Skip directly to content

PubMed Lung Transplant

Subscribe to PubMed Lung Transplant feed PubMed Lung Transplant
NCBI: db=pubmed; Term=lung transplant
Updated: 2 hours 14 min ago

Outcome of unexplained acute respiratory distress syndrome with diffuse alveolar damage after lung transplantation.

2 hours 14 min ago

Outcome of unexplained acute respiratory distress syndrome with diffuse alveolar damage after lung transplantation.

Intensive Care Med. 2018 Jan 20;:

Authors: Stéphan F, de Montpréville VT, Diarra C, Pilorge C, Fadel E, Ghigna MR

PMID: 29353458 [PubMed - as supplied by publisher]

Outcomes and mortality prediction model of critically ill adults with acute respiratory failure and interstitial lung disease.

2 hours 14 min ago

Outcomes and mortality prediction model of critically ill adults with acute respiratory failure and interstitial lung disease.

Chest. 2018 Jan 15;:

Authors: Gannon W, Lederer DJ, Biscotti M, Javaid A, Patel N, Brodie D, Bacchetta M, Baldwin M

Abstract
BACKGROUND: We aimed to examine short- and long-term mortality in a mixed population of interstitial lung disease (ILD) patients with acute respiratory failure, and to identify those at lower versus higher risk of in-hospital death.
METHODS: We conducted a single-center retrospective cohort study of 126 consecutive adults with ILD admitted to an intensive care unit (ICU) for respiratory failure at a tertiary care hospital between 2010 and 2014 who did not undergo lung transplantation during their hospitalization. We examined associations of ICU-day 1 characteristics with in-hospital and 1-year mortality using Poisson regression, and examined survival using Kaplan Meier curves. We created a risk score for in-hospital mortality using a model developed with penalized regression.
RESULTS: In-hospital mortality was 66%, and 1-year mortality was 80%. Those with connective tissue disease related ILD had better short-term and long-term mortality compared to unclassifiable ILD (adjusted-RR 0.6, 95% CI: 0.3-0.9 and RR 0.6, 95% CI: 0.4-0.9, respectively). Our prediction model includes male sex, interstitial pulmonary fibrosis diagnosis, use of invasive mechanical ventilation and/or extracorporeal life support, no ambulation within 24 hours of ICU admission, body mass index, and simplified acute physiology score-II. The optimism-corrected c-statistic was 0.73, and model calibration was excellent (p=0.99). In-hospital mortality rates for the low, moderate, and high risk groups were 33%, 65%, and 96%, respectively.
CONCLUSIONS: We created a risk score that classifies ILD patients with acute respiratory failure from low to high risk for in-hospital mortality. The score could aid providers in counseling these patients and their families.

PMID: 29353024 [PubMed - as supplied by publisher]

Bronchiolitis obliterans syndrome is associated with increased p-glycoprotein expression and loss of glucocorticoid receptor from steroid resistant pro-inflammatory CD8+T cells.

Sun, 01/21/2018 - 11:04

Bronchiolitis obliterans syndrome is associated with increased p-glycoprotein expression and loss of glucocorticoid receptor from steroid resistant pro-inflammatory CD8+T cells.

Clin Exp Immunol. 2018 Jan 20;:

Authors: Hodge G, Hodge S, Nguyen PT, Yeo A, Sarkar P, Badiei A, Holmes-Liew CL, Reynolds PN, Holmes M

