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Protective lung strategy

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https://www.readbyqxmd.com/read/29045567/individualized-positive-end-expiratory-pressure-in-obese-patients-during-general-anaesthesia-a-randomized-controlled-clinical-trial-using-electrical-impedance-tomography
#1
C Nestler, P Simon, D Petroff, S Hammermüller, D Kamrath, S Wolf, A Dietrich, L M Camilo, A Beda, A R Carvalho, A Giannella-Neto, A W Reske, H Wrigge
Background: General anaesthesia leads to atelectasis, reduced end-expiratory lung volume (EELV), and diminished arterial oxygenation in obese patients. We hypothesized that a combination of a recruitment manoeuvre (RM) and individualized positive end-expiratory pressure (PEEP) can avoid these effects. Methods: Patients with a BMI ≥35 kg m-2 undergoing elective laparoscopic surgery were randomly allocated to mechanical ventilation with a tidal volume of 8 ml kg-1 predicted body weight and (i) an RM followed by individualized PEEP titrated using electrical impedance tomography (PEEPIND) or (ii) no RM and PEEP of 5 cm H2O (PEEP5)...
October 16, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29043832/high-frequency-oscillation-for-adult-patients-with-acute-respiratory-distress-syndrome-a-systematic-review-and-meta-analysis
#2
Ewan Goligher, Laveena Munshi, Neill Kj Adhikari, Maureen O Meade, Carol Hodgson, Hannah Wunsch, Elizabeth Uleryk, Ognjen Gajic, Marcelo Amato, Niall D Ferguson, Gordon D Rubenfeld, Eddy Fan
RATIONALE: By minimizing tidal lung strain and maintaining alveolar recruitment, high frequency oscillatory ventilation (HFOV) may protect against ventilator-induced lung injury. OBJECTIVES: To summarize the current evidence in support of the use of HFOV in adult patients with ARDS. METHODS: We conducted a systematic review and meta-analysis of randomized trials comparing mortality rates with the use of HFOV vs. conventional mechanical ventilation for adult patients with acute respiratory distress syndrome...
October 18, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29024815/identification-of-a-novel-autophagic-inhibitor-cepharanthine-to-enhance-the-anti-cancer-property-of-dacomitinib-in-non-small-cell-lung-cancer
#3
Zheng-Hai Tang, Wen-Xiang Cao, Xia Guo, Xiao-Yang Dai, Jia-Hong Lu, Xiuping Chen, Hong Zhu, Jin-Jian Lu
Inhibition of autophagy is a promising strategy for non-small cell lung cancer (NSCLC) treatment, which is in the clinical trials. However, only chloroquine is used in clinic as an autophagic inhibitor and the inhibitory effect of chloroquine on autophagy is finite. Therefore, the development of an alternative autophagic inhibitor for NSCLC therapy becomes necessary. In the present study, cepharanthine (CEP), an alkaloid extracted from Stephania cepharantha Hayata, was identified as a novel autophagic inhibitor in NSCLC cells...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29023811/placental-growth-factor-inhibition-targets-pulmonary-angiogenesis-and-represents-a-novel-therapy-for-hepatopulmonary-syndrome-in-mice
#4
Sarah Raevens, Anja Geerts, Annelies Paridaens, Sander Lefere, Xavier Verhelst, Anne Hoorens, Jo Van Dorpe, Tania Maes, Ken R Bracke, Christophe Casteleyn, Bart Jonckx, Thomas Horvatits, Valentin Fuhrmann, Hans Van Vlierberghe, Christophe Van Steenkiste, Lindsey Devisscher, Isabelle Colle
Hepatopulmonary syndrome (HPS) is a severe complication of cirrhosis with increased risk of mortality. Pulmonary microvascular alterations are key features of HPS, but underlying mechanisms are incompletely understood, and studies on HPS are limited to rats. Placental growth factor (PlGF), a pro-angiogenic molecule that is selectively involved in pathological angiogenesis, may play an important role in HPS development, however, its role has never been investigated. In this study, we validated an HPS model by common bile duct ligation (CBDL) in mice, investigated the kinetic changes in pulmonary angiogenesis and inflammation during HPS development, and provide evidence for a novel therapeutic strategy by targeting pathological angiogenesis...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28991240/polypharmacology-based-ceritinib-repurposing-using-integrated-functional-proteomics
#5
Brent M Kuenzi, Lily L Remsing Rix, Paul A Stewart, Bin Fang, Fumi Kinose, Annamarie T Bryant, Theresa A Boyle, John M Koomen, Eric B Haura, Uwe Rix
Targeted drugs are effective when they directly inhibit strong disease drivers, but only a small fraction of diseases feature defined actionable drivers. Alternatively, network-based approaches can uncover new therapeutic opportunities. Applying an integrated phenotypic screening, chemical and phosphoproteomics strategy, here we describe the anaplastic lymphoma kinase (ALK) inhibitor ceritinib as having activity across several ALK-negative lung cancer cell lines and identify new targets and network-wide signaling effects...
