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Role of miR-29 as marker of risk of acute rejection after heart transplant.

Thu, 07/27/2017 - 12:45
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Role of miR-29 as marker of risk of acute rejection after heart transplant.

Br J Biomed Sci. 2017 Jul 26;:1-6

Authors: Guo S, Guo X, Wang S, Nie Q, Ni G, Wang C

Abstract
BACKGROUND: Circulating miRNAs are potential biomarkers of the pathogenesis of certain diseases and in monitoring therapeutic responses. We hypothesized that serum miR-29 can determine risk of acute cardiac allograft rejection.
METHODS: Peripheral vein blood was collected from 50 healthy volunteers and 506 patients during post-transplant surveillance. Serum cardiac troponin I (cTnI) and miR-29 was detected by ELISA and qRT-PCR assay respectively. Rejection risk was defined as International Society of Heart and Lung Transplant score from leukocyte infiltration of an endomyocardial biopsy. No evidence of rejection was defined as grade R0, mild as R1, moderate as 2R and severe as 3R. Specificity and sensitivity of miR-29 to discriminate rejection was determined by the area under the curve (AUC) of receiver operating characteristic curve analysis. Correlations between miR29 and rejection grade were compared.
RESULTS: Serum miR-29 was 100.8 ± 42.4 copies/μl in R0 groups (P = 0.164 versus controls), 537.5 ± 84.3 copies/μl in R1 groups (P = 0.024) and 1478.4 ± 198.7 copies/μl in the joint R2/R3 groups (P = 0.001). MiR-29 was 1963.5 ± 214.7 six months after transplantation, 1242.5 ± 103.8 after a year, 825.6 ± 58.2 after 2 years, 413.8 ± 61.9 after 3 years and 270.6 ± 34.6 ng/mL after 4 years (P < 0.001). The level of miR-29 correlated positively with cTnI, NT-proBNP, white blood cell counts, and negatively with lymphocyte counts (all P < 0.001). The AUC values (95% CI) for discriminating R0 and R1 was 0.81 (0.75-0.89), and was 0.79 (0.72-0.86) for R0 and R2/R3 (both P < 0.01).
CONCLUSION: miR-29 is a promising predictor of the risk of heart transplant rejection.

PMID: 28745139 [PubMed - as supplied by publisher]

Bedside Tracheostomy on Pediatric ICU Subjects Supported by Extracorporeal Membrane Oxygenation.

Thu, 07/27/2017 - 12:45
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Bedside Tracheostomy on Pediatric ICU Subjects Supported by Extracorporeal Membrane Oxygenation.

Respir Care. 2017 Jul 25;:

Authors: Schwartz SP, Bonadonna D, Hartwig MG, Cheifetz IM

Abstract
BACKGROUND: Tracheostomy facilitates ambulatory extracorporeal membrane oxygenation (ECMO) as a bridge to recovery or lung transplantation in patients with respiratory failure, yet data on this procedure in this population are lacking. This report describes a series of pediatric ICU patients who had a bedside tracheostomy performed while being supported on ECMO and examines the potential impact of this procedure on active rehabilitation and sedation requirements.
METHODS: This retrospective case series reviews all patients in the pediatric ICU who received a tracheostomy while being supported on ECMO at a single tertiary care center for the past 3 y. This descriptive report reviews the surgical procedure, anticoagulation management, adjustments to sedation, and complications.
RESULTS: Nine subjects between January 2013 and December 2015 were identified for review. The subjects ranged in age from 7 y to 25 y. All tracheostomies were performed as bedside procedures in the pediatric ICU. All subjects but one were supported by venovenous ECMO. Surgical approaches included open tracheostomy (2 subjects, 22%), percutaneous tracheostomy (1 subject, 11%), and a hybrid approach (6 subjects, 67%). Anticoagulation was held for all subjects surrounding the procedure. Three subjects had superficial bleeding after the procedure, but only one required re-exploration of the surgical field. All subjects made substantial sedation weans within 72 h of tracheostomy. With these weans, subjects were better able to participate in rehabilitation. Five subjects (55.6%) ambulated on ECMO. The rate of survival to hospital discharge was 67%, and no deaths were related to the tracheostomy procedure.
CONCLUSION: Bedside tracheostomy can feasibly be performed on pediatric patients being supported with ECMO as a way to improve mobility, promote ambulation, and decrease sedation. Timing and ideal surgical approach require further study to fully maximize benefits and minimize risks.

