Articles

A 29-mRNA host response test from blood accurately distinguishes bacterial and viral infections among emergency department patients

Whether or not to administer antibiotics is a common and challenging clinical decision in patients with suspected infections presenting to the emergency department (ED). We prospectively validate InSep, a 29-m...

Authors: Asimina Safarika, James W. Wacker, Konstantinos Katsaros, Nicky Solomonidi, George Giannikopoulos, Antigone Kotsaki, Ioannis M. Koutelidakis, Sabrina M. Coyle, Henry K. Cheng, Oliver Liesenfeld, Timothy E. Sweeney and Evangelos J. Giamarellos-Bourboulis

Endothelial cell regulation of systemic haemodynamics and metabolism acts through the HIF transcription factors

The vascular endothelium has important endocrine and paracrine roles, particularly in the regulation of vascular tone and immune function, and it has been implicated in the pathophysiology of a range of cardio...

Authors: Simon Lambden, Andrew S. Cowburn, David Macias, Tessa A. C. Garrud, Bernardo J. Krause, Dino A. Giussani, Charlotte Summers and Randall S. Johnson

Norepinephrine and dobutamine improve cardiac index equally by supporting opposite sides of the heart in an experimental model of chronic pulmonary hypertension

Pulmonary hypertension is a significant risk factor in patients undergoing surgery. The combined effects of general anaesthesia and positive pressure ventilation can aggravate this condition and cause increase...

Authors: Janus Adler Hyldebrandt, Nikolaj Bøgh, Camilla Omann and Peter Agger

Dynamic compliance in flow-controlled ventilation

Authors: Dietmar Enk, Julia Abram, Patrick Spraider and Tom Barnes

Continuous intra-gastral monitoring of intra-abdominal pressure in critically ill children: a validation study

In critically ill children, detection of intra-abdominal hypertension (IAH > 10 mmHg) and abdominal compartment syndrome (ACS = IAH + organ dysfunction) is paramount and usually monitored through intra-vesical...

Authors: T. Kaussen, M. Gutting, F. Lasch, D. Boethig, A. von Gise, J. Dingemann, H. Koeditz, T. Jack, M. Sasse, P. Beerbaum and M. Boehne

The effect of targeting Tie2 on hemorrhagic shock-induced renal perfusion disturbances in rats

Hemorrhagic shock is associated with acute kidney injury and increased mortality. Targeting the endothelial angiopoietin/Tie2 system, which regulates endothelial permeability, previously reduced hemorrhagic sh...

Authors: Anoek L. I. van Leeuwen, Nicole A. M. Dekker, Paul Van Slyke, Esther de Groot, Marc G. Vervloet, Joris J. T. H. Roelofs, Matijs van Meurs and Charissa E. van den Brom

Tissue adhesives for bacterial inhibition in extracorporeal membrane oxygenation cannulae

One of the most serious complications of extracorporeal membrane oxygenation (ECMO) therapy is ECMO cannulae infection, which can occur at quadruple the rate of central venous catheter infections, and signific...

Authors: India Pearse, Amanda Corley, Yue Qu and John Fraser

Sepsis: deriving biological meaning and clinical applications from high-dimensional data

The pathophysiology of sepsis is multi-facetted and highly complex. As sepsis is a leading cause of global mortality that still lacks targeted therapies, increased understanding of its pathogenesis is vital fo...

Authors: Alex R. Schuurman, Tom D. Y. Reijnders, Robert F. J. Kullberg, Joe M. Butler, Tom van der Poll and W. Joost Wiersinga

Haptoglobin treatment prevents cell-free hemoglobin exacerbated mortality in experimental rat sepsis

Authors: Christian A. Schaer, Victor Jeger, Thomas Gentinetta, Donat R. Spahn, Florence Vallelian, Alain Rudiger and Dominik J. Schaer

End-tidal to arterial PCO₂ ratio: a bedside meter of the overall gas exchanger performance

The physiological dead space is a strong indicator of severity and outcome of acute respiratory distress syndrome (ARDS). The “ideal” alveolar PCO₂, in equilibrium with pulmonary capillary PCO₂, is a central conc...

Authors: Matteo Bonifazi, Federica Romitti, Mattia Busana, Maria Michela Palumbo, Irene Steinberg, Simone Gattarello, Paola Palermo, Leif Saager, Konrad Meissner, Michael Quintel, Davide Chiumello and Luciano Gattinoni

Treatment with senicapoc in a porcine model of acute respiratory distress syndrome

Senicapoc is a potent and selective blocker of KCa3.1, a calcium-activated potassium channel of intermediate conductance. In the present study, we investigated whether there is a beneficial effect of senicapoc...

