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  1. Article ; Online: Scarred Lung. An Update on Radiation-Induced Pulmonary Fibrosis

    Natalia Jarzebska / Ekaterina S. Karetnikova / Alexander G. Markov / Michael Kasper / Roman N. Rodionov / Peter M. Spieth

    Frontiers in Medicine, Vol

    2021  Volume 7

    Abstract: Radiation-induced pulmonary fibrosis is a common severe long-time complication of radiation therapy for tumors of the thorax. Current therapeutic options used in the clinic include only supportive managements strategies, such as anti-inflammatory ... ...

    Abstract Radiation-induced pulmonary fibrosis is a common severe long-time complication of radiation therapy for tumors of the thorax. Current therapeutic options used in the clinic include only supportive managements strategies, such as anti-inflammatory treatment using steroids, their efficacy, however, is far from being satisfactory. Recent studies have demonstrated that the development of lung fibrosis is a dynamic and complex process, involving the release of reactive oxygen species, activation of Toll-like receptors, recruitment of inflammatory cells, excessive production of nitric oxide and production of collagen by activated myofibroblasts. In this review we summarized the current state of knowledge on the pathophysiological processes leading to the development of lung fibrosis and we also discussed the possible treatment options.
    Keywords radiation ; pulmonary fibrosis ; macromolecular damage ; nitric oxide ; dimethylarginine dimethylaminohydrolase ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Enhancing Anticoagulation Monitoring and Therapy in Patients Undergoing Microvascular Reconstruction in Maxillofacial Surgery

    Tom A. Schröder / Henry Leonhardt / Dominik Haim / Christian Bräuer / Kiriaki K. Papadopoulos / Oliver Vicent / Andreas Güldner / Martin Mirus / Jürgen Schmidt / Hanns C. Held / Oliver Tiebel / Thomas Birkner / Jan Beyer-Westendorf / Günter Lauer / Peter M. Spieth / Thea Koch / Lars Heubner

    Journal of Personalized Medicine, Vol 12, Iss 8, p

    A Prospective Observational Trial

    2022  Volume 1229

    Abstract: Background: In reconstructive surgery, loss of a microvascular free flap due to perfusion disorders, especially thrombosis, is a serious complication. In recent years, viscoelastic testing (VET) has become increasingly important in point-of-care (POC) ... ...

    Abstract Background: In reconstructive surgery, loss of a microvascular free flap due to perfusion disorders, especially thrombosis, is a serious complication. In recent years, viscoelastic testing (VET) has become increasingly important in point-of-care (POC) anticoagulation monitoring. This paper describes a protocol for enhanced anticoagulation monitoring during maxillofacial flap surgery. Objective: The aim of the study will be to evaluate, in a controlled setting, the predictive value of POC devices for the type of flap perfusion disorders due to thrombosis or bleeding. VET, Platelet monitoring (PM) and standard laboratory tests (SLT) are comparatively examined. Methods/Design: This study is an investigator-initiated prospective trial in 100 patients undergoing maxillofacial surgery. Patients who undergo reconstructive surgery using microvascular-free flaps will be consecutively enrolled in the study. All patients provide blood samples for VET, PM and SLT at defined time points. The primary outcome is defined as free flap loss during the hospital stay. Statistical analyses will be performed using t-tests, including the Bonferroni adjustment for multiple comparisons. Discussion: This study will help clarify whether VET can improve individualized patient care in reconstruction surgery. A better understanding of coagulation in relation to flap perfusion disorders may allow real-time adaption of antithrombotic strategies and potentially prevent flap complications.
    Keywords coagulation monitoring ; viscoelastic testing ; maxillofacial surgery ; free flap thrombosis ; point-of-care coagulation ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase

    Vinitha N. Ragavan / Pramod C. Nair / Natalia Jarzebska / Ramcharan Singh Angom / Luana Ruta / Elisa Bianconi / Silvia Grottelli / Natalia D. Tararova / Daniel Ryazanskiy / Steven R. Lentz / Sara Tommasi / Jens Martens-Lobenhoffer / Toshiko Suzuki-Yamamoto / Masumi Kimoto / Elena Rubets / Sarah Chau / Yingjie Chen / Xinli Hu / Nadine Bernhardt /
    Peter M. Spieth / Norbert Weiss / Stefan R. Bornstein / Debabrata Mukhopadhyay / Stefanie M. Bode-Böger / Renke Maas / Ying Wang / Antonio Macchiarulo / Arduino A. Mangoni / Barbara Cellini / Roman N. Rodionov

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 16

    Abstract: Abstract Dimethylarginine dimethylaminohydrolase 1 (DDAH1) protects against cardiovascular disease by metabolising the risk factor asymmetric dimethylarginine (ADMA). However, the question whether the second DDAH isoform, DDAH2, directly metabolises ADMA ...