PMID: 28743722 [PubMed - as supplied by publisher]

Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

Thu, 07/27/2017 - 12:45
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Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

Biochem Pharmacol. 2017 Aug 15;138:193-204

Authors: Ahmed LA, Rizk SM, El-Maraghy SA

Abstract
Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60mg/kg). Endothelial progenitor cells were in vitro preconditioned with pinocembrin (25mg/L) for 30min before being i.v. injected into rats 2weeks after monocrotaline administration. Four weeks after monocrotaline administration, blood pressure, electrocardiography and right ventricular systolic pressure were recorded. Rats were sacrificed and serum was separated for determination of endothelin-1 and asymmetric dimethylarginine levels. Right ventricles and lungs were isolated for estimation of tumor necrosis factor-alpha and transforming growth factor-beta contents as well as caspase-3 activity. Moreover, protein expression of matrix metalloproteinase-9 and endothelial nitric oxide synthase in addition to myocardial connexin-43 was assessed. Finally, histological analysis of pulmonary arteries, cardiomyocyte cross-sectional area and right ventricular hypertrophy was performed and cryosections were done for estimation of cell homing. Preconditioning with pinocembrin provided a significant improvement in endothelial progenitor cells' effect towards reducing monocrotaline-induced elevation of inflammatory, fibrogenic and apoptotic markers. Furthermore, preconditioned cells induced a significant amelioration of endothelial markers and cell homing and prevented monocrotaline-induced changes in right ventricular function and histological analysis compared with native cells alone. In conclusion, pinocembrin significantly improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

PMID: 28450224 [PubMed - indexed for MEDLINE]

Advances in Stem Cell and Cell-Based Gene Therapy Approaches for Experimental Acute Lung Injury: A Review of Preclinical Studies.

Thu, 07/27/2017 - 12:45
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Advances in Stem Cell and Cell-Based Gene Therapy Approaches for Experimental Acute Lung Injury: A Review of Preclinical Studies.

Hum Gene Ther. 2016 Oct;27(10):802-812

Authors: Mei SH, Dos Santos CC, Stewart DJ

Abstract
Given the failure of pharmacological interventions in acute respiratory distress syndrome (ARDS), researchers have been actively pursuing novel strategies to treat this devastating, life-threatening condition commonly seen in the intensive care unit. There has been considerable research on harnessing the reparative properties of stem and progenitor cells to develop more effective therapeutic approaches for respiratory diseases with limited treatment options, such as ARDS. This review discusses the preclinical literature on the use of stem and progenitor cell therapy and cell-based gene therapy for the treatment of preclinical animal models of acute lung injury (ALI). A variety of cell types that have been used in preclinical models of ALI, such as mesenchymal stem cells, endothelial progenitor cells, and induced pluripotent stem cells, were evaluated. At present, two phase I trials have been completed and one phase I/II clinical trial is well underway in order to translate the therapeutic benefit gleaned from preclinical studies in complex animal models of ALI to patients with ARDS, paving the way for what could potentially develop into transformative therapy for critically ill patients. As we await the results of these early cell therapy trials, future success of stem cell therapy for ARDS will depend on selection of the most appropriate cell type, route and timing of cell delivery, enhancing effectiveness of cells (i.e., potency), and potentially combining beneficial cells and genes (cell-based gene therapy) to maximize therapeutic efficacy. The experimental models and scientific methods exploited to date have provided researchers with invaluable knowledge that will be leveraged to engineer cells with enhanced therapeutic capabilities for use in the next generation of clinical trials.

PMID: 27531647 [PubMed - indexed for MEDLINE]

Sohlh2 inhibits human ovarian cancer cell invasion and metastasis by transcriptional inactivation of MMP9.

Thu, 07/27/2017 - 12:45
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Sohlh2 inhibits human ovarian cancer cell invasion and metastasis by transcriptional inactivation of MMP9.

