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Sepsis ,ARDS,

Risa Inagawa, Hideshi Okada, Genzou Takemura, Kodai Suzuki, Chihiro Takada, Hirohisa Yano, Yoshiaki Ando, Takahiro Usui, Yasuaki Hotta, Nagisa Miyazaki, Akiko Tsujimoto, Ryogen Zaikokuji, Atsumu Matsumoto, Tomonori Kawaguchi, Tomoaki Doi, Takahiro Yoshida, Shozo Yoshida, Keisuke Kumada, Hiroaki Ushikoshi, Izumi Toyoda, Shinji Ogura
BACKGROUND: The most recent diagnostic criteria for sepsis includes organ failure. Microvascular endothelial injury is thought to lead to the multiple organ failure seen in sepsis, although the precise mechanism is still controversial. Acute respiratory distress syndrome (ARDS) is the primary complication during the sequential development of multiple organ dysfunction in sepsis, and endothelial injury is deeply involved. Sugar-protein glycocalyx coats all healthy vascular endothelium, and its disruption is one factor thought to contribute to microvascular endothelial dysfunction during sepsis...
March 16, 2018: Chest
Daisuke Kudo, Shigeki Kushimoto, Noriko Miyagawa, Tetsuya Sato, Masatsugu Hasegawa, Fumihito Ito, Sathoshi Yamanouchi, Hiroyuki Honda, Kohkichi Andoh, Hajime Furukawa, Yasuo Yamada, Yuta Tsujimoto, Manabu Okuyama
PURPOSE: Disseminated intravascular coagulations (DIC), acute respiratory distress syndrome (ARDS), and acute kidney injury (AKI) are major organ dysfunctions that occur in patients with sepsis. This study aimed to elucidate the impact of these organ dysfunctions on mortality in patients with severe sepsis. MATERIAL AND METHODS: A prospective observational study was performed in 10 ICUs to obtain data from patients with severe sepsis. Multivariate analyses to examine in-hospital mortality were performed...
March 7, 2018: Journal of Critical Care
Katerina Kaziani, Alice G Vassiliou, Anastasia Kotanidou, Chariclea Athanasiou, Ioanna Korovesi, Konstantinos Glynos, Stylianos E Orfanos
INTRODUCTION: Pulmonary capillary endothelium-bound (PCEB) angiotensin-converting enzyme (ACE) activity is a direct and quantifiable index of pulmonary endothelial function that decreases early in acute respiratory distress syndrome (ARDS) and correlates with its severity. Endothelial dysfunction is a major pathophysiology that underlies sepsis-related ARDS. Recombinant human activated protein C (rhAPC), now withdrawn from the market, has been used in the recent past as an endothelial-protective treatment in patients with septic organ dysfunction...
March 2018: Infectious Diseases and Therapy
Shujun Zhou, Gui Wang, Wenbin Zhang
The present study aimed to investigate the effects of the Toll-like receptor (TLR)4/myeloid differentiation primary response (MyD)88 signaling pathway on sepsis-associated acute respiratory distress syndrome (ARDS) in rats, and the involvement of macrophage activation and the inflammatory response. A total of 36 specific pathogen-free male Sprague-Dawley rats were selected to establish the rat model of sepsis-associated ARDS using cecal ligation and puncture (CLP). Rats were assigned into the Ab (anti-TLR4 monoclonal antibody)-CLP, CLP and Sham groups...
April 2018: Experimental and Therapeutic Medicine
Michelle Biehl, Adil Ahmed, Rahul Kashyap, Amelia Barwise, Ognjen Gajic
OBJECTIVE: To evaluate the long-term survival of patients at similar risk for hospital-acquired acute respiratory distress syndrome (ARDS) who did and did not develop ARDS. METHODS: We conducted long-term follow-up of a population-based nested case-control study in a consecutive cohort of adult Olmsted County, Minnesota, patients admitted from January 1, 2001, through December 31, 2010. Patients in whom ARDS developed during their hospital stay (cases) were matched to similar-risk patients without ARDS (controls) by 6 characteristics: age, sex, sepsis, high-risk surgery, ratio of oxygen saturation to fraction of inspired oxygen, and ARDS risk according to the Lung Injury Prediction Score...
