individual patient's projected outcomes. The implementation of dynamic counseling is an important concept in more accurately predicting life expectancy for IPF patients who are frequently haunted by the prospects of a dismal survival.

PMID: 22797563 [PubMed - as supplied by publisher]

Preventing ventilator-associated pneumonia: does the evidence support the practice?

Fri, 08/10/2012 - 19:10
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Preventing ventilator-associated pneumonia: does the evidence support the practice?

JAMA. 2012 Jun 20;307(23):2534-9

Authors: O'Grady NP, Murray PR, Ames N

Abstract
Ventilator-associated pneumonia (VAP) is among the most common infections in patients requiring endotracheal tubes with mechanical ventilation. Ventilator-associated pneumonia is associated with increased hospital costs, a greater number of days in the intensive care unit, longer duration of mechanical ventilation, and higher mortality. Despite widely accepted recommendations for interventions designed to reduce rates of VAP, few studies have assessed the ability of these interventions to improve patient outcomes. As the understanding of VAP advances and new technologies to reduce VAP become available, studies should directly assess patient outcomes before the health care community implements specific prevention approaches in clinical practice.

PMID: 22797453 [PubMed - indexed for MEDLINE]

Long-term mechanical circulatory support (destination therapy): On track to compete with heart transplantation?

Fri, 08/10/2012 - 19:10
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Long-term mechanical circulatory support (destination therapy): On track to compete with heart transplantation?

J Thorac Cardiovasc Surg. 2012 Jul 13;

Authors: Kirklin JK, Naftel DC, Pagani FD, Kormos RL, Stevenson L, Miller M, Young JB

Abstract
OBJECTIVES: Average 2-year survival after cardiac transplantation is approximately 80%. The evolution and subsequent approval of larger pulsatile and, more recently, continuous flow mechanical circulatory support (MCS) technology for destination therapy (DT) offers the potential for triage of some patients awaiting cardiac transplantation to DT. METHODS: The National Heart, Lung, and Blood Institute Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is a national multi-institutional study of long-term MCS. Between June 2006 and December 2011, 127 pulsatile and 1160 continuous flow pumps (24% of total primary left ventricular assist devices [LVADs]) carried an initial strategy of DT therapy. RESULTS: By multivariable analysis, risk factors (P < .05) for mortality after DT included older age, larger body mass index, history of cancer, history of cardiac surgery, INTERMACS level I (cardiogenic shock), dialysis, increased blood urea nitrogen, use of a pulsatile flow device, and use of a right ventricular assist device (RVAD). Among patients with a continuous flow LVAD who were not in cardiogenic shock, a particularly favorable survival was associated with no cancer, patients not in cardiogenic shock, and blood urea nitrogen less than 50 mg/dL, resulting in 1- and 2-year survivals of 88% and 80%. CONCLUSIONS: (1) Evolution from pulsatile to continuous flow technology has dramatically improved 1- and 2-year survivals; (2) DT is not appropriate for patients with rapid hemodynamic deterioration or severe right ventricular failure; (3) important subsets of patients with continuous flow DT now enjoy survival that is competitive with heart transplantation out to about 2 years.

PMID: 22795459 [PubMed - as supplied by publisher]

Extracorporeal membrane oxygenation as a bridge to lung transplantation and recovery.

Fri, 08/10/2012 - 19:10
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Extracorporeal membrane oxygenation as a bridge to lung transplantation and recovery.

J Thorac Cardiovasc Surg. 2012 Jul 13;

Authors: Javidfar J, Brodie D, Iribarne A, Jurado J, Lavelle M, Brenner K, Arcasoy S, Sonett J, Bacchetta M