Authors: Asbjørn G. Petersen, Peter C. Lind, Anne-Sophie B. Jensen, Mark A. Eggertsen, Asger Granfeldt and Ulf Simonsen

Triiodothyronine prevents tissue hypoxia in experimental sepsis: potential therapeutic implications

Authors: Iordanis S. Mourouzis, Athanasios I. Lourbopoulos, Athanasios G. Trikas, Ioulia K. Tseti and Constantinos I. Pantos

Mechanical ventilation preserves diaphragm mitochondrial function in a rat sepsis model

To describe the effect of mechanical ventilation on diaphragm mitochondrial oxygen consumption, ATP production, reactive oxygen species (ROS) generation, and cytochrome c oxidase activity and content, and thei...

Authors: P. Eyenga, D. Roussel, B. Rey, P. Ndille, L. Teulier, F. Eyenga, C. Romestaing, J. Morel, V. Gueguen-Chaignon and S-S. Sheu

Point-of-care detection of lactate in cerebrospinal fluid

Measurements of cerebrospinal fluid (CSF) lactate can aid in detecting infections of the central nervous system and surrounding structures. Neurosurgical patients with temporary lumbar or ventricular CSF drain...

Authors: C. Stephani, A. H. K. Choi and O. Moerer

Evaluation of automated microvascular flow analysis software AVA 4: a validation study

Real-time automated analysis of videos of the microvasculature is an essential step in the development of research protocols and clinical algorithms that incorporate point-of-care microvascular analysis. In re...

Authors: Christian S. Guay, Mariam Khebir, T. Shiva Shahiri, Ariana Szilagyi, Erin Elizabeth Cole, Gabrielle Simoneau and Mohamed Badawy

A role for bronchial epithelial autotaxin in ventilator-induced lung injury

The pathophysiology of acute respiratory distress syndrome (ARDS) may eventually result in heterogeneous lung collapse and edema-flooded airways, predisposing the lung to progressive tissue damage known as ven...

Authors: Ioanna Nikitopoulou, Ioanna Ninou, Nikolaos Manitsopoulos, Ioanna Dimopoulou, Stylianos E. Orfanos, Vassilis Aidinis and Anastasia Kotanidou

Association of transcranial Doppler blood flow velocity slow waves with delayed cerebral ischemia in patients suffering from subarachnoid hemorrhage: a retrospective study

Cerebral vasospasm (VS) and delayed cerebral ischemia (DCI) constitute major complications following subarachnoid hemorrhage (SAH). A few studies have examined the relationship between different indices of cer...

Authors: Vasilios E. Papaioannou, Karol P. Budohoski, Michal M. Placek, Zofia Czosnyka, Peter Smielewski and Marek Czosnyka

National Preclinical Sepsis Platform: developing a framework for accelerating innovation in Canadian sepsis research

Despite decades of preclinical research, no experimentally derived therapies for sepsis have been successfully adopted into routine clinical practice. Factors that contribute to this crisis of translation incl...

Authors: Asher A. Mendelson, Casey Lansdell, Alison E. Fox-Robichaud, Patricia Liaw, Jaskirat Arora, Jean-François Cailhier, Gediminas Cepinskas, Emmanuel Charbonney, Claudia dos Santos, Dhruva Dwivedi, Christopher G. Ellis, Dean Fergusson, Kirsten Fiest, Sean E. Gill, Kathryn Hendrick, Victoria T. Hunniford…

Rapid changes in mucociliary transport in the tracheal epithelium caused by unconditioned room air or nebulized hypertonic saline and mannitol are not determined by frequency of beating cilia

Inspired air is heated and humidified in the nose before it reaches lower airways. This mechanism is bypassed during tracheostomy, directly exposing the airways to colder and drier air from the environment, kn...

Authors: Susyn Joan Kelly, Paul Martinsen and Stanislav Tatkov

Longitudinal multi-omics transition associated with fatality in critically ill COVID-19 patients

Critically ill COVID-19 patients have significantly increased risk of death. Although several circulating biomarkers are thought to be related to COVID-19 severity, few studies have focused on the characterist...

Authors: Chaoyang Sun, Yuzhe Sun, Ping Wu, Wencheng Ding, Shiyou Wang, Jiafeng Li, Langchao Liang, Chaochao Chai, Yu Fu, Zhiming Li, Linnan Zhu, Jia Ju, Xin Liao, Xiaoyuan Huang, Ling Feng, Ding Ma…

Is an EAA > 0.6 in severe COVID-19 patients synonymous with a toxic and pro-inflammatory endotoxin profile, and should we treat it?

