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Utility of PET scan in diagnosis and monitoring descending necrotizing mediastinitis complicating Lemierre's syndrome.

Sat, 08/05/2017 - 12:45
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Utility of PET scan in diagnosis and monitoring descending necrotizing mediastinitis complicating Lemierre's syndrome.

Intern Emerg Med. 2017 Aug 03;:

Authors: Carandini T, Longari V, Mendogni P, Gaffuri M, Ceriani E

PMID: 28776174 [PubMed - as supplied by publisher]

Viridans group streptococci bloodstream infections in neutropenic adult patients with hematologic malignancy: Single center experience.

Sat, 08/05/2017 - 12:45
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Viridans group streptococci bloodstream infections in neutropenic adult patients with hematologic malignancy: Single center experience.

Folia Microbiol (Praha). 2017 Aug 03;:

Authors: Radocha J, Paterová P, Zavřelová A, Víšek B, Gabalec F, Žemličková H, Žák P

Abstract
Viridans group streptococci bloodstream infections (VGS BSI) remain a significant cause of mortality and morbidity in patients with severe neutropenia. The goal of our study was to evaluate clinical course and microbiological susceptibility of VGS BSI at our center. Retrospective analysis of all microbiologically documented bloodstream infections caused by VGS during the 9-year time period (from January 2006 until December 2014) was carried out. Only patients with severe neutropenia (< 500/μL) were included in the study. Clinical outcome and microbiological susceptibility pattern of isolates were recorded. Fifty-one individual patients with episode of VGS BSI were identified. The most frequent agent was Streptococcus mitis (23/51 cases, 45.1%). 88.2% (45/51) of patients were on recommended ciprofloxacin prophylaxis. 20/51 (39.2%) of patients suffered from mucositis at the time of diagnosis (10 patients had oral mucositis, 2 patients had bowel mucositis, and 8 patients both). Twenty-six patients (51.0%) had clinically relevant lung damage caused by VGS BSI (i.e., acute lung injury or acute respiratory distress syndrome). Twenty-four (47.0%) patients presented with bilateral lung infiltrated upon chest imaging, and two (4.0%) patients had unilateral lung infiltrates. Three patients (5.9%) died due to VGS BSI until day 28 of observation. No difference in signs of shock syndrome was observed in the patients during transplantation procedures compared to patients without transplantation as well as in a group received previous high-dose chemotherapy with cytosinarabinoside or in patients with mucositis. Only 3/51 of isolates (5.9%) were resistant to penicillin. All isolates were susceptible to empirical treatment. While the penicillin resistance of VGS remains low in middle Europe, initial antibiotic therapy of febrile neutropenia are still effective in most cases. The mortality and complication rates of VGS BSI were comparable to other studies, and no specific risk factor of shock presence could be identified.

PMID: 28776170 [PubMed - as supplied by publisher]

Delivering an in-Home Exercise Program via Telerehabilitation: A Pilot Study of Lung Transplant Go (LTGO).

Sat, 08/05/2017 - 12:45
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Delivering an in-Home Exercise Program via Telerehabilitation: A Pilot Study of Lung Transplant Go (LTGO).

Int J Telerehabil. 2016;8(2):15-26

Authors: Choi J, Hergenroeder AL, Burke L, Dabbs AD, Morrell M, Saptono A, Parmanto B

Abstract
We evaluated the feasibility, safety, system usability, and intervention acceptability of Lung Transplant Go (LTGO), an 8-week in-home exercise intervention for lung transplant recipients using a telerehabilitation platform, and described changes in physical function and physical activity from baseline to post-intervention. The intervention was delivered to lung transplant recipients in their home via the Versatile and Integrated System for TeleRehabilitation (VISYTER). The intervention focused on aerobic and strengthening exercises tailored to baseline physical function. Participants improved walk distance (6-minute walk distance), balance (Berg Balance Scale), lower body strength (30-second chair stand test) and steps walked (SenseWear Armband®). No adverse events were reported. Participants rated the program highly positively in regard to the technology and intervention. The telerehabilitation exercise program was feasible, safe, and acceptable. Our findings provide preliminary support for the LTGO intervention to improve physical function and promote physical activity in lung transplant recipients.

PMID: 28775798 [PubMed]

Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension.

Sat, 08/05/2017 - 12:45
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Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension.

