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Reverse cardiac remodelling after lung transplantation in Eisenmenger syndrome.

Sat, 06/10/2017 - 12:45
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Reverse cardiac remodelling after lung transplantation in Eisenmenger syndrome.

Acta Cardiol. 2017 Apr;72(2):230-231

Authors: Pavsic N, Salobir B, Prokselj K

PMID: 28597783 [PubMed - in process]

Improved metabolism and redox state with a novel preservation solution: implications for donor lungs after cardiac death (DCD).

Sat, 06/10/2017 - 12:45
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Improved metabolism and redox state with a novel preservation solution: implications for donor lungs after cardiac death (DCD).

Pulm Circ. 2017 Apr-Jun;7(2):494-504

Authors: Schipper DA, Louis AV, Dicken DS, Johnson K, Smolenski RT, Black SM, Runyan R, Konhilas J, Garcia JGN, Khalpey Z

Abstract
Lungs donated after cardiac death (DCD) are an underutilized resource for a dwindling donor lung transplant pool. Our study investigates the potential of a novel preservation solution, Somah, to better preserve statically stored DCD lungs, for an extended time period, when compared to low-potassium dextran solution (LPD). We hypothesize that Somah is a metabolically superior organ preservation solution for hypothermic statically stored porcine DCD lungs, possibly improving lung transplant outcomes. Porcine DCD lungs (n = 3 per group) were flushed with and submerged in cold preservation solution. The lungs were stored up to 12 h, and samples were taken from lung tissue and the preservation medium throughout. Metabolomic and redox potential were analyzed using high performance liquid chromatography, mass spectrometry, and RedoxSYS®, comparing substrate and pathway utilization in both preservation solutions. Glutathione reduction was seen in Somah but not in LPD during preservation. Carnitine, carnosine, and n-acetylcarnosine levels were elevated in the Somah medium compared with LPD throughout. Biopsies of Somah exposed lungs demonstrated similar trends after 2 h, up to 12 h. Adenosine gradually decreased in Somah medium over 12 h, but not in LPD. An inversely proportional increase in inosine was found in Somah. Higher oxidative stress levels were measured in LPD. Our study suggests suboptimal metabolic preservation in lungs stored in LPD. LPD had poor antioxidant potential, cytoprotection, and an insufficient redox potential. These findings may have immediate clinical implications for human organs; however, further investigation is needed to evaluate DCD lung preservation in Somah as a viable option for transplant.

PMID: 28597777 [PubMed - in process]

Right ventricular ST-elevation myocardial infarction as a cause of death in idiopathic pulmonary arterial hypertension.

Sat, 06/10/2017 - 12:45
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Right ventricular ST-elevation myocardial infarction as a cause of death in idiopathic pulmonary arterial hypertension.

Pulm Circ. 2017 Apr-Jun;7(2):555-558

Authors: Zhan Y, Burstein B, Abualsaud AO, Nosair M, Hirsch AM, Lesenko L, Langleben D

Abstract
A 32-year-old woman with advanced idiopathic pulmonary arterial hypertension (PAH), treated with oral tadalafil and intravenous epoprostenol, presented with typical angina pectoris of one day's duration. Her electrocardiogram, previously typical of pulmonary hypertension, revealed an acute ST-elevation myocardial infarction in the anterior precordial leads. She had a prior coronary angiogram, in preparation for lung transplantation, that revealed normal coronary arteries. Urgent coronary angiography showed acute occlusion of several acute marginal coronary branches that feed the right ventricle (RV). Coronary angioplasty and stenting was unable to adequately restore coronary perfusion. Despite support, she developed progressive cardiogenic shock and died three days later. This is an unusual complication of PAH.

PMID: 28597772 [PubMed - in process]

Longitudinal change in pulmonary arterial capacitance as an indicator of prognosis and response to therapy and in pulmonary arterial hypertension.

Sat, 06/10/2017 - 12:45
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Longitudinal change in pulmonary arterial capacitance as an indicator of prognosis and response to therapy and in pulmonary arterial hypertension.

