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Clamshell Closure With Absorbable Sternal Pins in Lung Transplant Recipients.

Mon, 07/24/2017 - 12:45
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Clamshell Closure With Absorbable Sternal Pins in Lung Transplant Recipients.

Ann Thorac Surg. 2017 Aug;104(2):e207-e209

Authors: Olland A, Reeb J, Guinard S, Seitlinger J, Santelmo N, Kessler R, Falcoz PE, Massard G

Abstract
Clamshell (bilateral anterolateral thoracotomy combined to transverse sternotomy) is an invasive surgical approach that is helpful in particular situations, especially bilateral lung transplantation. The closure technique remains challenging because clamshell incision can end with override, separation, or sternal pseudarthrosis complications. We describe the use of new absorbable sternal pins to stabilize the sternal closure and to help avoid additional sternal complications.

PMID: 28734456 [PubMed - in process]

Successful Lung Transplantation Using a Deceased Donor Mechanically Ventilated for Ten Months.

Mon, 07/24/2017 - 12:45
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Successful Lung Transplantation Using a Deceased Donor Mechanically Ventilated for Ten Months.

Ann Thorac Surg. 2017 Aug;104(2):e177-e179

Authors: Tanaka S, Miyoshi K, Sugimoto S, Yamane M, Kobayashi M, Oto T

Abstract
A successful outcome after lung transplant was achieved using lungs donated from a teenage boy who underwent prolonged mechanical ventilation. The donor experienced hypoxic brain damage and was declared brain dead 324 days after tracheal intubation. At the time of referral, the donor's lungs revealed diffuse radiologic infiltration and atelectasis but excellent function, with a PaO2/FiO2 ratio of 450. The lungs were transplanted to a 10-year-old girl with bronchiolitis obliterans. She developed grade 2 primary graft dysfunction, but recovered quickly. She is doing well and has not experienced any other critical adverse events 12 months after lung transplantation.

PMID: 28734446 [PubMed - in process]

Current approaches to the management of idiopathic pulmonary fibrosis.

Mon, 07/24/2017 - 06:46
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Current approaches to the management of idiopathic pulmonary fibrosis.

Respir Med. 2017 Aug;129:24-30

Authors: Raghu G, Richeldi L

Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease associated with dyspnoea, cough and impaired quality of life. Currently, the aims of patient care are to improve outcomes for patients by slowing the progression of the disease, extending life, and improving quality of life. A prompt, accurate diagnosis is important to enable patients to receive treatment early in the course of the disease and to be considered for lung transplantation. Two anti-fibrotic drugs, nintedanib and pirfenidone, have been shown to reduce decline in lung function in patients with IPF. In addition to pharmacological therapy, optimal management of IPF includes treatment of comorbidities, symptom relief, pulmonary rehabilitation, and palliative care. Patient education is important to enable patients to make decisions about their care and to help them manage their disease and the side-effects of anti-fibrotic drugs. Research continues into new treatments and combinations of treatments that may improve outcomes for patients with this devastating disease.

PMID: 28732832 [PubMed - in process]

Heterogeneity of lung disease associated with NK2 homeobox 1 mutations.

Mon, 07/24/2017 - 06:46
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Heterogeneity of lung disease associated with NK2 homeobox 1 mutations.

Respir Med. 2017 Aug;129:16-23

Authors: Nattes E, Lejeune S, Carsin A, Borie R, Gibertini I, Balinotti J, Nathan N, Marchand-Adam S, Thumerelle C, Fauroux B, Bosdure E, Houdouin V, Delestrain C, Louha M, Couderc R, De Becdelievre A, Fanen P, Funalot B, Crestani B, Deschildre A, Dubus JC, Epaud R

Abstract
We retrospectively studied the clinical presentation, treatment modalities and outcome in 16 patients with heterozygous NKX2-1 mutation associated with chronic lung disease. Twelve different NKX2-1 mutations, including 4 novel mutations, were identified in the 16 patients. Nine patients presented with brain-lung-thyroid syndrome, 3 had neurological and lung symptoms and 4 had only pulmonary symptoms. Ten patients had neonatal respiratory distress, and 6 of them developed infiltrative lung disease (ILD). The other patients were diagnosed with ILD in childhood (n = 3) or in adulthood (n = 3). The median age at diagnosis was 36 months (IQ 3.5-95). Patient testing included HRCT (n = 13), BALF analysis (n = 6), lung biopsies (n = 3) and lung function tests (n = 6). Six patients required supplemental oxygen support with a median duration of 18 months (IQ 2.5-29). All symptomatic ILD patients (n = 12) benefited from a treatment consisting of steroids, azithromycin (n = 9), and/or hydroxychloroquine (n = 4). The median follow-up was 36 months (IQ 24-71.5). One patient died of respiratory failure at 18 months and another is waiting for lung transplantation. In summary, the initial diagnosis was based on clinical presentation and radiological features, but the presentation was heterogeneous. Definitive diagnosis required genetic analysis, which should be performed, even in absence of neurological or thyroid symptoms.