Eur Respir J. 2017 Aug;50(2):

Authors: Boucly A, Weatherald J, Savale L, Jaïs X, Cottin V, Prevot G, Picard F, de Groote P, Jevnikar M, Bergot E, Chaouat A, Chabanne C, Bourdin A, Parent F, Montani D, Simonneau G, Humbert M, Sitbon O

Abstract
Current European guidelines recommend periodic risk assessment for patients with pulmonary arterial hypertension (PAH). The aim of our study was to determine the association between the number of low-risk criteria achieved within 1 year of diagnosis and long-term prognosis.Incident patients with idiopathic, heritable and drug-induced PAH between 2006 and 2016 were analysed. The number of low-risk criteria present at diagnosis and at first re-evaluation were assessed: World Health Organization (WHO)/New York Heart Association (NYHA) functional class I or II, 6-min walking distance (6MWD) >440 m, right atrial pressure <8 mmHg and cardiac index ≥2.5 L·min(-1)·m(-2)1017 patients were included (mean age 57 years, 59% female, 75% idiopathic PAH). After a median follow-up of 34 months, 238 (23%) patients had died. Each of the four low-risk criteria independently predicted transplant-free survival at first re-evaluation. The number of low-risk criteria present at diagnosis (p<0.001) and at first re-evaluation (p<0.001) discriminated the risk of death or lung transplantation. In addition, in a subgroup of 603 patients with brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements, the number of three noninvasive criteria (WHO/NYHA functional class, 6MWD and BNP/NT-proBNP) present at first re-evaluation discriminated prognostic groups (p<0.001).A simplified risk assessment tool that quantifies the number of low-risk criteria present accurately predicted transplant-free survival in PAH.

PMID: 28775050 [PubMed - in process]

[Expert Knowledge and Supporting Advice for the Clinical Use of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis].

Sat, 08/05/2017 - 12:45
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[Expert Knowledge and Supporting Advice for the Clinical Use of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis].

Pneumologie. 2017 Aug 03;:

Authors: Behr J, Günther A, Kreuter M, Koschel D, Prasse A, Pfeifer M, Costabel U

Abstract
In October 2016, a group of German IPF experts were invited by Boehringer Ingelheim to meet in Frankfurt with the aim, (a) to discuss relevant aspects of the management and treatment of idiopathic pulmonary fibrosis (IPF) using nintedanib; and, (b) to provide supportive advice for daily clinical practice with nintedanib. The resulting information compiled in this document is confined to practical issues regarding the use of nintedanib in patients with IPF. Where different therapeutic options were available, the choice of IPF medication was not discussed and the experts alluded to current guidelines for the diagnosis and treatment of IPF.The participants discussed a comprehensive spectrum of clinical questions related to 10 different topics, including patient-related aspects at initiation of IPF therapy, the treatment of anticoagulated IPF patients, and the handling of nintedanib-related adverse events such as gastrointestinal side effects and elevated liver enzymes. In addition, the experts evaluated therapeutic options for IPF patients with continuous disease progression, clinical scenarios that justify discontinuation of nintedanib treatment, and therapeutic options for IPF patients with an acute exacerbation or severe infection. Finally, the participants discussed the handling of nintendanib before/after elective surgical intervention (e. g. lung transplantation) and the current evidence for antifibrotic combination therapy in patients with IPF.For each topic discussed, the resulting information incorporates published evidence from clinical trials. In case of insufficient or lacking evidence, the experts have formulated recommendations based on their personal clinical experience and evaluation.

PMID: 28772332 [PubMed - as supplied by publisher]

Implantation of a left ventricular assist device to provide long-term support for end-stage Duchenne muscular dystrophy-associated cardiomyopathy.

Sat, 08/05/2017 - 12:45
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Implantation of a left ventricular assist device to provide long-term support for end-stage Duchenne muscular dystrophy-associated cardiomyopathy.

