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 48 min ago

The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection.

Thu, 08/10/2017 - 12:45
Related Articles

The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection.

Sci Rep. 2017 Aug 08;7(1):7563

Authors: Payne GA, Li J, Xu X, Jackson P, Qin H, Pollock DM, Wells JM, Oparil S, Leesar M, Patel RP, Blalock JE, Gaggar A

Abstract
The extracellular matrix (ECM) is a dynamic, bioactive structure critical to organ development, structure and function. Excessive remodeling of the ECM is a hallmark of a variety of inflammatory conditions including vascular disease. Endothelin-1 (ET1) synthesis is understood to promote cardiovascular diseases including acute cardiac transplant rejection; however, the contribution of ECM-derived chemokines (matrikines) to vascular inflammation remains poorly understood. Herein we report that the matrikine acetylated Pro-Gly-Pro (PGP) stimulates vascular inflammation through activation of endothelial CXC Chemokine Receptor 2 (CXCR2) and production of endothelin-1 both in vitro and in vivo. As a proof of hypothesis, we demonstrate that coronary PGP levels associate with both circulating endothelin-1 and acute rejection in cardiac transplant patients (sensitivity of 100% and specificity of 86%). These findings establish PGP as a novel mediator in cardiovascular disease, and implicate bioactive matrix fragments as underappreciated agents potentially active in numerous conditions propagated by progressive vascular inflammation.

PMID: 28790330 [PubMed - in process]

[Critical Care Managements after Lung Transplantation].

Thu, 08/10/2017 - 12:45
Related Articles

[Critical Care Managements after Lung Transplantation].

Kyobu Geka. 2017 Jul;70(8):701-707

Authors: Anraku M

Abstract
Lung transplantation is a viable treatment option for patients with end-stage lung diseases such as interstitial pneumonia/pulmonary fibrosis, emphysema, pulmonary hypertension, and so on. Collecting available clinical, physiological, serological, and surgical information of both donor and recipient is vital when planning relevant postoperative managements. The goal of the managements is to keep the transplanted lung (s) functional while preventing/treating infection, rejection, and ischemiareperfusion lung injury. Immunosuppressive therapy, anti-mycobacterial/viral therapy, and cardio-pulmonary supports should be optimized without causing unfavorable side-effects that can lead to kidney, liver, digestive and neurological malfunction. During the post-transplant intensive care period, satisfying the endorgan oxygen requirement is the key to maintain vital organ stability. Aggressive rehabilitation should be utilized as soon as the hemodynamic status allows it. Deep venous thrombosis and subsequent pulmonary embolism should be prevented by giving anti-coagulants and active mobilization, because the incidence could be underrecognized. Avoiding multifactorial allograft injuries can improve not only short-term graft function, but also long-term patients' outcome after lung transplantation.

PMID: 28790293 [PubMed - in process]

Serum exosomal protein profiling for the non-invasive detection of cardiac allograft rejection.

Thu, 08/10/2017 - 12:45
Related Articles

Serum exosomal protein profiling for the non-invasive detection of cardiac allograft rejection.

J Heart Lung Transplant. 2017 Jul 19;:

Authors: Kennel PJ, Saha A, Maldonado DA, Givens R, Brunjes DL, Castillero E, Zhang X, Ji R, Yahi A, George I, Mancini DM, Koller A, Fine B, Zorn E, Colombo PC, Tatonetti N, Chen EI, Schulze PC

Abstract
BACKGROUND: Exosomes are cell-derived circulating vesicles that play an important role in cell-cell communication. Exosomes are actively assembled and carry messenger RNAs, microRNAs and proteins. The "gold standard" for cardiac allograft surveillance is endomyocardial biopsy (EMB), an invasive technique with a distinct complication profile. The development of novel, non-invasive methods for the early diagnosis of allograft rejection is warranted. We hypothesized that the exosomal proteome is altered in acute rejection, allowing for a distinction between non-rejection and rejection episodes.
METHODS: Serum samples were collected from heart transplant (HTx) recipients with no rejection, acute cellular rejection (ACR) and antibody-mediated rejection (AMR). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of serum exosome was performed using a mass spectrometer (Orbitrap Fusion Tribrid).
RESULTS: Principal component analysis (PCA) revealed a clustering of 3 groups: (1) control and heart failure (HF); (2) HTx without rejection; and (3) ACR and AMR. A total of 45 proteins were identified that could distinguish between groups (q < 0.05). Comparison of serum exosomal proteins from control, HF and non-rejection HTx revealed 17 differentially expressed proteins in at least 1 group (q < 0.05). Finally, comparisons of non-rejection HTx, ACR and AMR serum exosomes revealed 15 differentially expressed proteins in at least 1 group (q < 0.05). Of these 15 proteins, 8 proteins are known to play a role in the immune response. Of note, the majority of proteins identified were associated with complement activation, adaptive immunity such as immunoglobulin components and coagulation.
CONCLUSIONS: Characterizing of circulating exosomal proteome in different cardiac disease states reveals unique protein expression patterns indicative of the respective pathologies. Our data suggest that HTx and allograft rejection alter the circulating exosomal protein content. Exosomal protein analysis could be a novel approach to detect and monitor acute transplant rejection and lead to the development of predictive and prognostic biomarkers.

