Bibliometric Analysis of Literature on Acute Respiratory Distress Syndrome Treatments Published Between 2000 and 2019

Bibliometric Analysis of Literature on Acute Respiratory Distress Syndrome Treatments Published Between 2000 and 2019 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Bibliometric Analysis of Literature on Acute Respiratory Distress Syndrome Treatments Published Between 2000 and 2019 Zong-Yu Wang, Zhi-Chao Zhou, Jie Zheng, Zhu-Kai Cong, Xi Zhu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-128479/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Acute respiratory distress syndrome (ARDS) is a common and extensively researched condition, and treatment modalities are continuously being developed and improved. Although the literature on ARDS treatment is vast, there have not been any bibliographic analyses examining trends in this area. We aimed to systematically evaluate the literature on ARDS treatments published between 2000 and 2019, from the perspective of bibliometrics. Methods: Literature retrieval was performed in PubMed and in the Web of Science Core Collection, and analyzed for publication and temporal trends. CiteSpace was used to perform co-occurrence analysis for institutions, and reference co-citation analysis for research topics. Burst keyword detection was used to predict future areas of research interest in the field. Results: A total of 13,933 articles were retrieved. The journal Critical Care Medicine published the largest number of articles (956, 6.86%). The University of Toronto was affiliated with the most publications (574, 4.28%) and had the highest degree of betweenness centrality, indicating extensive inter-institution collaboration. The papers on ARDS treatment published between 2000 and 2019 were grouped into 10 major clusters, 3 of which indicated recent activity (“acute lung injury,” “long-term outcome” and “extracorporeal membrane oxygenation”). Fifteen burst keywords/terms were identified, including extracorporeal membrane oxygenation, meta-analysis and oxidative stress. Conclusions: On the basis of the literature published in the preceding 20 years, the exploration of ARDS treatment is an ongoing concern. Extracorporeal membrane oxygenation was an active focus of research in this field. It and oxidative stress are likely to become major topics of research interest in the near future. Meta-analysis will be a popular method in analyzing the efficacy of ARDS treatments. Health Economics & Outcomes Research Pulmonology acute respiratory distress syndrome treatment visualization analysis bibliometrics reference co-citation analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by non-cardiogenic pulmonary edema, diffuse endothelial injury and bilateral pulmonary infiltrates, which can be devastating to critically ill patients in the intensive care unit, and places a burden on the healthcare system. The LUNG SAFE study reported that 23.4% of patients receiving mechanical ventilation were ARDS cases and that the hospital mortality rate in patients with severe ARDS was 46.1% [ 1 ]. The first report of the syndrome was published in 1967 [ 2 ], and discussions of how best to define the new clinical entity have been going on for many decades, from the American-European Consensus Conference definition to the Berlin definition, and the same is true regarding the development of ARDS treatment. In 1969, a treatment with continuous positive-pressure breathing was proposed [ 3 ], and positive end-expiratory pressure (PEEP) therapy was evaluated in 11 ARDS patients in 1973 [ 4 ].Ventilation with a low tidal volume (6 mL/kg predicted body weight) and a plateau pressure of 30 cm of water or less was shown to improve survival in patients with ARDS [ 5 ], and these strategies are recommended in clinical practice guidelines. ARDS management strategies began to take shape, but more therapies need to be developed. Recruitment maneuvers, the technique that sustained high airway pressure for a period of time in order to expand the collapsed alveoli during mechanical ventilation, are still under debate, although they can reverse hypoxemia [ 6 ]. The findings of a recent randomized clinical trial did not support the routine use of recruitment maneuvers and titrated PEEP because of increased 28-day mortality in patients with moderate-to-severe ARDS [ 7 ]. These examples illustrate the evolution in thinking and clinical practice around the treatment of ARDS, but individual examples cannot provide a comprehensive overview of this evolution. The entire published literature on ARDS, however, contains a detailed history of this evolution in terms of: trends; leading journals in the publication of ARDS research; and the investigators and institutions behind this research, along with their interrelationships and influences. A detailed and comprehensive overview of this nature may provide policy makers, funding agencies and researchers with important information to facilitate identification of key research topics, financial support for meaningful research and collaboration possibilities in this field. Although ARDS treatments have been reviewed [ 8 , 9 ], there have not been any bibliographic analyses examining trends in topics, journals and research institutions. Recognizing the absence of such a published survey, we undertook to perform a bibliographic analysis of papers related to ARDS therapy published over the last 20 years. Bibliometric analysis is a useful method for identifying impactful authors and regions, constructing collaboration networks, and distilling key research topics in particular areas [ 10 ]. In this study, bibliometric analysis was used to achieve three goals: map the overall layout of ARDS research from the perspective of publication dates, journals, keywords and citations; identify core research institutions and their direct collaborative networks; and highlight current and potential future areas of research focus. Methods Data collection Literature retrieval was performed in both PubMed and the Web of Science Core Collection on Aug 3, 2020. We selected “respiratory distress syndrome, adult” as a subject heading, which was combined in PubMed searches with several subheadings (therapy, diet therapy, drug therapy, nursing, prevention and control, and surgery). We then searched for ARDS-treatment articles in Web of Science using the same strategy. Both sets from the literature were merged, and duplicates were removed. Articles, reviews and letters published between 2000 and 2019, inclusive, were kept for further analysis. Figure 1 shows a flowchart of the literature retrieval strategy. More details on the retrieval process are given in Additional File 1. Informed consent was not necessary as our study analyzed published literature without any identifying information about participants in the research reported. Analysis and visualization The identified articles were systematically analyzed using the Web of Science website and CiteSpace (5.7.R1, Chaomei Chen) [ 11 ]. Web of Science has built-in statistics tools to graph publication trends by year, language and journal. CiteSpace is a tool for visualizing and analyzing scientific literature, by constructing the knowledge structure based on citation relationship among literatures in the research field. Among the bibliometric analysis methods, we selected reference co-citation analysis [ 12 ] and analysis of institutional collaboration networks for articles published between 2000 and 2019 [ 13 ]. The indicators used in the evaluation were “modularity” and “betweenness centrality,” as follows. The degree to which a network can be divided into several independent blocks is measured by modularity [ 14 ]. Its value ranges from 0 to 1, and a relatively high value means a well-structured network [ 15 ]. Betweenness centrality is a quantitative indicator of the influence of institutions, calculated as the fraction of shortest paths going through a given node that denotes an institution in the cooperative network [ 16 ]. A citation is regarded as a reasoned and solid index of scientific communication. Co-citation analysis enables the identification of the inner structure of research disciplines. A co-citation exists if two references or authors appear in the same bibliography, and is interpreted as the measure for similarity of content of the two references or authors [ 17 ]. In this study, the 50 most cited articles in successive 3-year intervals (e.g., 2000–2002, 2003–2005) were collected, and all references from each 50-article block were used to create the individual networks. Log-likelihood ratio weighting was used to analyze the contents of each cluster. “Burst keyword detection,” a computing technique