ESC Heart Fail. 2017 Aug;4(3):379-383

Authors: Stoller D, Araj F, Amin A, Fitzsimmons C, Morlend R, Thibodeau JT, Ramaciotti C, Drazner MH, Meyer DM, Mammen PPA

Abstract
A young man with Duchenne muscular dystrophy presented to the UT Southwestern Neuromuscular Cardiomyopathy Clinic with advanced heart failure. Despite maximal medical therapy, his cardiac function continued to decline requiring initiation of inotrope therapy. Given the patient's clinical deterioration, a left ventricular assist device (LVAD) was implanted as destination therapy after undergoing a multidisciplinary assessment. The patient tolerated the surgical implantation of the LVAD without any significant complications, and he has had a relatively unremarkable course 38 months post-LVAD implantation. A critical factor contributing to the long-term success of this patient was the decision to select an LVAD that would not disrupt the diaphragm and thus preserve the respiratory muscle strength. This case demonstrates that permanent mechanical LVADs should be considered for appropriately selected Duchenne muscular dystrophy patients with medically refractory end-stage cardiomyopathy.

PMID: 28772036 [PubMed]

Challenges in the implementation of EAACI Guidelines on Allergen Immunotherapy: A global perspective on the regulation of allergen products.

Sat, 08/05/2017 - 12:45
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Challenges in the implementation of EAACI Guidelines on Allergen Immunotherapy: A global perspective on the regulation of allergen products.

Allergy. 2017 Aug 03;:

Authors: Bonertz A, Roberts G, Hoefnagel M, Timon M, Slater J, Rabin R, Bridgewater J, Pini C, Pfaar O, Akdis C, Goldstein J, Poulsen LK, van Ree R, Rhyner C, Barber D, Palomares O, Sheikh A, Pawankar R, Hamerlijnk D, Klimek L, Agache I, Angier E, Casale T, Fernandez-Rivas M, Halken S, Jutel M, Lau S, Pajno G, Sturm G, Maria Varga E, van Wijk RG, Bonini S, Muraro A, Vieths S

Abstract
Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly by either obtaining a marketing authorisation or by being distributed as named patient products. Exemptions from marketing authorisations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration. This article is protected by copyright. All rights reserved.

PMID: 28771830 [PubMed - as supplied by publisher]

Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype.

Sat, 08/05/2017 - 12:45
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Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype.

PLoS Comput Biol. 2017 Aug;13(8):e1005629

Authors: Sharon E, Shi H, Kharbanda S, Koh W, Martin LR, Khush KK, Valantine H, Pritchard JK, De Vlaminck I

Abstract
Quantification of cell-free DNA (cfDNA) in circulating blood derived from a transplanted organ is a powerful approach to monitoring post-transplant injury. Genome transplant dynamics (GTD) quantifies donor-derived cfDNA (dd-cfDNA) by taking advantage of single-nucleotide polymorphisms (SNPs) distributed across the genome to discriminate donor and recipient DNA molecules. In its current implementation, GTD requires genotyping of both the transplant recipient and donor. However, in practice, donor genotype information is often unavailable. Here, we address this issue by developing an algorithm that estimates dd-cfDNA levels in the absence of a donor genotype. Our algorithm predicts heart and lung allograft rejection with an accuracy that is similar to conventional GTD. We furthermore refined the algorithm to handle closely related recipients and donors, a scenario that is common in bone marrow and kidney transplantation. We show that it is possible to estimate dd-cfDNA in bone marrow transplant patients that are unrelated or that are siblings of the donors, using a hidden Markov model (HMM) of identity-by-descent (IBD) states along the genome. Last, we demonstrate that comparing dd-cfDNA to the proportion of donor DNA in white blood cells can differentiate between relapse and the onset of graft-versus-host disease (GVHD). These methods alleviate some of the barriers to the implementation of GTD, which will further widen its clinical application.

PMID: 28771616 [PubMed - in process]

Solid Organ Transplant-Transmitted Tuberculosis Linked to a Community Outbreak - California, 2015.

Sat, 08/05/2017 - 12:45
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Solid Organ Transplant-Transmitted Tuberculosis Linked to a Community Outbreak - California, 2015.

MMWR Morb Mortal Wkly Rep. 2017 Aug 04;66(30):801-805

Authors: Kay A, Barry PM, Annambhotla P, Greene C, Cilnis M, Chin-Hong P, Arger N, McNitt L, Neidlinger N, Shah N, Basavaraju SV, Kuehnert M, Shaw T

