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[Italian Cystic Fibrosis Register - Report 2010].

Tue, 10/17/2017 - 12:45
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[Italian Cystic Fibrosis Register - Report 2010].

Epidemiol Prev. 2016 Mar-Apr;40(2 Suppl 2):1-47

Authors: Amato A, Ferrigno L, Salvatore M, Toccaceli V, Gruppo di lavoro RIFC/ICFR Working Group

Abstract
UNLABELLED: The Italian National CF Registry (INCFR) is based on the official agreement between the clinicians of the Italian National Referral Centers for Cystic Fibrosis and the researchers of the Istituto Superiore di Sanità (National Center for Rare Diseases; National Center for Epidemiology, Surveillance and Health Care Promotion). OBJECTIVES The main aim of INCFR is to contribute to the improvement in CF patients health care and clinical management through: i. the estimates of CF prevalence and incidence in Italy; ii. the analyses of medium and long term clinical and epidemiological trends of the disesase; iii. the identification of the main health care needs at regional and national level to contribute to the Health Care programmes and to the distribution of resources. MATERIALS AND METHODS Analyses and results described in the present Report are referred to patients in charge to the Italian National Referral Centers for Cystic Fibrosis in 2010. Data were sent by Centers by means of a specific software (Camilla, Ibis Informatica). The Italian National Referral Centers for Cystic Fibrosis sent a total of 5,271 individual records; 1,112 records were excluded from the analyses due to restricted inclusion criteria. The total number of patients included in INCFR for analyses is 4,159. RESULTS INCFR database includes all prevalent cases at 1th January 2010 as well as all new diagnoses done in 2010. The present Report has been organized into 9 sections. 1. Demography: estimated 2010 CF prevalence was 7/100,000 residents in Italy; 52% of the patients were male, CF distribution showed higher frequency in patients aged 7 to 35 years. In 2010, 48.9% of the patients were more than 18 years old. 2. Diagnoses: most of the CF patients were diagnosed before two years of age (66.7%); a significant percentage of patients (11.4%) was diagnosed in adult-age. 3. New diagnoses (2010): new diagnoses were 168. Sixty-five percent of them was diagnosed before the second year of age and 17%in adulthood. No differences were observed between male and female. Incidence at birth was estimated 1/4,854 living births. 4.
GENETICS: in 95.9% of patients, 2 (or more) CFTR mutations were identified. [delta]508F mutation was the most frequent (45.1%). 5. Respiratory function: analyses were performed on 2,966 out of 3,341 patients aged 7 years or older. FEV1 (Forced Expiratory Volume in the first second) scores progressively decreased before adult age, in accordance with the natural history of the disease. 6. Nutrition: most critical periods are during the first 6 months of life and during adolescence. Fourteen per cent of the patients within 2-18 years resulted malnourished. From 18 years onwards, optimal BodyMass Index (BMI) values were detected in 36.5%of males and in 28%of females. BMI also improved during age. 7. Transplantation: in 2010, 20 patients (10 males and 10 females) were bi-pulmunary transplanted; age was comprised between 11 and 46 years, median age at transplantation was 27.5 years. Eleven out of the 20 patients resulted still alive on the 31th December 2010. 8. Microbiology: analyses were performed on 3.272 patients (887 did not report these data) and were exclusively referred to tests performed in 2010. A percentage of 34 patients, younger than 18 years of age, was characterized by the presence of Pseudomonas aeruginosa compared to 61.8% of the older patients. Prevalence of Burkholderia Cepacia was 0.8% in patients aged up to 17 years; in patients aged more than 17 years, prevalence was 6.8%. Staphylococcus aureus meticillino sensitive prevalence was not correlated with patients' age. 9.
MORTALITY: 34 patients aged from 0 to 45 years died in 2010 (16 males and 18 females). Respiratory insufficiency was the main cause of death (73.5%). CONCLUSIONS The report aims at being an instrument for CF community, with particular attention to the needs of patients and their families. Information collected within INCFR are an important starting point for further studies from health care perspectives. Finally, INCFR represents an important tool to foster research and innovative treatment for CF, as the rareness of the disease is a constraint to clinical trials and other studies set-up. A significant subset of data are regularly sent to the European Registry of Cystic Fibrosis.

PMID: 27291389 [PubMed - indexed for MEDLINE]

Multicentric evaluation of the impact of central tumour location when comparing rates of N1 upstaging in patients undergoing video-assisted and open surgery for clinical Stage I non-small-cell lung cancer.

Sun, 10/15/2017 - 18:48

Multicentric evaluation of the impact of central tumour location when comparing rates of N1 upstaging in patients undergoing video-assisted and open surgery for clinical Stage I non-small-cell lung cancer.