Pulm Circ. 2017 Apr-Jun;7(2):399-408

Authors: Medrek SK, Kloefkorn C, Nguyen DTM, Graviss EA, Frost AE, Safdar Z

Abstract
Pulmonary arterial hypertension (PAH) is a chronic progressive disease that leads to right heart failure and death. Pulmonary arterial capacitance (PAC), defined as stroke volume divided by the pulmonary pulse pressure, has been identified as a prognostic factor in PAH. The impact of changes in PAC over time, however, is unclear. We evaluated changes in PAC over time to determine if such changes predicted transplant-free survival. A single-center retrospective study of consecutive group 1 PAH patients who had two or more right heart catheterizations (RHC) between January 2007 and June 2016 was undertaken. Hemodynamic data, clinical data, and outcomes were collected. Univariate and multivariate Cox proportional-hazards modelling to identify the contribution of risk factors for a composite outcome of death or lung transplantation was done. Mixed-effects logistic regression was performed to investigate the association between the change in PAC value over time and the composite outcome. A P value < 0.05 was considered significant. In total, 109 consecutive patients with a total of 300 RHC data were identified. PAC correlated inversely with functional status ( P < 0.001) and inversely with pulmonary vascular resistance ( P < 0.001). PAC values increased with the addition of new PAH-specific medications. Mixed effects logistic regression modeling using longitudinal data showed that a decrease in PAC over the study period was associated with increased mortality and transplantation (adjusted P = 0.039) over the study period. Change in PAC was a better predictor of outcome over the study period than baseline PAC or changes in other hemodynamic or clinical parameters. Decreases in PAC were predictive of increased mortality or transplantation in patients with group 1 PAH. There was a trend towards increased PAC in response to the addition of a PAH-specific medication. Our data support the use of PAC as a therapeutic target in PAH.

PMID: 28597758 [PubMed - in process]

[Early bilateral nephrectomy in neonatal autosomal recessive polycystic kidney disease : Improved prognosis or unnecessary effort?]

Sat, 06/10/2017 - 12:45
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[Early bilateral nephrectomy in neonatal autosomal recessive polycystic kidney disease : Improved prognosis or unnecessary effort?]

Urologe A. 2017 Jun 08;:

Authors: Riechardt S, Koch M, Oh J, Fisch M

Abstract
BACKGROUND: Neonatal autosomal recessive polycystic kidney disease (ARPKD) is associated with giant kidneys, lung hypoplasia, pulmonal hypertension, and end-stage renal failure. Depending on the study, mortality is reported to range between 20 and 80%.
OBJECTIVES: Does bilateral nephrectomy improve survival?
PATIENTS AND METHODS: Between 2010 and 2016, we treated 7 children with prenatally diagnosed ARPKD. All had a planned delivery by cesarean section. After birth, oscillated ventilation with nitrogen enrichment was initiated to achieve maximum oxygenation and to decrease pumonary hypertension. All children had bilateral massive kidney hyperplasia (length 13-16 cm).
RESULTS: Nephrectomy on one side was performed within 72 h together with placement of a peritoneal dialysis catheter in the intensive care unit. Contralateral nephrectomy was performed after 1-2 weeks when the child was stabilized by dialysis. In 2 children, kidney transplantation has already been performed and they are doing fine. One child died after 10 months due to infection. The other children are stable on home peritoneal dialysis awaiting transplantation.
CONCLUSIONS: Early bilateral nephrectomy in neonatal ARPKD is feasible, but requires distinctive care at a pediatric intensive care unit and a high amount of organizational efforts to treat these children adequately in the first few days. In our experience, the procedure is a promising approach to improve ventilation and enable dialysis. However, kidney transplantation, best from a living donor, is required within the first years of life.

PMID: 28597060 [PubMed - as supplied by publisher]

Invasive Mucormycosis Induced Pneumopericardium: A Rare Cause of Pneumopericardium in an Immunocompromised Patient.

Sat, 06/10/2017 - 12:45
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Invasive Mucormycosis Induced Pneumopericardium: A Rare Cause of Pneumopericardium in an Immunocompromised Patient.

Case Rep Infect Dis. 2017;2017:1424618

Authors: Khan S, Waqar Elahi M, Ullah W, Abdullah HMA, Ahmad E, Al Mohajer M, Majeed A

Abstract
Mucor and Rhizopus cause life-threatening infections primarily involving the lungs and sinuses, which disseminate very rapidly by necrosis and infarction of the contiguous tissues. We present a case of a 64-year-old African American posttransplant patient who presented with a productive cough and weight loss. He had a past surgical history of renal transplant for renal cell carcinoma and was on dual immunosuppressive therapy, that is, mycophenolate and tacrolimus. During his hospital stay, he developed a pneumopericardium due to the direct extension of a lung lesion. The diagnosis was made by radiological imaging and PCR result which was consistent with Mucor species. He was treated with antifungal therapy. The purpose of this report is to highlight the unusual association of mucormycosis with pneumopericardium.