Abstract
Immunosuppressive therapy fails to suppress the production of pro-inflammatory cytokines, particularly by CD8+T cells, in stable lung transplant recipients and those undergoing chronic rejection, suggesting that some patients may become relatively resistant to immunosuppressants such as glucocorticoids (GC). We have shown loss of GC receptor (GCR) from the CD8+ cells, and we hypothesized that the drug membrane efflux pump, p-glycoprotein-1 (Pgp), may also be involved in lymphocyte steroid resistance following lung transplant. Pgp/GCR expression and IFNγ/TNFα pro-inflammatory cytokine production was measured in blood lymphocytes from 15 stable lung transplant patients, 10 patients with bronchiolitis obliterans syndrome (BOS) and 10 healthy aged-matched controls (± prednisolone ± Pgp inhibitor, cyclosporin A ± GCR activator, Compound A) using flow cytometry. Both Pgp+ and Pgp- lymphocyte subsets from all subjects produced IFNγ/TNFα pro-inflammatory cytokines. Pgp expression was increased in CD8+Pgp+T cells and correlated with IFNγ/TNFα expression and BOS grade. Reduced GCR was observed in CD8+Pgp-T, NKT-like and NK cells from stable patients compared with controls, and further reduced in CD8+Pgp-T cells in BOS. Addition of 2.5ng/ml cyclosporine A and 1µM prednisolone significantly inhibit IFNγ/TNFα production by CD8+Pgp+ T cells from BOS patients. Addition of 10µM Compound A and 1µM prednisolone significantly inhibit IFNγ/TNFα production by CD8+Pgp- T cells from BOS patients. BOS is associated with increased Pgp expression and loss of GCR from steroid resistant pro-inflammatory CD8+T cells. Treatments that inhibit Pgp and upregulate GCR in CD8+T cells may improve graft survival. This article is protected by copyright. All rights reserved.

PMID: 29352737 [PubMed - as supplied by publisher]

Epithelial Progenitor Cells Take Center Stage in Lung Transplantation.

Sat, 01/20/2018 - 13:45

Epithelial Progenitor Cells Take Center Stage in Lung Transplantation.

Am J Respir Crit Care Med. 2018 Jan 19;:

Authors: Smirnova NF, Eickelberg O

PMID: 29350973 [PubMed - as supplied by publisher]

Clostridium difficile Infection is Associated with Graft Loss in Solid Organ Transplant Recipients.

Sat, 01/20/2018 - 13:45

Clostridium difficile Infection is Associated with Graft Loss in Solid Organ Transplant Recipients.

Am J Transplant. 2018 Jan 19;:

Authors: Cusini A, Béguelin C, Stampf S, Boggian K, Garzoni C, Koller M, Manuel O, Meylan P, Mueller NJ, Hirsch H, Weisser M, Berger C, van Delden C, Swiss Transplant Cohort Study

Abstract
Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched two control subjects per case by age at transplantation, sex and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred and fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10'000 patient days was 0.47 (95% confidence interval (CI): [0.38, 0.58]), with the highest rate in lung (1.48, 95% CI: [0.93, 2.24]). In multivariable analysis, proven infections (hazard ratio (HR) 2.82, 95% CI: [1.29, 6.19]) and antibiotic treatments (HR=4.51, 95% CI: [2.03, 10.0]) during the preceding three months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI post-transplantation had an increased risk of graft loss (HR=2.24, 95% CI: [1.15, 4.37], p=0.02). These findings may help to improve the management of SOT recipients. This article is protected by copyright. All rights reserved.

PMID: 29349869 [PubMed - as supplied by publisher]

Patent Foramen Ovale Repair at the Time of Double Lung Transplantation: Necessary or Not?

Sat, 01/20/2018 - 13:45

Patent Foramen Ovale Repair at the Time of Double Lung Transplantation: Necessary or Not?

Clin Transplant. 2018 Jan 19;:

Authors: Hess NR, Esper SA, Tuft M, Morrell M, D'Cunha J

Abstract
INTRODUCTION: Patient foramen ovale (PFO) is a common and often incidental intraoperative finding during lung transplantation (LTx). We sought to characterize the potential outcomes related to the decision-making of whether the PFO was repaired or left unrepaired.
METHODS: We retrospectively evaluated bilateral LTx recipients between 2005 and 2015 from our prospective database. Incidence of postoperative stoke, 90-day mortality, and overall survival was compared between the PFO-positive and PFO-negative groups, and secondly compared between repaired PFO (rPFO) and non-repaired PFO (nrPFO) groups.
RESULTS: 831 LTx recipients were analyzed: 185 PFO-positive (140 nrPFO, 45 rPFO) and 646 PFO-negative. Study groups were similar with regard to age and comorbidity. Presence of PFO was not associated with a difference in postoperative stroke (P=0.89) or 90-day mortality (P=0.64). In patients with PFO, intraoperative repair resulted in a lower, but non-significant rate of stroke (0%vs5%;P=0.20) and no difference in mortality (P=0.26). As expected, PFO and PFO repair were both associated with a higher incidence of cardiopulmonary bypass utilization, but no difference in pump related complications.
CONCLUSIONS: The protective effect of PFO repair remains unclear. However, is not associated with an increased incidence of stroke or postoperative mortality following LTx. This suggests that repair of PFO, with its inherent increase in surgical complexity, is not required and outcomes are acceptable. This article is protected by copyright. All rights reserved.

PMID: 29349838 [PubMed - as supplied by publisher]

Timing of Spirometry May Impact Hospital Length of Stay for Cystic Fibrosis Pulmonary Exacerbation.

Sat, 01/20/2018 - 13:45

Timing of Spirometry May Impact Hospital Length of Stay for Cystic Fibrosis Pulmonary Exacerbation.

Lung. 2018 Jan 18;:

Authors: Krivchenia K, Tumin D, Nemastil CJ, Tobias JD, Hayes D

Abstract
PURPOSE: The optimal timing of spirometry during hospitalization for acute pulmonary exacerbation (PEx) in patients with cystic fibrosis (CF) is unclear. We retrospectively evaluated whether measuring spirometry earlier during hospitalization was associated with a shorter length of stay (LOS).
METHODS: In this retrospective study, we analyzed data from the electronic medical record of CF patients 6 years of age and older admitted to a single center for acute PEx requiring IV antibiotic therapy between 2009 and 2016. After excluding patient encounters with missing data on covariates, random-effects linear regression was used to predict LOS as a function of days to first pulmonary function testing (PFT), which was spirometry for our study.
RESULTS: One thousand thirty-five hospitalizations of 242 patients met inclusion criteria, with 801 including complete data on covariates. Mean LOS was 10 ± 7 days, with mean time to first PFT of 4 ± 3 days after admission. In multivariable analysis, each additional day to first PFT was associated with 0.97 days longer LOS (95% CI 0.29, 1.64; p = 0.005).
CONCLUSIONS: As CF researchers and clinicians work to improve management of PEx, the timing of spirometry during hospitalization remains an important question. Obtaining objective lung function data earlier during the course of therapy may provide information which can lead to reduced hospital LOS for PEx.

PMID: 29349537 [PubMed - as supplied by publisher]

Prognostic value of long non-coding RNA PVT1 as a novel biomarker in various cancers: a meta-analysis.

Sat, 01/20/2018 - 13:45

Prognostic value of long non-coding RNA PVT1 as a novel biomarker in various cancers: a meta-analysis.

Oncotarget. 2017 Dec 22;8(68):113174-113184

Authors: Zhu S, Shuai P, Yang C, Zhang Y, Zhong S, Liu X, Chen K, Ran Q, Yang H, Zhou Y

Abstract
Background: Plasmacytoma variant translocation 1 (PVT1) has recently been reported to be aberrantly expressed and serves as a prognostic biomarker in many types of cancers. However, its prognostic significance remains controversial. Here, we conducted a meta-analysis to investigate the prognostic value of PVT1 expression in cancers.
Results: A total of 2109 patients from 20 studies were included. The results showed that elevated PVT1 expression predicted a poor outcome for overall survival (OS) in nine types of cancers (HR = 1.40, 95% CI: 1.21-1.59). Subgroup analysis indicated that there was a significant association between PVT1 overexpression and poor OS of patients with gastric cancer, gynecology cancer and lung cancer. Furthermore, we also found a negative significant relationship between PVT1 expression and disease-free survival (HR = 1.83, 95% CI: 1.39-2.27), progression-free survival (HR = 1.63, 95% CI: 1.34-1.93) and recurrence-free survival (HR = 1.74, 95% CI: 1.01-2.47). In addition, the level of PVT1 expression was positively related to tumor size, TNM stage, lymph node metastasis and distant metastases.
Materials and Methods: A systematic search was performed through the PubMed, EMBASE, Web of Science, Ovid and Cochrane library databases for eligible studies on prognostic value of PVT1 in cancers from inception up to June, 2017. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association between PVT1 expression and clinical outcomes.
Conclusions: PVT1 expression positively related to tumor size, TNM stages, lymph node metastasis and distant metastases, and served as a prognostic biomarker in different types of cancers.