Eur J Cardiothorac Surg. 2017 Sep 27;:

Authors: Decaluwé H, Petersen RH, Brunelli A, Pompili C, Seguin-Givelet A, Gust L, Aigner C, Falcoz PE, Rinieri P, Augustin F, Sokolow Y, Verhagen A, Depypere L, Papagiannopoulos K, Gossot D, D'Journo XB, Guerrera F, Baste JM, Schmid T, Stanzi A, Van Raemdonck D, Bardet J, Thomas PA, Massard G, Fieuws S, Moons J, Dooms C, De Leyn P, Hansen HJ, MITIG-ESTS

Abstract
OBJECTIVES: Large retrospective series have indicated lower rates of cN0 to pN1 nodal upstaging after video-assisted thoracic surgery (VATS) compared with open resections for Stage I non-small-cell lung cancer (NSCLC). The objective of our multicentre study was to investigate whether the presumed lower rate of N1 upstaging after VATS disappears after correction for central tumour location in a multivariable analysis.
METHODS: Consecutive patients operated for PET-CT based clinical Stage I NSCLC were selected from prospectively managed surgical databases in 11 European centres. Central tumour location was defined as contact with bronchovascular structures on computer tomography and/or visibility on standard bronchoscopy.
RESULTS: Eight hundred and ninety-five patients underwent pulmonary resection by VATS (n = 699, 9% conversions) or an open technique (n = 196) in 2014. Incidence of nodal pN1 and pN2 upstaging was 8% and 7% after VATS and 15% and 6% after open surgery, respectively. pN1 was found in 27% of patients with central tumours. Less central tumours were operated on by VATS compared with the open technique (12% vs 28%, P < 0.001). Logistic regression analysis showed that only tumour location had a significant impact on N1 upstaging (OR 6.2, confidence interval 3.6-10.8; P < 0.001) and that the effect of surgical technique (VATS versus open surgery) was no longer significant when accounting for tumour location.
CONCLUSIONS: A quarter of patients with central clinical Stage I NSCLC was upstaged to pN1 at resection. Central tumour location was the only independent factor associated with N1 upstaging, undermining the evidence for lower N1 upstaging after VATS resections. Studies investigating N1 upstaging after VATS compared with open surgery should be interpreted with caution due to possible selection bias, i.e. relatively more central tumours in the open group with a higher chance of N1 upstaging.

PMID: 29029062 [PubMed - as supplied by publisher]

Intralobar pulmonary sequestration with an aortic aneurysm.

Sun, 10/15/2017 - 18:48

Intralobar pulmonary sequestration with an aortic aneurysm.

Eur J Cardiothorac Surg. 2017 Oct 04;:

Authors: Menager JB, Mercier O

PMID: 29029028 [PubMed - as supplied by publisher]

Insulin deficient mouse β-cells do not fully mature but can be remedied through insulin replacement by islet transplantation.

Sun, 10/15/2017 - 18:48

Insulin deficient mouse β-cells do not fully mature but can be remedied through insulin replacement by islet transplantation.

Endocrinology. 2017 Sep 27;:

Authors: Ramzy A, Mojibian M, Kieffer TJ

Abstract
Insulin receptor insufficiency in β-cells leads to impaired insulin secretion and reduced β-cell hyperplasia in response to hyperglycemia. Selective insulin receptor deficiency in β-cells in later embryological development may lead to compensatory β-cell hyperplasia. Though these findings suggest insulin signaling on the β-cell is important for β-cell function, they are confounded by loss of signaling by the IGFs through the insulin receptor. To determine if insulin itself is necessary for β-cell development and maturation, we performed a characterization of pancreatic islets in mice with deletions of both non-allelic insulin genes (Ins1-/-Ins2-/-). We immunostained neonatal Ins1-/-Ins2-/- and Ins1+/+Ins2+/+ pancreas and performed qPCR on isolated neonatal islets. Insulin deficient islets had reduced expression of factors normally expressed in maturing β-cells including muscoloaponeurotic fibrosarcoma oncogene homolog A (MAFA), homeodomain transcription factor 6.1 (NKX6.1), and the glucose transporter 2 (GLUT2). Ins1-/-Ins2-/- β-cells expressed progenitor factors associated with stem cells or dedifferentiated β-cells including v-myc avian myolocytomatosis viral oncogene lung carcinoma derived (L-MYC), and homeobox protein NANOG. We replaced insulin by injection or islet transplantation to keep mice alive into adulthood to determine if insulin replacement was sufficient for the completed maturation of insulin deficient β-cells. Short-term insulin Glargine (Lantus®) injections partially rescued the β-cell phenotype, whereas long-term replacement of insulin by isogenic islet transplantation supported the formation of more mature β-cells. Our findings suggest that tightly regulated glycemia, insulin species, and/or other islet factors are necessary for β-cell maturation.