PMID: 28596926 [PubMed]

Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research.

Sat, 06/10/2017 - 12:45
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Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research.

Eur Respir J. 2017 Jun;49(6):

Authors: Hill AT, Haworth CS, Aliberti S, Barker A, Blasi F, Boersma W, Chalmers JD, De Soyza A, Dimakou K, Elborn JS, Feldman C, Flume P, Goeminne PC, Loebinger MR, Menendez R, Morgan L, Murris M, Polverino E, Quittner A, Ringshausen FC, Tino G, Torres A, Vendrell M, Welte T, Wilson R, Wong C, O'Donnell A, Aksamit T, EMBARC/BRR definitions working group

Abstract
There is a need for a clear definition of exacerbations used in clinical trials in patients with bronchiectasis. An expert conference was convened to develop a consensus definition of an exacerbation for use in clinical research.A systematic review of exacerbation definitions used in clinical trials from January 2000 until December 2015 and involving adults with bronchiectasis was conducted. A Delphi process followed by a round-table meeting involving bronchiectasis experts was organised to reach a consensus definition. These experts came from Europe (representing the European Multicentre Bronchiectasis Research Collaboration), North America (representing the US Bronchiectasis Research Registry/COPD Foundation), Australasia and South Africa.The definition was unanimously approved by the working group as: a person with bronchiectasis with a deterioration in three or more of the following key symptoms for at least 48 h: cough; sputum volume and/or consistency; sputum purulence; breathlessness and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND a clinician determines that a change in bronchiectasis treatment is required.The working group proposes the use of this consensus-based definition for bronchiectasis exacerbation in future clinical research involving adults with bronchiectasis.

PMID: 28596426 [PubMed - in process]

Left Main Coronary Artery Compression in Patients With Pulmonary Arterial Hypertension and Angina.

Sat, 06/10/2017 - 12:45
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Left Main Coronary Artery Compression in Patients With Pulmonary Arterial Hypertension and Angina.

J Am Coll Cardiol. 2017 Jun 13;69(23):2808-2817

Authors: Galiè N, Saia F, Palazzini M, Manes A, Russo V, Bacchi Reggiani ML, Dall'Ara G, Monti E, Dardi F, Albini A, Rinaldi A, Gotti E, Taglieri N, Marrozzini C, Lovato L, Zompatori M, Marzocchi A

Abstract
BACKGROUND: Left main coronary artery (LMCA) compression is increasingly recognized as a cause of angina in pulmonary arterial hypertension (PAH).
OBJECTIVES: This study aimed to evaluate the prevalence of LMCA extrinsic compression from a dilated pulmonary artery (PA) in patients with PAH and angina or angina-like symptoms, determine the usefulness of screening with computed tomography coronary angiography (CTCA), and assess the safety and efficacy of percutaneous coronary interventions (PCIs).
METHODS: All patients with PAH and angina or angina-like symptoms attending the center between May 1, 2008, and December 31, 2013, underwent CTCA. Patients with confirmed LMCA stenosis on selective coronary angiography had PCI.
RESULTS: Of 765 patients with PAH, 121 had angina or angina-like symptoms. Ninety-four patients had abnormal CTCA based on the relationship between the PA and the LMCA and underwent selective coronary angiography. LMCA stenosis ≥50% was detected in 48 of the 94 patients. Forty-five patients underwent PCI with stenting, of whom 41 had sustained angina symptom relief. The 3 other patients had surgical PA reduction plasty. Nine months after PCI, 5 patients had LMCA restenosis and PCI was successfully repeated. The best predictor of LMCA stenosis ≥50% was a PA diameter ≥40 mm. Rates for death or double-lung transplant and the composite rates for death, double-lung transplant, or restenosis at 36 months were 5% and 30%, respectively.
CONCLUSIONS: The prevalence of LMCA compression in patients with PAH and angina is high. These results suggest that CTCA is indicated in patients with PAH and angina or angina-like symptoms. PCI was well tolerated, improved symptoms, and resulted in favorable long-term outcomes.