    Abstract Abstract Dimethylarginine dimethylaminohydrolase 1 (DDAH1) protects against cardiovascular disease by metabolising the risk factor asymmetric dimethylarginine (ADMA). However, the question whether the second DDAH isoform, DDAH2, directly metabolises ADMA has remained unanswered. Consequently, it is still unclear if DDAH2 may be a potential target for ADMA-lowering therapies or if drug development efforts should focus on DDAH2’s known physiological functions in mitochondrial fission, angiogenesis, vascular remodelling, insulin secretion, and immune responses. Here, an international consortium of research groups set out to address this question using in silico, in vitro, cell culture, and murine models. The findings uniformly demonstrate that DDAH2 is incapable of metabolising ADMA, thus resolving a 20-year controversy and providing a starting point for the investigation of alternative, ADMA-independent functions of DDAH2.
    Keywords Science ; Q
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Mechanical Ventilation Strategies Targeting Different Magnitudes of Collapse and Tidal Recruitment in Porcine Acid Aspiration-Induced Lung Injury

    Juliane Haase / Dorina C. Buchloh / Sören Hammermüller / Peter Salz / Julia Mrongowius / Nadja C. Carvalho / Alessandro Beda / Anna Rau / Henning Starke / Peter M. Spieth / Claudia Gittel / Thomas Muders / Hermann Wrigge / Andreas W. Reske

    Journal of Clinical Medicine, Vol 8, Iss 8, p

    2019  Volume 1250

    Abstract: Reducing ventilator-associated lung injury by individualized mechanical ventilation (MV) in patients with Acute Respiratory Distress Syndrome (ARDS) remains a matter of research. We randomly assigned 27 pigs with acid aspiration-induced ARDS to three ... ...

    Abstract Reducing ventilator-associated lung injury by individualized mechanical ventilation (MV) in patients with Acute Respiratory Distress Syndrome (ARDS) remains a matter of research. We randomly assigned 27 pigs with acid aspiration-induced ARDS to three different MV protocols for 24 h, targeting different magnitudes of collapse and tidal recruitment (collapse&TR): the ARDS-network (ARDSnet) group with low positive end-expiratory pressure (PEEP) protocol (permissive collapse&TR); the Open Lung Concept (OLC) group, PaO 2 /FiO 2 >400 mmHg, indicating collapse&TR <10%; and the minimized collapse&TR monitored by Electrical Impedance Tomography (EIT) group, standard deviation of regional ventilation delay, SD RVD . We analyzed cardiorespiratory parameters, computed tomography (CT), EIT, and post-mortem histology. Mean PEEP over post-randomization measurements was significantly lower in the ARDSnet group at 6.8 ± 1.0 cmH 2 O compared to the EIT (21.1 ± 2.6 cmH 2 O) and OLC (18.7 ± 3.2 cmH 2 O) groups (general linear model (GLM) p < 0.001). Collapse&TR and SD RVD , averaged over all post-randomization measurements, were significantly lower in the EIT and OLC groups than in the ARDSnet group (collapse p < 0.001, TR p = 0.006, SD RVD p < 0.004). Global histological diffuse alveolar damage (DAD) scores in the ARDSnet group (10.1 ± 4.3) exceeded those in the EIT (8.4 ± 3.7) and OLC groups (6.3 ± 3.3) ( p = 0.16). Sub-scores for edema and inflammation differed significantly (ANOVA p < 0.05). In a clinically realistic model of early ARDS with recruitable and nonrecruitable collapse, mechanical ventilation involving recruitment and high-PEEP reduced collapse&TR and resulted in improved hemodynamic and physiological conditions with a tendency to reduced histologic lung damage.
    Keywords acute respiratory distress syndrome ; lung protective mechanical ventilation ; positive end-expiratory pressure ; lung recruitment ; electrical impedance tomography ; Medicine ; R
    Subject code 290 ; 333
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Correlation of lung collapse and gas exchange - a computer tomographic study in sheep and pigs with atelectasis in otherwise normal lungs.