PMID: 28732825 [PubMed - in process]

Prognostic Factors in Lung Transplantation after Hematopoietic Stem Cell Transplantation.

Sat, 07/22/2017 - 12:45

Prognostic Factors in Lung Transplantation after Hematopoietic Stem Cell Transplantation.

Transplantation. 2017 Jul 21;:

Authors: Chen-Yoshikawa TF, Sugimoto S, Shiraishi T, Minami M, Matsuda Y, Chida M, Maeda S, Aoyama A, Okada Y, Okumura M, Iwasaki A, Miyoshi S, Oto T, Date H

Abstract
BACKGROUND: Lung transplantation is the final life-saving option for patients with pulmonary complications after hematopoietic stem cell transplantation (HSCT). Patients undergoing HSCT for hematologic diseases are thought to be high-risk candidates for lung transplantation; therefore, few lung transplants are performed for these patients, and few studies have been reported. This study aimed to describe the characteristics and outcomes of lung transplantation in patients with pulmonary complications after HSCT.
METHODS: We retrospectively investigated 62 patients who underwent lung transplantation after HSCT. All data were collected from 6 lung transplant centers in Japan.
RESULTS: Seventeen patients underwent cadaveric lung transplantation, whereas 45 underwent living-donor lobar lung transplantation (LDLLT). In the LDLLT group, 18 patients underwent LDLLT after HSCT in which 1 of the donors had also served as a donor for HSCT. Seven patients underwent single LDLLT for which the donor was the same as the patient from whom stem cells were obtained for HSCT. Preoperative hypercapnia was observed in 52 patients (84%). Thirteen patients (21%) required mechanical ventilation preoperatively. Fifty-five patients underwent HSCT for hematologic malignancies, and 4 (7%) relapsed after lung transplantation. The 5-year survival rate was 64.2%. In a multivariable analysis, patients younger than 45 years and those with the same donor for both procedures exhibited significantly better survival (p = 0.012 and 0.041, respectively).
CONCLUSIONS: Lung transplantation for pulmonary complications after HSCT was performed safely and yielded better survival, especially in younger recipients for whom both lung transplantation and HSCT involved the same donor.

PMID: 28731908 [PubMed - as supplied by publisher]

PD-1 expression on CD8(+) T cells regulates their differentiation within lung allografts and is critical for tolerance induction.

Sat, 07/22/2017 - 12:45
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PD-1 expression on CD8(+) T cells regulates their differentiation within lung allografts and is critical for tolerance induction.

Am J Transplant. 2017 Jul 20;:

Authors: Takahashi T, Hsiao HM, Tanaka S, Li W, Higashikubo R, Scozzi D, Bharat A, Ritter JH, Krupnick AS, Gelman AE, Kreisel D

Abstract
Immunological requirements for rejection and tolerance induction differ between various organs. While memory CD8(+) T cells are considered a barrier to immunosuppression-mediated acceptance of most tissues and organs, tolerance induction after lung transplantation is critically dependent on central memory CD8(+) T lymphocytes. Here we demonstrate that costimulation blockade-mediated tolerance after lung transplantation is dependent on PD-1 expression on CD8(+) T cells. In the absence of PD-1 expression, CD8(+) T cells form prolonged interactions with graft-infiltrating CD11c(+) cells, their differentiation is skewed towards an effector memory phenotype and grafts are rejected acutely. These findings extend the notion that requirements for tolerance induction after lung transplantation differ from other organs. Thus, immunosuppressive strategies for lung transplant recipients need to be tailored based on the unique immunological properties of this organ. This article is protected by copyright. All rights reserved.

PMID: 28730633 [PubMed - as supplied by publisher]

Bedside selection of positive end-expiratory pressure by electrical impedance tomography in hypoxemic patients: a feasibility study.