February 27, 2018: Mayo Clinic Proceedings
Christine K Federspiel, Theis S Itenov, Kala Mehta, Raymond K Hsu, Morten H Bestle, Kathleen D Liu
BACKGROUND: Duration of acute kidney injury (AKI) has been recognized a risk factor for adverse outcomes following AKI. We sought to examine the relationship of AKI duration and recurrent AKI with short-term outcomes in critically ill patients who were mechanically ventilated and met criteria for the acute respiratory distress syndrome. METHODS: Participants in the NHLBI ARDS Network SAILS multicenter trial who developed AKI were included in this analysis and divided into groups based on AKI duration...
February 23, 2018: Annals of Intensive Care
Yudai Takatani, Kenji Ono, Hiromi Suzuki, Masato Inaba, Makoto Sawada, Naoyuki Matsuda
Hypothermia is a significant sign of sepsis, which is associated with poor prognosis, but few mechanisms underlying the regulation of hypothermia are known. Inducible nitric oxide synthase (iNOS) is a key inflammatory mediator of sepsis. However, the therapeutic benefit of iNOS inhibition in sepsis is still controversial, and requires elucidation in an accurate model system. In this study, wild-type (WT) mice showed temperature drops in a biphasic manner at the early and late phase of sepsis, and all mice died within 48 h of sepsis...
February 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Mohamed A T Mohamed, Tareq Maraqa, Matthew D Bacchetta, Michael McShane, Kenneth L Wilson
Introduction: Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been gaining use to bridge the recovery from acute respiratory distress syndrome (ARDS) refractory to conventional treatment. However, these interventions are often limited to higher echelons of military care. We present a case of lung salvage from severe ARDS in an Afghani soldier with VV-ECMO at a Role-2 (R2) facility in an austere military environment in Afghanistan. Case: A 25-year-old Afghani soldier presented to an R2 facility with blast lung injury and multiple penetrating injuries following an explosion...
February 13, 2018: Military Medicine
Maurizio Turzo, Julian Vaith, Felix Lasitschka, Markus A Weigand, Cornelius J Busch
BACKGROUND: ATP-regulated potassium channels (KATP) regulate pulmonary vascular tone and are involved in hypoxic pulmonary vasoconstriction (HPV). In patients with inflammation like sepsis or ARDS, HPV is impaired, resulting in a ventilation-perfusion mismatch and hypoxia. Since increase of vascular KATP channel Kir6.1 has been reported in animal models of endotoxemia, we studied the expression and physiological effects of Kir6.1 in murine endotoxemic lungs. We hypothesized that inhibition of overexpressed Kir6...
February 13, 2018: Respiratory Research
Andry Van de Louw, Ruchi J Desai, Junjia Zhu, David F Claxton
Acute respiratory complications occur frequently during the early phase of acute myeloid leukemia (AML) but information on the most severe form, acute respiratory distress syndrome (ARDS), is lacking. We retrospectively analyzed 280 patients with newly diagnosed AML in order to describe the incidence, risk factors and early mortality associated with ARDS within 15 d. Univariate and then multivariate analysis were performed. ARDS developed in 9% of patients and was associated with 64% day-30 mortality. White blood cell count on admission was an independent risk factor for ARDS (OR = 1...
February 12, 2018: Leukemia & Lymphoma
Christian Bime, Nima Pouladi, Saad Sammani, Ken Batai, Nancy Casanova, Tong Zhou, Carrie L Kempf, Xiaoguang Sun, Sara M Camp, Ting Wang, Rick A Kittles, Yves A Lussier, Tiffanie K Jones, John P Reilly, Nuala J Meyer, Jason D Christie, Jason Karnes, Manuel Gonzalez-Garay, David C Christiani, Charles R Yates, Mark M Wurfel, Gianfranco U Meduri, Joe G N Garcia
RATIONALE: Genetic factors are involved in acute respiratory distress syndrome (ARDS) susceptibility. Identification of novel candidate genes associated with increased risk and severity will improve our understanding of ARDS pathophysiology and enhance efforts to develop novel preventive and therapeutic approaches. METHODS: A genome-wide association study was performed on 232 African-American patients with ARDS and 162 at-risk controls. The Identify Candidate Causal single nucleotide polymorphisms (SNPs) and Pathways platform was used to infer the association of known gene sets with the top prioritized intragenic SNPs...