Mol Carcinog. 2016 Jul;55(7):1127-37

Authors: Zhang H, Hao C, Wang Y, Ji S, Zhang X, Zhang W, Zhao Q, Sun J, Hao J

Abstract
Identifying key mediators of cancer invasion and metastasis is crucial to the development of new and more effective therapies. We previously identified Sohlh2 as an important inhibitor of ovarian cancer cell proliferation. However, the function of Sohlh2 in cell migration and invasion remains unknown. In this paper, we report a novel Sohlh2 to MMP9 signaling pathway in the invasive ovarian cancer. Using immunohistochemistry staining, we revealed Sohlh2 expression was inversely correlated with the invasive human ovarian cancers. In vitro experiments, forced expression of Sohlh2 led to a significant reduction in cancer cell migration and invasion. Conversely, silencing of Sohlh2 enhanced ovarian cancer cell migration and invasion. Experiments using nude mice demonstrated that the ectopic Sohlh2 expression inhibited the HO8910 cell capability of the metastasis to the lungs and livers. Ectopic overexpression of Sohlh2 in the invasive HO8910 cells reduced the MMP9 expression, whereas Sohlh2 knockdown from the non-invasive, SKOV3 cells increased the MMP9 expression. Promoter activation and binding analyses indicated that Sohlh2 repressed the MMP9 expression by directly acting on the MMP9 gene promoter. Inhibition of MMP9 dramatically blocked the Sohlh2 knockdown-enhanced SKOV3 cell invasion, and ectopic expression of MMP9 compensated for the anti-invasive activity of Sohlh2 in HO8910 cells. Overall, these results demonstrate for the first time that Sohlh2 functions as a tumor metastasis suppressor. Modulation of Sohlh2 expression has the potential to be a target for cancer therapy. © 2015 Wiley Periodicals, Inc.

PMID: 26153894 [PubMed - indexed for MEDLINE]

Long-term follow-up of pulmonary function in Fabry disease: A bi-center observational study.

Wed, 07/26/2017 - 12:45
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Long-term follow-up of pulmonary function in Fabry disease: A bi-center observational study.

PLoS One. 2017;12(7):e0180437

Authors: Franzen DP, Nowak A, Haile SR, Mottet D, Bonani M, Dormond O, Kohler M, Krayenbuehl PA, Barbey F

Abstract
INTRODUCTION: Fabry disease (FD) is a lysosomal storage disorder leading to decreased α-galactosidase A enzyme activity and subsequent abnormal accumulation of glycosphingolipids in various organs. Although histological evidence of lung involvement has been demonstrated, the functional impact of these changes is less clear.
MATERIALS AND METHODS: Adult patients with FD who had yearly pulmonary function tests (PFT) at two centers from 1999 thru 2015 were eligible for this observational study. Primary outcome measures were the change in forced expiratory volume in the first second (FEV1) and FEV1/FVC over time. As secondary outcome we investigated sex, smoking, enzyme replacement therapy (ERT), residual enzyme activity, and Mainz Severity Score Index as possible predictors.
RESULTS: 95 patients (41% male, 38.2 ± 14.5 years) were included. The overall prevalence of bronchial obstruction (BO, (FEV1/FVC < 70%)) was 46%, with male sex, age and smoking as significant predictors. FEV1 decreased 29 ml per year (95% CI -36, -22 ml, p<0.0001). FEV1 decline was significantly higher in males (p = 0.009) and in patients on ERT (p = 0.004). Conclusion: Pulmonary involvement seems to be a relevant manifestation of Fabry disease, and routine PFTs should therefore be included in the multidisciplinary follow-up of these patients.

PMID: 28742806 [PubMed - in process]

Prof. Konrad Hoetzenecker: extracorporeal life support, a bridge to lung transplantation.

Wed, 07/26/2017 - 12:45
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Prof. Konrad Hoetzenecker: extracorporeal life support, a bridge to lung transplantation.

J Thorac Dis. 2017 Jun;9(6):E581-E582

Authors: Gao S

PMID: 28740703 [PubMed]

Immunosuppression after lung transplantation: the search for the holy grail continues.

Wed, 07/26/2017 - 12:45
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Immunosuppression after lung transplantation: the search for the holy grail continues.