Sat, 07/22/2017 - 12:45
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Bedside selection of positive end-expiratory pressure by electrical impedance tomography in hypoxemic patients: a feasibility study.

Ann Intensive Care. 2017 Dec;7(1):76

Authors: Eronia N, Mauri T, Maffezzini E, Gatti S, Bronco A, Alban L, Binda F, Sasso T, Marenghi C, Grasselli G, Foti G, Pesenti A, Bellani G

Abstract
BACKGROUND: Positive end-expiratory pressure (PEEP) is a key element of mechanical ventilation. It should optimize recruitment, without causing excessive overdistension, but controversy exists on the best method to set it. The purpose of the study was to test the feasibility of setting PEEP with electrical impedance tomography in order to prevent lung de-recruitment following a recruitment maneuver. We enrolled 16 patients undergoing mechanical ventilation with PaO2/FiO2 <300 mmHg. In all patients, under constant tidal volume (6-8 ml/kg) PEEP was set based on the PEEP/FiO2 table proposed by the ARDS network (PEEPARDSnet). We performed a recruitment maneuver and monitored the end-expiratory lung impedance (EELI) over 10 min. If the EELI signal decreased during this period, the recruitment maneuver was repeated and PEEP increased by 2 cmH2O. This procedure was repeated until the EELI maintained a stability over time (PEEPEIT).
RESULTS: The procedure was feasible in 87% patients. PEEPEIT was higher than PEEPARDSnet (13 ± 3 vs. 9 ± 2 cmH2O, p < 0.001). PaO2/FiO2 improved during PEEPEIT and driving pressure decreased. Recruited volume correlated with the decrease in driving pressure but not with oxygenation improvement. Finally, regional alveolar hyperdistention and collapse was reduced in dependent lung layers and increased in non-dependent lung layers.
CONCLUSIONS: In hypoxemic patients, a PEEP selection strategy aimed at stabilizing alveolar recruitment guided by EIT at the bedside was feasible and safe. This strategy led, in comparison with the ARDSnet table, to higher PEEP, improved oxygenation and reduced driving pressure, allowing to estimate the relative weight of overdistension and recruitment.

PMID: 28730554 [PubMed]

Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung.

Sat, 07/22/2017 - 12:45
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Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung.

J Allergy Clin Immunol. 2017 Jul 17;:

Authors: Mouraux S, Bernasconi E, Pattaroni C, Koutsokera A, Aubert JD, Claustre J, Pison C, Royer PJ, Magnan A, Kessler R, Benden C, Soccal PM, Marsland BJ, Nicod LP, SysCLAD Consortium

Abstract
BACKGROUND: Homeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by Chronic Lung Allograft Dysfunction (CLAD), an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling.
OBJECTIVE: To assess whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling post-transplantation.
METHODS: Microbiota DNA and host total RNA were isolated from 189 bronchoalveolar lavages obtained from 116 patients post-lung transplantation. Expression of a set of 11 genes encoding either matrix components, or factors involved in matrix synthesis or degradation (anabolic and catabolic remodeling, respectively), was quantified by real-time quantitative PCR. Microbiota composition was characterized using 16S ribosomal RNA gene sequencing and culture.
RESULTS: We identified four host gene expression profiles, amongst which catabolic remodeling, associated with high expression of metallopeptidase-7, -9, and -12, diverged from anabolic remodeling linked to maximal thrombospondin and platelet-derived growth factor D expression. While catabolic remodeling aligned with a microbiota dominated by pro-inflammatory bacteria (e.g. Staphylococcus, Pseudomonas and Corynebacterium), anabolic remodeling was linked to typical members of the healthy steady state (e.g. Prevotella, Streptococcus and Veillonella). Mechanistic assays provided direct evidence that these bacteria can impact upon host macrophage-fibroblast activation and matrix deposition.
CONCLUSION: Host-microbes interplay potentially determines remodeling activities in the transplanted lung highlighting new therapeutic opportunities to ultimately improve long-term lung transplant outcome.

PMID: 28729000 [PubMed - as supplied by publisher]

Role of Intrinsic Factors in the Growth of Transplanted Organs Following Transplantation.

Fri, 07/21/2017 - 12:45
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Role of Intrinsic Factors in the Growth of Transplanted Organs Following Transplantation.