Abstract
In the spring of 2015, a local health department (LHD) in county A notified the California Department of Public Health (CDPH) about three adults with close ties to one another and a congregate community site who had received diagnoses of tuberculosis (TB) disease within a 3-month period. Subsequent review revealed matching TB genotypes indicating that the cases were likely part of a chain of TB transmission. Only three TB cases in California in the preceding 2 years shared this same genotype. One of those three previous cases occurred in a lung-transplant recipient who had no identified epidemiologic links to the outbreak. CDPH, multiple LHDs, and CDC conducted an investigation and determined that the lung-transplant donor (patient 1) was epidemiologically linked to the three outbreak cases and had a tuberculin skin test (TST) conversion detected in 2012 upon reentry at a local jail. Three other solid organ recipients from this donor were identified; none had developed TB disease. This investigation suggests that review of organ donors' medical records from high-risk environments, such as jails, might reveal additional information about TB risk. The evaluation of TB in organ recipients could include genotyping analysis (1) and coordination among local, state, and national partners to evaluate the potential for donor-derived TB.

PMID: 28771459 [PubMed - in process]

Pitfalls in developing new compounds for idiopathic pulmonary fibrosis.

Sat, 08/05/2017 - 12:45
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Pitfalls in developing new compounds for idiopathic pulmonary fibrosis.

Curr Opin Pulm Med. 2017 Sep;23(5):426-431

Authors: Nathan SD, Martinez FJ

Abstract
PURPOSE OF REVIEW: The development and availability of nintedanib and pirfenidone has heralded a new era in the management of idiopathic pulmonary fibrosis (IPF). Both agents demonstrate that the disease can be successfully modulated with therapeutic interventions, but neither are a cure and IPF remains a deadly disease.
RECENT FINDINGS: There have been many lessons about the natural history of IPF and clinical trial design, not only from the clinical development programs for nintedanib and pirfenidone, but also the numerous negative trials that predated these.
SUMMARY: In this review, we attempt to synthesize how the field of IPF and clinical trials has evolved, the lessons learnt, and how these might inform and enable more efficient future clinical trial designs that are primed for success.

PMID: 28771451 [PubMed - in process]

Epithelial-to-Mesenchymal Transition and MicroRNAs in Lung Cancer.

Sat, 08/05/2017 - 12:45
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Epithelial-to-Mesenchymal Transition and MicroRNAs in Lung Cancer.

Cancers (Basel). 2017 Aug 03;9(8):

Authors: Legras A, Pécuchet N, Imbeaud S, Pallier K, Didelot A, Roussel H, Gibault L, Fabre E, Le Pimpec-Barthes F, Laurent-Puig P, Blons H

Abstract
Despite major advances, non-small cell lung cancer (NSCLC) remains the major cause of cancer-related death in developed countries. Metastasis and drug resistance are the main factors contributing to relapse and death. Epithelial-to-mesenchymal transition (EMT) is a complex molecular and cellular process involved in tissue remodelling that was extensively studied as an actor of tumour progression, metastasis and drug resistance in many cancer types and in lung cancers. Here we described with an emphasis on NSCLC how the changes in signalling pathways, transcription factors expression or microRNAs that occur in cancer promote EMT. Understanding the biology of EMT will help to define reversing process and treatment strategies. We will see that this complex mechanism is related to inflammation, cell mobility and stem cell features and that it is a dynamic process. The existence of intermediate phenotypes and tumour heterogeneity may be debated in the literature concerning EMT markers, EMT signatures and clinical consequences in NSCLC. However, given the role of EMT in metastasis and in drug resistance the development of EMT inhibitors is an interesting approach to counteract tumour progression and drug resistance. This review describes EMT involvement in cancer with an emphasis on NSCLC and microRNA regulation.

PMID: 28771186 [PubMed]

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation.

Sat, 08/05/2017 - 12:45
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Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation.

Front Med (Lausanne). 2017;4:109

Authors: Koutsokera A, Royer PJ, Antonietti JP, Fritz A, Benden C, Aubert JD, Tissot A, Botturi K, Roux A, Reynaud-Gaubert ML, Kessler R, Dromer C, Mussot S, Mal H, Mornex JF, Guillemain R, Knoop C, Dahan M, Soccal PM, Claustre J, Sage E, Gomez C, Magnan A, Pison C, Nicod LP, SysCLAD Consortium

Abstract
BACKGROUND: Chronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after lung transplantation (LT). RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described.
METHODS: LT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis.
RESULTS: Among patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs). Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS.
CONCLUSION: Although these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach.

PMID: 28770204 [PubMed]

Sudden Death in a Patient with Pulmonary Veno-occlusive Disease (PVOD) and Severe Pulmonary Hypertension.