    Samuel J Wolf / Alexander P Reske / Sören Hammermüller / Eduardo L V Costa / Peter M Spieth / Pierre Hepp / Alysson R Carvalho / Jens Kraßler / Hermann Wrigge / Marcelo B P Amato / Andreas W Reske

    PLoS ONE, Vol 10, Iss 8, p e

    2015  Volume 0135272

    Abstract: Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial ... ...

    Abstract Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations.Shunt, PaO2 and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS). Atelectasis was calculated by computed tomography relative to total lung mass (Mtotal). We logarithmically transformed PaO2 (lnPaO2) to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range).Mtotal was 768 (715-884) g in sheep and 543 (503-583) g in pigs. Atelectasis was 26 (16-47) % in sheep and 18 (13-23) % in pigs. PaO2 (FiO2 = 1.0) was 242 (106-414) mmHg in sheep and 480 (437-514) mmHg in pigs. Shunt was 39 (29-51) % in sheep and 15 (11-20) % in pigs. Atelectasis correlated closely with lnPaO2 (R2 = 0.78) and shunt (R2 = 0.79) in sheep (P-values<0.0001). The correlation of atelectasis with lnPaO2 (R2 = 0.63) and shunt (R2 = 0.34) was weaker in pigs, but R2 increased to 0.71 for lnPaO2 and 0.72 for shunt 12 hours after induction of ARDS. In both, sheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO2 and shunt.In lung-healthy sheep, atelectasis correlates closely with lnPaO2 and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV) than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed relationships may aid in assessing ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 630
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Positive end-expiratory pressure and variable ventilation in lung-healthy rats under general anesthesia.

    Luciana M Camilo / Mariana B Ávila / Luis Felipe S Cruz / Gabriel C M Ribeiro / Peter M Spieth / Andreas A Reske / Marcelo Amato / Antonio Giannella-Neto / Walter A Zin / Alysson R Carvalho

    PLoS ONE, Vol 9, Iss 11, p e

    2014  Volume 110817

    Abstract: OBJECTIVES: Variable ventilation (VV) seems to improve respiratory function in acute lung injury and may be combined with positive end-expiratory pressure (PEEP) in order to protect the lungs even in healthy subjects. We hypothesized that VV in ... ...

    Abstract OBJECTIVES: Variable ventilation (VV) seems to improve respiratory function in acute lung injury and may be combined with positive end-expiratory pressure (PEEP) in order to protect the lungs even in healthy subjects. We hypothesized that VV in combination with moderate levels of PEEP reduce the deterioration of pulmonary function related to general anesthesia. Hence, we aimed at evaluating the alveolar stability and lung protection of the combination of VV at different PEEP levels. DESIGN: Randomized experimental study. SETTING: Animal research facility. SUBJECTS: Forty-nine male Wistar rats (200-270 g). INTERVENTIONS: Animals were ventilated during 2 hours with protective low tidal volume (VT) in volume control ventilation (VCV) or VV and PEEP adjusted at the level of minimum respiratory system elastance (Ers), obtained during a decremental PEEP trial subsequent to a recruitment maneuver, and 2 cmH2O above or below of this level. MEASUREMENTS AND MAIN RESULTS: Ers, gas exchange and hemodynamic variables were measured. Cytokines were determined in lung homogenate and plasma samples and left lung was used for histologic analysis and diffuse alveolar damage scoring. A progressive time-dependent increase in Ers was observed independent on ventilatory mode or PEEP level. Despite of that, the rate of increase of Ers and lung tissue IL-1 beta concentration were significantly lower in VV than in VCV at the level of the PEEP of minimum Ers. A significant increase in lung tissue cytokines (IL-6, IL-1 beta, CINC-1 and TNF-alpha) as well as a ventral to dorsal and cranial to caudal reduction in aeration was observed in all ventilated rats with no significant differences among groups. CONCLUSIONS: VV combined with PEEP adjusted at the level of the PEEP of minimal Ers seemed to better prevent anesthesia-induced atelectasis and might improve lung protection throughout general anesthesia.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. 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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