PMID: 29348896 [PubMed]

Treprostinil inhibits proliferation and extracellular matrix deposition by fibroblasts through cAMP activation.

Sat, 01/20/2018 - 13:45

Treprostinil inhibits proliferation and extracellular matrix deposition by fibroblasts through cAMP activation.

Sci Rep. 2018 Jan 18;8(1):1087

Authors: Lambers C, Roth M, Jaksch P, Muraközy G, Tamm M, Klepetko W, Ghanim B, Zhao F

Abstract
Idiopathic pulmonary fibrosis (IPF) is characterized by peripheral lung fibrosis and increased interstitial extracellular matrix (ECM) deposition. In IPF, tumor growth factor (TGF)-β1 which is the major stimulus of ECM deposition, and platelet derived growth factor (PDGF)-BB is a potent stimulus of fibrosis. Thus, the effect of Treprostinil on TGF-ß1 and PDGF-induced fibroblast proliferation and ECM deposition was investigated. Human peripheral lung fibroblasts of seven IPF patients and five lung donors were stimulated by PDGF, or TGF-β1, or the combination. Cells were pre-incubated (30 min) with either Treprostinil, forskolin, di-deoxyadenosine (DDA), or vehicle. Treprostinil time dependently activated cAMP thereby preventing PDGF-BB induced proliferation and TGF-β1 secretion. Cell counts indicated proliferation; α-smooth muscle actin (α-SMA) indicted differentiation, and collagen type-1 or fibronectin deposition remodeling. Myo-fibroblast indicating α-SMA expression was significantly reduced and its formation was altered by Treprostinil. Collagen type-I and fibronectin deposition were also reduced by Treprostinil. The effect of Treprostinil on collagen type-I deposition was cAMP sensitive as it was counteracted by DDA, while the effect on fibronectin was not cAMP mediated. Treprostinil antagonized the pro-fibrotic effects of both PDGF-BB and TGF-β1 in primary human lung fibroblasts. The data presented propose a therapeutic relevant anti-fibrotic effect of Treprostinil in IPF.

PMID: 29348469 [PubMed - in process]

First histopathological evidence of irreversible pulmonary vascular disease in dasatinib-induced pulmonary arterial hypertension.

Sat, 01/20/2018 - 13:45

First histopathological evidence of irreversible pulmonary vascular disease in dasatinib-induced pulmonary arterial hypertension.

Eur Respir J. 2018 Jan 18;:

Authors: Daccord C, Letovanec I, Yerly P, Bloch J, Ogna A, Nicod LP, Aubert JD

PMID: 29348153 [PubMed - as supplied by publisher]

Chronic obstructive pulmonary disease guidelines in Europe: a look into the future.

Sat, 01/20/2018 - 13:45

Chronic obstructive pulmonary disease guidelines in Europe: a look into the future.

Respir Res. 2018 Jan 18;19(1):11

Authors: Miravitlles M, Roche N, Cardoso J, Halpin D, Aisanov Z, Kankaanranta H, Kobližek V, Śliwiński P, Bjermer L, Tamm M, Blasi F, Vogelmeier CF

Abstract
Clinical practice guidelines are ubiquitous and are developed to provide recommendations for the management of many diseases, including chronic obstructive pulmonary disease. The development of these guidelines is burdensome, demanding a significant investment of time and money. In Europe, the majority of countries develop their own national guidelines, despite the potential for overlap or duplication of effort. A concerted effort and consolidation of resources between countries may alleviate the resource-intensity of maintaining individual national guidelines. Despite significant resource investment into the development and maintenance of clinical practice guidelines, their implementation is suboptimal. Effective strategies of guideline dissemination must be given more consideration, to ensure adequate implementation and improved patient care management in the future.