Sat, 08/05/2017 - 12:45
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Sudden Death in a Patient with Pulmonary Veno-occlusive Disease (PVOD) and Severe Pulmonary Hypertension.

Intern Med. 2017;56(15):2025-2031

Authors: Saito M, Ohshima N, Matsui H, Hebisawa A, Ohta K

Abstract
A 58-year-old woman was referred to our hospital with a chief complaint of exertional dyspnea. Bronchoscopy failed to establish a diagnosis, and the patient subsequently died suddenly due to respiratory insufficiency because of advanced pulmonary hypertension (PH). The pathological diagnosis at autopsy was pulmonary veno-occlusive disease (PVOD). PVOD is difficult to diagnose antemortem and has a poor prognosis. Lung transplantation is the only curative treatment for PVOD.

PMID: 28768975 [PubMed - in process]

Muir-Torre syndrome: multiple sebaceous neoplasms and visceral malignancy manifesting after cardiac transplantation and iatrogenic immunosuppression.

Sat, 08/05/2017 - 12:45
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Muir-Torre syndrome: multiple sebaceous neoplasms and visceral malignancy manifesting after cardiac transplantation and iatrogenic immunosuppression.

Int J Dermatol. 2017 Feb;56(2):e26-e27

Authors: Shaw KC, Altmayer SA, Driscoll MS

PMID: 27868185 [PubMed - indexed for MEDLINE]

Disseminated nocardiosis after unrelated bone marrow transplantation.

Sat, 08/05/2017 - 12:45
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Disseminated nocardiosis after unrelated bone marrow transplantation.

Transpl Infect Dis. 2016 Dec;18(6):942-945

Authors: Hino Y, Doki N, Senoo Y, Sekiya N, Kurosawa S, Tsuboi S, Ohashi K

Abstract
Nocardiosis is a rare bacterial infection occurring mainly in patients with deficient cell-mediated immunity. Although disseminated nocardiosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a rare complication, it is associated with high mortality. Moreover, after allo-HSCT, nocardiosis may be mistaken for other bacterial or fungal infections because clinical and radiographic findings of pulmonary, cerebral, and cutaneous nocardiosis lesions are non-specific. Here, we report a case of disseminated nocardiosis (caused by Nocardia abscessus) with skin, pulmonary, liver, lymph node, and multiple brain abscesses in a patient after allo-HSCT. The patient initially responded clinically and radiographically to imipenem/cilastin and trimethoprim-sulfamethoxazole therapy. Clinicians should be aware of the possibility of nocardiosis in allo-HSCT recipients who are treated with multiple immunosuppressive agents to control chronic graft-versus-host disease. Accurate diagnosis and identification of disseminated nocardiosis is important to ensure administration of the correct antibiotic regimen.

PMID: 27696601 [PubMed - indexed for MEDLINE]

An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer.

Sat, 08/05/2017 - 12:45
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An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer.

Cancer Res. 2016 Oct 01;76(19):5870-5880

Authors: Jin CS, Wada H, Anayama T, McVeigh PZ, Hu HP, Hirohashi K, Nakajima T, Kato T, Keshavjee S, Hwang D, Wilson BC, Zheng G, Yasufuku K

Abstract
Early detection and efficient treatment modality of early-stage peripheral lung cancer is essential. Current nonsurgical treatments for peripheral lung cancer show critical limitations associated with various complications, requiring alternative minimally invasive therapeutics. Porphysome nanoparticle-enabled fluorescence-guided transbronchial photothermal therapy (PTT) of peripheral lung cancer was developed and demonstrated in preclinical animal models. Systemically administered porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast, as confirmed in three subtypes of orthotopic human lung cancer xenografts (A549, H460, and H520) in mice and in an orthotopic VX2 tumor in rabbits. An in-house prototype fluorescence bronchoscope demonstrated the capability of porphysomes for in vivo imaging of lung tumors in the mucosal/submucosal layers, providing real-time fluorescence guidance for transbronchial PTT. Porphysomes also enhanced the efficacy of transbronchial PTT significantly and resulted in selective and efficient tumor tissue ablation in the rabbit model. A clinically used cylindrical diffuser fiber successfully achieved tumor-specific thermal ablation, showing promising evidence for the clinical translation of this novel platform to impact upon nonsurgical treatment of early-stage peripheral lung cancer. Cancer Res; 76(19); 5870-80. ©2016 AACR.