J Thorac Dis. 2017 Jun;9(6):1412-1414

Authors: Schwarz S, Jaksch P, Klepetko W, Hoetzenecker K

PMID: 28740645 [PubMed]

An optimized non-destructive protocol for testing mechanical properties in decellularized rabbit trachea.

Wed, 07/26/2017 - 12:45
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An optimized non-destructive protocol for testing mechanical properties in decellularized rabbit trachea.

Acta Biomater. 2017 Jul 21;:

Authors: Den Hondt M, Vanaudenaerde BM, Maughan EF, Butler CR, Crowley C, Verbeken EK, Verleden SE, Vranckx JJ

Abstract
Successful tissue-engineered tracheal transplantation relies on the use of non-immunogenic constructs, which can vascularize rapidly, support epithelial growth, and retain mechanical properties to that of native trachea. Current strategies to assess mechanical properties fail to evaluate the trachea to its physiological limits, and lead to irreversible destruction of the construct. Our aim was to develop and evaluate a novel non-destructive method for biomechanical testing of tracheae in a rabbit decellularization model. To validate the performance of this method, we simultaneously analyzed quantitative and qualitative graft changes in response to decellularization, as well as in-vivo biocompatibility of implanted scaffolds. Rabbit tracheae underwent two, four and eight cycles of detergent-enzymatic decellularization. Biomechanical properties were analyzed by calculating luminal volume of progressively inflated and deflated tracheae with microCT. DNA, glycosaminoglycan and collagen contents were compared to native trachea. Scaffolds were prelaminated in vivo. Native, two- and four-cycle tracheae showed equal mechanical properties. Collapsibility of eight-cycle tracheae was significantly increased from -40 cmH2O (-3.9 kPa). Implantation of two- and four-cycle decellularized scaffolds resulted in favorable flap-ingrowth; eight-cycle tracheae showed inadequate integration. We showed a more limited detergent-enzymatic decellularization successfully removing non-cartilaginous immunogenic matter without compromising extracellular matrix content or mechanical stability. With progressive cycles of decellularization, important loss of functional integrity was detected upon mechanical testing and in-vivo implantation. This instability was not revealed by conventional quantitative nor qualitative architectural analyses. These experiments suggest that non-destructive, functional evaluation, e.g. by microCT, may serve as an important tool for mechanical screening of scaffolds before clinical implementation.

PMID: 28739545 [PubMed - as supplied by publisher]

Exercise Capacity Impairment Can Predict Postoperative Pulmonary Complications after Liver Transplantation.

Tue, 07/25/2017 - 12:45

Exercise Capacity Impairment Can Predict Postoperative Pulmonary Complications after Liver Transplantation.

Respiration. 2017 Jul 22;:

Authors: Magalhães CBA, Nogueira IC, Marinho LS, Daher EF, Garcia JHP, Viana CFG, de Bruin PFC, Pereira EDB

Abstract
BACKGROUND: Postoperative respiratory complications (PRCs) are common after liver transplantation (LT) and contribute significantly to the related morbidity and mortality.
OBJECTIVE: The aim of this paper was to determine the incidence of PRCs after LT and the value of simple exercise capacity measures as independent predictors of PRCs.
METHODS: We conducted a prospective cohort study of consecutive adults submitted to LT at a University Hospital in Fortaleza Brazil from March 2013 to March 2015. At baseline, exercise capacity was assessed with the 6-minute walk test (6MWT) and the 6-minute step test (6MST), lung function was tested by spirometry, and respiratory muscle strength was measured by maximal respiratory pressure. Additional relevant pre- and intraoperative data were collected through interview and chart review, and their association with the incidence of PRCs was evaluated.
RESULTS: The study included 100 subjects, 44% of whom presented at least 1 of the PRCs. In the univariate analysis, poor 6MST and 6MWT results and a longer preoperative cold ischemia time were associated with PRCs. The logistic regression analysis showed that PRCs were less likely to occur when preoperative walking distances were longer: the odds ratio (95% CI) was reduced to 0.589 (0.357-0.971) for each 50 m walked (p = 0.03). Likewise, PRCs were more likely to occur in patients with longer preoperative cold ischemia times: the odds ratio (95% CI) increased to 1.008 (1.002-1.015) for each minute (p = 0.01).
CONCLUSION: The incidence of PRCs is high in LT patients. A prolonged cold ischemia time and preoperative 6MWT results were independent predictors of PRCs in this patient population.