PMID: 29347928 [PubMed - in process]

Interleukin-10-Overexpressing Mesenchymal Stromal Cells Induce a Series of Regulatory Effects in the Inflammatory System and Promote the Survival of Endotoxin-Induced Acute Lung Injury in Mice Model.

Sat, 01/20/2018 - 13:45
Related Articles

Interleukin-10-Overexpressing Mesenchymal Stromal Cells Induce a Series of Regulatory Effects in the Inflammatory System and Promote the Survival of Endotoxin-Induced Acute Lung Injury in Mice Model.

DNA Cell Biol. 2018 Jan;37(1):53-61

Authors: Wang C, Lv D, Zhang X, Ni ZA, Sun X, Zhu C

Abstract
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening inflammatory conditions with no effective pharmacological treatment. Previous studies suggested that mesenchymal stromal/stem cell (MSC) infusion resulted in better survival in mouse ALI models and presented low toxicity in human subjects. Therefore, in this study, we investigated the possibility of treating a murine model of ALI using MSCs with constant interleukin-10 overexpression (IL-10-MSC) by retroviral infection. ALI in mice was induced by intratracheal lipopolysaccharides (LPS) instillation. After 96 h, 80% of mice receiving IL-10-MSCs survived, whereas the survival rate of the mice receiving other treatments was only 20-50%. Mice receiving IL-10-MSCs also demonstrated significantly less weight loss (p < 0.01), and lower protein level and TNF concentration in the BAL (p < 0.01). Interestingly, IL-10-MSCs given to mice 3 and 1 day before ALI induction still conferred significant protection against ALI. While direct IL-10 transfusion resulted in an intensive, but transient peak in serum IL-10 level, IL-10-MSCs provided a milder, but more persistent increase in serum IL-10 level, together with significantly higher levels of IL-10-producing T cells and B cells, both in the spleen and in the lung. IL-10-MSCs given 3 days before LPS challenge resulted in higher pulmonary infiltration of IL-10-producing T cells and B cells in mice. On average, mice that survived the LPS challenge for 96 h presented higher pulmonary infiltration of IL-10-producing T cells and B cells than mice that deceased within the experimental period. Together, these results demonstrated that IL-10-MSCs offered superior protection against LPS-induced ALI when given before or at the time of ALI induction, and significantly increased the frequencies of IL-10-expressing T cells and B cells. IL-10-MSCs may thus represent a promising new treatment option in ALI/ARDS.

PMID: 29072959 [PubMed - indexed for MEDLINE]

Blocking Surgically Induced Lysyl Oxidase Activity Reduces the Risk of Lung Metastases.

Sat, 01/20/2018 - 13:45
Related Articles

Blocking Surgically Induced Lysyl Oxidase Activity Reduces the Risk of Lung Metastases.

Cell Rep. 2017 Apr 25;19(4):774-784

Authors: Rachman-Tzemah C, Zaffryar-Eilot S, Grossman M, Ribero D, Timaner M, Mäki JM, Myllyharju J, Bertolini F, Hershkovitz D, Sagi I, Hasson P, Shaked Y

Abstract
Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX) activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX. Furthermore, the lungs of recipient mice injected with plasma from post-surgical colorectal cancer patients are more prone to metastatic seeding than mice injected with baseline plasma. Downregulation of LOX activity or levels reduces lung metastasis after surgery and increases survival, highlighting the potential of LOX inhibition in reducing the risk of metastasis following surgery.

PMID: 28445728 [PubMed - indexed for MEDLINE]

Epithelial grafting of a decellularized whole-tracheal segment: an in vivo experimental model.