PMID: 28789823 [PubMed - as supplied by publisher]

Exercise capacity in young adults after hematopoietic cell transplantation in childhood.

Wed, 08/09/2017 - 12:45

Exercise capacity in young adults after hematopoietic cell transplantation in childhood.

Am J Transplant. 2017 Aug 08;:

Authors: Öberg A, Genberg M, Malinovschi A, Hedenström H, Frisk P

Abstract
A symptom-limited incremental cycle ergometer test was performed in 17 young adults treated with hematopoietic cell transplantation and total body irradiation for hematological malignancies during childhood. They were compared with 17 sex- and age-matched healthy controls. Assessments of pulmonary function, cardiac function, body composition and levels of growth hormone were also included. The median follow-up was 17.7 years. Patients achieved 63.2% of the predicted peak workload, whereas controls achieved 96.1% (p<0.001). All patients, but only one control, failed to achieve a peak workload >80% (p<0.001). Fat-free mass was significantly lower (43.5 vs 57.6 kg, p<0.001) and fat mass percentage was significantly higher (31.8 vs 24.2%, p=0.011) in the patients. The peak workload adjusted for fat-free mass was significantly lower in the patients (3.3 vs 4.3, p<0.001). In the patients, peak workload correlated significantly with total lung capacity (r=0.54, p=0.025). In summary, long-term survivors have significantly decreased exercise capacity compared with healthy individuals. Together with their altered body composition, this may predispose them to cardiovascular disease. This article is protected by copyright. All rights reserved.

PMID: 28787762 [PubMed - as supplied by publisher]

Heparin-binding protein, lysozyme and inflammatory cytokines in bronchoalveolar lavage fluid as diagnostic tools for pulmonary infection in lung transplanted patients.

Wed, 08/09/2017 - 12:45

Heparin-binding protein, lysozyme and inflammatory cytokines in bronchoalveolar lavage fluid as diagnostic tools for pulmonary infection in lung transplanted patients.

Am J Transplant. 2017 Aug 08;:

Authors: Stjärne Aspelund A, Hammarström H, Inghammar M, Larsson H, Hansson L, Christensson B, Påhlman LI

Abstract
Pulmonary infection is a common complication after lung transplantation and early detection is crucial for outcome. However, the condition can be clinically difficult to diagnose and to distinguish from rejection. The aim of this prospective study was to evaluate Heparin-binding protein (HBP), lysozyme and the cytokines Interleukin (IL)-1β, IL-6, IL-8, IL-10 and Tumour Necrosis Factor (TNF) in bronchoalveolar lavage fluid (BALF) as potential biomarkers for pulmonary infection in lung transplanted (Lntx) patients. One hundred and thirteen BALF samples from 29 Lntx recipients were collected at routine scheduled bronchoscopies at 3 and 6 months, or on clinical indication. Samples were classified into no, possible, probable or definite infection at the time of sampling. Rejection was defined by biopsy results. HBP, lysozyme and cytokines were analysed in BALF and correlated to likelihood of infection and rejection. All biomarkers were significantly increased in BALF during infection, while patients with rejection presented low levels that were comparable to non-infection samples. HBP, IL-1β and IL-8 were the best diagnostic markers of infection with area under the receiver operating characteristic curve values of 0,88, 0.91 and 0.90 respectively. In conclusion, HBP, IL-1β and IL-8 could be useful diagnostic markers of pulmonary infection in Lntx patients. This article is protected by copyright. All rights reserved.

PMID: 28787761 [PubMed - as supplied by publisher]

Effect of Azithromycin on Airflow Decline-Free Survival After Allogeneic Hematopoietic Stem Cell Transplant: The ALLOZITHRO Randomized Clinical Trial.

Wed, 08/09/2017 - 12:45

Effect of Azithromycin on Airflow Decline-Free Survival After Allogeneic Hematopoietic Stem Cell Transplant: The ALLOZITHRO Randomized Clinical Trial.