PMID: 28738386 [PubMed - as supplied by publisher]

Regulation of Clinical Xenotransplantation-Time for a Reappraisal.

Tue, 07/25/2017 - 12:45

Regulation of Clinical Xenotransplantation-Time for a Reappraisal.

Transplantation. 2017 Aug;101(8):1766-1769

Authors: Cooper DKC, Pierson RN, Hering BJ, Mohiuddin MM, Fishman JA, Denner J, Ahn C, Azimzadeh AM, Buhler LH, Cowan PJ, Hawthorne WJ, Kobayashi T, Sachs DH

Abstract
The continual critical shortage of organs and cells from deceased human donors has stimulated research in the field of cross-species transplantation (xenotransplantation), with the pig selected as the most suitable potential source of organs. Since the US Food and Drug Administration concluded a comprehensive review of xenotransplantation in 2003, considerable progress has been made in the experimental laboratory to improve cell and organ xenograft survival in several pig-to-nonhuman primate systems that offer the best available models to predict clinical outcomes. Survival of heart, kidney, and islet grafts in nonhuman primates is now being measured in months or even years. The potential risks associated with xenotransplantation, for example, the transfer of an infectious microorganism, that were highlighted in the 2003 Food and Drug Administration guidance and subsequent World Health Organization consensus documents have been carefully studied and shown to be either less likely than previously thought or readily manageable by donor selection or recipient management strategies. In this context, we suggest that the national regulatory authorities worldwide should re-examine their guidelines and regulations regarding xenotransplantation, so as to better enable design and conduct of safe and informative clinical trials of cell and organ xenotransplantation when and as supported by the preclinical data. We identify specific topics that we suggest require reconsideration.

PMID: 28737658 [PubMed - in process]

Advances in transfusion medicine: gastrointestinal bleeding.

Tue, 07/25/2017 - 12:45

Advances in transfusion medicine: gastrointestinal bleeding.

Transfus Med. 2017 Jul 24;:

Authors: Oakland K, Jairath V, Murphy MF

Abstract
Gastrointestinal bleeding is a common medical and surgical emergency and is the second most common indication for red blood cell (RBC) transfusion in the UK. Most transfusion guidelines recommend the use of restrictive blood transfusion in stable gastrointestinal bleeding. This review explores the evidence supporting this practice, including whether it is safe in lower as well as upper gastrointestinal bleeding, and the risks of restrictive transfusion in patients with cardiovascular disease. There is a lack of evidence supporting the use of platelet and fresh frozen plasma transfusion in gastrointestinal bleeding. The aim of this review is to serve as a practical guide to transfusion in stable gastrointestinal bleeding.

PMID: 28737229 [PubMed - as supplied by publisher]

Metformin therapy reduces the risk of malignancy after heart transplantation.

Tue, 07/25/2017 - 12:45
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Metformin therapy reduces the risk of malignancy after heart transplantation.

J Heart Lung Transplant. 2017 Jun 23;:

Authors: Peled Y, Lavee J, Raichlin E, Katz M, Arad M, Kassif Y, Peled A, Asher E, Elian D, Har-Zahav Y, Shlomo N, Freimark D, Goldenberg I, Klempfner R

Abstract
BACKGROUND: Malignancy and diabetes mellitus (DM) cause significant morbidity and mortality after heart transplantation (HTx). Metformin, one of the most commonly used anti-diabetic drugs worldwide, has also been shown to exhibit anti-tumor activity. We therefore investigated the association between metformin therapy and malignancy after HTx.
METHODS: The study population comprised 237 patients who underwent HTx between 1991 and 2016 and were prospectively followed-up. Clinical data were recorded on prospectively designed forms. The primary outcome was any cancer recorded during 15 years of follow-up. Treatment with metformin and the development of DM after HTx were assessed as time-dependent factors in the analyses.
RESULTS: Of the 237 study patients, 85 (36%) had diabetes. Of the DM patients, 48 (56%) were treated with metformin. Kaplan-Meier survival analysis showed that, at 15 years after HTx, malignancy rate was 4% for DM patients treated with metformin, 62% for those who did not receive metformin and 27% for non-DM patients (log-rank test, p < 0.0001). Consistently, multivariate analysis showed that for DM patients, metformin therapy was independently associated with a significant 90% reduction (hazard ratio = 0.10; 95% confidence interval 0.02 to 0.40; p = 0.001) in the risk of the development of a malignancy. DM patients who were treated with metformin had a markedly lower risk (65%; p = 0.001) for the development of a malignancy or death after HTx as compared with non-DM patients.
CONCLUSIONS: Our findings suggest that metformin therapy is independently associated with a significant reduction in the risk of malignancy after HTx.