Fri, 01/19/2018 - 13:45

Epithelial grafting of a decellularized whole-tracheal segment: an in vivo experimental model.

Interact Cardiovasc Thorac Surg. 2018 Jan 15;:

Authors: Den Hondt M, Vanaudenaerde BM, Verbeken EK, Vranckx JJ

Abstract
OBJECTIVES: Prerequisites for successful trachea transplantation include the use of a biocompatible construct, submucosal vascularization and an epithelial covering. Implantation of non-epithelialized tracheal scaffolds may lead to stenosis. However, epithelial grafting or seeding can only be attempted onto a well-vascularized submucosal bed. Our aim was to investigate a method to prevent stenosis during prelamination of non-epithelialized, gently decellularized rabbit tracheae and to evaluate whether grafting of revascularized constructs with buccal mucosa is feasible.
METHODS: Allotracheae underwent two 48-h cycles of detergent-enzymatic decellularization using sodium deoxycholate and DNAse. In the first series, 12 circular scaffolds were implanted bilaterally in lateral thoracic artery flaps (n = 6 rabbits). Right-sided transplants were covered internally with Integra™. In the second series, 10 decellularized tracheae covered with Integra were prelaminated in flaps (n = 10 rabbits). Twenty-one days after implantation, revascularized tracheae were grafted with buccal mucosa. A macroscopic, histological analysis and immunohistochemistry were performed on explants.
RESULTS: In the first series, tracheae without Integra covering developed significantly greater intraluminal (P = 0.032) and subepithelial narrowing (P = 0.0345) compared with tracheae with Integra covering. All tracheae exhibited insufficient submucosal revascularization. In the second series, submucosal revascularization was incomplete in the first 2 constructs, which were implanted circularly. These tracheae only showed marginal buccal graft ingrowth. To accelerate revascularization, the subsequent 8 transplants were opened longitudinally before implantation. Compared to circularly implanted tracheae, submucosal revascularization of these transplants was superior (P = 0.0008). Graft adherence was complete in 6 opened constructs. Mild lymphocytic infiltration within the buccal graft was detected in 5 specimens.
CONCLUSIONS: We observed satisfactory host integration of opened tracheae that were temporarily covered with Integra during revascularization and subsequently grafted with buccal mucosa. Integra successfully prevented stenosis during revascularization. This model may provide an example of an immunosuppressive-free approach in the treatment of long-segment tracheal lesions. With the aid of further refinements such as a respiratory epithelial lining, an orthotopically transplantable construct could be created.

PMID: 29346567 [PubMed - as supplied by publisher]

Scaffold-free trachea regeneration by tissue engineering with bio-3D printing.

Fri, 01/19/2018 - 13:45

Scaffold-free trachea regeneration by tissue engineering with bio-3D printing.

Interact Cardiovasc Thorac Surg. 2018 Jan 15;:

Authors: Taniguchi D, Matsumoto K, Tsuchiya T, Machino R, Takeoka Y, Elgalad A, Gunge K, Takagi K, Taura Y, Hatachi G, Matsuo N, Yamasaki N, Nakayama K, Nagayasu T

Abstract
OBJECTIVES: Currently, most of the artificial airway organs still require scaffolds; however, such scaffolds exhibit several limitations. Alternatively, the use of an autologous artificial trachea without foreign materials and immunosuppressants may solve these issues and constitute a preferred tool. The rationale of this study was to develop a new scaffold-free approach for an artificial trachea using bio-3D printing technology. Here, we assessed the circumferential tracheal replacement using scaffold-free trachea-like grafts generated from isolated cells in an inbred animal model.
METHODS: Chondrocytes and mesenchymal stem cells were isolated from F344 rats. Rat lung microvessel endothelial cells were purchased. Our bio-3D printer generates spheroids consisting of several types of cells to create 3D structures. The bio-3D-printed artificial trachea from spheroids was matured in a bioreactor and transplanted into F344 rats as a tracheal graft under general anaesthesia. The mechanical strength of the artificial trachea was measured, and histological and immunohistochemical examinations were performed.
RESULTS: Tracheal transplantation was performed in 9 rats, which were followed up postoperatively for 23 days. The average tensile strength of artificial tracheas before transplantation was 526.3 ± 125.7 mN. The bio-3D-printed scaffold-free artificial trachea had sufficient strength to transplant into the trachea with silicone stents that were used to prevent collapse of the artificial trachea and to support the graft until sufficient blood supply was obtained. Chondrogenesis and vasculogenesis were observed histologically.
CONCLUSIONS: The scaffold-free isogenic artificial tracheas produced by a bio-3D printer could be utilized as tracheal grafts in rats.