used to identify mutations in information, was used to determine new research foci in the field [ 18 ]. A keyword burst is characterized by the intensity of the burst and by its duration. Results Temporal distribution of papers A total of 13,933 papers were collected for analysis. Figure 2 graphs the number of articles published by year, and indicates a general upward trend in research into ARDS treatments, from 466 articles in 2000 to 918 in 2019. Publication language The articles returned in the search had been published in 15 languages. Of the 13,933 papers, 13,460 (96.61%) were published in English, 221 (1.59%) in German, 121 (0.87%) in French, 89 (0.64%) in Spanish, 15 (0.11%) in Portuguese and 27 (0.2%) in other languages. Core journals A total of 1,592 scholarly journals published articles on ARDS treatment during the period of interest. The top 10 journals (Table 1 ) accounted for 28.1% of all documents published (3,914 articles). The journals publishing the most ARDS research were Critical Care Medicine , Intensive Care Medicine , American Journal of Respiratory and Critical Care Medicine , and Critical Care . Table 1 The 10 journals publishing the most research articles on the treatment of acute respiratory distress syndrome Journal N (%) Country Impact factor in 2019 Critical Care Medicine 956 (6.86%) USA 7.414 Intensive Care Medicine 601 (4.31%) USA 17.679 American Journal of Respiratory and Critical Care Medicine 479 (3.44%) USA 17.452 Critical Care 460 (3.30%) England 6.407 American Journal of Physiology-Lung Cellular and Molecular Physiology 309 (2.22%) USA 4.406 Respiratory Care 260 (1.87%) USA 2.066 Chest 254 (1.82%) Netherlands 8.308 Current Opinion in Critical Care 200 (1.44%) USA 2.92 Journal of Critical Care 200 (1.44%) USA 2.685 Shock 195 (1.40%) USA 2.96 N (%), number of articles published by the journal and percentage of the total articles assessed in this study. Country refers to the country associated with the publisher. Impact factors are derived from Journal Citation Reports (2019) published by the Institute for Scientific Information of the United States. Research institutions The researchers who published the literature included in this study were affiliated with a total of 9,468 institutions. Table 2 lists the top 15 institutions, which accounted for 28.64% of the total articles. The University of Toronto was associated with the most publications, followed by the University of California, San Francisco, and Harvard University. Extensive collaborations were observed between institutions (Fig. 3 ). The University of Toronto, the University of California, San Francisco, Harvard University and the University of Washington had high betweenness centrality. Table 2 Ranking of the 15 institutions most active in researching treatments for acute respiratory distress syndrome, based on numbers of publications Institution N (%) Betweenness centrality University of Toronto 574 (4.28%) 0.29 University of California, San Francisco 395 (2.95%) 0.17 Harvard University 327 (2.44%) 0.15 Massachusetts General Hospital 257 (1.92%) 0.12 University of Pennsylvania 237 (1.77%) 0.07 University of Sao Paulo 229 (1.71%) 0.04 Johns Hopkins University 228 (1.70%) 0.07 Vanderbilt University 217 (1.62%) 0.1 University of Washington 216 (1.61%) 0.14 University of Pittsburgh 210 (1.57%) 0.09 University of Milan 203 (1.52%) 0.02 University of Michigan 201 (1.5%) 0.03 St. Michael's Hospital 195 (1.46%) 0.09 University Colorado 179 (1.34%) 0.08 Mayo Clinic 170 (1.27%) 0.03 N (%), number of articles and percentage of the total articles assessed in this study. Betweenness centrality is a quantitative indicator of the influence of institutions in a collaborative network of academic institutions. Analysis of reference co-citation We used all references from the 50 most-cited publications in each successive 3-year grouping to construct each individual network, and then synthesized the individual networks for a total of 243,830 references. We performed reference co-citation analysis to generalize clusters and construct a knowledge map in timeline view, which grouped publications on ARDS treatment into nine major clusters (Fig. 4 ). The network in this study had a modularity of 0.717, which is typically considered relatively high. We focused on the major clusters that were sorted and tagged by the number of co-cited references. A total of 10 clusters were included in the analysis (Table 3 ). Three of these clusters (key terms “acute lung injury,” “long-term outcome” and “extracorporeal membrane oxygenation”) have been active in recent years. Table 3 Characteristics of co-citation clusters Cluster Size a Beginning year Ending year Activity b Tag name c #0 46 2001 2010 inactive ventilatory strategies #1 38 2013 2017 active acute lung injury #2 37 2007 2015 active long-term outcome #3 31 1995 2002 inactive high-frequency ventilation #4 27 2006 2018 active extracorporeal membrane oxygenation #5 19 1999 2002 inactive computed tomography #6 17 1996 1999 inactive inhaled nitric oxide #7 7 2001 2004 inactive severe sepsis #8 7 2003 2008 inactive pharmacological treatment #9 6 2009 2012 inactive mesenchymal stem cell a Number of published articles. b Persistence of a theme over the past 5 years (yes/no). c Typical word assigned to represent the main content of the cluster using a log-likelihood ratio algorithm. The timeline view of reference co-citation analysis (Fig. 4 ) shows that the duration of research into extracorporeal membrane oxygenation was the longest, lasting from 2006 to 2018. The use of nitric oxide in treatment was no longer a topic of research papers after 1999. Some references were included in multiple clusters, acting as a link. Table 4 lists the core articles in the main co-citation clusters. Table 4 Core articles in the main co-citation clusters Cluster and tag name Lead author Publishing year Theme #4 ECMO Peek GJ [ 20 ] 2009 ECMO, severe adult respiratory failure #4 ECMO Davies A [ 21 ] 2009 ECMO, influenza A #4 ECMO Bein T [ 22 ] 2013 Extracorporeal carbon dioxide removal, ultraprotective ventilation #4 ECMO Schmidt M [ 23 ] 2013 ECMO, outcome assessment #0 Ventilatory strategies Meade MO [ 25 ] 2008 Open-lung strategy, ARDS #0 Ventilatory strategies Mercat A [ 26 ] 2008 PEEP setting strategy, ARDS #2 Long-term outcome Briel M [ 29 ] 2010 Higher versus lower PEEP, ARDS #2 Long-term outcome Papazian L [ 35 ] 2010 Neuromuscular blocker, ARDS #2 Long-term outcome Ranieri VM [ 36 ] 2012 Berlin definition, ARDS #2 Long-term outcome Ferguson ND [ 37 ] 2013 High-frequency oscillatory ventilation, ARDS #2 Long-term outcome Young D [ 38 ] 2013 High-frequency oscillatory ventilation, ARDS #2 Long-term outcome Guérin C [ 30 ] 2013 Prone positioning, ARDS #1 Acute lung injury Amato MBP [ 33 ] 2015 Driving pressure, ARDS #1 Acute lung injury Bellani G [ 1 ] 2016 Epidemiology, patterns of care, mortality, ARDS #1 Acute lung injury Slutsky AS [ 31 ] 2013 Ventilator-induced lung injury #1 Acute lung injury Frat JP [ 34 ] 2015 High-flow oxygen, acute hypoxemic respiratory failure #1 Acute lung injury Calfee CS [ 32 ] 2014 ARDS subphenotypes #0 Ventilatory strategies Gattinoni L [ 28 ] 2001 Prone positioning, acute respiratory failure #0 Ventilatory strategies Brower RG [ 39 ] 2004 Higher versus lower PEEP, ARDS #0 Ventilatory strategies Rubenfeld GD [ 40 ] 2005 Incidence and outcomes, acute lung injury #0 Ventilatory strategies Wiedemann HP [ 27 ] 2006 Fluid-management strategy, acute lung injury ARDS, acute respiratory distress syndrome; ECMO, extracorporeal membrane oxygenation; PEEP, positive end-expiratory pressure. Analysis of burst keywords Keyword co-occurrence analysis returned 59 keywords. The keyword citation burst (citation increase over a given period) identified 15 keywords with strong citation bursts over the past decade (Table 5 ). Extracorporeal membrane oxygenation, listed in both full and abbreviated forms, was an area of active research between 2013 and 2018. Meta-analysis and randomized controlled trials also had high burst strength, especially meta-analysis in recent years. Two active keywords related to basic ARDS research were NF-kappa B, a key nuclear transcription factor regulating inflammatory responses in ARDS [ 19 ], and oxidative stress. Recruitment, protective ventilation, and noninvasive ventilation were often-used keywords connected to ARDS treatment between 2013 and 2016. Keywords relating to pathogenic factors such as risk, infection, pneumonia and sepsis are still in use. Table 5 Keywords with the strongest citation burst in papers on treatment of acute respiratory distress syndrome in the past two decades Keywords Strength Beginning year Ending year extracorporeal