J Immunobiol. 2017 Jun;2(2):

Authors: Shah JA, Tanabe T, Yamada K

Abstract
Shortages in the availability of transplantable organs have forced the transplant community to seek alternative methods to increase the supply of available organs. In our recent study following α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidney xenotransplantation, we found that certain recipients developed increased serum creatinine, possibly due to the rapid growth of orthotopic pig grafts in smaller baboon recipients. To test our hypothesis, we assessed whether the growth of outbred (Yorkshire) organ transplants (kidney and lung) in miniature swine was regulated by intrinsic (graft) factors. Yorkshire kidneys reached 3.7× their initial volume over 3 months vs. 1.2× for miniature swine kidneys over a similar time period. A similar pattern was seen in porcine lung allografts as well. Following xenotransplantation, a review of our results suggests that there is a threshold for kidney graft volume of 25 cm(3)/kg of recipient body weight at which cortical ischemia is induced in transplanted GalT-KO kidneys in baboons. These results suggest that intrinsic factors are in part responsible for the growth of donor organs and this should be taken into consideration for growth-curve-mismatched transplants.

PMID: 28725880 [PubMed]

Sustained benefit from combined plasmapheresis and allogeneic mesenchymal stem cells transplantation therapy in systemic sclerosis.

Fri, 07/21/2017 - 12:45
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Sustained benefit from combined plasmapheresis and allogeneic mesenchymal stem cells transplantation therapy in systemic sclerosis.

Arthritis Res Ther. 2017 Jul 19;19(1):165

Authors: Zhang H, Liang J, Tang X, Wang D, Feng X, Wang F, Hua B, Wang H, Sun L

Abstract
BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease involving the skin and several internal organs. Most therapies available for this disease are symptomatic. Given the difficulty in treating SSc, we conducted this study to investigate the effect of combined plasmapheresis (PE) and allogeneic mesenchymal stem cells transplantation (MSCT) therapy on SSc.
METHODS: Fourteen patients underwent three repeated PE treatments with subsequent pulse cyclophosphamide on days 1, 3 and 5. Patients received a single MSCT (1 × 10(6) cells/kg of body weight) on day 8. During follow up, evaluations performed included complete physical examination, serologic testing, and organ function.
RESULTS: The mean modified Rodnan skin score (MRSS) improved from 20.1 ± 3.1 to 13.8 ± 10.2 (P < 0.001) at 12 months of follow up. Three patients had interstitial lung disease, all had improvement of lung function and improved computed tomography (CT) images after 12 months of combined therapy. This combined treatment also significantly decreased the anti-Scl70 autoantibody titer and serum transforming growth factor-β and vascular endothelial growth factor levels during follow up.
CONCLUSION: The results indicate that PE combined with MSCT is a feasible treatment associated with possible clinical benefit for SSc patients.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT00962923 . Registered on 19 August 2009.

PMID: 28724445 [PubMed - in process]

Hepatitis E Virus-Associated Meningoencephalitis in a Lung Transplant Recipient Diagnosed by Clinical Metagenomic Sequencing.

Thu, 07/20/2017 - 10:01
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Hepatitis E Virus-Associated Meningoencephalitis in a Lung Transplant Recipient Diagnosed by Clinical Metagenomic Sequencing.

Open Forum Infect Dis. 2017;4(3):ofx121

Authors: Murkey JA, Chew KW, Carlson M, Shannon CL, Sirohi D, Sample HA, Wilson MR, Vespa P, Humphries RM, Miller S, Klausner JD, Chiu CY

Abstract
Hepatitis E virus (HEV) infection uncommonly causes chronic hepatitis and neurologic disease. We describe a case of genotype 3a HEV meningoencephalitis diagnosed by metagenomic next-generation sequencing, illustrating the power of an unbiased molecular approach to microbial testing and the first reported case of HEV infection presumably acquired through lung transplantation.

PMID: 28721353 [PubMed]

Intracellular interactions of umeclidinium and vilanterol in human airway smooth muscle.

Thu, 07/20/2017 - 10:01
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Intracellular interactions of umeclidinium and vilanterol in human airway smooth muscle.