PMID: 29346562 [PubMed - as supplied by publisher]

Blood and lymphatic vessels contribute to the impact of the immune microenvironment on clinical outcome in non-small-cell lung cancer.

Fri, 01/19/2018 - 13:45

Blood and lymphatic vessels contribute to the impact of the immune microenvironment on clinical outcome in non-small-cell lung cancer.

Eur J Cardiothorac Surg. 2018 Jan 15;:

Authors: Armani G, Madeddu D, Mazzaschi G, Bocchialini G, Sogni F, Frati C, Lorusso B, Falco A, Lagrasta CA, Cavalli S, Mangiaracina C, Vilella R, Becchi G, Gnetti L, Corradini E, Quaini E, Urbanek K, Goldoni M, Carbognani P, Ampollini L, Quaini F

Abstract
OBJECTIVES: Lymphangiogenesis plays a critical role in the immune response, tumour progression and therapy effectiveness. The aim of this study was to determine whether the interplay between the lymphatic and the blood microvasculature, tumour-infiltrating lymphocytes and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint constitutes an immune microenvironment affecting the clinical outcome of patients with non-small-cell lung cancer.
METHODS: Samples from 50 squamous cell carcinomas and 42 adenocarcinomas were subjected to immunofluorescence to detect blood and lymphatic vessels. CD3pos, CD8pos and PD-1pos tumour-infiltrating lymphocytes and tumour PD-L1 expression were assessed by immunohistochemical analysis.
RESULTS: Quantification of vascular structures documented a peak of lymphatics at the invasive margin together with a decreasing gradient of blood and lymphatic vessels from the peritumour area throughout the neoplastic core. Nodal involvement and pathological stage were strongly associated with vascularization, and an increased density of vessels was detected in samples with a higher incidence of tumour-infiltrating lymphocytes and a lower expression of PD-L1. Patients with a high PD-L1 to PD-1 ratio and vascular rarefaction had a gain of 10 months in overall survival compared to those with a low ratio and prominent vascularity.
CONCLUSIONS: Microvessels are an essential component of the cancer immune microenvironment. The clinical impact of the PD-1/PD-L1-based immune contexture may be implemented by the assessment of microvascular density to potentially identify patients with non-small-cell lung cancer who could benefit from immunotherapy and antiangiogenic treatment.

PMID: 29346540 [PubMed - as supplied by publisher]

Quantifying Frailty in Post Lung Transplant Patients - Can We Predict Who Will Need Readmission?

Fri, 01/19/2018 - 13:45

Quantifying Frailty in Post Lung Transplant Patients - Can We Predict Who Will Need Readmission?

Transplantation. 2018 Jan 18;:

Authors: Neujahr DC

PMID: 29346258 [PubMed - as supplied by publisher]

Causes, Preventability, and Cost of Unplanned Rehospitalizations Within 30 Days of Discharge Following Lung Transplantation.

Fri, 01/19/2018 - 13:45

Causes, Preventability, and Cost of Unplanned Rehospitalizations Within 30 Days of Discharge Following Lung Transplantation.