Authors: Patrick M. Honore, Sebastien Redant and David De Bels

The surviving sepsis campaign: fluid resuscitation and vasopressor therapy research priorities in adult patients

To expand upon the priorities of fluid resuscitation and vasopressor therapy research priorities identified by a group of experts assigned by the Society of Critical Care Medicine and the European Society of I...

Authors: Ishaq Lat, Craig M. Coopersmith, Daniel De Backer and Craig M. Coopersmith

Correction to: ICU-outcomes in CAR-T patients—A single centre experience

An amendment to this paper has been published and can be accessed via the original article.

Authors: T. Materski, M. John, T. Pirani, R. Benjamin, A. Kuhnl, V. Potter, R. Sanderson and V. Metaxa

Correction to: Dysregulated expression of the b2-adrenergic receptor insepsis

An amendment to this paper has been published and can be accessed via the original article.

Authors: A. Kleyman, A. Cesar, G. Stanzani, N. Arulkumaran, W. Khaliq, DT. Andreis, B. Bollen Pinto, M. Waugh and M. Singer

COVID-19 and VILI: developing a mobile app for measurement of mechanical power at a glance

The COVID-19 pandemic has increased the need for a bedside tool for lung mechanics assessment and ventilator-induced lung injury (VILI) monitoring. Mechanical power is a unifying concept including all the comp...

Authors: Angelo Senzi, Marco Bindi, Iacopo Cappellini, Lucia Zamidei and Guglielmo Consales

A novel experimental porcine model to assess the impact of differential pulmonary blood flow on ischemia–reperfusion injury after unilateral lung transplantation

Primary graft dysfunction (PGD) remains a major obstacle after lung transplantation. Ischemia–reperfusion injury is a known contributor to the development of PGD following lung transplantation. We developed a ...

Authors: Anna Elisabeth Frick, Michaela Orlitová, Arno Vanstapel, Sofie Ordies, Sandra Claes, Dominique Schols, Tobias Heigl, Janne Kaes, Berta Saez-Gimenez, Robin Vos, Geert M. Verleden, Bart Vanaudenaerde, Stijn E. Verleden, Dirk E. Van Raemdonck and Arne P. Neyrinck

Lung ultrasound and computed tomography to monitor COVID-19 pneumonia in critically ill patients: a two-center prospective cohort study

Lung ultrasound can adequately monitor disease severity in pneumonia and acute respiratory distress syndrome. We hypothesize lung ultrasound can adequately monitor COVID-19 pneumonia in critically ill patients.

Authors: Micah L. A. Heldeweg, Jorge E. Lopez Matta, Mark E. Haaksma, Jasper M. Smit, Carlos V. Elzo Kraemer, Harm-Jan de Grooth, Evert de Jonge, Lilian J. Meijboom, Leo M. A. Heunks, David J. van Westerloo and Pieter R. Tuinman

Serum cytokines profile of critically ill COVID-19 patients with cardiac dysfunction

Authors: François Bagate, Nicolas Maziers, Sophie Hue, Paul Masi, Armand Mekontso Dessap and Nicolas de Prost

Bedside monitoring of lung volume available for gas exchange

Bedside measurement of lung volume may provide guidance in the personalised setting of respiratory support, especially in patients with the acute respiratory distress syndrome at risk of ventilator-induced lun...

Authors: Minh C. Tran, Douglas C. Crockett, John N. Cronin, João Batista Borges, Göran Hedenstierna, Anders Larsson, Andrew D. Farmery and Federico Formenti

In vitro testing of cyanoacrylate tissue adhesives and sutures for extracorporeal membrane oxygenation cannula securement

Extracorporeal membrane oxygenation (ECMO), an invasive mechanical therapy, provides cardio-respiratory support to critically ill patients when maximal conventional support has failed. ECMO is delivered via la...

Authors: India Pearse, Amanda Corley, Nicole Bartnikowski and John F. Fraser

The effects of tidal volume size and driving pressure levels on pulmonary complement activation: an observational study in critically ill patients

Mechanical ventilation can induce or even worsen lung injury, at least in part via overdistension caused by too large volumes or too high pressures. The complement system has been suggested to play a causative...

Authors: Friso M. de Beer, Luuk Wieske, Gerard van Mierlo, Diana Wouters, Sacha Zeerleder, Lieuwe D. Bos, Nicole P. Juffermans, Marcus J. Schultz, Tom van der Poll, Wim K. Lagrand and Janneke Horn

Effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of airway secretions in endotracheal tubes: substudy of a randomized clinical trial

Accumulated airway secretions in the endotracheal tube increase work of breathing and may favor airway colonization eventually leading to pneumonia. The aim of this preplanned substudy of the ‘Preventive Nebul...