PMID: 28736111 [PubMed - as supplied by publisher]

Effects of pre-load variations on hemodynamic parameters with a pulsatile autoregulated artificial heart during the early post-operative period.

Tue, 07/25/2017 - 12:45
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Effects of pre-load variations on hemodynamic parameters with a pulsatile autoregulated artificial heart during the early post-operative period.

J Heart Lung Transplant. 2017 Jul 08;:

Authors: Bizouarn P, Roussel JC, Trochu JN, Perlès JC, Latrémouille C

PMID: 28736110 [PubMed - as supplied by publisher]

Effects of Sildenafil and Tadalafil on Edema and Reactive Oxygen Species Production in an Experimental Model of Lung Ischemia-Reperfusion Injury.

Tue, 07/25/2017 - 12:45
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Effects of Sildenafil and Tadalafil on Edema and Reactive Oxygen Species Production in an Experimental Model of Lung Ischemia-Reperfusion Injury.

Transplant Proc. 2017 Jul - Aug;49(6):1461-1466

Authors: Guerra-Mora JR, Perales-Caldera E, Aguilar-León D, Nava-Sanchez C, Díaz-Cruz A, Díaz-Martínez NE, Santillán-Doherty P, Torres-Villalobos G, Bravo-Reyna CC

Abstract
BACKGROUND: Lung ischemia-reperfusion injury is characterized by formation of reactive oxygen species and cellular swelling leading to pulmonary edema and primary graft dysfunction. Phosphodiesterase 5 inhibitors could ameliorate lung ischemia-reperfusion injury by interfering in many molecular pathways. The aim of this work was to evaluate and compare the effects of sildenafil and tadalafil on edema and reactive oxygen species formation in an ex vivo nonhuman animal model of lung ischemia-reperfusion injury.
METHODS: Thirty-two Wistar rats were distributed, treated, perfused and the cardiopulmonary blocks were managed as follows: control group: immediate excision and reperfusion without pretreatment; ischemia reperfusion group: treatment with dimethylsulfoxide 0.9% and excision 1 hour later; sildenafil group: treatment with sildenafil (0.7 mg/kg) and excision 1 hour later; and tadalafil group: treatment with tadalafil (0.15 mg/kg) and excision 2 hours later. All cardiopulmonary blocks except control group were preserved for 8 hours and then reperfused. Pulmonary arterial pressure, pulmonary venous pressure, and capillary filtration coefficient were measured. Reactive oxygen species were measured.
RESULTS: Edema was similar between control and sildenafil groups, but significantly greater in the ischemia-reperfusion (P ≤ .04) and tadalafil (P ≤ .003) groups compared with the sildenafil group. The malondialdehyde levels were significantly lower in the sildenafil (P ≤ .001) and tadalafil (P ≤ .001) groups than the ischemia-reperfusion group.
CONCLUSIONS: Administration of sildenafil, but not tadalafil, decreased edema in lung ischemia-reperfusion injury. Both drugs decreased reactive oxygen species formation in a lung ischemia-reperfusion injury model.

PMID: 28736024 [PubMed - in process]

Extracorporeal Life Support as a Bridge to Lung Transplantation in Patients With Acute Respiratory Failure.

Tue, 07/25/2017 - 12:45
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Extracorporeal Life Support as a Bridge to Lung Transplantation in Patients With Acute Respiratory Failure.