PMID: 28595696 [PubMed - in process]

CT-Based Local Distribution Metric Improves Characterization of COPD.

Fri, 06/09/2017 - 15:46
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CT-Based Local Distribution Metric Improves Characterization of COPD.

Sci Rep. 2017 Jun 07;7(1):2999

Authors: Hoff BA, Pompe E, Galbán S, Postma DS, Lammers JJ, Ten Hacken NHT, Koenderman L, Johnson TD, Verleden SE, de Jong PA, Hoesein FAAM, van den Berge M, Ross BD, Galbán CJ

Abstract
Parametric response mapping (PRM) of paired CT lung images has been shown to improve the phenotyping of COPD by allowing for the visualization and quantification of non-emphysematous air trapping component, referred to as functional small airways disease (fSAD). Although promising, large variability in the standard method for analyzing PRM(fSAD) has been observed. We postulate that representing the 3D PRM(fSAD) data as a single scalar quantity (relative volume of PRM(fSAD)) oversimplifies the original 3D data, limiting its potential to detect the subtle progression of COPD as well as varying subtypes. In this study, we propose a new approach to analyze PRM. Based on topological techniques, we generate 3D maps of local topological features from 3D PRM(fSAD) classification maps. We found that the surface area of fSAD (S(fSAD)) was the most robust and significant independent indicator of clinically meaningful measures of COPD. We also confirmed by micro-CT of human lung specimens that structural differences are associated with unique S(fSAD) patterns, and demonstrated longitudinal feature alterations occurred with worsening pulmonary function independent of an increase in disease extent. These findings suggest that our technique captures additional COPD characteristics, which may provide important opportunities for improved diagnosis of COPD patients.

PMID: 28592874 [PubMed - in process]

Immune checkpoint inhibitors and allogeneic hematopoietic stem cell transplantation.

Fri, 06/09/2017 - 15:46
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Immune checkpoint inhibitors and allogeneic hematopoietic stem cell transplantation.

Rinsho Ketsueki. 2017;58(5):506-513

Authors: Kondo E, Maeda Y

Abstract
Immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1 antibodies, have revolutionized cancer therapy, particularly in the treatment of malignant melanoma and lung cancer. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is another form of immunotherapy and is being widely used to cure high-risk hematological malignancies. However, more than one-third of patients suffer a relapse after allo-HCT and often have a poor prognosis. A phase I/Ib study to assess the safety and efficacy of ipilimumab (anti-CTLA-4 antibody) for the treatment of relapsed hematological malignancies after allo-HCT has shown that induction treatment with ipilimumab led to remissions in some patients, including those with myeloid malignancies, without eliciting severe graft versus host disease (GVHD). The efficacy of treatment with anti-PD-1 antibodies before or after allo-HCT has been reported in some case reports and in one retrospective study, but one case of fatal GVHD caused by anti-PD-1 antibody therapy after allo-HCT raises a concern. Considering that remission status after transplantation is a strong prognostic factor in allo-HCT, immune checkpoint inhibitors might work better during post-remission consolidation than during induction. Further studies on immune checkpoint inhibitors in the treatment of hematological malignancies are warranted.

PMID: 28592767 [PubMed - in process]

The Conundrum of Equitable Organ Allocation in Heart Transplantation: The Moving Target of Candidate Risk Score.

Thu, 06/08/2017 - 12:45
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The Conundrum of Equitable Organ Allocation in Heart Transplantation: The Moving Target of Candidate Risk Score.

Transplantation. 2017 Jun 06;:

Authors: Potena L, Khush KK

PMID: 28590947 [PubMed - as supplied by publisher]

Spontaneous pneumothorax in diffuse cystic lung diseases.

Thu, 06/08/2017 - 12:45
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Spontaneous pneumothorax in diffuse cystic lung diseases.