membrane oxygenation 67.91 2013 2018 ECMO 54.72 2015 2018 meta-analysis 50.56 2015 2018 oxidative stress 31.35 2015 2018 noninvasive ventilation 29.57 2015 2016 risk factor 29.35 2009 2014 randomized controlled trial 27.84 2009 2010 infection 27.54 2011 2012 protective ventilation 17.35 2013 2014 NF-kappa B 13.44 2013 2018 survival 12.37 2013 2014 recruitment 10.06 2013 2014 randomized controlled trial 7.4 2013 2015 pneumonia 7.11 2009 2011 severe sepsis 6.62 2013 2016 Strength denotes the rate of increase in citations over a given period. Higher strength values denote more active research. ECMO, extracorporeal membrane oxygenation. Discussion We have presented a visual analysis of the research literature into the treatment of ARDS, which revealed the following epistemological characteristics. The body of literature has grown over time, with Critical Care Medicine and Intensive Care Medicine publishing multiple papers on the topic. Many of the researchers publishing on the topic were affiliated with the University of Toronto, St. Michael’s Hospital, the University of Washington, and the University of California, San Francisco. Co-citation analysis grouped the references into eight major co-citation clusters indicating research interests within the field of ARDS therapy. The 15 keywords thus identified may be helpful in formulating future research. The growth in the number of publications indicates that an increasing number of researchers were studying ARDS treatments, frequently in collaboration with researchers in other institutions. Nearly one-third of the literature was published in just 10 journals, indicating that ARDS treatment was within the scope of research published by these journals. Reference co-citation analysis was used to assess the co-citation relevance between papers, and to categorize the data into major clusters representing research interests. In our study, the reference network was grouped into eight clearly defined co-citation clusters. Active research in this field appears to be dominated currently by extracorporeal membrane oxygenation and acute lung injury. Extracorporeal membrane oxygenation, as an approach to cardiopulmonary support, has been shown to improve the survival of patients with severe respiratory failure [ 20 ], and was used in influenza A (H1N1)-associated ARDS [ 21 ]. Related topics of research discussion were criteria for extracorporeal membrane oxygenation, extracorporeal carbon dioxide removal and long-term outcomes of this approach [ 22 , 23 ]. However, the most recent study (EOLIA trial) in patients with severe ARDS showed no benefit, in terms of 60-day mortality, with extracorporeal membrane oxygenation [ 24 ]. The ventilatory strategies cluster, which contained the most articles, including comprehensive topics involving the open lung [ 25 ], PEEP level setting [ 26 ] and fluid-management strategy [ 27 ], short-term prone positioning, and the burden of ARDS [ 28 ], has been inactive since 2010. The clusters marked with long-term outcome and acute lung injury have developed and remain active. In particular, the former was in an inherent relationship with the cluster of ventilatory strategies, and we found some overlapping topics in their core literature, such as PEEP [ 29 ] and prone positioning [ 30 ]. Treatment outcome has always been the focus of attention in research into ARDS and, perhaps for this reason, the long-term outcome cluster kept in close contact with the acute lung injury cluster and extracorporeal membrane oxygenation, which served as a bridge among the clusters. The core articles targeting prognosis of ARDS were contained in the aforementioned clusters. From the timeline view, “acute lung injury” was the recent cluster, and is still active. The themes of core articles contained ventilator-induced lung injury [ 31 ], the exploration on sub-phenotypes of ARDS [ 32 ], driving pressure [ 33 ], the effect of high-flow oxygen on acute hypoxemic respiratory failure [ 34 ], and the reassessment of ARDS burden [ 1 ]. These topics seemed to be unfocused but involved basic data, issues of wide concern, and exploration of new direction, which were often co-cited in the papers to provide basic support and guide the elaboration, and probably developed over time. A heavily cited keyword is considered an indicator of a topic of research interest, or an emerging trend. Extracorporeal membrane oxygenation and its abbreviation (ECMO) take the top two spots in the ranking of citation burst strength in recent years, indicating that this topic will continue to be studied. Meta-analysis can comprehensively analyze the results of previous randomized controlled trials on ARDS, to come to more-objective conclusions, and it is still expected to be the popular research methodology based on the strength value obtained. In the field of basic research, oxidative stress has become a popular topic of investigation in ARDS therapy. Table 5 shows the progress in ARDS research through the evolution of burst keywords over the past decade. Factors that can precipitate ARDS, which appeared in the literature we analyzed, were pneumonia, infection and severe sepsis, in chronological order. A similar evolution was reflected in the therapeutic methods, from lung recruitment and protective ventilation, to noninvasive ventilation, to extracorporeal membrane oxygenation. To perform the co-citation clustering analysis, we selected the Web of Science as our final literature source, which may have excluded some studies. Valuable articles can also be found in evidence-based medicine databases such as the Cochrane Library and citation databases such as Scopus. When constructing the retrieval strategy, we listed a large number of technical terms related to ARDS treatment, and limited the scope to treatment, possibly ignoring the literature related to diagnosis, prevention and control of ARDS, which may influence treatment. We selected as many search terms as possible, to cover as much of the relevant literature as we could. Research topics that are deemed exciting are often pursued intensively during a given period and result in multiple publications, but the findings may not be clinically valuable with the passage of time and further investigation, weakening the value of the research topic. Finally, we did not include conference abstracts in our search, which may have influenced the weighting of results. Conclusions On the basis of the bibliographic analysis of the literature in the last 20 years, the research into ARDS treatment has been receiving continuous attention. Extracorporeal membrane oxygenation is currently a topic of active research, and it and oxidative stress are likely to be the research interests in the near future. Meta-analysis of original studies will still be a popular research method in this field. List of Abbreviations ARDS, acute respiratory distress syndrome; PEEP, positive end-expiratory pressure; ECMO, extracorporeal membrane oxygenation. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Availability of data and materials The supporting data are provided in the online supplementary material. Competing interests None declared. Funding This study was funded by the National Science and Technology Major Project (grant number 2018ZX10101004), the National Natural Science Foundation of China (grant number 81372043), Beijing Natural Science Foundation (grant number 7162199), and Peking University Third Hospital Foundation (grant number Y76478-01). Authors’ contributions Z.Y.W. designed the study and manuscript content and contributed to drafting the manuscript. Z.C.Z. contributed to the manuscript content, collected and analyzed the data, and drafted the manuscript. J.Z. and Z.K.C. contributed to the manuscript content. X.Z. contributed to the study concept and critical evaluation of the manuscript. All authors approved the submission of this version for publication. Acknowledgments X.Z. takes responsibility for the content of the manuscript, including the data and analysis. The authors appreciate the contribution of Wei Li to the study concept and the contribution of Yuan Zhang to coordinating cooperation. We thank Hugh McGonigle and Claire Barnes, PhD, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript. References Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016;315:788–800. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet (London, England). 1967;2:319–23. Ashbaugh DG, Petty TL, Bigelow DB, Harris TM. Continuous positive-pressure breathing (CPPB) in adult respiratory distress syndrome. The Journal of thoracic and cardiovascular surgery. 1969;57:31–41. King EG, Jones RL, Patakas DA. Evaluation of positive end-expiratory pressure therapy in the adult respiratory distress syndrome. Canadian Anaesthetists' Society journal. 