October 9, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28979565/protective-ventilation-with-veno-venous-lung-assist-in-respiratory-failure-a-protocol-for-a-multicentre-randomised-controlled-trial-of-extracorporeal-carbon-dioxide-removal-in-patients-with-acute-hypoxaemic-respiratory-failure
#6
J J McNamee, M A Gillies, N A Barrett, A M Agus, R Beale, A Bentley, A Bodenham, S J Brett, D Brodie, S J Finney, A J Gordon, M Griffiths, D Harrison, C Jackson, C McDowell, C McNally, G D Perkins, W Tunnicliffe, A Vuylsteke, T S Walsh, M P Wise, D Young, D F McAuley
One of the few interventions to demonstrate improved outcomes for acute hypoxaemic respiratory failure is reducing tidal volumes when using mechanical ventilation, often termed lung protective ventilation. Veno-venous extracorporeal carbon dioxide removal (vv-ECCO2R) can facilitate reducing tidal volumes. pRotective vEntilation with veno-venouS lung assisT (REST) is a randomised, allocation concealed, controlled, open, multicentre pragmatic trial to determine the clinical and cost-effectiveness of lower tidal volume mechanical ventilation facilitated by vv-ECCO2R in patients with acute hypoxaemic respiratory failure...
May 2017: J Intensive Care Soc
https://www.readbyqxmd.com/read/28979556/protective-mechanical-ventilation-in-united-kingdom-critical-care-units-a-multicentre-audit
#7
Christopher P Newell, Matthew J Martin, Neil Richardson, Christopher P Bourdeaux
Lung protective ventilation is becoming increasingly used for all critically ill patients being mechanically ventilated on a mandatory ventilator mode. Compliance with the universal application of this ventilation strategy in intensive care units in the United Kingdom is unknown. This 24-h audit of ventilation practice took place in 16 intensive care units in two regions of the United Kingdom. The mean tidal volume for all patients being ventilated on a mandatory ventilator mode was 7.2(±1.4) ml kg(-1) predicted body weight and overall compliance with low tidal volume ventilation (≤6...
May 2017: J Intensive Care Soc
https://www.readbyqxmd.com/read/28977826/ilomastat-a-synthetic-inhibitor-of-mmps-prevents-lung-injury-induced-by-%C3%AE-ray-irradiation-in-mice
#8
Xiaoman Li, Dehui Ma, Xiaodan Zha, Dongqin Quan, Dong Pan, Manji Sun, Burong Hu, Baoquan Zhao
Lung injury is one of the pathological features in human or animal after radiation and the main side effect for patient after lung cancer radiotherapy. The efficient protective strategy still needs to exploit and the underlying mechanisms remain to be investigated. We found that the expression and activity of matrix metalloproteinases (MMPs) significantly increased at the early stage of radiation-induced lung injury (RILI). Pretreatment with Ilomastat, a synthetic inhibitor of MMPs, decreased the expression and activity of MMPs and significantly alleviated the lung inflammation and fibrosis in the irradiated mice, as well as enhanced the survival of irradiated mice...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977263/does-the-use-of-high-peep-levels-prevent-ventilator-induced-lung-injury
#9
Guillermo Bugedo, Jaime Retamal, Alejandro Bruhn
Overdistention and intratidal alveolar recruitment have been advocated as the main physical mechanisms responsible for ventilator-induced lung injury. Limiting tidal volume has a demonstrated survival benefit in patients with acute respiratory distress syndrome and is recognized as the cornerstone of protective ventilation. In contrast, the use of high positive end-expiratory pressure levels in clinical trials has yielded conflicting results and remains controversial. In the present review, we will discuss the benefits and limitations of the open lung approach and will discuss some recent experimental and clinical trials on the use of high versus low/moderate positive end-expiratory pressure levels...