PMID: 29029025 [PubMed - as supplied by publisher]

The Prognostic Significance of Measurable ("Minimal") Residual Disease in Acute Myeloid Leukemia.

Sun, 10/15/2017 - 18:48

The Prognostic Significance of Measurable ("Minimal") Residual Disease in Acute Myeloid Leukemia.

Curr Hematol Malig Rep. 2017 Oct 13;:

Authors: Buccisano F, Hourigan CS, Walter RB

Abstract
PURPOSE OF REVIEW: The purpose of this review was to evaluate recent literature on detection methodologies for, and prognostic significance of, measurable ("minimal") residual disease (MRD) in acute myeloid leukemia (AML).
RECENT FINDINGS: There is no "one-fits-all" approach to MRD testing in AML. Most exploited to date are methods relying on immunophenotypic aberrancies (identified via multiparameter flow cytometry) or genetic abnormalities (identified via PCR-based assays). Current methods have important shortcomings, including the lack of assay platform standardization/harmonization across laboratories. In parallel to refinements of existing technologies and data analysis/interpretation, new methodologies (e.g., next-generation sequencing-based assays) are emerging that eventually may complement or replace existing ones. This dynamic evolution of MRD testing has complicated comparisons between individual studies. Nonetheless, an ever-growing body of data demonstrates that a positive MRD test at various time points throughout chemotherapy and hematopoietic cell transplantation identifies patients at particularly high risks of disease recurrence and short survival even after adjustment for other risk factors.

PMID: 29027628 [PubMed - as supplied by publisher]

Early predictors of mortality in children with pulmonary complications after haematopoietic stem cell transplantation.

Sun, 10/15/2017 - 18:48
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Early predictors of mortality in children with pulmonary complications after haematopoietic stem cell transplantation.

Pediatr Transplant. 2017 Oct 12;:

Authors: Choi YH, Jeong HJ, An HY, Kim YS, Lee EJ, Lee B, Kang HJ, Shin HY, Park JD

Abstract
PC are a main cause of death following HSCT in children. We aimed to evaluate early predictors of mortality in paediatric recipients with PCs. A retrospective observational study of 35 patients with 49 episodes of PI on chest radiography (of 124 patients) who had undergone HSCT at a tertiary university hospital between January 2011 and December 2012 was performed. During follow-up (median 26.1 months), 15 episodes led to death (30.6%). An aetiologic diagnosis was made by non-invasive tests in 24 episodes (49.0%) and by adding bronchoalveolar lavage and/or lung biopsy in 7 episodes with diagnostic yield (77.8%, P = .001). Thus, a specific diagnosis was obtained in 63.3% of the episodes. Aetiology identification and treatment modification after diagnosis did not decrease mortality (P = .057, P = .481). However, the number of organ dysfunctions at the beginning of PI was higher in the mortality group, compared to the survivor group (1.7 ± 1.2 vs 0.32 ± 0.59; P = .001). Hepatic dysfunction (OR, 11.145; 95% CI, 1.23 to 101.29; P = .032) and neutropaenia (OR, 10.558; 95% CI, 1.07 to 104.65; P = .044) were independently associated with risk of mortality. Therefore, hepatic dysfunction and neutropaenia are independent early predictors of mortality in HSCT recipients with PCs.

PMID: 29027353 [PubMed - as supplied by publisher]

Single-center experience with intraoperative extracorporeal membrane oxygenation use in lung transplantation.

Sun, 10/15/2017 - 18:48
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Single-center experience with intraoperative extracorporeal membrane oxygenation use in lung transplantation.

Int J Artif Organs. 2017 Oct 09;:0

Authors: Cosgun T, Tomaszek S, Opitz I, Wilhelm M, Schuurmans MM, Weder W, Inci I