1973;20:546–58. Acute RDSN, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The New England journal of medicine. 2000;342:1301–08. Borges JB, Okamoto VN, Matos GFJ, Caramez MPR, Arantes PR, Barros F, et al. Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome. Am J Resp Crit Care. 2006;174:268–78. Writing GFTA, Cavalcanti AB, Suzumura ÉA, Laranjeira LN, Paisani DDM, Damiani LP, et al. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2017;318:1335–45. Fan E, Brodie D, Slutsky AS. Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment. JAMA. 2018;319:698. Papazian L, Aubron C, Brochard L, Chiche J, Combes A, Dreyfuss D, et al. Formal guidelines: management of acute respiratory distress syndrome. Ann Intensive Care. 2019;9:69. Guler AT, Waaijer CJF, Palmblad M. Scientific workflows for bibliometrics. Scientometrics. 2016;107:385–98. Chen C. CiteSpace II: Detecting and visualizing emerging trends and transient patterns in scientific literature. Journal of the American Society for Information Science & Technology. 2006;57:359–77. Yang D, Wang X, Wang Z, Yang Z, Bian X. A scientometric analysis on hepatocellular carcinoma magnetic resonance imaging research from 2008 to 2017. Quant Imag Med Surg. 2019;9:465–76. Chen C. Science Mapping: A Systematic Review of the Literature. Journal of Data and Information Science. 2017;2:1–40. Shibata N, Kajikawa Y, Takeda Y, Matsushima K. Detecting emerging research fronts based on topological measures in citation networks of scientific publications. Technovation. 2008;28:775. Chen C, Fidelia I, Jianhua H. The structure and dynamics of cocitation clusters: A multiple-perspective cocitation analysis. Journal of the American Society for Information Science & Technology. 2010;61:1386–409. Barthélemy M. Betweenness centrality in large complex networks. Eur Phys J B. 2004;38:163–68. Gmür M. Co-citation analysis and the search for invisible colleges: A methodological evaluation. Scientometrics. 2003;57:27–57. Kleinberg J. Bursty and Hierarchical Structure in Streams. Data Min Knowl Disc. 2003;7:373–97. Arshad, Rahman, Fabeha, Fazal. Blocking NF-κB: an inflammatory issue. Proceedings of the American Thoracic Society. 2011;8:497–503. Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet (London, England). 2009;374:1351–63. Australia ANZE, Davies A, Jones D, Bailey M, Beca J, Bellomo R, et al. Extracorporeal Membrane Oxygenation for 2009 Influenza A(H1N1) Acute Respiratory Distress Syndrome. JAMA. 2009;302:1888–95. Bein T, Weber-Carstens S, Goldmann A, Müller T, Staudinger T, Brederlau J, et al. Lower tidal volume strategy (≈ 3 ml/kg) combined with extracorporeal CO2 removal versus 'conventional' protective ventilation (6 ml/kg) in severe ARDS: the prospective randomized Xtravent-study. Intens Care Med. 2013;39:847–56. Schmidt M, Zogheib E, Rozé H, Repesse X, Lebreton G, Luyt C, et al. The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. Intens Care Med. 2013;39:1704–13. Combes A, Hajage D, Capellier G, Demoule A, Lavoué S, Guervilly C, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2018;378:1965–75. Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper DJ, et al. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008;299:637–45. Mercat A, Richard JM, Vielle B, Jaber S, Osman D, Diehl J, et al. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008;299:646–55. National Heart LABI, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, et al. Comparison of two fluid-management strategies in acute lung injury. The New England journal of medicine. 2006;354:2564–75. Gattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D, Labarta V, et al. Effect of prone positioning on the survival of patients with acute respiratory failure. The New England journal of medicine. 2001;345:568–73. Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, et al. Higher vs Lower Positive End-Expiratory Pressure in Patients With Acute Lung Injury and Acute Respiratory Distress Syndrome: Systematic Review and Meta-analysis. JAMA. 2010;303:865–73. Guérin C, Reignier J, Richard J, Beuret P, Gacouin A, Boulain T, et al. Prone positioning in severe acute respiratory distress syndrome. New Engl J Med. 2013;368:2159–68. Slutsky AS, Ranieri VM. Ventilator-induced lung injury. New Engl J Med. 2013;369:2126–36. Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014;2:611–20. Amato MBP, Meade MO, Slutsky AS, Brochard L, Costa ELV, Schoenfeld DA, et al. Driving Pressure and Survival in the Acute Respiratory Distress Syndrome. New Engl J Med. 2015;372:747–55. Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372:2185–96. Papazian L, Forel J, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. The New England journal of medicine. 2010;363:1107–16. ARDS DTF, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307:2526–33. Ferguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L, Austin P, et al. High-frequency oscillation in early acute respiratory distress syndrome. New Engl J Med. 2013;368:795–805. Young D, Lamb SE, Shah S, MacKenzie I, Tunnicliffe W, Lall R, et al. High-frequency oscillation for acute respiratory distress syndrome. New Engl J Med. 2013;368:806–13. Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, et al. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. The New England journal of medicine. 2004;351:327–36. Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, et al. Incidence and outcomes of acute lung injury. The New England journal of medicine. 2005;353:1685–93. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-128479","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":6704249,"identity":"868b0543-6025-430b-b0bd-40d2ca30978b","order_by":0,"name":"Zong-Yu Wang","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zong-Yu","middleName":"","lastName":"Wang","suffix":""},{"id":6704250,"identity":"9246eca3-acf1-4131-9938-e915a741b029","order_by":1,"name":"Zhi-Chao Zhou","email":"","orcid":"","institution":"Peking University Health Science Library","correspondingAuthor":false,"prefix":"","firstName":"Zhi-Chao","middleName":"","lastName":"Zhou","suffix":""},{"id":6704251,"identity":"8ab0b703-6a85-4257-9af3-87d6d9218d26","order_by":2,"name":"Jie Zheng","email":"","orcid":"","institution":"Peking University Health Science Library","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Zheng","suffix":""},{"id":6704252,"identity":"720beab5-8aa8-4732-b913-e1871f0ee5fa","order_by":3,"name":"Zhu-Kai Cong","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhu-Kai","middleName":"","lastName":"Cong","suffix":""},{"id":6704253,"identity":"21a3fb2b-eb43-4909-88f3-a9c430adaec2","order_by":4,"name":"Xi Zhu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtUlEQVRIiWNgGAWjYDACZgY2MM3PzHz4AWlaJNvZ0gyItQeixeA8j4IEUeoNjrM/e8xTYxdtfJiHwYChxiaaoBbJZoZ0Y55jybnbDvMeeMBwLC23gZAWfmaGY9K8DQeAWvgSDBgbDhPWwsbM2AbWsrmZx0CCKC3AsGUDa9nATKwWyWY2Nsk5QL/MOAwM5ARi/GJw/vgziTc1drn9/YcPP/hQY0NYCypIIE35KBgFo2AUjAJcAAA/ADeEZRKZpAAAAABJRU5ErkJggg==","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":true,"prefix":"","firstName":"Xi","middleName":"","lastName":"Zhu","suffix":""}],"badges":[],"createdAt":"2020-12-14 16:30:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-128479/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-128479/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":4454645,"identity":"1c859f9e-5818-49d6-8acc-7ae0c6364627","added_by":"auto","created_at":"2020-12-22 21:45:36","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":103442,"visible":true,"origin":"","legend":"Flowchart of literature selection.","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-128479/v1/aec8775392b541d3db0d956f.jpg"},{"id":4454644,"identity":"79ef50aa-dde7-4886-a4c3-425e892d7a5d","added_by":"auto","created_at":"2020-12-22 21:45:36","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":62844,"visible":true,"origin":"","legend":"Numbers of articles on acute respiratory distress syndrome published over time.","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-128479/v1/263049eb33855813e86a25f8.jpg"},{"id":4454697,"identity":"e02c309f-6086-4504-9d13-9b1c2d917061","added_by":"auto","created_at":"2020-12-22 21:48:36","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":192016,"visible":true,"origin":"","legend":"Map of institutions active in publishing research on the treatment of acute respiratory distress syndrome between 2000 and 2019. Larger typeface indicates a larger number of articles published by researchers affiliated with the institution. Core institutions are marked with a purple ring and greater width of the ring indicates high centrality. The thickness of the curve in connecting lines represents collaborative intensity between institutions, with thicker lines denoting more-intense collaborations.