Int J Chron Obstruct Pulmon Dis. 2017;12:1903-1913

Authors: Shaikh N, Johnson M, Hall DA, Chung KF, Riley JH, Worsley S, Bhavsar PK

Abstract
BACKGROUND: Intracellular mechanisms of action of umeclidinium (UMEC), a long-acting muscarinic receptor antagonist, and vilanterol (VI), a long-acting β2-adrenoceptor (β2R) agonist, were investigated in target cells: human airway smooth-muscle cells (ASMCs).
MATERIALS AND METHODS: ASMCs from tracheas of healthy lung-transplant donors were treated with VI, UMEC, UMEC and VI combined, or control compounds (salmeterol, propranolol, ICI 118.551, or methacholine [MCh]). Cyclic adenosine monophosphate (cAMP) was measured using an enzyme-linked immunosorbent assay, intracellular free calcium ([Ca(2+)]i) using a fluorescence assay, and regulator of G-protein signaling 2 (RGS2) messenger RNA using real-time quantitative polymerase chain reaction.
RESULTS: VI and salmeterol (10(-12)-10(-6) M) induced cAMP production from ASMCs in a concentration-dependent manner, which was greater for VI at all concentrations. β2R antagonism by propranolol or ICI 118.551 (10(-12)-10(-4) M) resulted in concentration-dependent inhibition of VI-induced cAMP production, and ICI 118.551 was more potent. MCh (5×10(-6) M, 30 minutes) attenuated VI-induced cAMP production (P<0.05), whereas pretreatment with UMEC (10(-8) M, 1 hour) restored the magnitude of VI-induced cAMP production. ASMC stimulation with MCh (10(-11)-5×10(-6) M) resulted in a concentration-dependent increase in [Ca(2+)]i, which was attenuated with UMEC pretreatment. Reduction of MCh-induced [Ca(2+)]i release was greater with UMEC + VI versus UMEC. UMEC enhanced VI-induced RGS2 messenger RNA expression.
CONCLUSION: These data indicate that UMEC reverses cholinergic inhibition of VI-induced cAMP production, and is a more potent muscarinic receptor antagonist when in combination with VI versus either alone.

PMID: 28721035 [PubMed - in process]

Professor Christian Cabrol (1925 to 2017).

Thu, 07/20/2017 - 10:01
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Professor Christian Cabrol (1925 to 2017).

J Heart Lung Transplant. 2017 Jul 08;:

Authors: Copeland J

PMID: 28720213 [PubMed - as supplied by publisher]

Changing the curve in chronic lung allograft dysfunction: Implications of chronic lung allograft dysfunction phenotypes in assessing treatment interventions.

Thu, 07/20/2017 - 10:01
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Changing the curve in chronic lung allograft dysfunction: Implications of chronic lung allograft dysfunction phenotypes in assessing treatment interventions.

J Heart Lung Transplant. 2017 May 29;:

Authors: Mooney JJ

PMID: 28720212 [PubMed - as supplied by publisher]

Analysis of long term CD4+CD25highCD127- T-reg cells kinetics in peripheral blood of lung transplant recipients.

Thu, 07/20/2017 - 10:01
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Analysis of long term CD4+CD25highCD127- T-reg cells kinetics in peripheral blood of lung transplant recipients.

BMC Pulm Med. 2017 Jul 18;17(1):102

Authors: Piloni D, Morosini M, Magni S, Balderacchi A, Scudeller L, Cova E, Oggionni T, Stella G, Tinelli C, Antonacci F, D'Armini AM, Meloni F

Abstract
BACKGROUND: The role of CD4(+)CD25(high)CD127(-) T-reg cells in solid-organ Transplant (Tx) acceptance has been extensively studied. In previous studies on kidney and liver recipients, peripheral T-reg cell counts were associated to graft survival, while in lung Tx, there is limited evidence for similar findings. This study aims to analyze long term peripheral kinetics of T-reg-cells in a cohort of lung recipients and tests its association to several clinical variables.
METHODS: From jan 2009 to dec 2014, 137 lung Tx recipients were submitted to an immunological follow up (median: 105.9 months (6.7-310.5)). Immunological follow up consisted of a complete blood peripheral immuno-phenotype, inclusive of CD4(+)CD25(high)CD127(-) T and FOXP3+ cells. We tested the association between T-reg and relevant variables by linear OR regression models for repeated measures, adjusting for time from Tx. Also, by ordered logistic models for panel data, the association between Chronic Lung Allograft Dysfuncton (CLAD) onset/progression and T-reg counts in the previous 3 months was tested.
RESULTS: Among all variables analyzed at multivariate analysis: Bronchiolitis Obliterans Syndrome (OR -6.51, p < 0.001), Restrictive Allograft Syndrome (OR -5.19, p = 0.04) and Extracorporeal photopheresis (OR -5.65, p < 0.001) were significantly associated to T-reg cell. T-reg cell counts progressively decreased according to the severity of CLAD. Furthermore, patients with higher mean T-reg counts in a trimester had a significantly lower risk (OR 0.97, p = 0.012) of presenting CLAD or progressing in the graft dysfunction in the following trimester.
CONCLUSIONS: Our present data confirm animal observations on the possible role of T-reg in the evolution of CLAD.

