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  1. Article ; Online: Volatile organic compound profiling to explore primary graft dysfunction after lung transplantation

    Pierre-Hugues Stefanuto / Rosalba Romano / Christiaan A. Rees / Mavra Nasir / Louit Thakuria / Andre Simon / Anna K. Reed / Nandor Marczin / Jane E. Hill

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 10

    Abstract: Abstract Primary graft dysfunction (PGD) is a major determinant of morbidity and mortality following lung transplantation. Delineating basic mechanisms and molecular signatures of PGD remain a fundamental challenge. This pilot study examines if the ... ...

    Abstract Abstract Primary graft dysfunction (PGD) is a major determinant of morbidity and mortality following lung transplantation. Delineating basic mechanisms and molecular signatures of PGD remain a fundamental challenge. This pilot study examines if the pulmonary volatile organic compound (VOC) spectrum relate to PGD and postoperative outcomes. The VOC profiles of 58 bronchoalveolar lavage fluid (BALF) and blind bronchial aspirate samples from 35 transplant patients were extracted using solid-phase-microextraction and analyzed with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry. The support vector machine algorithm was used to identify VOCs that could differentiate patients with severe from lower grade PGD. Using 20 statistically significant VOCs from the sample headspace collected immediately after transplantation (< 6 h), severe PGD was differentiable from low PGD with an AUROC of 0.90 and an accuracy of 0.83 on test set samples. The model was somewhat effective for later time points with an AUROC of 0.80. Three major chemical classes in the model were dominated by alkylated hydrocarbons, linear hydrocarbons, and aldehydes in severe PGD samples. These VOCs may have important clinical and mechanistic implications, therefore large-scale study and potential translation to breath analysis is recommended.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Leflunomide treatment for patients hospitalised with COVID-19

    Ling Li / Ines Kralj-Hans / David Fluck / Pankaj Sharma / Siva Mahendran / Zhong Chen / Rita Pereira / Kieran Brack / Sreenivasa Rao Kondapally Seshasai / Jonathan D Belsey / Nandor Marczin / Kuo Li / Adrian Wesek / Alexia Lamorgese / Fatima Omar / Kapila Ranasinghe / Megan McGee / Shiliang Li / Ritesh Aggarwal /
    Ajay Bulle / Aparna Kodre / Shashank Sharma / Isaac John / Hong Lin Li / Maia Aquino / Vicky Frost / Kirsty Gibson / Maria Croft / Anna Joseph / Maggie Grout / Arun Dewan

    BMJ Open, Vol 13, Iss

    DEFEAT-COVID randomised controlled trial

    2023  Volume 4

    Abstract: Objective To evaluate the clinical efficacy and safety of leflunomide (L) added to the standard-of-care (SOC) treatment in COVID-19 patients hospitalised with moderate/critical clinical symptoms.Design Prospective, open-label, multicentre, stratified, ... ...

    Abstract Objective To evaluate the clinical efficacy and safety of leflunomide (L) added to the standard-of-care (SOC) treatment in COVID-19 patients hospitalised with moderate/critical clinical symptoms.Design Prospective, open-label, multicentre, stratified, randomised clinical trial.Setting Five hospitals in UK and India, from September 2020 to May 2021.Participants Adults with PCR confirmed COVID-19 infection with moderate/critical symptoms within 15 days of onset.Intervention Leflunomide 100 mg/day (3 days) followed by 10–20 mg/day (7 days) added to standard care.Primary outcomes The time to clinical improvement (TTCI) defined as two-point reduction on a clinical status scale or live discharge prior to 28 days; safety profile measured by the incidence of adverse events (AEs) within 28 days.Results Eligible patients (n=214; age 56.3±14.9 years; 33% female) were randomised to SOC+L (n=104) and SOC group (n=110), stratified according to their clinical risk profile. TTCI was 7 vs 8 days in SOC+L vs SOC group (HR 1.317; 95% CI 0.980 to 1.768; p=0.070). Incidence of serious AEs was similar between the groups and none was attributed to leflunomide. In sensitivity analyses, excluding 10 patients not fulfilling the inclusion criteria and 3 who withdrew consent before leflunomide treatment, TTCI was 7 vs 8 days (HR 1.416, 95% CI 1.041 to 1.935; p=0.028), indicating a trend in favour of the intervention group. All-cause mortality rate was similar between groups, 9/104 vs 10/110. Duration of oxygen dependence was shorter in the SOC+L group being a median 6 days (IQR 4–8) compared with 7 days (IQR 5–10) in SOC group (p=0.047).Conclusion Leflunomide, added to the SOC treatment for COVID-19, was safe and well tolerated but had no major impact on clinical outcomes. It may shorten the time of oxygen dependence by 1 day and thereby improve TTCI/hospital discharge in moderately affected COVID-19 patients.Trial registration numbers EudraCT Number: 2020-002952-18, NCT05007678.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Ethylene, an early marker of systemic inflammation in humans