Curr Opin Pulm Med. 2017 Jul;23(4):323-333

Authors: Cooley J, Lee YCG, Gupta N

Abstract
PURPOSE OF REVIEW: Diffuse cystic lung diseases (DCLDs) are a heterogeneous group of disorders with varying pathophysiologic mechanisms that are characterized by the presence of air-filled lung cysts. These cysts are prone to rupture, leading to the development of recurrent spontaneous pneumothoraces. In this article, we review the epidemiology, clinical features, and management DCLD-associated spontaneous pneumothorax, with a focus on lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, and pulmonary Langerhans cell histiocytosis.
RECENT FINDINGS: DCLDs are responsible for approximately 10% of apparent primary spontaneous pneumothoraces. Computed tomography screening for DCLDs (Birt-Hogg-Dubé syndrome, lymphangioleiomyomatosis, and pulmonary Langerhans cell histiocytosis) following the first spontaneous pneumothorax has recently been shown to be cost-effective and can help facilitate early diagnosis of the underlying disorders. Patients with DCLD-associated spontaneous pneumothorax have a very high rate of recurrence, and thus pleurodesis should be considered following the first episode of spontaneous pneumothorax in these patients, rather than waiting for a recurrent episode. Prior pleurodesis is not a contraindication to future lung transplant.
SUMMARY: Although DCLDs are uncommon, spontaneous pneumothorax is often the sentinel event that provides an opportunity for diagnosis. By understanding the burden and implications of pneumothoraces in DCLDs, clinicians can facilitate early diagnosis and appropriate management of the underlying disorders.

PMID: 28590337 [PubMed - in process]

Elevated prostaglandin E2 post-bone marrow transplant mediates interleukin-1β-related lung injury.

Thu, 06/08/2017 - 12:45
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Elevated prostaglandin E2 post-bone marrow transplant mediates interleukin-1β-related lung injury.

Mucosal Immunol. 2017 Jun 07;:

Authors: Martínez-Colón GJ, Taylor QM, Wilke CA, Podsiad AB, Moore BB

Abstract
Hematopoietic stem cell transplant (HSCT) treats or cures a variety of hematological and inherited disorders. Unfortunately, patients who undergo HSCT are susceptible to infections by a wide array of opportunistic pathogens. Pseudomonas aeruginosa bacteria can have life-threatening effects in HSCT patients by causing lung pathology that has been linked to high levels of the potent pro-inflammatory cytokine, interleukin-1β (IL-1β). Using a murine bone marrow transplant (BMT) model, we show that overexpression of prostaglandin E2 (PGE2) post-BMT signals via EP2 or EP4 to induce cyclic adenosine monophosphate (cAMP), which activates protein kinase A or the exchange protein activated by cAMP (Epac) to induce cAMP response element binding-dependent transcription of IL-1β leading to exacerbated lung injury in BMT mice. Induction of IL-1β by PGE2 is time and dose dependent. Interestingly, IL-1β processing post-P. aeruginosa infection occurs via the enzymatic activity of either caspase-1 or caspase-8. Furthermore, PGE2 can limit autophagy-mediated killing of P. aeruginosa in alveolar macrophages, yet autophagy does not have a role in PGE2-mediated upregulation of IL-1β. Reducing PGE2 levels with indomethacin improved bacterial clearance and reduced IL-1β-mediated acute lung injury in P. aeruginosa-infected BMT mice.Mucosal Immunology advance online publication 7 June 2017; doi:10.1038/mi.2017.51.

PMID: 28589946 [PubMed - as supplied by publisher]

Renal cell carcinoma with inferior vena cava thrombus extending to the right atrium diagnosed during pregnancy.

Thu, 06/08/2017 - 12:45
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Renal cell carcinoma with inferior vena cava thrombus extending to the right atrium diagnosed during pregnancy.

Ther Adv Urol. 2017 Dec;9(6):155-159

Authors: Ghanney EC, Cavallo JA, Levin MA, Reddy R, Bander J, Mella M, Stone J, Schwartz M, Haines K, Gidwani U, Mehrazin R

Abstract
Only one case of renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus diagnosed and treated during pregnancy has been reported in the literature. In that report, the tumor thrombus extended to the infrahepatic IVC (level II tumor thrombus). In the present case, a 37-year-old woman with lupus anticoagulant antibodies was diagnosed with RCC and IVC tumor thrombus extending to the right atrium (level IV tumor thrombus) at 24 weeks of pregnancy. The fetus was safely delivered by cesarean section at 30 weeks of gestation. At 4 days later, an open right radical nephrectomy and IVC and right atrial thrombectomy were performed on cardiopulmonary bypass (CPB) once the patient's hemodynamic status had been optimized. Fetal and maternal concerns included the risk of a thromboembolic event (due to increased hypercoagulability from pregnancy, active malignancy, and lupus anticoagulant), intraoperative hemorrhage risk (due to extensive venous collaterals and anticoagulation), and fetal morbidity and mortality (due to fetal lung immaturity). Standardized guidelines for treatment of RCC with or without IVC tumor thrombus during pregnancy are unavailable due to the infrequency of such cases. Treatment decisions are therefore individualized and this case report may inform the management of future patients diagnosed with RCC with level IV tumor thrombus during pregnancy.