Abstract
BACKGROUND: Studies have shown that survival after lung transplantation is impaired if extracorporeal membrane oxygenation (ECMO) support is implemented. We investigated the outcome and potential independent risk factors on survival in recipients undergoing lung transplantation with intraoperative ECMO support.
MATERIALS AND METHODS: Medical records of recipients were retrospectively evaluated (January 2000-December 2014). Retransplantation and bridge to transplantation on ECMO were excluded. Recipients (n = 291) were divided into 2 groups: those who needed intraoperative ECMO support (Group 1, n = 134) and those who did not receive intraoperative ECMO support (Group 2, n = 157). Independent risk factors were identified by a stepwise backward regression analysis.
RESULTS: 1-year survival was 84.2% in Group 1 vs. 90.4% in Group 2, and 5-year survival was 52.8% in Group 1 vs. 70.5% in Group 2 (p = 0.002). Multivariate analysis indicated that recipient age (p = 0.001), renal replacement therapy (p = 0.001) and intraoperative ECMO support (p = 0.03) were significant risk factors for overall survival. The rate of postoperative early surgical complications was comparable between the two groups (p = 0.09). The number of patients requiring renal replacement therapy and experiencing late pulmonary complications was significantly higher in Group 1 (p = 0.02).
CONCLUSIONS: Our data showed that lung transplantation with intraoperative ECMO support is associated with poor outcomes.

PMID: 29027193 [PubMed - as supplied by publisher]

Acute phase dynamics of circulating tumor cells after paclitaxel and doxorubicin chemotherapy in breast cancer mouse models.

Sun, 10/15/2017 - 18:48
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Acute phase dynamics of circulating tumor cells after paclitaxel and doxorubicin chemotherapy in breast cancer mouse models.

Breast Cancer Res Treat. 2017 Oct 12;:

Authors: Adachi Y, Yoshimura M, Nishida K, Usuki H, Shibata K, Hattori M, Kondo N, Yatabe Y, Iwata H, Kikumori T, Kodera Y, Nakanishi H

Abstract
PURPOSE: Circulating tumor cells (CTCs) can provide a potentially minimal invasive source for monitoring chemotherapeutic effects. However, detailed in vivo dynamics of CTC after chemotherapy remain largely unknown.
METHODS: We monitored CTC number and morphology early after chemotherapy using a newly developed cytology-based CTC detection device and triple-negative breast cancer mouse CTC models with spontaneous lung metastatic potential.
RESULTS: Paclitaxel inhibited cell growth of breast cancer cells by mainly G2/M cell cycle arrest and partly apoptosis, whereas doxorubicin inhibited cell growth mainly by apoptosis and partly G2 cell cycle arrest in vitro. The number of CTCs was significantly increased 3-10 days after paclitaxel and doxorubicin chemotherapy and decreased thereafter in two mouse CTC models. The transiently increased CTCs early post-chemotherapy consisted of not only G2/M arrested cells (apoptotic cells), but also morphologically near-intact live cells. This heterogeneous cell population of CTCs was similar to that of primary tumor tissue after chemotherapy.
CONCLUSIONS: These results indicate that CTCs can be mobilized from the primary tumor in rapid response to chemotherapy and suggest the possibility that CTC monitoring from both numerical and morphological viewpoints early after chemotherapy using a cytology-based CTC detection device would be a useful diagnostic tool for predicting drug sensitivity/resistance in preclinical and clinical setting.

PMID: 29027049 [PubMed - as supplied by publisher]

Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study.

Sun, 10/15/2017 - 18:48
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Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study.

Eur Respir J. 2017 Oct;50(4):

Authors: Dal Negro RW, Wedzicha JA, Iversen M, Fontana G, Page C, Cicero AF, Pozzi E, Calverley PMA, RESTORE group, RESTORE study

Abstract
Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) exacerbations and antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration.The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40-80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III. Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months. The primary outcome was the number of acute exacerbations during the study.In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the exacerbation rate by 19.4% (0.91 versus 1.13 exacerbations·patient(-1)·year(-1) for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patient(-1)·year(-1) for erdosteine and placebo, respectively; p=0.002). No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patient(-1)·year(-1) for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group. Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023). Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation.In patients with COPD, erdosteine can reduce both the rate and duration of exacerbations. The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups.

PMID: 29025888 [PubMed - in process]

Potential circulating miRNA signature for early detection of NSCLC.

Sun, 10/15/2017 - 18:48
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Potential circulating miRNA signature for early detection of NSCLC.