April 2017: Revista Brasileira de Terapia Intensiva
https://www.readbyqxmd.com/read/28976703/the-effects-of-nrf2-modulation-on-the-initiation-and-progression-of-chemically-and-genetically-induced-lung-cancer
#10
Shasha Tao, Montserrat Rojo de la Vega, Eli Chapman, Aikseng Ooi, Donna D Zhang
Targeting the transcription factor NRF2 has been recognized as a feasible strategy for cancer prevention and treatment, but many of the mechanistic details underlying its role in cancer development and progression are lacking. Therefore, careful mechanistic studies of the NRF2 pathway in cancer initiation and progression are needed to identify which therapeutic avenue-activation or inhibition-is appropriate in a given context. Moreover, while numerous reports confirm the protective effect of NRF2 activation against chemical carcinogenesis little is known of its role in cancer arising from spontaneous mutations...
October 4, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28976121/strategies-used-in-the-clinical-trials-of-gene-therapy-for-cancer
#11
Thekkuttuparambil Ananthanarayanan Ajith
Advances in understanding and manipulating genes have set the stage for scientists to alter a person's genetic material to prevent or treat diseases. Over the past decade, somatic gene therapy has been increasingly applied in clinical trials where the genetic material (DNA and RNA) introduced into a person's cell. Mutation and inactivation of the tumor suppressor genes are the unified concept of the development of tumor in humans. Therefore, researchers have discovered potential of gene therapies in the treatment of cancer...
September 2017: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/28974367/multiplex-peptide-mhc-tetramer-staining-using-mass-cytometry-for-deep-analysis-of-the-influenza-specific-t-cell-response-in-mice
#12
M Fehlings, S Chakarov, Y Simoni, B Shivshankar, F Ginhoux, E W Newell
Antigen-specific T cells play a crucial role for the host protective immunity against viruses and other diseases. The combination of mass cytometry together with a combinatorial multiplex tetramer staining has successfully been applied for probing and characterization of multiple antigen-specific CD8(+) T cells in human blood samples. The present study shows that this approach can also be used to rapidly identify the magnitude of influenza-specific CD8(+) T cell peptide dominance across lymph nodes and lungs in a murine model of a highly pathological influenza infection...
September 30, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28972662/single-center-experience-in-urgent-lung-transplantation-program-in-a-country-with-a-shortage-of-donors-does-the-end-justify-the-means
#13
Marco Schiavon, Giulio Faggi, Guido Di Gregorio, Calabrese Francesca, Francesca Lunardi, Giuseppe Marulli, Paolo Feltracco, Monica Loy, Marco Damin, Emanuele Cozzi, Dario Gregori, Fiorella Calabrese, Federico Rea
In rapidly deteriorating patients awaiting lung transplantation (LT), supportive strategies are only temporary and Urgent LT (ULT) remains the last option. The few publications on this topic report conflicting results. According to the Italian national program, patients on mechanical ventilation and/or extracorporeal membrane oxygenation may be included in urgent list. We reviewed our experience from January 2012 to December 2014 with ULT and Elective LT (ELT), focusing on outcomes. In the study period, 16 patients received ULT, while 51 received ELT...
October 3, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28967439/new-evidence-in-one-lung-ventilation
#14
H Meleiro, I Correia, P Charco Mora
Mechanical ventilation in thoracic surgery has undergone significant changes in recent years due to the implementation of the protective ventilation. This review will analyze recent ventilatory strategies in one-lung ventilation. A MEDLINE research was performed using Mesh term "One-Lung Ventilation" including randomized clinical trials, metanalysis, reviews and systematic reviews published in the last 6 years. Search was performed on 21st March 2017. A total of 75 articles were initially found. After title and abstract review 14 articles were included...
September 26, 2017: Revista Española de Anestesiología y Reanimación
https://www.readbyqxmd.com/read/28964260/factors-associated-with-hospitalization-in-bronchiectasis-exacerbations-a-one-year-follow-up-study
#15
Rosario Menéndez, Raúl Méndez, Eva Polverino, Edmundo Rosales-Mayor, Isabel Amara-Elori, Soledad Reyes, Tomás Posadas, Laia Fernández-Barat, Antoni Torres
BACKGROUND: Bronchiectasis (BE) is a chronic structural lung disease with frequent exacerbations, some of which require hospital admission though no clear associated factors have been identified. We aimed to evaluate factors associated with hospitalization due to exacerbations during a 1-year follow-up period. METHODS: A prospective observational study was performed in patients recruited from specialized BE clinics. We considered all exacerbations diagnosed and treated with antibiotics during a follow-up period of 1 year...