PMID: 27543602 [PubMed - indexed for MEDLINE]

Optimum support by high-flow nasal cannula in acute hypoxemic respiratory failure: effects of increasing flow rates.

Wed, 08/02/2017 - 10:00
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Optimum support by high-flow nasal cannula in acute hypoxemic respiratory failure: effects of increasing flow rates.

Intensive Care Med. 2017 Jul 31;:

Authors: Mauri T, Alban L, Turrini C, Cambiaghi B, Carlesso E, Taccone P, Bottino N, Lissoni A, Spadaro S, Volta CA, Gattinoni L, Pesenti A, Grasselli G

Abstract
PURPOSE: Limited data exist on the correlation between higher flow rates of high-flow nasal cannula (HFNC) and its physiologic effects in patients with acute hypoxemic respiratory failure (AHRF). We assessed the effects of HFNC delivered at increasing flow rate on inspiratory effort, work of breathing, minute ventilation, lung volumes, dynamic compliance and oxygenation in AHRF patients.
METHODS: A prospective randomized cross-over study was performed in non-intubated patients with patients AHRF and a PaO2/FiO2 (arterial partial pressure of oxygen/fraction of inspired oxygen) ratio of ≤300 mmHg. A standard non-occlusive facial mask and HFNC at different flow rates (30, 45 and 60 l/min) were randomly applied, while maintaining constant FiO2 (20 min/step). At the end of each phase, we measured arterial blood gases, inspiratory effort, based on swings in esophageal pressure (ΔPes) and on the esophageal pressure-time product (PTPPes), and lung volume, by electrical impedance tomography.
RESULTS: Seventeen patients with AHRF were enrolled in the study. At increasing flow rate, HFNC reduced ΔPes (p < 0.001) and PTPPes (p < 0.001), while end-expiratory lung volume (ΔEELV), tidal volume to ΔPes ratio (V T/ΔPes, which corresponds to dynamic lung compliance) and oxygenation improved (p < 0.01 for all factors). Higher HFNC flow rate also progressively reduced minute ventilation (p < 0.05) without any change in arterial CO2 tension (p = 0.909). The decrease in ΔPes, PTPPes and minute ventilation at increasing flow rates was better described by exponential fitting, while ΔEELV, V T/ΔPes and oxygenation improved linearly.
CONCLUSIONS: In this cohort of patients with AHRF, an increasing HFNC flow rate progressively decreased inspiratory effort and improved lung aeration, dynamic compliance and oxygenation. Most of the effect on inspiratory workload and CO2 clearance was already obtained at the lowest flow rate.

PMID: 28762180 [PubMed - as supplied by publisher]

Therapeutic strategies for locally recurrent and metastatic de-differentiated liposarcoma with herpes simplex virus-thymidine kinase-expressing mesenchymal stromal cells.

Wed, 08/02/2017 - 10:00
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Therapeutic strategies for locally recurrent and metastatic de-differentiated liposarcoma with herpes simplex virus-thymidine kinase-expressing mesenchymal stromal cells.

Cytotherapy. 2017 Jul 28;:

Authors: Lee H, Jo EB, Kim SJ, Yang HM, Kim YM, Sung YC, Park JB, Hong D, Park H, Choi YL, Kim SJ

Abstract
BACKGROUND AIMS: Major challenges in de-differentiated liposarcoma (DDLPS) therapy are the high rate of sequential recurrence (>80%) and metastasis (20-30%) following surgical removal. However, well-defined therapeutic strategies for this rare malignancy are lacking and are critically needed.
METHODS: We investigated a new approach to DDLPS therapy with mesenchymal stromal cells expressing herpes simplex virus-thymidine kinase (MSC-TK). In an effort to evaluate this efficacy, in vitro cytotoxicity of MSC-TK against DDLPS cells was analyzed using an apoptosis assay. For pre-clinical study, the MSC-TK-induced reduction in recurrence and metastasis was validated in a recurrent DDLPS model after the macroscopic complete resection and lung metastasis DDLPS model.
RESULTS: MSC-TK induced apoptosis in DDLPS cells by bystander effects via gap junction intracellular communication (GJIC) of toxic ganciclovir (GCV). Recurrent DDLPS models following no residual tumor/microscopic tumor resection and lung metastasis DDLPS models were established, which suggested clinical relevance. MSC-TK markedly reduced locoregional recurrence rates and prolonged recurrence-free survival, thus increasing overall survival in the recurrent DDLPS model. MSC-TK followed by GCV treatment yielded a statistically significant reduction in early- and advanced-stage lung metastasis.
DISCUSSION: This therapeutic strategy may serve as an alternative or additional strategy by applying MSC-TK to target residual tumors following surgical resection, thus reducing local relapse and metastasis in these patients.