Cancer Genet. 2017 Oct;216-217:150-158

Authors: Arab A, Karimipoor M, Irani S, Kiani A, Zeinali S, Tafsiri E, Sheikhy K

Abstract
Circulating microRNAs (c-miRNAs) are promising biomarkers for screening, early detection and prognosis of cancer. The purpose of this investigation was to identify a panel of c-miRNAs in plasma that could contribute to early detection of non-small cell lung cancer (NSCLC). We profiled the expression of 44 unique plasma miRNAs in training set of 34 NSCLC patients and 20 matched healthy individuals by miRCURY LNA™ Universal RT microRNA PCR Panel and calculated dysregulation fold changes using the 2-ΔΔCt equation. Selected plasma miRNAs were then validated by SYBR green q-RT PCR using an independent validation set of plasma samples from NSCLC patients (n: 72) and NC (n: 50). In the validation set, the receiver operating characteristic (ROC) curves were generated for four miRNAs. In the training set, 17 miRNAs were significantly up-regulated and nine were down-regulated in the plasma from NSCLC patients versus matched normal controls. Four miRNAs (miR-21, miR-328, miR-375 and miR-141) were selected for validating their diagnostic value in the testing set. ROC plot analysis showed that a high specificity (98%) and sensitivity (82.7%) in miR-141 in comparing early NSCLC patient and controls. So among these four plasma miRNAs only miR-141 could be promising biomarkers for early detection of NSCLC. In addition to, we found a significant positive correlation between stage and miR-21 expression level (95% CI: 0.687-0.863; p-value < 0.0001). Considering the accessibility and stability of circulating miRNAs, plasma miR-141 is a useful biomarker early detection of NSCLC as a supplement in future screening studies.

PMID: 29025589 [PubMed - in process]

Transfusion-Related Acute Lung Injury (TRALI) and Transfusion-Associated Circulatory Overload (TACO) in Liver Transplantation: A Case Report and Focused Review.

Sun, 10/15/2017 - 18:48
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Transfusion-Related Acute Lung Injury (TRALI) and Transfusion-Associated Circulatory Overload (TACO) in Liver Transplantation: A Case Report and Focused Review.

Semin Cardiothorac Vasc Anesth. 2017 Oct 01;:1089253217736298

Authors: Smith NK, Kim S, Hill B, Goldberg A, DeMaria S, Zerillo J

Abstract
Liver transplantation (LT) is a complex procedure in a patient with multi-organ system dysfunction and coagulation defects. The surgical procedure involves dissection, major vessel manipulation, and pathophysiologic effects of graft storage and reperfusion. As a result, LT frequently involves significant hemorrhage. Subsequent massive transfusion carries high risk of transfusion-associated complications. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the leading causes of transfusion associated mortality. In this case report and focused review, we present data that suggest that patients undergoing liver transplantation may be at higher risk for TRALI and TACO than the general population. Anesthesiologists can play a role in decreasing these risks by increasing recognition and reporting of TRALI and TACO, using point of care testing with thromboelastography to guide and decrease transfusion, and considering alternatives to traditional blood products like solvent/detergent plasma.

PMID: 29025378 [PubMed - as supplied by publisher]

Intranasal administration of mesenchymoangioblast-derived mesenchymal stem cells abrogates airway fibrosis and airway hyperresponsiveness associated with chronic allergic airways disease.

Sun, 10/15/2017 - 18:48
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Intranasal administration of mesenchymoangioblast-derived mesenchymal stem cells abrogates airway fibrosis and airway hyperresponsiveness associated with chronic allergic airways disease.

FASEB J. 2017 Sep;31(9):4168-4178

Authors: Royce SG, Rele S, Broughton BRS, Kelly K, Samuel CS

Abstract
Structural changes known as airway remodeling (AWR) characterize chronic/severe asthma and contribute to lung dysfunction. Thus, we assessed the in vivo efficacy of induced pluripotent stem cell and mesenchymoangioblast-derived mesenchymal stem cells (MCA-MSCs) on AWR in a murine model of chronic allergic airways disease (AAD)/asthma. Female Balb/c mice were subjected to a 9-wk model of ovalbumin (Ova)-induced chronic AAD and treated intravenously or intranasally with MCA-MSCs from weeks 9 to 11. Changes in airway inflammation (AI), AWR, and airway hyperresponsiveness (AHR) were assessed. Ova-injured mice presented with AI, goblet cell metaplasia, epithelial thickening, increased airway TGF-β1 levels, subepithelial myofibroblast and collagen accumulation, total lung collagen concentration, and AHR (all P < 0.001 vs. uninjured control group). Apart from epithelial thickness, all other parameters measured were significantly, although not totally, decreased by intravenous delivery of MCA-MSCs to Ova-injured mice. In comparison, intranasal delivery of MCA-MSCs to Ova-injured mice significantly decreased all parameters measured (all P < 0.05 vs. Ova group) and, most notably, normalized aberrant airway TGF-β1 levels, airway/lung fibrosis, and AHR to values measured in uninjured animals. MCA-MSCs also increased collagen-degrading gelatinase levels. Hence, direct delivery of MCA-MSCs offers great therapeutic benefit for the AWR and AHR associated with chronic AAD.-Royce, S. G., Rele, S., Broughton, B. R. S., Kelly, K., Samuel, C. S. Intranasal administration of mesenchymoangioblast-derived mesenchymal stem cells abrogates airway fibrosis and airway hyperresponsiveness associated with chronic allergic airways disease.