PMID: 28588653 [PubMed - in process]

Cytokine filtration modulates pulmonary metabolism and edema formation during ex vivo lung perfusion.

Thu, 06/08/2017 - 12:45
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Cytokine filtration modulates pulmonary metabolism and edema formation during ex vivo lung perfusion.

J Heart Lung Transplant. 2017 May 20;:

Authors: Iskender I, Cosgun T, Arni S, Trinkwitz M, Fehlings S, Yamada Y, Cesarovic N, Yu K, Frauenfelder T, Jungraithmayr W, Weder W, Inci I

Abstract
BACKGROUND: Ex vivo lung perfusion (EVLP) has improved the process of donor lung management. Cytokine accumulation during EVLP has been shown to correlate with worse outcome after lung transplantation. Our objective in this study was to test the safety and efficacy of cytokine filtration during EVLP in a large animal model.
METHODS: Pig donor lungs were preserved for 24 hours at 4°C, followed by 12 hours of EVLP, according to the Toronto protocol. The perfusate was continuously run through an absorbent device (CytoSorb) via a veno-venous shunt from the reservoir in the filter group. EVLP was performed according to the standard protocol in the control group (n = 5 each). EVLP physiology, lung X-ray, perfusate biochemistry, inflammatory response and microscopic injury were assessed.
RESULTS: Cytokine filtration significantly improved airway pressure and dynamic compliance during the 12-hour perfusion period. Lung X-rays acquired at the end of perfusion showed increased consolidation in the control group. Electrolyte imbalance, determined by increased hydrogen, potassium and calcium ion concentrations in the perfusate, was markedly worsened in the control group. Glucose consumption and lactate production were markedly reduced, along with the lactate/pyruvate ratio in the filter group. Cytokine expression profile, tissue myeloperoxidase activity and microscopic lung injury were significantly reduced in the filter group.
CONCLUSIONS: Continuous perfusate filtration through sorbent beads is effective and safe during prolonged EVLP. Cytokine removal decreased the development of pulmonary edema and electrolyte imbalance through the suppression of anaerobic glycolysis and neutrophil activation in this setting. Further studies are needed to test the beneficial effect of cytokine filtration on post-transplant lung function.

PMID: 28587802 [PubMed - as supplied by publisher]

Con: Extracorporeal Membrane Oxygenation Should Not Routinely Replace Cardiopulmonary Bypass As the Preferred Method of Support During Lung Transplantation.

Thu, 06/08/2017 - 12:45
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Con: Extracorporeal Membrane Oxygenation Should Not Routinely Replace Cardiopulmonary Bypass As the Preferred Method of Support During Lung Transplantation.

J Cardiothorac Vasc Anesth. 2017 Feb 20;:

Authors: Tong MZ

PMID: 28587759 [PubMed - as supplied by publisher]

Potential Number of Organ Donors After Euthanasia in Belgium.

Thu, 06/08/2017 - 12:45
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Potential Number of Organ Donors After Euthanasia in Belgium.

JAMA. 2017 04 11;317(14):1476-1477

Authors: Bollen J, van Smaalen T, Ten Hoopen R, van Heurn E, Ysebaert D, van Mook W

PMID: 28399240 [PubMed - indexed for MEDLINE]

Clinical mutational profiling of 1006 lung cancers by next generation sequencing.

Wed, 06/07/2017 - 12:45

Clinical mutational profiling of 1006 lung cancers by next generation sequencing.