JAMA. 2017 Aug 08;318(6):557-566

Authors: Bergeron A, Chevret S, Granata A, Chevallier P, Vincent L, Huynh A, Tabrizi R, Labussiere-Wallet H, Bernard M, Chantepie S, Bay JO, Thiebaut-Bertrand A, Thepot S, Contentin N, Fornecker LM, Maillard N, Risso K, Berceanu A, Blaise D, Peffault de La Tour R, Chien JW, Coiteux V, Socié G, ALLOZITHRO Study Investigators

Abstract
Importance: Bronchiolitis obliterans syndrome has been associated with increased morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). Previous studies have suggested that azithromycin may reduce the incidence of post-lung transplant bronchiolitis obliterans syndrome.
Objective: To evaluate if the early administration of azithromycin can improve airflow decline-free survival after allogeneic HSCT.
Design, Setting, and Participants: The ALLOZITHRO parallel-group trial conducted in 19 French academic transplant centers and involving participants who were at least 16 years old, had undergone allogeneic HSCT for a hematological malignancy, and had available pretransplant pulmonary function test results. Enrollment was from February 2014 to August 2015 with follow-up through April 26, 2017.
Interventions: Patients were randomly assigned to receive 3 times a week either 250 mg of azithromycin (n = 243) or placebo (n = 237) for 2 years, starting at the time of the conditioning regimen.
Main Outcomes and Measures: The primary efficacy end point was airflow decline-free survival at 2 years after randomization. Main secondary end points were overall survival and bronchiolitis obliterans syndrome at 2 years.
Results: Thirteen months after enrollment, the independent data and safety monitoring board detected an unanticipated imbalance across blinded groups in the number of hematological relapses, and the treatment was stopped December 26, 2016. Among 480 randomized participants, 465 (97%) were included in the modified intention-to-treat analysis (mean age, 52 [SD, 14] years; 75 women [35%]). At the time of data cutoff, 104 patients (22%; 54 azithromycin vs 50 placebo) had experienced an airflow decline; 138 patients (30%) died (78 azithromycin vs 60 placebo). Two-year airflow decline-free survival was 32.8% (95% CI, 25.9%-41.7%) with azithromycin and 41.3% (95% CI, 34.1%-50.1%) with placebo (unadjusted hazard ratio [HR], 1.3; 95% CI, 1.02-1.70; P = .03). Of the 22 patients (5%) who experienced bronchiolitis obliterans syndrome, 15 (6%) were in the azithromycin group and 7 (3%) in the placebo group (P = .08). The azithromycin group had increased mortality, with a 2-year survival of 56.6% (95% CI, 50.2%-63.7%) vs 70.1% (95% CI, 64.2%-76.5%) in the placebo group (unadjusted HR, 1.5; 95% CI, 1.1-2.0; P = .02). In a post hoc analysis, the 2-year cumulative incidence of hematological relapse was 33.5% (95% CI, 27.3%-39.7%) with azithromycin vs 22.3% (95% CI, 16.4%-28.2%) with placebo (unadjusted cause-specific HR, 1.7; 95% CI, 1.2-2.4; P = .002).
Conclusions and Relevance: Among patients undergoing allogeneic HSCT for hematological malignancy, early administration of azithromycin resulted in worse airflow decline-free survival than did placebo; these findings are limited by early trial termination. The potential for harm related to relapse requires further investigation.
Trial Registration: clinicaltrials.gov Identifier: NCT01959100.

PMID: 28787506 [PubMed - in process]

Technique and Outcomes of Less Invasive Lung Retransplantation.

Wed, 08/09/2017 - 12:45

Technique and Outcomes of Less Invasive Lung Retransplantation.

Transplantation. 2017 Aug 05;:

Authors: Sommer W, Ius F, Kühn C, Avsar M, Salman J, Siemeni T, Müller C, Schwerk N, Greer M, Gottlieb J, Welte T, Haverich A, Tudorache I, Warnecke G

Abstract
BACKGROUND: Lung retransplantation is a demanding procedure with outcomes lagging primary transplantation. We implemented less invasive surgical techniques aiming at improving early outcomes. Here, we wish to describe these techniques and analyze clinical outcomes.
METHODS: Since April 2010 a protocol of less invasive techniques was applied to all lung retransplantations. This protocol comprises bilateral lung retransplantation via sternum-sparing anterolateral thoracotomies, off-pump surgery, and empiric administration of 2 g fibrinogen and 2 platelet concentrates. Patient charts were retrospectively reviewed starting in April 2010 until May 2016 for this study and compared to a cohort of patients undergoing lung retransplantation between January 2005 and March 2010.
RESULTS: From April 2010 through March 2016, 774 total lung transplantations were performed at our center, 49 were retransplantations. In the era 01/2005-03/2010, a total of 480 lung transplantations were performed, of those being 38 retransplantations. Mean operation time in the era 04/2010-05/2016 was significantly longer as compared to the era 01/2005-03/2010, median time until extubation was significantly shorter in the era 04/2010-05/2016 (1(1-2) days vs. 11.5(1-24) days, p=0.0009). Similarly, median intensive care unit stay time was shorter in the era 04/2010-05/2016 (4(2-5.5) days vs. 12.5(3-30.5) days, p=0.003). Patient survival was significantly better in the era starting in April 2010 at 30 days (98% vs. 76.3%, p=0.002) as well as at 1-year (80.6% vs. 63.2%, p=0.01).
CONCLUSIONS: Less invasive retransplantation of the lung via sternum-sparing anterolateral thoracotomies and off-pump is a safe procedure with low associated morbidity and favorable mid-term survival.