PMID: 28626025 [PubMed - indexed for MEDLINE]

Patterns of Vasculature in Mouse Models of Lung Cancer Are Dependent on Location.

Sun, 10/15/2017 - 18:48
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Patterns of Vasculature in Mouse Models of Lung Cancer Are Dependent on Location.

Mol Imaging Biol. 2017 Apr;19(2):215-224

Authors: Vilalta M, Hughes NP, Von Eyben R, Giaccia AJ, Graves EE

Abstract
PURPOSE: Preclinical studies of hypoxia are generally done using ectopic xenograft tumors, which behave differently from human tumors. Our previous findings have shown that subcutaneously implanted lung tumors exhibit more hypoxia than their orthotopic implanted or spontaneous K-ras-induced counterparts. We hypothesize that differences in hypoxia are due to site-specific differences in vascularity and perfusion.
PROCEDURES: To compare the presence and functionality of vessels in these tumor models, we studied vascular perfusion in vivo in real time.
RESULTS: Orthotopically implanted and spontaneous K-ras-induced lung tumors showed elevated perfusion, demonstrating vasculature functionality. Little contrast agent uptake was observed within the subcutaneously implanted tumors, indicating vascular dysfunction. These findings were corroborated at the microscopic level with Hoechst 33342 and Meca-32 staining.
CONCLUSIONS: From these observations, we concluded that differences in hypoxia in experimental models is related to vessel perfusion. Thus, appropriate selection of preclinical lung tumor models is essential for the study of hypoxia, angiogenesis and therapies targeting these phenomena.

PMID: 27709411 [PubMed - indexed for MEDLINE]

Mesenchymal Stromal Cell-Derived Extracellular Vesicles Provide Long-term Survival after Total Body Irradiation without additional Hematopoietic Stem Cell Support.

Fri, 10/13/2017 - 12:45

Mesenchymal Stromal Cell-Derived Extracellular Vesicles Provide Long-term Survival after Total Body Irradiation without additional Hematopoietic Stem Cell Support.

Stem Cells. 2017 Oct 11;:

Authors: Schoefinius JS, Brunswig-Spickenheier B, Speiseder T, Krebs S, Just U, Lange C

Abstract
The therapeutic effect of mesenchymal stromal cells (MSC) in tissue regeneration is based mainly on the secretion of bioactive molecules. Here, we report that the radioprotective effect of mouse bone marrow derived MSC (mMSC) can be attributed to extracellular vesicles (EV) released from mMSC. The transplantation of mMSC-derived EV into lethally irradiated mice resulted in long-term survival but no improvement in short-term reconstitution of the recipients. Importantly, the radiation rescue was efficient without additional hematopoietic support. In vitro we show a protection by EV of irradiated hematopoietic stem cells (HSC) but not progenitor cells using stroma-cell cultures and colony-forming assays. After systemic infusion into lethally irradiated recipients, labeled EV traveled freely through the body reaching the bone marrow within two hours. We further show that long-term repopulating Sca-1 positive and c-kit low-positive stem cells were directly targeted by EV leading to long-term survival. Collectively, our data suggest EV as an effective first-line treatment to combat radiation-induced hematopoietic failure which might also be helpful in alleviating myelosuppression due to chemotherapy and toxic drug reaction. We suggest the infusion of MSC-derived EV as efficient and immediate treatment option after irradiation injuries. This article is protected by copyright. All rights reserved.

PMID: 29024236 [PubMed - as supplied by publisher]

Honokiol Increases CD4+ T Cell Activation and Decreases TNF but Fails to Improve Survival Following Sepsis.

Fri, 10/13/2017 - 12:45

Honokiol Increases CD4+ T Cell Activation and Decreases TNF but Fails to Improve Survival Following Sepsis.

Shock. 2017 Oct 11;:

Authors: Klingensmith NJ, Chen CW, Liang Z, Burd EM, Farris AB, Arbiser JL, Ford ML, Coopersmith CM