\nNote: The designations employed and the presentation of the material on this map do not imply the expression of any opinion whatsoever on the part of Research Square concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. This map has been provided by the authors.","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-128479/v1/40b4e75b26b4e2203d64cbb2.jpg"},{"id":4454646,"identity":"58b76525-fd92-46db-85e2-31e1ee4067c4","added_by":"auto","created_at":"2020-12-22 21:45:36","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":124453,"visible":true,"origin":"","legend":"Timeline view of the knowledge map from reference co-citation analysis of research into treatments for acute respiratory distress syndrome published between 2000 and 2019. Ten classified clusters, tagged with characteristic names, are represented by colored line segments and numbered from 0 to 9 (from the largest to smallest number of references). Tag names were assigned by a tag word extraction algorithm (log-likelihood ratio algorithm). The left endpoints of colored horizontal lines indicate the year when co-citation links in the fields appeared for the first time, and their length denotes the duration of publication of relevant research articles. Lines connecting the clusters reflect the co-citation relationship, and often-cited articles are highlighted by dots or rings.","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-128479/v1/1ebf7df5e72958eaff356dc5.jpg"},{"id":13639352,"identity":"a57026d6-9ad6-4f21-9cfa-c9943af948d1","added_by":"auto","created_at":"2021-09-17 08:55:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":474970,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-128479/v1/23be9195-724b-4bfa-a23b-aae96f98736a.pdf"},{"id":4454647,"identity":"2fc77757-799d-4b8f-a2cb-e534a49c7d03","added_by":"auto","created_at":"2020-12-22 21:45:36","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":45302,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-128479/v1/1422f287dbac36d79e652559.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eBibliometric Analysis of Literature on Acute Respiratory Distress Syndrome Treatments Published Between 2000 and 2019\u003c/p\u003e","fulltext":[{"header":"Background","content":" \u003cp\u003eAcute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by non-cardiogenic pulmonary edema, diffuse endothelial injury and bilateral pulmonary infiltrates, which can be devastating to critically ill patients in the intensive care unit, and places a burden on the healthcare system. The LUNG SAFE study reported that 23.4% of patients receiving mechanical ventilation were ARDS cases and that the hospital mortality rate in patients with severe ARDS was 46.1% [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The first report of the syndrome was published in 1967 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], and discussions of how best to define the new clinical entity have been going on for many decades, from the American-European Consensus Conference definition to the Berlin definition, and the same is true regarding the development of ARDS treatment. In 1969, a treatment with continuous positive-pressure breathing was proposed [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], and positive end-expiratory pressure (PEEP) therapy was evaluated in 11 ARDS patients in 1973 [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].Ventilation with a low tidal volume (6\u0026nbsp;mL/kg predicted body weight) and a plateau pressure of 30\u0026nbsp;cm of water or less was shown to improve survival in patients with ARDS [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and these strategies are recommended in clinical practice guidelines. ARDS management strategies began to take shape, but more therapies need to be developed. Recruitment maneuvers, the technique that sustained high airway pressure for a period of time in order to expand the collapsed alveoli during mechanical ventilation, are still under debate, although they can reverse hypoxemia [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The findings of a recent randomized clinical trial did not support the routine use of recruitment maneuvers and titrated PEEP because of increased 28-day mortality in patients with moderate-to-severe ARDS [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These examples illustrate the evolution in thinking and clinical practice around the treatment of ARDS, but individual examples cannot provide a comprehensive overview of this evolution. The entire published literature on ARDS, however, contains a detailed history of this evolution in terms of: trends; leading journals in the publication of ARDS research; and the investigators and institutions behind this research, along with their interrelationships and influences.\u003c/p\u003e \u003cp\u003eA detailed and comprehensive overview of this nature may provide policy makers, funding agencies and researchers with important information to facilitate identification of key research topics, financial support for meaningful research and collaboration possibilities in this field. Although ARDS treatments have been reviewed [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], there have not been any bibliographic analyses examining trends in topics, journals and research institutions. Recognizing the absence of such a published survey, we undertook to perform a bibliographic analysis of papers related to ARDS therapy published over the last 20\u0026nbsp;years. Bibliometric analysis is a useful method for identifying impactful authors and regions, constructing collaboration networks, and distilling key research topics in particular areas [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In this study, bibliometric analysis was used to achieve three goals: map the overall layout of ARDS research from the perspective of publication dates, journals, keywords and citations; identify core research institutions and their direct collaborative networks; and highlight current and potential future areas of research focus.\u003c/p\u003e "},{"header":"Methods","content":" \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eLiterature retrieval was performed in both PubMed and the Web of Science Core Collection on Aug 3, 2020. We selected \u0026ldquo;respiratory distress syndrome, adult\u0026rdquo; as a subject heading, which was combined in PubMed searches with several subheadings (therapy, diet therapy, drug therapy, nursing, prevention and control, and surgery). We then searched for ARDS-treatment articles in Web of Science using the same strategy. Both sets from the literature were merged, and duplicates were removed. Articles, reviews and letters published between 2000 and 2019, inclusive, were kept for further analysis. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows a flowchart of the literature retrieval strategy. More details on the retrieval process are given in Additional File 1. Informed consent was not necessary as our study analyzed published literature without any identifying information about participants in the research reported.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eAnalysis and visualization\u003c/h2\u003e \u003cp\u003eThe identified articles were systematically analyzed using the Web of Science website and CiteSpace (5.7.R1, Chaomei Chen) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Web of Science has built-in statistics tools to graph publication trends by year, language and journal. CiteSpace is a tool for visualizing and analyzing scientific literature, by constructing the knowledge structure based on citation relationship among literatures in the research field. Among the bibliometric analysis methods, we selected reference co-citation analysis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] and analysis of institutional collaboration networks for articles published between 2000 and 2019 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The indicators used in the evaluation were \u0026ldquo;modularity\u0026rdquo; and \u0026ldquo;betweenness centrality,\u0026rdquo; as follows. The degree to which a network can be divided into several independent blocks is measured by modularity [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Its value ranges from 0 to 1, and a relatively high value means a well-structured network [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Betweenness centrality is a quantitative indicator of the influence of institutions, calculated as the fraction of shortest paths going through a given node that denotes an institution in the cooperative network [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. A citation is regarded as a reasoned and solid index of scientific communication. Co-citation analysis enables the identification of the inner structure of research disciplines. A co-citation exists if two references or authors appear in the same bibliography, and is interpreted as the measure for similarity of content of the two references or authors [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In this study, the 50 most cited articles in successive 3-year intervals (e.g., 2000\u0026ndash;2002, 2003\u0026ndash;2005) were collected, and all references from each 50-article block were used to create the individual networks. Log-likelihood ratio weighting was used to analyze the contents of each cluster. \u0026ldquo;Burst keyword detection,\u0026rdquo; a computing technique used to identify mutations in information, was used to determine new research foci in the field [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A keyword burst is characterized by the intensity of the burst and by its duration.