PMID: 28787308 [PubMed - as supplied by publisher]

Pediatric lung transplantation and end of life care in cystic fibrosis: Barriers and successful strategies.

Wed, 08/09/2017 - 12:45

Pediatric lung transplantation and end of life care in cystic fibrosis: Barriers and successful strategies.

Pediatr Pulmonol. 2017 Aug 08;:

Authors: Dellon E, Goldfarb SB, Hayes D, Sawicki GS, Wolfe J, Boyer D

Abstract
Pediatric lung transplantation has advanced over the years, providing a potential life-prolonging therapy to patients with cystic fibrosis. Despite this, many challenges in lung transplantation remain and result in worse outcomes than other solid organ transplants. As CF lung disease progresses, children and their caregivers are often simultaneously preparing for lung transplantation and end of life. In this article, we will discuss the current barriers to success in pediatric CF lung transplantation as well as approaches to end of life care in this population.

PMID: 28786560 [PubMed - as supplied by publisher]

Bone marrow mesenchymal stem cells ameliorate lung injury through anti-inflammatory and antibacterial effect in COPD mice.

Wed, 08/09/2017 - 12:45
Related Articles

Bone marrow mesenchymal stem cells ameliorate lung injury through anti-inflammatory and antibacterial effect in COPD mice.

J Huazhong Univ Sci Technolog Med Sci. 2017 Aug;37(4):496-504

Authors: Liu HM, Liu YT, Zhang J, Ma LJ

Abstract
The anti-inflammatory and antibacterial mechanisms of bone marrow mesenchymal stem cells (MSCs) ameliorating lung injury in chronic obstructive pulmonary disease (COPD) mice induced by cigarette smoke and Haemophilus Parainfluenza (HPi) were studied. The experiment was divided into four groups in vivo: control group, COPD group, COPD+HPi group, and COPD+HPi+MSCs group. The indexes of emphysematous changes, inflammatory reaction and lung injury score, and antibacterial effects were evaluated in all groups. As compared with control group, emphysematous changes were significantly aggravated in COPD group, COPD+HPi group and COPD+HPi+MSCs group (P<0.01), the expression of necrosis factor-kappaB (NF-κB) signal pathway and proinflammatory cytokines in bronchoalveolar lavage fluid (BALF) were increased (P<0.01), and the phagocytic activity of alveolar macrophages was downregulated (P<0.01). As compared with COPD group, lung injury score, inflammatory cells and proinflammatory cytokines were significantly increased in the BALF of COPD+HPi group and COPD+HPi+MSCs group (P<0.01). As compared with COPD+HPi group, the expression of tumor necrosis factor-α stimulated protein/gene 6 (TSG-6) was increased, the NF-κB signal pathway was depressed, proinflammatory cytokine was significantly reduced, the anti-inflammatory cytokine IL-10 was increased, and lung injury score was significantly reduced in COPD+HPi+MSCs group. Meanwhile, the phagocytic activity of alveolar macrophages was significantly enhanced and bacterial counts in the lung were decreased. The results indicated cigarette smoke caused emphysematous changes in mice and the phagocytic activity of alveolar macrophages was decreased. The lung injury of acute exacerbation of COPD mice induced by cigarette smoke and HPi was alleviated through MSCs transplantation, which may be attributed to the fact that MSCs could promote macrophages into anti-inflammatory phenotype through secreting TSG-6, inhibit NF-кB signaling pathway, and reduce inflammatory response through reducing proinflammatory cytokines and promoting the expression of the anti-inflammatory cytokine. Simultaneously, MSCs could enhance phagocytic activity of macrophages and bacterial clearance. Meanwhile, we detected anti-inflammatory and antibacterial activity of macrophages regulated by MSCs in vitro. As compared with RAW264.7+HPi+CSE group, the expression of NF-кB p65, IL-1β, IL-6 and TNF-α was significantly reduced, and the phagocytic activity of macrophages was significantly increased in RAW264.7+HPi+CSE+MSCs group (P<0.01). The result indicated the macrophages co-cultured with MSCs may inhibit NF-кB signaling pathway and promote phagocytosis by paracrine mechanism.