PMID: 28720146 [PubMed - in process]

Intratracheal instillation of neutrophils rescues bacterial overgrowth initiated by trauma damage-associated molecular patterns.

Thu, 07/20/2017 - 10:01
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Intratracheal instillation of neutrophils rescues bacterial overgrowth initiated by trauma damage-associated molecular patterns.

J Trauma Acute Care Surg. 2017 May;82(5):853-860

Authors: Itagaki K, Riça I, Zhang J, Gallo D, DePrato M, Otterbein LE, Hauser CJ

Abstract
BACKGROUND: Nosocomial pneumonias are common in trauma patients and so interventions to prevent and treat nosocomial pneumonia may improve outcomes. Our prior work strongly suggests that tissue injury predisposes to infections like nosocomial pneumonia because mitochondrial debris originating from injured cells contains damage-associated molecular patterns that can reduce neutrophil (PMN) migration into the airway and diminish PMN function in response to bacterial inoculation of the airway. This suggested that putting exogenous "normal" PMN into the airway might be beneficial.
METHODS: Postinjury pneumonia (PNA) commonly arises in two groups, early, community-acquired PNA (CAP) and later hospital-acquired PNA (HAP). Posttraumatic early-onset CAP and late-onset HAP were modeled in CD-1 mice using Staphylococcus aureus or Pseudomonas aeruginosa instilled intratracheal (i.t.) at clinically relevant times with or without extrapulmonary injuries mimicked by an intraperitoneal application of mitochondrial damage-associated molecular patterns. We applied bone marrow-derived PMN (BM-PMN) intratracheally to assess their effect on bacterial clearance in the lung.
RESULTS: BM-PMN instillation i.t. had no untoward clinical effects on recipient animals. In both the early/CAP and late/HAP models, clearance of the bacterial inoculum from the lung was suppressed by mitochondrial debris and restored to uninjured levels by i.t. instillation of exogenous BM-PMN. Furthermore, PMN instillation cleared the inoculum of P. aeruginosa that could not be cleared by uninjured mice. Instillation of PMN into the lung, even across strains (CD-1 vs. C57BL/6) had no injurious effect.
CONCLUSION: These initial studies suggest PMN instillation (i.t.) is worthy of further study as a potential adjunctive therapy aimed at decreasing the morbidity of lung infections in trauma patients. Moreover, PMN instillation (i.t.) may represent a unique means of preventing or treating pneumonia after serious injury that is completely independent of the need for antibiotic use.

PMID: 28431414 [PubMed - indexed for MEDLINE]

Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells.

Thu, 07/20/2017 - 10:01
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Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells.

Sci Rep. 2016 Mar 10;6:22850

Authors: Mezzapelle R, Rrapaj E, Gatti E, Ceriotti C, Marchis FD, Preti A, Spinelli AE, Perani L, Venturini M, Valtorta S, Moresco RM, Pecciarini L, Doglioni C, Frenquelli M, Crippa L, Recordati C, Scanziani E, de Vries H, Berns A, Frapolli R, Boldorini R, D'Incalci M, Bianchi ME, Crippa MP

Abstract
Malignant Mesothelioma is a highly aggressive cancer, which is difficult to diagnose and treat. Here we describe the molecular, cellular and morphological characterization of a syngeneic system consisting of murine AB1, AB12 and AB22 mesothelioma cells injected in immunocompetent BALB/c mice, which allows the study of the interplay of tumor cells with the immune system. Murine mesothelioma cells, like human ones, respond to exogenous High Mobility Group Box 1 protein, a Damage-Associated Molecular Pattern that acts as a chemoattractant for leukocytes and as a proinflammatory mediator. The tumors derived from AB cells are morphologically and histologically similar to human MM tumors, and respond to treatments used for MM patients. Our system largely recapitulates human mesothelioma, and we advocate its use for the study of MM development and treatment.