\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":" \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eTemporal distribution of papers\u003c/h2\u003e \u003cp\u003eA total of 13,933 papers were collected for analysis. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e graphs the number of articles published by year, and indicates a general upward trend in research into ARDS treatments, from 466 articles in 2000 to 918 in 2019.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePublication language\u003c/h2\u003e \u003cp\u003eThe articles returned in the search had been published in 15 languages. Of the 13,933 papers, 13,460 (96.61%) were published in English, 221 (1.59%) in German, 121 (0.87%) in French, 89 (0.64%) in Spanish, 15 (0.11%) in Portuguese and 27 (0.2%) in other languages.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCore journals\u003c/h2\u003e \u003cp\u003eA total of 1,592 scholarly journals published articles on ARDS treatment during the period of interest. The top 10 journals (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) accounted for 28.1% of all documents published (3,914 articles). The journals publishing the most ARDS research were \u003cem\u003eCritical Care Medicine\u003c/em\u003e, \u003cem\u003eIntensive Care Medicine\u003c/em\u003e, \u003cem\u003eAmerican Journal of Respiratory and Critical Care Medicine\u003c/em\u003e, and \u003cem\u003eCritical Care\u003c/em\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe 10 journals publishing the most research articles on the treatment of acute respiratory distress syndrome\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJournal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCountry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImpact factor in 2019\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCritical Care Medicine\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e956 (6.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.414\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eIntensive Care Medicine\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e601 (4.31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17.679\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAmerican Journal of Respiratory and Critical Care Medicine\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e479 (3.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17.452\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCritical Care\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e460 (3.30%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEngland\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.407\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAmerican Journal of Physiology-Lung Cellular and Molecular Physiology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e309 (2.22%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.406\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRespiratory Care\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e260 (1.87%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eChest\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e254 (1.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNetherlands\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8.308\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCurrent Opinion in Critical Care\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e200 (1.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eJournal of Critical Care\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e200 (1.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.685\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eShock\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e195 (1.40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eN (%), number of articles published by the journal and percentage of the total articles assessed in this study. Country refers to the country associated with the publisher. Impact factors are derived from \u003cem\u003eJournal Citation Reports\u003c/em\u003e (2019) published by the Institute for Scientific Information of the United States.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eResearch institutions\u003c/h2\u003e \u003cp\u003eThe researchers who published the literature included in this study were affiliated with a total of 9,468 institutions. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e lists the top 15 institutions, which accounted for 28.64% of the total articles. The University of Toronto was associated with the most publications, followed by the University of California, San Francisco, and Harvard University. Extensive collaborations were observed between institutions (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The University of Toronto, the University of California, San Francisco, Harvard University and the University of Washington had high betweenness centrality.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRanking of the 15 institutions most active in researching treatments for acute respiratory distress syndrome, based on numbers of publications\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInstitution\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBetweenness centrality\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity of Toronto\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e574 (4.28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity of California, San Francisco\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e395 (2.95%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHarvard University\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e327 (2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMassachusetts General Hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e257 (1.92%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity of Pennsylvania\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e237 (1.77%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity of Sao Paulo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e229 (1.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJohns Hopkins University\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e228 (1.70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVanderbilt University\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e217 (1.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity of Washington\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e216 (1.61%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity of Pittsburgh\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e210 (1.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity of\u0026nbsp;Milan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e203 (1.52%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity of\u0026nbsp;Michigan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e201 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSt.\u0026nbsp;Michael's\u0026nbsp;Hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e195 (1.46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity Colorado\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e179 (1.34%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMayo Clinic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e170 (1.27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eN (%), number of articles and percentage of the total articles assessed in this study. Betweenness centrality is a quantitative indicator of the influence of institutions in a collaborative network of academic institutions.