PMID: 28786060 [PubMed - in process]

Epithelial Sodium Channel-α Mediates the Protective Effect of the TNF-Derived TIP Peptide in Pneumolysin-Induced Endothelial Barrier Dysfunction.

Wed, 08/09/2017 - 12:45
Related Articles

Epithelial Sodium Channel-α Mediates the Protective Effect of the TNF-Derived TIP Peptide in Pneumolysin-Induced Endothelial Barrier Dysfunction.

Front Immunol. 2017;8:842

Authors: Czikora I, Alli AA, Sridhar S, Matthay MA, Pillich H, Hudel M, Berisha B, Gorshkov B, Romero MJ, Gonzales J, Wu G, Huo Y, Su Y, Verin AD, Fulton D, Chakraborty T, Eaton DC, Lucas R

Abstract
BACKGROUND: Streptococcus pneumoniae is a major etiologic agent of bacterial pneumonia. Autolysis and antibiotic-mediated lysis of pneumococci induce release of the pore-forming toxin, pneumolysin (PLY), their major virulence factor, which is a prominent cause of acute lung injury. PLY inhibits alveolar liquid clearance and severely compromises alveolar-capillary barrier function, leading to permeability edema associated with pneumonia. As a consequence, alveolar flooding occurs, which can precipitate lethal hypoxemia by impairing gas exchange. The α subunit of the epithelial sodium channel (ENaC) is crucial for promoting Na(+) reabsorption across Na(+)-transporting epithelia. However, it is not known if human lung microvascular endothelial cells (HL-MVEC) also express ENaC-α and whether this subunit is involved in the regulation of their barrier function.
METHODS: The presence of α, β, and γ subunits of ENaC and protein phosphorylation status in HL-MVEC were assessed in western blotting. The role of ENaC-α in monolayer resistance of HL-MVEC was examined by depletion of this subunit by specific siRNA and by employing the TNF-derived TIP peptide, a specific activator that directly binds to ENaC-α.
RESULTS: HL-MVEC express all three subunits of ENaC, as well as acid-sensing ion channel 1a (ASIC1a), which has the capacity to form hybrid non-selective cation channels with ENaC-α. Both TIP peptide, which specifically binds to ENaC-α, and the specific ASIC1a activator MitTx significantly strengthened barrier function in PLY-treated HL-MVEC. ENaC-α depletion significantly increased sensitivity to PLY-induced hyperpermeability and in addition, blunted the protective effect of both the TIP peptide and MitTx, indicating an important role for ENaC-α and for hybrid NSC channels in barrier function of HL-MVEC. TIP peptide blunted PLY-induced phosphorylation of both calmodulin-dependent kinase II (CaMKII) and of its substrate, the actin-binding protein filamin A (FLN-A), requiring the expression of both ENaC-α and ASIC1a. Since non-phosphorylated FLN-A promotes ENaC channel open probability and blunts stress fiber formation, modulation of this activity represents an attractive target for the protective actions of ENaC-α in both barrier function and liquid clearance.
CONCLUSION: Our results in cultured endothelial cells demonstrate a previously unrecognized role for ENaC-α in strengthening capillary barrier function that may apply to the human lung. Strategies aiming to activate endothelial NSC channels that contain ENaC-α should be further investigated as a novel approach to improve barrier function in the capillary endothelium during pneumonia.

PMID: 28785264 [PubMed]

Catheter ablation of organized atrial arrhythmias in orthotopic heart transplantation.

Wed, 08/09/2017 - 12:45
Related Articles

Catheter ablation of organized atrial arrhythmias in orthotopic heart transplantation.

J Heart Lung Transplant. 2017 Jul 21;:

Authors: Mouhoub Y, Laredo M, Varnous S, Leprince P, Waintraub X, Gandjbakhch E, Hébert JL, Frank R, Maupain C, Pavie A, Hidden-Lucet F, Duthoit G

Abstract
BACKGROUND: Organized atrial arrhythmias (OAAs) are common after orthotopic heart transplantation (OHT). Some controversies remain about their clinical presentation, relationship with atrial anastomosis and electrophysiologic features. The objectives of this retrospective study were to determine the mechanisms of OAAs after OHT and describe the outcomes of radiofrequency catheter ablation (RFCA).
METHODS: Thirty consecutive transplanted patients (mean age 48 ± 17 years, 86.6% male) underwent 3-dimensional electroanatomic mapping and RFCA of their OAA from 2004 to 2012 at our center.
RESULTS: Twenty-two patients had biatrial anastomosis and 8 had bicaval anastomosis. Macro-reentry was the arrhythmia mechanism for 96% of patients. The electrophysiologic diagnoses were: cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL) in 93% of patients (n = 28); perimitral AFL in 3% (n = 1); and focal atrial tachycardia (FAT) in 3% (n = 1). In 5 patients with biatrial anastomosis, a right FAT was inducible. Primary RFCA success was obtained in 93% of patients. Mean follow-up time was 39 ± 26.8 months. Electrical repermeation between recipient and donor atria, present in 20% of patients (n = 6), did not account for any of the OAAs observed. Survival without OAA relapse at 12, 24 and 60 months was 93%, 89% and 79%, respectively.
CONCLUSIONS: CTI-dependent AFL accounted for most instances of OAA after OHT, regardless of anastomosis type. Time from transplantation to OAA was shorter with bicaval than with biatrial anastomosis. RFCA was safe and provided good long-term results.