Abstract
OBJECTIVE: Respiratory failure develops in many patients on lung transplant waiting lists before a suitable donor organ becomes available. Extracorporeal membrane oxygenation may be used to bridge such patients to recovery or lung transplantation. METHODS: This is a review of a single-institution's experience with placing patients on extracorporeal membrane oxygenation with the intention of bridging them to lung transplantation. End points included successful bridging, duration of extracorporeal membrane oxygenation support, extubation, weaning from extracorporeal membrane oxygenation, overall survival, and extracorporeal membrane oxygenation-related complications. During an approximate 5-year period, acute respiratory failure developed in 18 patients (median age, 34 years) on the institution's lung transplant waiting list (8 hypoxemic, 9 hypercarbic, and 1 combined) who were placed on extracorporeal membrane oxygenation (13 venovenous and 5 venoarterial). RESULTS: All patients achieved appropriate extracorporeal membrane oxygenation blood flow rates (median, 4.05 L/min) and good gas exchange (median, on extracorporeal membrane oxygenation partial pressure of arterial carbon dioxide 43 mm Hg and partial pressure of arterial oxygen 196 mm Hg). Thirteen patients (72%) were successfully bridged: 10 to transplant and 3 returned to baseline function. Eleven patients (61%) survived beyond 3 months, including the 10 (56%) who underwent transplantation and are still alive. The median duration of extracorporeal membrane oxygenation support for patients who underwent transplantation was 6 days (3.5-31 days) versus 13.5 days (11-19 days) for those who did not undergo transplantation (P = .45). Six patients (33%) were extubated on extracorporeal membrane oxygenation, 4 of whom underwent transplantation. Four patients (22%) who were too unstable for conventional interhospital transfer were transported on extracorporeal membrane oxygenation to Columbia University Medical Center. This subgroup had a 75% bridge to transplant or recovery rate and 100% survival in transplanted patients. CONCLUSIONS: Extracorporeal membrane oxygenation is a safe and effective means of bridging well-selected patients with refractory respiratory failure to lung transplantation or return to their baseline condition.

PMID: 22795457 [PubMed - as supplied by publisher]

Patients with cystic fibrosis have inducible IL-17(+)IL-22(+) memory cells in lung draining lymph nodes.

Fri, 08/10/2012 - 19:10
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Patients with cystic fibrosis have inducible IL-17(+)IL-22(+) memory cells in lung draining lymph nodes.

J Allergy Clin Immunol. 2012 Jul 11;

Authors: Chan YR, Chen K, Duncan SR, Lathrop KL, Latoche JD, Logar AJ, Pociask DA, Wahlberg BJ, Ray P, Ray A, Pilewski JM, Kolls JK

Abstract
BACKGROUND: IL-17 is an important cytokine signature of the T(H) differentiation pathway T(H)17. This T-cell subset is crucial in mediating autoimmune disease or antimicrobial immunity in animal models, but its presence and role in human disease remain to be completely characterized. OBJECTIVE: We set out to determine the frequency of T(H)17 cells in patients with cystic fibrosis (CF), a disease in which there is recurrent infection with known pathogens. METHODS: Explanted lungs from patients undergoing transplantation or organ donors (CF samples = 18; non-CF, nonbronchiectatic samples = 10) were collected. Hilar nodes and parenchymal lung tissue were processed and examined for T(H)17 signature by using immunofluorescence and quantitative real-time PCR. T cells were isolated and stimulated with antigens from Pseudomonas aeruginosa and Aspergillus species. Cytokine profiles and staining with flow cytometry were used to assess the reactivity of these cells to antigen stimulation. RESULTS: We found a strong IL-17 phenotype in patients with CF compared with that seen in control subjects without CF. Within this tissue, we found pathogenic antigen-responsive CD4(+)IL-17(+) cells. There were double-positive IL-17(+)IL-22(+) cells [T(H)17(22)], and the IL-22(+) population had a higher proportion of memory characteristics. Antigen-specific T(H)17 responses were stronger in the draining lymph nodes compared with those seen in matched parenchymal lungs. CONCLUSION: Inducible proliferation of T(H)17(22) with memory cell characteristics is seen in the lungs of patients with CF. The function of these individual subpopulations will require further study regarding their development. T cells are likely not the exclusive producers of IL-17 and IL-22, and this will require further characterization.

PMID: 22795370 [PubMed - as supplied by publisher]

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