    Laurent M. Paardekooper / Geert van den Bogaart / Matthijs Kox / Ilse Dingjan / Anne H. Neerincx / Maura B. Bendix / Martin ter Beest / Frans J. M. Harren / Terence Risby / Peter Pickkers / Nandor Marczin / Simona M. Cristescu

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 10

    Abstract: Abstract Ethylene is a major plant hormone mediating developmental processes and stress responses to stimuli such as infection. We show here that ethylene is also produced during systemic inflammation in humans and is released in exhaled breath. Traces ... ...

    Abstract Abstract Ethylene is a major plant hormone mediating developmental processes and stress responses to stimuli such as infection. We show here that ethylene is also produced during systemic inflammation in humans and is released in exhaled breath. Traces of ethylene were detected by laser spectroscopy both in vitro in isolated blood leukocytes exposed to bacterial lipopolysaccharide (LPS) as well as in vivo following LPS administration in healthy volunteers. Exposure to LPS triggers formation of ethylene as a product of lipid peroxidation induced by the respiratory burst. In humans, ethylene was detected prior to the increase of blood levels of inflammatory cytokines and stress-related hormones. Our results highlight that ethylene release is an early and integral component of in vivo lipid peroxidation with important clinical implications as a breath biomarker of bacterial infection.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2017-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2 trial)