Authors: Sophia van der Hoeven, Lorenzo Ball, Federico Constantino, David M. van Meenen, Paolo Pelosi, Ludo F. Beenen, Marcus J. Schultz and Frederique Paulus

Comparison of direct and indirect models of early induced acute lung injury

The animal experimental counterpart of human acute respiratory distress syndrome (ARDS) is acute lung injury (ALI). Most models of ALI involve reproducing the clinical risk factors associated with human ARDS, ...

Authors: Laura Chimenti, Luis Morales-Quinteros, Ferranda Puig, Marta Camprubi-Rimblas, Raquel Guillamat-Prats, Maria Nieves Gómez, Jessica Tijero, Lluis Blanch, Gustavo Matute-Bello and Antonio Artigas

The predictive validity for mortality of the driving pressure and the mechanical power of ventilation

Outcome prediction in critically ill patients under invasive ventilation remains extremely challenging. The driving pressure (ΔP) and the mechanical power of ventilation (MP) are associated with patient-center...

Authors: David M. P. van Meenen, Ary Serpa Neto, Frederique Paulus, Coen Merkies, Laura R. Schouten, Lieuwe D. Bos, Janneke Horn, Nicole P. Juffermans, Olaf L. Cremer, Tom van der Poll and Marcus J. Schultz

Continuous external negative pressure improves oxygenation and respiratory mechanics in Experimental Lung Injury in Pigs – A pilot proof-of-concept trial

Continuous external negative pressure (CENP) during positive pressure ventilation can recruit dependent lung regions. We hypothesised that CENP applied regionally to the thorax or the abdomen only, increases t...

Authors: Martin Scharffenberg, Jakob Wittenstein, Moritz Herzog, Sebastian Tauer, Luigi Vivona, Raphael Theilen, Thomas Bluth, Thomas Kiss, Thea Koch, Giuseppe Fiorentino, Marcelo Gama de Abreu and Robert Huhle

Liver–lung interactions in acute respiratory distress syndrome

Patients with liver diseases are at high risk for the development of acute respiratory distress syndrome (ARDS). The liver is an important organ that regulates a complex network of mediators and modulates orga...

Authors: Raquel Herrero, Gema Sánchez, Iris Asensio, Eva López, Antonio Ferruelo, Javier Vaquero, Laura Moreno, Alba de Lorenzo, Rafael Bañares and José A. Lorente

Alkaline phosphatase in pulmonary inflammation—a translational study in ventilated critically ill patients and rats

Alkaline phosphatase (AP), a dephosphorylating enzyme, is involved in various physiological processes and has been shown to have anti-inflammatory effects.

Authors: Jenny Juschten, Sarah A. Ingelse, Lieuwe D. J. Bos, Armand R. J. Girbes, Nicole P. Juffermans, Tom van der Poll, Marcus J. Schultz and Pieter Roel Tuinman

Prognostic classification based on P/F and PEEP in invasively ventilated ICU patients with hypoxemia—insights from the MARS study

Outcome prediction in patients with acute respiratory distress syndrome (ARDS) greatly improves when patients are reclassified based on predefined arterial oxygen partial pressure to fractional inspired oxygen...

Authors: Fabienne D. Simonis, Laura R. A. Schouten, Olaf L. Cremer, David S. Y. Ong, Gabriele Amoruso, Gilda Cinella, Marcus J. Schultz and Lieuwe D. Bos

Therapeutic application of recombinant human ADAMTS-13 improves shock reversal and coagulation status in a trauma hemorrhage and transfusion rat model

In hemorrhaging trauma patients, the endothelium is activated, resulting in excessive endothelial synthesis of von Willebrand Factor (vWF), which may enhance micro-thrombi formation, resulting in obstruction o...

Authors: Mathijs R. Wirtz, Daan P. van den Brink, Joris J. T. H. Roelofs, J. Carel Goslings and Nicole P. Juffermans

Effects of higher PEEP and recruitment manoeuvres on mortality in patients with ARDS: a systematic review, meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials

In patients with acute respiratory distress syndrome (ARDS), lung recruitment could be maximised with the use of recruitment manoeuvres (RM) or applying a positive end-expiratory pressure (PEEP) higher than wh...