PMID: 28784326 [PubMed - as supplied by publisher]

Report of the ISHLT Working Group on primary lung graft dysfunction Part IV: Prevention and treatment: A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation.

Wed, 08/09/2017 - 12:45
Related Articles

Report of the ISHLT Working Group on primary lung graft dysfunction Part IV: Prevention and treatment: A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation.

J Heart Lung Transplant. 2017 Jul 21;:

Authors: Van Raemdonck D, Hartwig MG, Hertz MI, Davis RD, Cypel M, Hayes D, Ivulich S, Kukreja J, Lease ED, Loor G, Mercier O, Paoletti L, Parmar J, Rampolla R, Wille K, Walia R, Keshavjee S

PMID: 28784325 [PubMed - as supplied by publisher]

The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Lung And Heart-Lung Transplantation Report-2017; Focus Theme: Allograft ischemic time.

Wed, 08/09/2017 - 12:45
Related Articles

The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Lung And Heart-Lung Transplantation Report-2017; Focus Theme: Allograft ischemic time.

J Heart Lung Transplant. 2017 Jul 19;:

Authors: Chambers DC, Yusen RD, Cherikh WS, Goldfarb SB, Kucheryavaya AY, Khusch K, Levvey BJ, Lund LH, Meiser B, Rossano JW, Stehlik J, International Society for Heart and Lung Transplantation

PMID: 28784324 [PubMed - as supplied by publisher]

Polymorphisms in genes related to the complement system and antibody-mediated cardiac allograft rejection.

Wed, 08/09/2017 - 12:45
Related Articles

Polymorphisms in genes related to the complement system and antibody-mediated cardiac allograft rejection.

J Heart Lung Transplant. 2017 Jul 15;:

Authors: Marrón-Liñares GM, Núñez L, Crespo-Leiro MG, Barge-Caballero E, Pombo J, Paniagua-Martin MJ, Suarez-Fuentetaja N, Cid J, Grille-Cancela Z, Muñiz-Garcia J, Tan CD, Rodríguez ER, Vázquez-Rodríguez JM, Hermida-Prieto M

Abstract
BACKGROUND: Heart transplantation (HT) is a life-saving treatment for patients with end-stage heart failure. One of the main problems after HT is the humoral response termed antibody-mediated rejection (AMR). Complement activation plays a key role in AMR contributing to graft damage. The aim of this study was to analyze genetic variants in genes related to the complement pathways that could be associated with the development of AMR.
METHODS: Analysis of 51 genes related to the complement pathway was performed by next-generation sequencing in 46 HT recipients, 23 with and 23 without AMR. Statistical analysis was performed with SNPstats and R.
RESULTS: We identified 2 single nucleotide polymorphisms, 1 in the mannose-binding lectin 2 gene (p.Gly54Asp-MBL2) and 1 in the complement factor properdin gene (p.Asn428(p=)-CFP), that showed significant association with the absence and development of AMR, respectively. Moreover, the presence of the rare allele in p.Gly54Asp-MBL2 control patients correlated with an immunodeficiency of mannose-binding lectin (6.24 ng/ml vs 207.50 ng/ml, p < 0.01), whereas the presence of the rare allele p.Asn428(p=)-CFP in patients with AMR correlated with higher levels of properdin protein (14.65 μg/ml vs 10.77 μg/ml, p < 0.05).
CONCLUSIONS: AMR is a complex phenotype affected by many recipient factors. Variants in p.Gly54Asp-MBL2 and p.Asn428(p=)-CFP genes, encoding mannose-binding lectin 2 and properdin, may influence the risk of AMR.

PMID: 28784323 [PubMed - as supplied by publisher]

Anesthesia for Lung Transplantation.

Wed, 08/09/2017 - 12:45
Related Articles

Anesthesia for Lung Transplantation.