    Joachim Gerss / Javier Ripollés-Melchor / Emmanuel Futier / Melanie Meersch / Carola Wempe / Detlef Kindgen-Milles / Alexander Zarbock / Markus W Hollmann / Sigismond Lasocki / Thomas Rimmele / Tim Rahmel / Michael Adamzik / Hartmuth Nowak / Ingeborg Welters / Brian Johnston / Ane Abad-motos / Alfredo Abad-gurumeta / Marc Moritz Berger / Davide Ricci /
    Maurizio Cecconi / Gudrun Kunst / Christian Stoppe / Christian Putensen / Marlies Ostermann / Sascha Ott / Brijesh Patel / Gabriele Baldini / Antoine Lamblin / Karen Williams / Elena Mancini / Christian Arndt / Hinnerk Wulf / Marc Irqsusi / Wim Vandenberghe / John Kellum / Raphael Weiss / Jackie Donovan / Lui G Forni / Giacomo Monti / Céline Monard / Markus A Weigand / Thorsten Brenner / Ulrich Jaschinski / Carlos Lopez / Maxime Leger / Emmanuel Rineau / Philipp Simon / María Gómez-Rojo / Lars Bergmann / Alicia Waite / Savino Spadaro / Alexander Wolf / Andrew Spence / Simon Dubler / Alexander PJ Vlaar / Patrick Schober / Ben C Creagh-Brown / Nandor Marczin / Emilio Maseda / Christian Strauss / Stefano Romagnoli / Christian Nusshag / Ulrich Gobel / Ángel Candela-Toha / Jon Silversides / Nuttha Lumlertgul / Khaschayar Saadat-Gilani / Vincent Legros / Timo Brandenburger / Thomas Dimski / Laura Huthmann / Claude Pelletier / Manon Schleß / Peter Rosenberger / Helene Häberle / Jan Gerrit Haaker / Matthias Gründel / Lucia Cattin / Laura Villarino Villa / Juan Victor Lorente / Christine Martin / Jan Larmann / Wolfgang Bauer / Giovanni Borghi / Benjamin O’Brien / Thilo von Groote / Antoine Guillaume Schneider / Silvia De Rosa / Diego Parise / Alice Bernard / Paula Fernández-Valdes-Bango / Irene Romero Bhathal / A Suarez-de-la-Rica / Gianluca Villa / Raquel García-Álvarez / Antonio Siniscalchi / Richard Ellerkmann / Florian Espeter / Christian Porschen / Mahan Sadjadi / Michael Storck / Tobias Brix / Dana Meschede / Wida Amini / Carina Stenger / Julius Freytag / Jens Brands / Matthias Unterberg / Britta Marko / Fabian Dusse / Wolfgang A Wetsch / Sandra E Stoll / Hendrik Drinhaus / Bernd W Böttiger / Onnen Mörer / Lars-Olav Harnisch / Roswitha Lubjuhn / Daniel Heise / Christian Bode / Andrea Sauer / Konrad Peukert / Lennart Wild / Philippe Kruse / Jan Menzenbach / Valbona Mirakaj / Sabine Hermann / Stefanie Decker / Mona Jung-König / Tobias Hölle / Sarah Dehne / Jörg Reutershan / Thomas Prüfer / Stefan Pielmeier / Indra Wimmelmeier / Michaela Scholz / Andrea Paris / Isabel Christina Gallego Zapata / Holger Pohl / Nirmeen Fayed / Kai Dielmann / Evelyn Martin / Tilo Koch / Alexander Mück / Philipp Deetjen / Ngoc Bich Mehlmann / Peter M Spieth / Andreas Güldner / Axel Rand / Maximillian Ragaller / Martin Mirus / Rebecca Bockholt / Marc Herzog / Maren Kleine-Brüggeney / Ant Isabelle Cristiani / Marion Ohl / Monica Vieira Da Silva / Gilda Filipe de Castro Reblo / Matthias Hilty / Katharina Spanaus / Benedetta Mura / Eleonora Terreni / Francesco Magiotti / Lorenzo Turi / Cristiana Laici / Chiara Capozzi / Andrea Castelli / Massimiliano Greco / Antonio Messina / Gianluca Castellani / Romina Aceto / Vinicio Danzi / Alessandro Rigobello / Massimo De Cal / Monica Zanella / Gaetano Scaramuzzo / Riccardo La Rosa / Paolo Priani / Alberto Volta Carlo / Stefano Turi / Martina Baiardo Redaelli / Marilena Marmiere / Kittisak Weerapolchai / Shelley Lorah / Fabiola D’Amato / Aneta Bociek / Rosario Lim / Benjie Cendreda / Reynaldo Dela Cuesta / Eirini Kosifidou / Zoka Milan / Juliana Fernanda / Emma Clarey / Daveena Meeks / Nicholas J Lees / Marco Scaramuzzi / Orinta Kviatkovske / Adam Glass / Christine Turley / Charlotte Quinn / Syeda Haider / Adam Rossiter / Syed Nasser / Ned Gilbert-Kawai / Tatjana Besse-Hammer / Eric Hoste / Hannah Schaubroeck / Jan De Waele / Jenni Breel / Eline de Klerk / Harm-Jan de Grooth / Lothar Schwarte / Alexander Loer / Alicia Ruiz-Escobar / Diana Fernández-García / Nerea Gómez-Pérez / Pascual Crespo-Aliseda / Cristina Cerro-Zaballos / Cristina Fernández-Martín / Eduardo Martín-Montero / Alejandro Suarez de la Rica / Héctor Berges Gutiérrez / Maria del Pino Heredia Pérez / Maria de los Reyes Bellido Fernández / Liena Izquierdo López / Javier Valiente Lourtau / Ma Angeles Ferre Colomer / Ma Azucena Pajares Moncho / Maria Jesús Montero Hernández / Esther Pérez Sancho / Silvia Polo Matínez / Pedro Rivera Soria / Maider Puyada Jáuregui / Hugo Rivera Ramos / Marta Antelo Adrán / Ramón Adalia Bartolomé / Patricia Galán Menéndez / Laura Llinares Espin / Yuri Santiago Loaiza Aldean / Víctor MoralesAriza / Rosalía Navarro-Perez / Luis Santé-Serna / Pedro de la Calle-Elguezabal / Rubén Sánchez-Martín / Inés De Soto / Pau Vallhonrat Alcántara / Laura Perelló Cerdà / Gal·la Rouras Hurtado / Paula Rodriguez Nieto / John Narros Sicluna / Angel Molero Molinero / Juan Pablo Nocete / Elena Murcia Sánchez / Stanislas Abrard / Marie-Luce Parrouffe / Frank Bidar / Lucie Aupetitgendre / Ugo Schiff / Bertille Paquette / Gaëlle Sellier / Nathalie Borgnetta / Benjamin Brochet / Thierry Floch / Julien Coffinet / Marion Leclercq-Rouget

    BMJ Open, Vol 13, Iss

    study protocol for an international, prospective, randomised controlled multicentre trial

    2023  Volume 3

    Abstract: Introduction Previous studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might ... ...

    Abstract Introduction Previous studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation.Methods and analysis The BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage.Ethics and dissemination The BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will ...
    Keywords Medicine ; R
    Subject code 616 ; 610
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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