Abstract
Honokiol is a biphenolic isolate extracted from the bark of the magnolia tree that has been used in traditional Chinese and Japanese medicine, and has more recently been investigated for its anti-inflammatory and anti-bacterial properties. Honokiol has previously been demonstrated to improve survival in sepsis models that have rapid 100% lethality. The purpose of this study was to determine the impact of Honokiol on the host response in a model of sepsis that more closely approximates human disease. Male and female C57BL/6 mice underwent cecal ligation and puncture (CLP) to induce polymicrobial intraabdominal sepsis. Mice were then randomized to receive an injection of either Honokiol (120 mg/kg/day) or vehicle and were sacrificed after 24 hours for functional studies or followed 7 days for survival. Honokiol treatment after sepsis increased the frequency of CD4 T cells and increased activation of CD4 T cells as measured by the activation marker CD69. Honokiol also increased splenic dendritic cells. Honokiol simultaneously decreased frequency and number of CD8 T cells. Honokiol decreased systemic TNF without impacting other systemic cytokines. Honokiol did not have a detectable effect on kidney function, lung physiology, liver function or intestinal integrity. In contrast to prior studies of Honokiol in a lethal model of sepsis, Honokiol did not alter survival at seven days (70% mortality for Honokiol vs. 60% mortality for vehicle). Honokiol is thus effective in modulating the host immune response and inflammation following a clinically relevant model of sepsis but is not sufficient to alter survival.

PMID: 29023360 [PubMed - as supplied by publisher]

Effects of Hypercapnia on Acute Cellular Rejection after Lung Transplantation in Rats.

Fri, 10/13/2017 - 12:45

Effects of Hypercapnia on Acute Cellular Rejection after Lung Transplantation in Rats.

Anesthesiology. 2017 Oct 12;:

Authors: Tan J, Liu Y, Jiang T, Wang L, Zhao C, Shen D, Cui X

Abstract
BACKGROUND: Hypercapnia alleviates pulmonary ischemia-reperfusion injury, regulates T lymphocytes, and inhibits immune reaction. This study aimed to evaluate the effect of hypercapnia on acute cellular rejection in a rat lung transplantation model.
METHODS: Recipient rats in sham-operated (Wistar), isograft (Wistar to Wistar), and allograft (Sprague-Dawley to Wistar) groups were ventilated with 50% oxygen, whereas rats in the hypercapnia (Sprague-Dawley to Wistar) group were administered 50% oxygen and 8% carbon dioxide for 90 min during reperfusion (n = 8). Recipients were euthanized 7 days after transplantation.
RESULTS: The hypercapnia group showed a higher oxygenation index (413 ± 78 vs. 223 ± 24), lower wet weight-to-dry weight ratio (4.23 ± 0.54 vs. 7.04 ± 0.80), lower rejection scores (2 ± 1 vs. 4 ± 1), and lower apoptosis index (31 ± 6 vs. 57 ± 4) as compared with the allograft group. The hypercapnia group showed lower CD8 (17 ± 4 vs. 31 ± 3) and CD68 (24 ± 3 vs. 43 ± 2), lower CD8 T cells (12 ± 2 vs. 35 ± 6), and higher CD4/CD8 ratio (2.2 ± 0.6 vs. 1.1 ± 0.4) compared to the allograft group. Tumor necrosis factor-α (208 ± 40 vs. 292 ± 49), interleukin-2 (30.6 ± 6.7 vs. 52.7 ± 8.3), and interferon-γ (28.1 ± 4.9 vs. 62.7 ± 10.1) levels in the hypercapnia group were lower than those in allograft group. CD4, CD4 T cells, and interleukin-10 levels were similar between groups.
CONCLUSIONS: Hypercapnia ameliorated acute cellular rejection in a rat lung transplantation model.

PMID: 29023354 [PubMed - as supplied by publisher]

Complete Resolution of Lymphoid Interstitial Pneumonia in a Patient With Juvenile Myelomonocytic Leukemia Treated With Allogeneic Bone Marrow Transplant: Killing 2 Birds With 1 Stone.

Fri, 10/13/2017 - 12:45

Complete Resolution of Lymphoid Interstitial Pneumonia in a Patient With Juvenile Myelomonocytic Leukemia Treated With Allogeneic Bone Marrow Transplant: Killing 2 Birds With 1 Stone.

J Pediatr Hematol Oncol. 2017 Oct 11;:

Authors: Vatsayan A, Talati R, Nagle K, Cabral L, Cammock S, Dimarino A, Egler R, Saab S, Dalal J

Abstract
Lymphoid interstitial pneumonia (LIP) is a rare disease characterized by benign reactive polyclonal proliferation of bronchus-associated lymphoid tissue after exposure to inhaled or circulating antigen(s), leading to a disease symptomatology similar to idiopathic interstitial pneumonia. Its association with diseases that are caused due to immune dysregulation (autoimmune diseases, congenital/acquired immunodeficiency, and allogeneic bone marrow transplant) and response to immunomodulatory/suppressive medications suggests an immunologic pathophysiology. Although LIP has been reported in association with lymphoproliferative diseases like Castleman disease, it has never been described in patients with leukemia. We report the first case of LIP in a patient with juvenile myelomonocytic leukemia (JMML) who was found to have a novel germline mutation of unknown significance in additional sex combs-like-1 (ASXL1) gene and a pathogenic somatic mutation of protein tyrosine phosphatase, nonreceptor type 11 (PTPN11) gene at diagnosis. The patient underwent a matched unrelated bone marrow transplant for JMML with complete resolution of JMML and LIP with no recurrence to date. We also emphasize the importance of considering LIP in differential diagnosis of pulmonary lesions seen in conjunction with hematologic malignancies and distinguishing it from malignant infiltration of the lung.