Transplant Proc. 2017 Jul - Aug;49(6):1430-1435

Authors: Yeo HJ, Lee S, Yoon SH, Lee SE, Cho WH, Jeon D, Kim YS, Kim D

Abstract
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is being used more often as a bridge to transplantation (BTT) in patients with acutely decompensated end-stage lung disease in Korea. ECMO as a BTT may be the only rescue strategy for severe acute respiratory failure, but many centers still consider it to be a relative contraindication to lung transplantation because of its poor outcome. Because there are not enough lung donors, it is important to determine their optimal use. We reviewed and analyzed our experiences with the use of ECMO as a BTT in patients with acute respiratory failure.
METHODS: This was a retrospective analysis of all patients with acutely decompensated end-stage lung disease treated with ECMO as a bridge to lung transplantation between March 2012 and February 2016.
RESULTS: Of the 194 patients who underwent respiratory ECMO over a 4-year period, a BTT strategy was used for 19 patients (median age, 58 years) on our institution's lung transplantation waiting list (15 veno-venous, 3 veno-veno-arterial, 1 veno-arterial). Fourteen patients (73.7%) were successfully bridged to transplantation; however, 3 died while on the waiting list and 2 returned to their baseline functions without transplantation. The overall in-hospital survival rate was 57.9% (11 of 19), including the 9 (64.3%) patients who underwent transplantation.
CONCLUSIONS: Our findings support the view that well-selected candidates with acutely decompensated end-stage lung disease may be safely bridged until a suitable donor is identified. ECMO is not able to reverse the course of patients; however, it could be a life-saving option for patients with acute respiratory failure requiring lung transplantation.

PMID: 28736018 [PubMed - in process]

Transesophageal Echocardiography Monitoring During Lung Transplantation.

Tue, 07/25/2017 - 12:45
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Transesophageal Echocardiography Monitoring During Lung Transplantation.

J Cardiothorac Vasc Anesth. 2017 Mar 30;:

Authors: Essandoh M, Bhatt A, Flores A, Whitson B

PMID: 28735810 [PubMed - as supplied by publisher]

Adaptive periodic paralysis allows weaning deep sedation overcoming the drowning syndrome in ECMO patients bridged for lung transplantation: A case series.

Mon, 07/24/2017 - 12:45
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Adaptive periodic paralysis allows weaning deep sedation overcoming the drowning syndrome in ECMO patients bridged for lung transplantation: A case series.

J Crit Care. 2017 Jul 17;42:157-161

Authors: Timofte I, Terrin M, Barr E, Kim J, Rinaldi J, Ladikos N, Menaker J, Tabatabai A, Kon Z, Griffith B, Pierson R, Pham S, Iacono A, Herr D

Abstract
PURPOSE: Sedation in extracorporeal membrane oxygenation (ECMO) is challenging. Patients require deep sedation because of extremely high respiratory rates and increased work of breathing ("Drowning Syndrome") resulting in altered intra-thoracic pressure and reduced pump flow associated with hemodynamic compromise and decreased oxygenation. However, deep sedation impedes essential active rehabilitation with physical therapy.
METHODS: We reviewed data on 3 ECMO patients for whom we used a novel approach to replace continuous drips with periodic sedation/paralysis. Initially our patients were on high dose narcotics, propofol, and dexmedetomidine and unable to interact and breathe comfortably. IV narcotics were weaned over 24h and were replaced by methadone. Dexmedetomidine was continued in order to block hyperadrenergic events. Propofol was weaned at a prescribed rate. When patients demonstrated agitation, decreased pump flow and hemodynamic compromise, diazepam was given in combination with a paralytic.
RESULTS: By replacing IV narcotic and propofol, with PRN diazepam and vecuronium, patients were off continuous drips in 1week and were able to actively participate in physical therapy.
CONCLUSION: Allowing patients to wake up by rapid weaning of continuous narcotics and anesthetic agents using Dexmedetomidine and periodic paralysis to favorably alter hemodynamics is a successful method to wean deep sedation in ECMO.

PMID: 28735156 [PubMed - as supplied by publisher]

Outcome of lung transplantation in idiopathic pulmonary fibrosis with previous anti-fibrotic therapy.

Mon, 07/24/2017 - 12:45
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Outcome of lung transplantation in idiopathic pulmonary fibrosis with previous anti-fibrotic therapy.