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eAnalysis of reference co-citation\u003c/h2\u003e \u003cp\u003eWe used all references from the 50 most-cited publications in each successive 3-year grouping to construct each individual network, and then synthesized the individual networks for a total of 243,830 references. We performed reference co-citation analysis to generalize clusters and construct a knowledge map in timeline view, which grouped publications on ARDS treatment into nine major clusters (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe network in this study had a modularity of 0.717, which is typically considered relatively high. We focused on the major clusters that were sorted and tagged by the number of co-cited references. A total of 10 clusters were included in the analysis (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Three of these clusters (key terms \u0026ldquo;acute lung injury,\u0026rdquo; \u0026ldquo;long-term outcome\u0026rdquo; and \u0026ldquo;extracorporeal membrane oxygenation\u0026rdquo;) have been active in recent years.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of co-citation clusters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCluster\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSize\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBeginning year\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEnding year\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eActivity\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTag name\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003einactive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eventilatory strategies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eactive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eacute lung injury\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eactive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003elong-term outcome\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1995\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003einactive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ehigh-frequency ventilation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eactive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eextracorporeal membrane oxygenation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003einactive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ecomputed tomography\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003einactive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003einhaled nitric oxide\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003einactive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003esevere sepsis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003einactive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003epharmacological treatment\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003einactive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003emesenchymal stem cell\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003eNumber of published articles. \u003csup\u003eb\u003c/sup\u003ePersistence of a theme over the past 5\u0026nbsp;years (yes/no). \u003csup\u003ec\u003c/sup\u003eTypical word assigned to represent the main content of the cluster using a log-likelihood ratio algorithm.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe timeline view of reference co-citation analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) shows that the duration of research into extracorporeal membrane oxygenation was the longest, lasting from 2006 to 2018. The use of nitric oxide in treatment was no longer a topic of research papers after 1999. Some references were included in multiple clusters, acting as a link. Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e lists the core articles in the main co-citation clusters.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCore articles in the main co-citation clusters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCluster and tag name\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLead author\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePublishing year\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTheme\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#4 ECMO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePeek GJ [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eECMO, severe adult respiratory failure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#4 ECMO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDavies A [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eECMO, influenza A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#4 ECMO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBein T [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eExtracorporeal carbon dioxide removal, ultraprotective ventilation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#4 ECMO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSchmidt M [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eECMO, outcome assessment\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#0 Ventilatory strategies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeade MO [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOpen-lung strategy, ARDS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#0 Ventilatory strategies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMercat A [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePEEP setting strategy, ARDS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#2 Long-term outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBriel M [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigher versus lower PEEP, ARDS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#2 Long-term outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePapazian L [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNeuromuscular blocker, ARDS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#2 Long-term outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRanieri VM [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBerlin definition, ARDS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#2 Long-term outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFerguson ND [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh-frequency oscillatory ventilation, ARDS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#2 Long-term outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYoung D [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh-frequency oscillatory ventilation, ARDS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#2 Long-term outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGu\u0026eacute;rin C [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eProne positioning, ARDS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#1 Acute lung injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmato MBP [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDriving pressure, ARDS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#1 Acute lung injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBellani G [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEpidemiology, patterns of care, mortality, ARDS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#1 Acute lung injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSlutsky AS [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVentilator-induced lung injury\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#1 Acute lung injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrat JP [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh-flow oxygen, acute hypoxemic respiratory failure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#1 Acute lung injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCalfee CS [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARDS subphenotypes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#0 Ventilatory strategies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGattinoni L [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eProne positioning, acute respiratory failure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#0 Ventilatory strategies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrower RG [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigher versus lower PEEP, ARDS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#0 Ventilatory strategies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRubenfeld GD [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIncidence and outcomes, acute lung injury\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e#0 Ventilatory strategies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWiedemann HP [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFluid-management strategy, acute lung injury\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eARDS, acute respiratory distress syndrome; ECMO, extracorporeal membrane oxygenation; PEEP, positive end-expiratory pressure.