Authors: Lorenzo Ball, Ary Serpa Neto, Valeria Trifiletti, Maura Mandelli, Iacopo Firpo, Chiara Robba, Marcelo Gama de Abreu, Marcus J. Schultz, Nicolò Patroniti, Patricia R. M. Rocco and Paolo Pelosi

Impact of downstream effects of glucocorticoid receptor dysfunction on organ function in critical illness-associated systemic inflammation

Glucocorticoids (GCs) are stress hormones that regulate developmental and physiological processes and are among the most potent anti-inflammatory drugs to suppress chronic and acute inflammation. GCs act throu...

Authors: Martin Wepler, Jonathan M. Preuss, Tamara Merz, Oscar McCook, Peter Radermacher, Jan P. Tuckermann and Sabine Vettorazzi

H₂S in acute lung injury: a therapeutic dead end(?)

This review addresses the plausibility of hydrogen sulfide (H₂S) therapy for acute lung injury (ALI) and circulatory shock, by contrasting the promising preclinical results to the present clinical reality. The re...

Authors: Tamara Merz, Nicole Denoix, Martin Wepler, Holger Gäßler, David A. C. Messerer, Clair Hartmann, Thomas Datzmann, Peter Radermacher and Oscar McCook

Fluids in ARDS: more pros than cons

In acute respiratory distress syndrome (ARDS), increased pulmonary vascular permeability makes the lung vulnerable to edema. The use of conservative as compared to liberal fluid strategies may increase the num...

Authors: Renata de S. Mendes, Paolo Pelosi, Marcus J. Schultz, Patricia R. M. Rocco and Pedro L. Silva

Metabolic substrate utilization in stress-induced immune cells

Immune cell activation leads to the acquisition of new functions, such as proliferation, chemotaxis, and cytokine production. These functional changes require continuous metabolic adaption in order to sustain ...

Authors: Xiaomin Zhang, Fabian Zink, Felix Hezel, Josef Vogt, Ulrich Wachter, Martin Wepler, Maurizio Loconte, Christine Kranz, Andreas Hellmann, Boris Mizaikoff, Peter Radermacher and Clair Hartmann

Comparative effects of flow vs. volume-controlled one-lung ventilation on gas exchange and respiratory system mechanics in pigs

Flow-controlled ventilation (FCV) allows expiratory flow control, reducing the collapse of the airways during expiration. The performance of FCV during one-lung ventilation (OLV) under intravascular normo- and...

Authors: Jakob Wittenstein, Martin Scharffenberg, Xi Ran, Diana Keller, Pia Michler, Sebastian Tauer, Raphael Theilen, Thomas Kiss, Thomas Bluth, Thea Koch, Marcelo Gama de Abreu and Robert Huhle

Ischaemic stroke-induced distal organ damage: pathophysiology and new therapeutic strategies

Acute ischaemic stroke is associated with a high risk of non-neurological complications, which include respiratory failure, cardiovascular dysfunction, kidney and liver injury, and altered immune and endocrine...

Authors: Chiara Robba, Denise Battaglini, Cynthia S. Samary, Pedro L. Silva, Lorenzo Ball, Patricia R. M. Rocco and Paolo Pelosi

Extracellular vesicles as regulators of kidney function and disease

Extracellular vesicles (EVs) are small, lipid bilayer-delimited particles of cellular origin that recently gained increasing attention for their potential use as diagnostic biomarkers, and beyond that for thei...

Authors: Felix Behrens, Johannes Holle, Wolfgang M. Kuebler and Szandor Simmons

Role of the adaptive immune response in sepsis

Sepsis is a syndrome of shock and dysfunction of multiple vital organs that is caused by an uncontrolled immune response to infection and has a high mortality rate. There are no therapies for sepsis, and it ha...

Authors: Jack Brady, Shahd Horie and John G. Laffey

Pathophysiology and clinical consequences of arterial blood gases and pH after cardiac arrest

Post cardiac arrest syndrome is associated with high morbidity and mortality, which is related not only to a poor neurological outcome but also to respiratory and cardiovascular dysfunctions. The control of ga...

Authors: Chiara Robba, Dorota Siwicka-Gieroba, Andras Sikter, Denise Battaglini, Wojciech Dąbrowski, Marcus J. Schultz, Evert de Jonge, Chloe Grim, Patricia RM Rocco and Paolo Pelosi

Changes in left ventricular electromechanical relations during targeted hypothermia

Targeted hypothermia, as used after cardiac arrest, increases electrical and mechanical systolic duration. Differences in duration of electrical and mechanical systole are correlated to ventricular arrhythmias...

Authors: Kristin Wisløff-Aase, Viesturs Kerans, Kristina Haugaa, Per Steinar Halvorsen, Helge Skulstad and Andreas Espinoza