Oncotarget. 2017 May 20;:

Authors: Illei PB, Belchis D, Tseng LH, Nguyen D, De Marchi F, Haley L, Riel S, Beierl K, Zheng G, Brahmer JR, Askin FB, Gocke CD, Eshleman JR, Forde PM, Lin MT

Abstract
Analysis of lung adenocarcinomas for actionable mutations has become standard of care. Here, we report our experience using next generation sequencing (NGS) to examine AKT1, BRAF, EGFR, ERBB2, KRAS, NRAS, and PIK3CA genes in 1006 non-small cell lung cancers in a clinical diagnostic setting. NGS demonstrated high sensitivity. Among 760 mutations detected, the variant allele frequency (VAF) was 2-5% in 33 (4.3%) mutations and 2-10% in 101 (13%) mutations. A single bioinformatics pipeline using Torrent Variant Caller, however, missed a variety of EGFR mutations. Mutations were detected in KRAS (36% of tumors), EGFR (19%) including 8 (0.8%) within the extracellular domain (4 at codons 108 and 4 at codon 289), BRAF (6.3%), and PIK3CA (3.7%). With a broader reportable range, exon 19 deletion and p.L858R accounted for only 36% and 26% of EGFR mutations and p.V600E accounted for only 24% of BRAF mutations. NGS provided accurate sequencing of complex mutations seen in 19% of EGFR exon 19 deletion mutations. Doublet (compound) EGFR mutations were observed in 29 (16%) of 187 EGFR-mutated tumors, including 69% with two non-p.L858R missense mutations and 24% with p.L858 and non-p.L858R missense mutations. Concordant VAFs suggests doublet EGFR mutations were present in a dominant clone and cooperated in oncogenesis. Mutants with predicted impaired kinase, observed in 25% of BRAF-mutated tumors, were associated with a higher incidence of concomitant activating KRAS mutations. NGS demonstrates high analytic sensitivity, broad reportable range, quantitative VAF measurement, single molecule sequencing to resolve complex deletion mutations, and simultaneous detection of concomitant mutations.

PMID: 28586760 [PubMed - as supplied by publisher]

Mesenchymal stem cells in idiopathic pulmonary fibrosis.

Wed, 06/07/2017 - 12:45

Mesenchymal stem cells in idiopathic pulmonary fibrosis.

Oncotarget. 2017 May 23;:

Authors: Li X, Yue S, Luo Z

Abstract
Idiopathic pulmonary fibrosis (IPF) is a major cause of respiratory failure in critically ill patients and common outcome of various lung interstitial diseases. Its mortality remains high, and no effective pharmacotherapy, in addition to artificial ventilation and transplantation, exists. As such, the administration of mesenchymal stem or stromal cells (MSCs) is currently investigated as a new therapeutic method for pulmonary fibrosis. Clinical trials on MSC-based therapy as a potential treatment for lung injury and fibrosis are also performed. MSCs can migrate to injured sites and secrete multiple paracrine factors and then regulate endothelial and epithelial permeability, decrease inflammation, enhance tissue repair, and inhibit bacterial growth. In this review, recent studies on stem cells, particularly MSCs, involved in alleviating lung inflammation and fibrosis and their potential MSC-induced mechanisms, including migration and differentiation, soluble factor and extracellular vesicle secretion, and endogenous regulatory functions, were summarized.

PMID: 28586311 [PubMed - as supplied by publisher]

Locating the Level and Extent of Congenital High Airway Obstruction: Fluid in the Airway Tract as Reference Points.

Wed, 06/07/2017 - 12:45

Locating the Level and Extent of Congenital High Airway Obstruction: Fluid in the Airway Tract as Reference Points.

J Ultrasound Med. 2017 Jun 06;:

Authors: Gowda M, Gupta S, Ali A, Paranthaman S

Abstract
Described here are a series of four cases of congenital high airway obstruction in the fetus. All of the patients presented in the second trimester and all had hydrops fetalis. Three cases had bilateral hyperinflated lungs, midline shift of heart, flattening or inversion of the diaphragm, and fetal ascites. Autopsy was performed in one of these three and showed laryngeal atresia. In one fetus, there was only a unilateral huge enlargement of the lung with mediastinal shift. On autopsy, this fetus had atresia of right main bronchus. All parents had terminated the pregnancy following the prenatal diagnosis. Laryngeal atresia is an extremely rare fetal anomaly with dismal prognosis. It is important to differentiate the condition from other lesions with a more favorable prognosis, such as congenital adenomatoid malformation of the lung. Much research is needed in the future to explore the therapeutic options, including fetoscopic intervention or transplantation of stem cell-derived airways.

PMID: 28586146 [PubMed - as supplied by publisher]

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