February 9, 2018: American Journal of Respiratory and Critical Care Medicine
Luiz Philippe S Sergio, Leda M F Lucinda, Maycon M Reboredo, Flavia de Paoli, Lídia M C Fonseca, Bruno V Pinheiro, Andre L Mencalha, Adenilson S Fonseca
Purpose/Aim of the study: Patients suffering from chronic obstructive pulmonary disease (COPD) in association with acute respiratory distress syndrome (ARDS) present oxidative stress in lung cells, with production of free radicals and DNA lesions in pulmonary and adjacent cells. Once the DNA molecule is damaged, a set of enzymatic mechanisms are trigged to preserve genetic code integrity and cellular homeostasis. These enzymatic mechanisms include the base and the nucleotide excision repair pathways, as well as telomere regulation...
February 8, 2018: Experimental Lung Research
Emma Lefrançais, Beñat Mallavia, Hanjing Zhuo, Carolyn S Calfee, Mark R Looney
Neutrophils dominate the early immune response in pathogen-induced acute lung injury, but efforts to harness their responses have not led to therapeutic advancements. Neutrophil extracellular traps (NETs) have been proposed as an innate defense mechanism responsible for pathogen clearance, but there are concerns that NETs may induce collateral damage to host tissues. Here, we detected NETs in abundance in mouse models of severe bacterial pneumonia/acute lung injury and in human subjects with acute respiratory distress syndrome (ARDS) from pneumonia or sepsis...
February 8, 2018: JCI Insight
Xianfeng Chen, Juntao Hu, Chi Zhang, Yiping Pan, Diansheng Tian, Fafa Kuang, Zhanhong Tang
OBJECTIVE: To investigate the mechanisms of protective effects of dexmedetomidine on lungs in patients of sepsis complicated with acute respiratory distress syndrome (ARDS). METHODS: The adult patients with sepsis complicated with ARDS, the oxygenation index (PaO2/FiO2) was 150-200 mmHg (1 mmHg = 0.133 kPa), acute physiology and chronic health evaluation II (APACHE II) score was 10-20, need mechanical ventilation (MV) treatment > 72 hours, and admitted to intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from September 2013 to June 2017 were enrolled...
February 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Bethany M Biron, Chun-Shiang Chung, Yaping Chen, Zachary Wilson, Eleanor A Fallon, Jonathan S Reichner, Alfred Ayala
Indirect acute respiratory distress syndrome (iARDS) is caused by a nonpulmonary inflammatory process resulting from insults such as nonpulmonary sepsis. Neutrophils are thought to play a significant role in mediating ARDS, with the development of iARDS being characterized by dysregulation and recruitment of activated neutrophils into the lung. Recently, a novel mechanism of microbial killing by neutrophils was identified through the formation of neutrophil extracellular traps (NETs). NETs are composed of large webs of decondensed chromatin released from activated neutrophils into the extracellular space; they are regulated by the enzyme peptidylarginine deiminase 4 (PAD4) through mediation of chromatin decondensation via citrullination of target histones...
January 26, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Srabani Mitra, Matthew Exline, Fabien Habyarimana, Mikhail Gavrilin, Paul Baker, Seth L Masters, Mark D Wewers, Anasuya Sarkar
RATIONALE: Lung endothelial cell apoptosis and injury occurs throughout all stages of acute lung injury (ALI/ARDS) and impacts disease progression. Caspases 1, 4 and 5 are essential for completion of the apoptotic program known as pyroptosis that also involves pro-inflammatory cytokines. OBJECTIVES: Because GSDM-D mediates pyroptotic death and is essential for pore formation, we hypothesized that it may direct caspase-1 encapsulated microparticle (MP) release and mediate endothelial cell death...