PMID: 28760351 [PubMed - as supplied by publisher]

Lung Transplantation Delays Gastric Motility in Patients without Prior Gastro-Intestinal Surgery - A Single Center Experience of 412 Consecutive patients.

Tue, 08/01/2017 - 21:53
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Lung Transplantation Delays Gastric Motility in Patients without Prior Gastro-Intestinal Surgery - A Single Center Experience of 412 Consecutive patients.

Clin Transplant. 2017 Jul 31;:

Authors: Hirji SA, Gulack BC, Englum BR, Speicher PJ, Ganapathi AM, Osho AA, Shimpi RA, Perez A, Hartwig MG

Abstract
PURPOSE: To examine the impact of lung transplantation on gastric motility.
METHODS: Adult recipients at a large, single center, who were retrospectively evaluated with solid gastric emptying (SGE) study post lung transplantation, but had no history of gastrointestinal intervention (i.e. pyloroplasty or fundoplication), were selected between June 2005 and August 2013. Multivariable logistic regression was performed to determine risk factors associated with delayed gastric emptying (DGE) after transplantation.
RESULTS: DGE was noted in 236 patients (57%) after transplantation. On multivariable logistic regression, an underlining diagnosis of cystic fibrosis (CF)/bronchiectasis (Adjusted Odds Ratio (AOR) 3.26, p < 0.01) was a significant risk factor in predicting DGE after lung transplantation. There was no survival difference between patients with postoperative DGE versus those without (Log-rank test p=0.53) CONCLUSIONS: Delayed gastric emptying is very common following lung transplantation, occurring in over half of all lung transplant recipients with increased prevalence in CF patients. The association with cystic fibrosis could be secondary to extra-pulmonary manifestations of the underlying disease, or indicative of increased intra-operative vagal nerve injury. We speculate that DGE may play a substantial role in the increased reflux induced allograft injury seen after lung transplantation. Further prospective studies are needed to validate this hypothesis. This article is protected by copyright. All rights reserved.

PMID: 28758244 [PubMed - as supplied by publisher]

Tracheal diverticula in advanced cystic fibrosis: Prevalence, features, and outcomes after lung transplantation.

Tue, 08/01/2017 - 21:53
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Tracheal diverticula in advanced cystic fibrosis: Prevalence, features, and outcomes after lung transplantation.

J Cyst Fibros. 2017 Jul 27;:

Authors: Kapnadak SG, Kicska GA, Ramos KJ, Marshall DA, Carroll TY, Pipavath SN, Mulligan MS, Goss CH, Aitken ML

Abstract
BACKGROUND: Tracheal diverticula (TD) are rare anomalies that may harbor infected secretions, posing potential risk to patients with lung disease. In an end-stage cystic fibrosis (CF) cohort, we describe the characteristics and associated post-lung transplant (LTx) outcomes of TD.
METHODS: Pre-transplant computed tomography (CT)'s were reviewed in CF patients undergoing LTx. TD were characterized radiographically and on autopsy when available. Pre-transplant clinical variables and post-transplant outcomes were compared by TD status.
RESULTS: Of 93 patients, 35 (37.6%) had TD. 58% of TD had fat-stranding, and post-mortem TD examinations revealed histology carrying intense submucosal inflammation, and purulent contents that cultured identical species to sputum. There was no difference in post-LTx survival [HR 1.77 (0.82-3.82), p=0.147], bacterial re-colonization, or rejection in patients with TD compared to those without. Patients with TD were more likely to die from infection, but the result was not statistically significant [HR 2.02 (0.62-6.63), p=0.245].
CONCLUSIONS: We found a high prevalence of TD in end-stage CF, where diverticula may represent a large-airway bacterial reservoir. TD were not associated with differences in post-LTx outcomes, but given the infectious concerns further investigation is necessary.

PMID: 28757079 [PubMed - as supplied by publisher]

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