September 30, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28961369/phosphoproteomics-profiling-of-non-small-cell-lung-cancer-cells-treated-with-a-novel-phosphatase-activator
#16
Danica D Wiredja, Marzieh Ayati, Sahar Mazhar, Jaya Sangodkar, Sean Maxwell, Daniela Schlatzer, Goutham Narla, Mehmet Koyutürk, Mark R Chance
Activation of protein phosphatase 2A (PP2A) is a promising anti-cancer therapeutic strategy, as this tumor suppressor has the ability to coordinately downregulate multiple pathways involved in the regulation of cellular growth and proliferation. In order to understand the systems-level perturbations mediated by PP2A activation, we carried out mass spectrometry-based phosphoproteomic analysis of two KRAS mutated non-small cell lung cancer (NSCLC) cell lines (A549 and H358) treated with a novel Small Molecule Activator of PP2A (SMAP)...
September 29, 2017: Proteomics
https://www.readbyqxmd.com/read/28960588/prospects-for-new-lung-cancer-treatments-that-target-emt-signaling
#17
REVIEW
Yuji Otsuki, Hideyuki Saya, Yoshimi Arima
Lung cancer is the most common cancer worldwide. Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, molecularly targeted therapy including epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitors, and immunotherapy. These treatments can be administered alone or in combination. Despite therapeutic advances, however, lung cancer remains the leading cause of cancer death. Recent studies have indicated that epithelial-mesenchymal transition (EMT) is associated with malignancy in various types of cancer, and activation of EMT signaling in cancer cells is widely considered to contribute to metastasis, recurrence, or therapeutic resistance...
September 27, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28959241/prophylactic-supplementation-of-bifidobacterium-longum-5-1a-protects-mice-from-ovariectomy-induced-exacerbated-allergic-airway-inflammation-and-airway-hyperresponsiveness
#18
Eduardo Mendes, Beatriz G Acetturi, Andrew M Thomas, Flaviano Dos S Martins, Amanda R Crisma, Gilson Murata, Tárcio T Braga, Niels O S Camâra, Adriana L Dos S Franco, João C Setubal, Willian R Ribeiro, Claudete J Valduga, Rui Curi, Emmanuel Dias-Neto, Wothan Tavares-de-Lima, Caroline M Ferreira
Asthma is a chronic inflammatory disease that affects more females than males after puberty, and its symptoms and severity in women change during menstruation and menopause. Recently, evidence has demonstrated that interactions among the microbiota, female sex hormones, and immunity are associated with the development of autoimmune diseases. However, no studies have investigated if therapeutic gut microbiota modulation strategies could affect asthma exacerbation during menstruation and menopause. Here we aimed to examine the preventive effects of a probiotic, Bifidobacterium longum 5(1A), on airway inflammation exacerbation in allergic ovariectomized mice...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28945469/pharmacologic-protection-of-mitochondrial-dna-integrity-may-afford-a-new-strategy-for-suppressing-lung-ischemia-reperfusion-injury
#19
Yong B Tan, Sujata Mulekar, Olena Gorodnya, Michael J Weyant, Martin R Zamora, Jon D Simmons, Tiago Machuka, Mark N Gillespie
Lung ischemia-reperfusion (IR) injury contributes to post-transplant complications, including primary graft dysfunction. Decades of reports show that reactive oxygen species generated during lung IR contribute to pulmonary vascular endothelial barrier disruption and edema formation, but the specific target molecule(s) that "sense" injury-inducing oxidant stress to activate signaling pathways culminating in pathophysiologic changes have not been established. This review discusses evidence that mitochondrial DNA (mtDNA) may serve as a molecular sentinel wherein oxidative mtDNA damage functions as an upstream trigger for lung IR injury...
September 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28941982/immune-efficacy-of-an-adenoviral-vector-based-swine-influenza-vaccine-against-antigenically-distinct-h1n1-strains-in-mice
#20
Yunpu Wu, Dawei Yang, Bangfeng Xu, Wenhua Liang, Jinyu Sui, Yan Chen, Huanliang Yang, Hualan Chen, Ping Wei, Chuanling Qiao
Avian-like H1N1 swine influenza viruses are prevalent in pigs and have occasionally crossed the species barrier and infected humans, which highlights the importance of preventing swine influenza. Human adenovirus serotype 5 (Ad5) has been tested in human influenza vaccine clinical trials and has exhibited a reliable safety profile. Here, we generated a replication-defective, recombinant adenovirus (designated as rAd5-avH1HA) expressing the hemagglutinin gene of an avian-like H1N1 virus (A/swine/Zhejiang/199/2013, ZJ/199/13)...
September 20, 2017: Antiviral Research
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