Anesthesiol Clin. 2017 Sep;35(3):473-489

Authors: Nicoara A, Anderson-Dam J

Abstract
Perioperative management of patients undergoing lung transplantation is challenging and requires constant communication among the surgical, anesthesia, perfusion, and nursing teams. Although all aspects of anesthetic management are important, certain intraoperative strategies (mechanical ventilation, fluid management, extracorporeal mechanical support deployment) have tremendous impact on the subsequent evolution of the lung transplant recipient, especially with respect to allograft function, and should be carefully considered. This review highlights some of the intraoperative anesthetic challenges and opportunities during lung transplantation.

PMID: 28784221 [PubMed - in process]

Plasma and bronchoalveolar lavage samples in acute lung allograft rejection: the potential role of cytokines as diagnostic markers.

Wed, 08/09/2017 - 12:45
Related Articles

Plasma and bronchoalveolar lavage samples in acute lung allograft rejection: the potential role of cytokines as diagnostic markers.

Respir Res. 2017 Aug 07;18(1):151

Authors: Speck NE, Schuurmans MM, Benden C, Robinson CA, Huber LC

Abstract
The role of differential cytology patterns in peripheral blood and bronchoalveolar lavage samples is increasingly investigated as a potential adjunct to diagnose acute and chronic allograft dysfunction after lung transplantation. While these profiles might facilitate the diagnosis of acute cellular rejection, low sensitivity and specificity of these patterns limit direct translation in a clinical setting. In this context, the identification of other biomarkers is needed. This review article gives an overview of cytokine profiles of plasma and bronchoalveolar lavage samples during acute cellular rejection. The value of these cytokines in supporting the diagnosis of acute cellular rejection is discussed. Current findings on the topic are highlighted and experimental settings for future research projects are identified.

PMID: 28784117 [PubMed - in process]

Role of High-Dose Chemotherapy With Autologous Stem-Cell Rescue in Men With Previously Treated Germ Cell Tumors.

Wed, 08/09/2017 - 12:45
Related Articles

Role of High-Dose Chemotherapy With Autologous Stem-Cell Rescue in Men With Previously Treated Germ Cell Tumors.

J Clin Oncol. 2017 Apr 01;35(10):1036-1040

Authors: Pagliaro LC

Abstract
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 39-year-old, previously healthy man presented with a left testicular mass, confirmed on ultrasound. He underwent left inguinal orchiectomy, which disclosed testicular carcinoma composed of 90% choriocarcinoma, 9% seminoma, and 1% teratoma. Imaging revealed numerous metastases in the lungs, liver, and brain. Prechemotherapy levels of serum tumor markers were alpha-fetoprotein (AFP) 2.0 ng/mL, human chorionic gonadotropin (hCG) 151,111 IU/L, and lactate dehydrogenase 588 U/L. He received four courses of etoposide, ifosfamide, and cisplatin chemotherapy, given without bleomycin because of the anticipated need for postchemotherapy thoracic surgery. He had an incomplete response to induction chemotherapy. The serum hCG level was 8.1 IU/L, and there were residual lesions in the liver and lungs whereas the brain metastases had nearly resolved. His Eastern Cooperative Oncology Group performance status was zero. He had no symptoms of ototoxicity or peripheral neurotoxicity. Repeat serum hCG levels after chemotherapy were 12.3 IU/L at 2 weeks and 325 IU/L at 4 weeks. He was referred to discuss optimal ongoing treatment.

PMID: 27992270 [PubMed - indexed for MEDLINE]

Adoptive transfer of ex vivo expanded Vγ9Vδ2 T cells in combination with zoledronic acid inhibits cancer growth and limits osteolysis in a murine model of osteolytic breast cancer.

Wed, 08/09/2017 - 12:45
Related Articles

Adoptive transfer of ex vivo expanded Vγ9Vδ2 T cells in combination with zoledronic acid inhibits cancer growth and limits osteolysis in a murine model of osteolytic breast cancer.

Cancer Lett. 2017 Feb 01;386:141-150

Authors: Zysk A, DeNichilo MO, Panagopoulos V, Zinonos I, Liapis V, Hay S, Ingman W, Ponomarev V, Atkins G, Findlay D, Zannettino A, Evdokiou A

Abstract
Bone metastases occur in over 75% of patients with advanced breast cancer and are responsible for high levels of morbidity and mortality. In this study, ex vivo expanded cytotoxic Vγ9Vδ2 T cells isolated from human peripheral blood were tested for their anti-cancer efficacy in combination with zoledronic acid (ZOL), using a mouse model of osteolytic breast cancer. In vitro, expanded Vγ9Vδ2 T cells were cytotoxic against a panel of human breast cancer cell lines, and ZOL pre-treatment further sensitised breast cancer cells to killing by Vγ9Vδ2 T cells. Vγ9Vδ2 T cells adoptively transferred into NOD/SCID mice localised to osteolytic breast cancer lesions in the bone, and multiple infusions of Vγ9Vδ2 T cells reduced tumour growth in the bone. ZOL pre-treatment potentiated the anti-cancer efficacy of Vγ9Vδ2 T cells, with mice showing further reductions in tumour burden. Mice treated with the combination also had reduced tumour burden of secondary pulmonary metastases, and decreased bone degradation. Our data suggests that adoptive transfer of Vγ9Vδ2 T cell in combination with ZOL may prove an effective immunotherapeutic approach for the treatment of breast cancer bone metastases.