J Heart Lung Transplant. 2017 Jul 05;:

Authors: Leuschner G, Stocker F, Veit T, Kneidinger N, Winter H, Schramm R, Weig T, Matthes S, Ceelen F, Arnold P, Munker D, Klenner F, Hatz R, Frankenberger M, Behr J, Neurohr C

Abstract
BACKGROUND: Anti-fibrotic drugs may interfere with wound-healing after major surgery, theoretically preventing sufficient bronchial anastomosis formation after lung transplantation (LTx). The aim of this study was to assess the impact of previous treatment with pirfenidone and nintedanib on outcomes after LTx in patients with idiopathic pulmonary fibrosis (IPF).
METHODS: All patients with IPF undergoing LTx at the University of Munich between January 2012 and November 2016 were retrospectively screened for previous use of anti-fibrotics. Post-transplant outcome and survival of patients with and without anti-fibrotic treatment were analyzed.
RESULTS: A total of 62 patients with IPF were transplanted (lung allocation score [mean ± SD] 53.1 ± 16.1). Of these, 23 (37.1%) received pirfenidone and 7 (11.3%) received nintedanib before LTx; the remaining 32 (51.6%) did not receive any anti-fibrotic drug (control group). Patients receiving anti-fibrotics were significantly older (p = 0.004) and their carbon monoxide diffusion capacity was significantly higher (p = 0.008) than in controls. Previous anti-fibrotic treatment did not increase blood product utilization, wound-healing or anastomotic complications after LTx. Post-transplant surgical revisions due to bleeding and/or impaired wound-healing were necessary in 18 (29.0%) patients (pirfenidone 30.4%, nintedanib 14.3%, control 31.3%; p = 0.66). Anastomosis insufficiency occurred in 2 (3.2%) patients, both in the control group. No patient died within the first 30 days post-LTx, and no significant differences regarding survival were seen during the follow-up (12-month survival: pirfenidone 77.0%, nintedanib 100%, control 90.6%; p = 0.29).
CONCLUSION: Our data show that previous use of anti-fibrotic therapy does not increase surgical complications or post-operative mortality after LTx.

PMID: 28734935 [PubMed - as supplied by publisher]

Respiratory Infections and Antibiotic Usage in Common Variable Immunodeficiency.

Mon, 07/24/2017 - 12:45
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Respiratory Infections and Antibiotic Usage in Common Variable Immunodeficiency.

J Allergy Clin Immunol Pract. 2017 Jul 19;:

Authors: Sperlich JM, Grimbacher B, Workman S, Haque T, Seneviratne SL, Burns SO, Reiser V, Vach W, Hurst JR, Lowe DM

Abstract
BACKGROUND: Patients with common variable immunodeficiency (CVID) suffer frequent respiratory tract infections despite immunoglobulin replacement and are prescribed significant quantities of antibiotics. The clinical and microbiological nature of these exacerbations, the symptomatic triggers to take antibiotics, and the response to treatment have not been previously investigated.
OBJECTIVES: To describe the nature, frequency, treatment, and clinical course of respiratory tract exacerbations in patients with CVID and to describe pathogens isolated during respiratory tract exacerbations.
METHODS: We performed a prospective diary card exercise in 69 patients with CVID recruited from a primary immunodeficiency clinic in the United Kingdom, generating 6210 days of symptom data. We collected microbiology (sputum microscopy and culture, atypical bacterial PCR, and mycobacterial culture) and virology (nasopharyngeal swab multiplex PCR) samples from symptomatic patients with CVID.
RESULTS: There were 170 symptomatic exacerbations and 76 exacerbations treated by antibiotics. The strongest symptomatic predictors for commencing antibiotics were cough, shortness of breath, and purulent sputum. There was a median delay of 5 days from the onset of symptoms to commencing antibiotics. Episodes characterized by purulent sputum responded more quickly to antibiotics, whereas sore throat and upper respiratory tract symptoms responded less quickly. A pathogenic virus was isolated in 56% of respiratory exacerbations and a potentially pathogenic bacteria in 33%.
CONCLUSIONS: Patients with CVID delay and avoid treatment of symptomatic respiratory exacerbations, which could result in structural lung damage. However, viruses are commonly represented and illnesses dominated by upper respiratory tract symptoms respond poorly to antibiotics, suggesting that antibiotic usage could be better targeted.

PMID: 28734862 [PubMed - as supplied by publisher]

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