PMID: 29023302 [PubMed - as supplied by publisher]

Bone Marrow Mononuclear Cells Transplantation in Treatment of Established Bronchopulmonary Dysplasia: A Case Report.

Fri, 10/13/2017 - 12:45
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Bone Marrow Mononuclear Cells Transplantation in Treatment of Established Bronchopulmonary Dysplasia: A Case Report.

Am J Case Rep. 2017 Oct 12;18:1090-1094

Authors: Liem NT, Anh TL, Thai TTH, Anh BV

Abstract
BACKGROUND Bronchopulmonary dysplasia (BDP) is an incurable disease. This study reports the successful treatment of a 30-week-old neonate with established bronchopulmonary dysplasia by bone marrow mononuclear cells (BM MNCs) transplantation. CASE REPORT The preterm infant with BPD requiring continuous oxygen administration for 4 months post-delivery underwent BM MNCs. Bone marrow was obtained from the patient's iliac crests and mononuclear cells were isolated by density gradient centrifugation method. BM MNCs were delivered via endotracheal and intravenous routes. After BM MNCs transplantation, remarkable improvements were observed in oxygen saturation and lung CT as the infant was gradually weaned off oxygen supply. CONCLUSIONS BM MNCs transplantation offers promising treatment of BPD.

PMID: 29021519 [PubMed - in process]

Successful Pulmonary Artery Embolization for the Management of Hemoptysis in a Patient with Eisenmenger Syndrome Caused by Patent Ductus Arteriosus.

Fri, 10/13/2017 - 12:45
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Successful Pulmonary Artery Embolization for the Management of Hemoptysis in a Patient with Eisenmenger Syndrome Caused by Patent Ductus Arteriosus.

Intern Med. 2017 Oct 11;:

Authors: Tamada N, Nakayama K, Shinkura Y, Yanaka KI, Katayama N, Okada T, Yamaguchi M, Matsumoto K, Tanaka H, Shinke T, Emoto N, Hirata KI

Abstract
The patient was a 19-year-old woman who was diagnosed with patent ductus arteriosus complicating Eisenmenger syndrome at a previous medical institution. She was referred to our hospital and arranged for lung transplantation. She developed hemoptysis after the introduction of i.v. epoprostenol, which was administered as a bridging treatment while the patient awaited lung transplantation. She continued to suffer from recurrent hemoptysis, even after switching from i.v. epoprostenol to i.v. treprostinil. Angiography of the systemic and pulmonary arteries revealed the vessel responsible for the recurrent hemoptysis and pulmonary artery embolization was successfully performed. It is essential to identify the culprit vessel and surgeons must not hesitate in performing embolization when patients develop lethal hemoptysis.

PMID: 29021475 [PubMed - as supplied by publisher]

The Efficacy of a Genetic Analysis of the BMPR2 Gene in a Patient with Severe Pulmonary Arterial Hypertension and an Atrial Septal Defect Treated with Bilateral Lung Transplantation.

Fri, 10/13/2017 - 12:45
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The Efficacy of a Genetic Analysis of the BMPR2 Gene in a Patient with Severe Pulmonary Arterial Hypertension and an Atrial Septal Defect Treated with Bilateral Lung Transplantation.

Intern Med. 2017 Oct 11;:

Authors: Tatebe S, Sugimura K, Aoki T, Yamamoto S, Yaoita N, Suzuki H, Sato H, Kozu K, Konno R, Satoh K, Fukuda K, Adachi O, Saito R, Nakanishi N, Morisaki H, Oyama K, Saiki Y, Okada Y, Shimokawa H

Abstract
Severe pulmonary arterial hypertension (PAH) rarely develops in children with an atrial septal defect (ASD), even those with a large defect. We herein report the case of a 27-year-old man with a moderate-sized secundum ASD and right ventricular failure due to severe PAH, which developed in his early teens. He was diagnosed as having a genetic mutation of the BMPR2 gene and was successfully treated with bilateral lung transplantation with ASD path closure. In patients with congenital heart disease, a genetic analysis may provide information about the lifetime risk of developing PAH.

PMID: 29021450 [PubMed - as supplied by publisher]

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