PMID: 27865798 [PubMed - indexed for MEDLINE]

Cancer pain relief achieved by disrupting tumor-driven semaphorin 3A signaling in mice.

Wed, 08/09/2017 - 12:45
Related Articles

Cancer pain relief achieved by disrupting tumor-driven semaphorin 3A signaling in mice.

Neurosci Lett. 2016 Oct 06;632:147-51

Authors: Maeda T, Yamada D, Kawahara K

Abstract
Cancer-induced bone pain (CIBP) is the most common pain arising from cancer and is inadequately managed with current standard therapeutics. While the etiology of CIBP remains to be fully elucidated, increasing evidence suggests that CIBP is uniquely complex. We tested whether semaphorin 3A (Sema3A) signals were involved in the development of CIBP in mice. The mouse model employed for CIBP - mice inoculated with Lewis lung carcinoma (LLC) cells injected into the femur intramedullary space - showed progressive decline in the weight bearing of the ipsilateral hind limb. The LLC cell inoculation resulted in a progressive increase in Sema3A mRNA expression over time and an increase in the number of Sema3A-immunoreactive cells in the ipsilateral femur. To define the role of Sema3A in development of CIBP, we employed a lentiviral expression system to establish a stable LLC cell line expressing scrambled shRNA for the control group (LLC/scramble) and shRNAs directed against Sema3A mRNA for the loss-of-function group (LLC/shSema3A). Inoculation of LLC/shSema3A did not cause upregulation of Sema3A mRNA expression and proliferation of the inoculated cells in the femur compared to that in mice inoculated with LLC/scramble. Mice inoculated with LLC/shSema3A, but not LLC/scramble, showed an attenuation of the significant decline in the weight bearing of the ipsilateral hind paw. Our findings indicate that Sema3A serves as a potential therapeutic target for CIBP.

PMID: 27592511 [PubMed - indexed for MEDLINE]

Extracellular ATP a New Player in Cancer Metabolism: NSCLC Cells Internalize ATP In Vitro and In Vivo Using Multiple Endocytic Mechanisms.

Wed, 08/09/2017 - 12:45
Related Articles

Extracellular ATP a New Player in Cancer Metabolism: NSCLC Cells Internalize ATP In Vitro and In Vivo Using Multiple Endocytic Mechanisms.

Mol Cancer Res. 2016 Nov;14(11):1087-1096

Authors: Qian Y, Wang X, Li Y, Cao Y, Chen X

Abstract
Intratumoral extracellular ATP concentrations are 1000 times higher than those in normal tissues of the same cell origin. However, whether or not cancer cells use the abundant extracellular ATP was unknown until we recently reported that cancer cells internalize ATP. The internalized ATP was found to substantially increase intracellular ATP concentration and promote cell proliferation and drug resistance in cancer cells. Here, using a nonhydrolyzable fluorescent ATP (NHF-ATP), radioactive and regular ATP, coupled with high and low molecular weight dextrans as endocytosis tracers and fluorescence microscopy and ATP assays, cultured human NSCLC A549 and H1299 cells as well as A549 tumor xenografts were found to internalize extracellular ATP at concentrations within the reported intratumoral extracellular ATP concentration range. In addition to macropinocytosis, both clathrin- and caveolae-mediated endocytosis significantly contribute to the ATP internalization, which led to an approximately 30% (within 45 minutes) or more than 50% (within 4 hours) increase in intracellular ATP levels after ATP incubation. This increase could not be accounted for by either purinergic receptor signaling or increased intracellular ATP synthesis rates in the ATP-treated cancer cells. These new findings significantly deepen our understanding of the Warburg effect by shedding light on how cancer cells in tumors, which are heterogeneous for oxygen and nutrition supplies, take up extracellular ATP and use the internalized ATP to perform multiple previously unrecognized functions of biological importance. They strongly suggest the existence of ATP sharing among cancer and stromal cells in tumors and simultaneously identify multiple new anticancer targets.
IMPLICATIONS: Extracellular ATP is taken up by human lung cancer cells and tumors via macropinocytosis and other endocytic processes to supplement their extra energy needs for cancer growth, survival, and drug resistance, thus providing novel targets for future cancer therapy. Mol Cancer Res; 14(11); 1087-96. ©2016 AACR.

PMID: 27578770 [PubMed - indexed for MEDLINE]

Pages