PMID: 26961782 [PubMed - indexed for MEDLINE]

StatPearls

Thu, 07/20/2017 - 10:01

StatPearls

Book. 2017 06

Authors:

Abstract
Human infection due to Rhodococcus equi was first reported in 1967 by a young man on immunosuppressant agents who was working in a stockyard. As the name implies, the infection is closely linked to animals, horses and foal are considered as the natural host. Other species of Rhodococcus similarly described as human pathogens include R. fascians, R. rhodochrous, and R. erythroplis. Rhodococcus belongs to the Norcadiaceae family which also comprises Nocardia, Mycobacterium, Corynebacterium, and Gordonia with some similarities among the group. Immunosuppression, especially defects in cell-mediated immunity, plays a major role in disease and is present in most reported cases even though infection has also been described less commonly in immunocompetent hosts. Common immunocompromised conditions where infection had been described include HIV, solid organ and stem cell transplant recipients, leukemia, lymphoma, lung cancer, and following chemotherapy, monoclonal antibodies, or prolonged steroid use.


PMID: 28723007

StatPearls

Thu, 07/20/2017 - 10:01

StatPearls

Book. 2017 06

Authors:

Abstract
Bronchiolitis obliterans is also known as obliterative bronchiolitis or constrictive bronchiolitis. When it occurs after lung transplantation or hematopoietic stem cell transplantation (HSCT) it is called bronchiolitis obliterans syndrome. Bronchiolitis obliterans is a type of obstructive lung disease of the small airways. It is a rare disease with characteristic features of fibrosis of terminal and distal bronchioles and spirometry showing airflow obstruction. It usually leads to progressive decline in lung function and has variable outcomes.


PMID: 28722895

Clinical Risk Factors and Prognostic Model for Primary Graft Dysfunction after Lung Transplantation in Patients with Pulmonary Hypertension.

Thu, 07/20/2017 - 01:01
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Clinical Risk Factors and Prognostic Model for Primary Graft Dysfunction after Lung Transplantation in Patients with Pulmonary Hypertension.

Ann Am Thorac Soc. 2017 Jul 18;:

Authors: Porteous MK, Lee JC, Lederer DJ, Palmer SM, Cantu E, Shah RJ, Bellamy SL, Lama VN, Bhorade SM, Crespo MM, McDyer JF, Wille KM, Localio AR, Orens JB, Shah PD, Weinacker AB, Arcasoy S, Wilkes DS, Ware LB, Christie JD, Kawut SM, Diamond JM, Lung Transplant Outcomes Group

Abstract
RATIONALE: Pulmonary hypertension from pulmonary arterial hypertension or parenchymal lung disease is associated with an increased risk of primary graft dysfunction after lung transplantation.
OBJECTIVE: We evaluated the clinical determinants of severe primary graft dysfunction in pulmonary hypertension and developed and validated a prognostic model.
METHODS: We conducted a retrospective cohort study of patients in the multi-center Lung Transplant Outcomes Group with pulmonary hypertension at transplant listing. Severe primary graft dysfunction was defined as PaO2/FiO2 200 with allograft infiltrates at 48 or 72 hours after transplantation. Donor, recipient, and operative characteristics were evaluated in a multivariable explanatory model. A prognostic model derived using donor and recipient characteristics was then validated in a separate cohort.
RESULTS: In the explanatory model of 826 patients with pulmonary hypertension, donor tobacco smoke exposure, higher recipient BMI, female sex, listing mean pulmonary artery pressure, right atrial pressure and creatinine at transplant, cardiopulmonary bypass use, transfusion volume, and reperfusion FiO2 were associated with primary graft dysfunction. Donor obesity was associated with a lower risk of primary graft dysfunction. Using a 20% threshold for elevated risk, the prognostic model had good negative predictive value in both derivation and validation cohorts (89.1%, 95%CI 85.3, 92.8 and 83.3%, 95%CI 78.5, 88.2 respectively), but low positive predictive value.
CONCLUSIONS: Several recipient, donor, and operative characteristics were associated with severe primary graft dysfunction in patients with pulmonary hypertension, including several risk factors not identified in the overall transplant population. A prognostic model with donor and recipient clinical risk factors alone had low positive predictive value, but high negative predictive value to rule out high risk of PGD.

PMID: 28719755 [PubMed - as supplied by publisher]

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