January 24, 2018: American Journal of Respiratory Cell and Molecular Biology
Takahiro Hiruma, Hitoshi Tsuyuzaki, Kanji Uchida, Bruce C Trapnell, Yoshiro Yamamura, Yoshiomi Kusakabe, Tokie Totsu, Takuji Suzuki, Shigeki Morita, Kent Doi, Eisei Noiri, Kensuke Nakamura, Susumu Nakajima, Naoki Yahagi, Naoto Morimura, Kyungho Chang, Yoshitsugu Yamada
Interferon-β (IFNβ) is reported to improve survival in patients with acute respiratory distress syndrome (ARDS), possibly by preventing sepsis-induced immunosuppression, but its therapeutic nature in ARDS pathogenesis is poorly understood. We investigated the therapeutic effects of IFNβ for post-septic ARDS to better understand its pathogenesis in mice. Post-septic ARDS was reproduced in mice by cecal ligation and puncture to induce sepsis followed 4 days later by intratracheal instillation of Pseudomonas aeruginosa to cause pneumonia with or without subcutaneous administration of IFNβ 1 day earlier...
January 24, 2018: American Journal of Respiratory Cell and Molecular Biology
Yang Liu, Hao Guan, Ju-Lei Zhang, Zhao Zheng, Hong-Tao Wang, Ke Tao, Shi-Chao Han, Lin-Lin Su, Dahai Hu
MiR-199a is a novel gene regulator with an important role in inflammation and lung injury. However, its role in the pathogenesis of sepsis-induced acute respiratory distress syndrome (ARDS) is currently unknown. Our study explored the role of miR-199a in sepsis-induced ARDS and its mechanism of action. First, we found that LPS could up-regulate miR-199a in alveolar macrophages. Down-regulation of miR-199a inhibited the up-regulation of inflammatory cytokines in alveolar macrophages and induced the remission of histopathologic changes, the reduction of pro-inflammatory cytokines, and the up-regulation of apoptosis protein expression in an ARDS lung, showing a protective role for miR-199a...
January 10, 2018: American Journal of Physiology. Cell Physiology
Stéphane Gaudry, David Hajage, Frédérique Schortgen, Laurent Martin-Lefevre, Charles Verney, Bertrand Pons, Eric Boulet, Alexandre Boyer, Guillaume Chevrel, Nicolas Lerolle, Dorothée Carpentier, Nicolas de Prost, Alexandre Lautrette, Anne Bretagnol, Julien Mayaux, Saad Nseir, Bruno Megarbane, Marina Thirion, Jean-Marie Forel, Julien Maizel, Hodane Yonis, Philippe Markowicz, Guillaume Thiery, Florence Tubach, Jean-Damien Ricard, Didier Dreyfuss
RATIONALE: The optimal strategy for initiation of renal replacement therapy (RRT) in patients with severe acute kidney injury in the context of septic shock and acute respiratory distress syndrome (ARDS) is unknown. OBJECTIVE: To examine the effect of an early compared to a delayed RRT initiation strategy on 60-day mortality according to the baseline sepsis status, ARDS status and severity. METHODS: Post-hoc analysis of the AKIKI (Artificial-Kidney-Initiation in Kidney-Injury) trial...
January 19, 2018: American Journal of Respiratory and Critical Care Medicine
Chao Cao, Chengfen Yin, Songtao Shou, Jun Wang, Lechang Yu, Xuening Li, Yanfen Chai
Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), remain the leading causes of morbidity and mortality in intensive care units. Ulinastatin (UTI), a serine protease inhibitor, possesses anti-inflammatory properties and has been suggested to modulate lipopolysaccharide (LPS)-induced sepsis; thus, it is now widely used in the treatment of pancreatitis, sepsis, and septic shock. Toll-like receptor 4 (TLR4), an essential LPS signaling receptor, plays a critical role in the activation of innate immunity...
January 10, 2018: Shock
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