Transplantation. 2018 Jan 18;:

Authors: Courtwright AM, Zaleski D, Gardo L, Ahya VN, Christie JD, Crespo M, Hadjiliadis D, Lee J, Molina M, Patel N, Porteous M, Cantu EE, Bermudez C, Diamond JM

Abstract
BACKGROUND: Unplanned rehospitalizations (UR) within 30 days of discharge are common following lung transplantation. It is unknown whether UR represent preventable gaps in care or necessary interventions for complex patients. The objective of this study was to assess the incidence, causes, risk factors, and preventability of UR following initial discharge after lung transplantation.
METHODS: This was a single-center prospective cohort study. Subjects completed a modified Short Physical Performance Battery (SPPB) to assess frailty at listing and at initial hospital discharge after transplantation and the State-Trait Anxiety Inventory (STAI) at discharge. For each UR a study staff member and the patient's admitting or attending clinician used an ordinal scale (0, not; 1, possibly; 2, definitely preventable) to rate readmission preventability. A total sum score ≥2 defined a preventable UR.
RESULTS: Of the 90 enrolled patients, 30 (33.3%) had an UR. The single most common reasons were infection (7 (23.3%)) and atrial tachyarrhythmia (5 (16.7%)). Among the 30 UR, 9 (30.0%) were deemed preventable. UR that happened before day 30 were more likely to be considered preventable than those between days 30-90 (30.0% versus 6.2%, p = 0.04). Discharge frailty, defined as SPPB<6, was the only variable associated with UR on multivariable analysis (OR = 3.4, 95% CI = 1.1-11.8, p = 0.04).
CONCLUSIONS: Although clinicians do not rate the majority of UR following lung transplant as preventable, discharge frailty is associated with UR. Further research should identify whether modification of discharge frailty can reduce UR.

PMID: 29346256 [PubMed - as supplied by publisher]

Regeneration of functional alveoli by adult human SOX9+ airway basal cell transplantation.

Fri, 01/19/2018 - 13:45
Related Articles

Regeneration of functional alveoli by adult human SOX9+ airway basal cell transplantation.

Protein Cell. 2018 Jan 17;:

Authors: Ma Q, Ma Y, Dai X, Ren T, Fu Y, Liu W, Han Y, Wu Y, Cheng Y, Zhang T, Zuo W

Abstract
Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9+ basal cells (BCs) located at airway epithelium rugae can regenerate adult human lung. Human SOX9+ BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9+ BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient's lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9+ BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3-12 months after cell transplantation. Altogether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future.

PMID: 29344809 [PubMed - as supplied by publisher]

Neurocognitive dysfunction in hematopoietic cell transplant recipients: expert review from the late effects and Quality of Life Working Committee of the CIBMTR and complications and Quality of Life Working Party of the EBMT.

Fri, 01/19/2018 - 13:45
Related Articles

Neurocognitive dysfunction in hematopoietic cell transplant recipients: expert review from the late effects and Quality of Life Working Committee of the CIBMTR and complications and Quality of Life Working Party of the EBMT.

Bone Marrow Transplant. 2018 Jan 17;:

Authors: Buchbinder D, Kelly DL, Duarte RF, Auletta JJ, Bhatt N, Byrne M, DeFilipp Z, Gabriel M, Mahindra A, Norkin M, Schoemans H, Shah AJ, Ahmed I, Atsuta Y, Basak GW, Beattie S, Bhella S, Bredeson C, Bunin N, Dalal J, Daly A, Gajewski J, Gale RP, Galvin J, Hamadani M, Hayashi RJ, Adekola K, Law J, Lee CJ, Liesveld J, Malone AK, Nagler A, Naik S, Nishihori T, Parsons SK, Scherwath A, Schofield HL, Soiffer R, Szer J, Twist I, Warwick AB, Wirk BM, Yi J, Battiwalla M, Flowers MDE, Savani B, Shaw BE

Abstract
Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and non-malignant diseases. Despite increasing survival rates, long-term morbidity following HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction following HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction following HCT. In this review, we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and to help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Lastly, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae following HCT.

PMID: 29343837 [PubMed - as supplied by publisher]

Pages