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eAnalysis of burst keywords\u003c/h2\u003e \u003cp\u003eKeyword co-occurrence analysis returned 59 keywords. The keyword citation burst (citation increase over a given period) identified 15 keywords with strong citation bursts over the past decade (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Extracorporeal membrane oxygenation, listed in both full and abbreviated forms, was an area of active research between 2013 and 2018. Meta-analysis and randomized controlled trials also had high burst strength, especially meta-analysis in recent years. Two active keywords related to basic ARDS research were NF-kappa B, a key nuclear transcription factor regulating inflammatory responses in ARDS [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and oxidative stress. Recruitment, protective ventilation, and noninvasive ventilation were often-used keywords connected to ARDS treatment between 2013 and 2016. Keywords relating to pathogenic factors such as risk, infection, pneumonia and sepsis are still in use.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eKeywords with the strongest citation burst in papers on treatment of acute respiratory distress syndrome in the past two decades\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKeywords\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStrength\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBeginning year\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEnding year\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eextracorporeal membrane oxygenation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e67.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECMO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e54.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emeta-analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e50.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eoxidative stress\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enoninvasive ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003erisk factor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003erandomized controlled trial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003einfection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eprotective ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNF-kappa B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esurvival\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003erecruitment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003erandomized controlled trial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esevere sepsis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eStrength denotes the rate of increase in citations over a given period. Higher strength values denote more active research. ECMO, extracorporeal membrane oxygenation.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e "},{"header":"Discussion","content":" \u003cp\u003eWe have presented a visual analysis of the research literature into the treatment of ARDS, which revealed the following epistemological characteristics. The body of literature has grown over time, with \u003cem\u003eCritical Care Medicine\u003c/em\u003e and \u003cem\u003eIntensive Care Medicine\u003c/em\u003e publishing multiple papers on the topic. Many of the researchers publishing on the topic were affiliated with the University of Toronto, St. Michael\u0026rsquo;s Hospital, the University of Washington, and the University of California, San Francisco. Co-citation analysis grouped the references into eight major co-citation clusters indicating research interests within the field of ARDS therapy. The 15 keywords thus identified may be helpful in formulating future research.\u003c/p\u003e \u003cp\u003eThe growth in the number of publications indicates that an increasing number of researchers were studying ARDS treatments, frequently in collaboration with researchers in other institutions. Nearly one-third of the literature was published in just 10 journals, indicating that ARDS treatment was within the scope of research published by these journals.\u003c/p\u003e \u003cp\u003eReference co-citation analysis was used to assess the co-citation relevance between papers, and to categorize the data into major clusters representing research interests. In our study, the reference network was grouped into eight clearly defined co-citation clusters. Active research in this field appears to be dominated currently by extracorporeal membrane oxygenation and acute lung injury. Extracorporeal membrane oxygenation, as an approach to cardiopulmonary support, has been shown to improve the survival of patients with severe respiratory failure [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], and was used in influenza A (H1N1)-associated ARDS [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Related topics of research discussion were criteria for extracorporeal membrane oxygenation, extracorporeal carbon dioxide removal and long-term outcomes of this approach [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, the most recent study (EOLIA trial) in patients with severe ARDS showed no benefit, in terms of 60-day mortality, with extracorporeal membrane oxygenation [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The ventilatory strategies cluster, which contained the most articles, including comprehensive topics involving the open lung [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], PEEP level setting [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] and fluid-management strategy [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], short-term prone positioning, and the burden of ARDS [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], has been inactive since 2010. The clusters marked with long-term outcome and acute lung injury have developed and remain active. In particular, the former was in an inherent relationship with the cluster of ventilatory strategies, and we found some overlapping topics in their core literature, such as PEEP [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] and prone positioning [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Treatment outcome has always been the focus of attention in research into ARDS and, perhaps for this reason, the long-term outcome cluster kept in close contact with the acute lung injury cluster and extracorporeal membrane oxygenation, which served as a bridge among the clusters. The core articles targeting prognosis of ARDS were contained in the aforementioned clusters. From the timeline view, \u0026ldquo;acute lung injury\u0026rdquo; was the recent cluster, and is still active. The themes of core articles contained ventilator-induced lung injury [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], the exploration on sub-phenotypes of ARDS [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], driving pressure [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], the effect of high-flow oxygen on acute hypoxemic respiratory failure [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], and the reassessment of ARDS burden [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. These topics seemed to be unfocused but involved basic data, issues of wide concern, and exploration of new direction, which were often co-cited in the papers to provide basic support and guide the elaboration, and probably developed over time.\u003c/p\u003e \u003cp\u003eA heavily cited keyword is considered an indicator of a topic of research interest, or an emerging trend. Extracorporeal membrane oxygenation and its abbreviation (ECMO) take the top two spots in the ranking of citation burst strength in recent years, indicating that this topic will continue to be studied. Meta-analysis can comprehensively analyze the results of previous randomized controlled trials on ARDS, to come to more-objective conclusions, and it is still expected to be the popular research methodology based on the strength value obtained. In the field of basic research, oxidative stress has become a popular topic of investigation in ARDS therapy. Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e shows the progress in ARDS research through the evolution of burst keywords over the past decade. Factors that can precipitate ARDS, which appeared in the literature we analyzed, were pneumonia, infection and severe sepsis, in chronological order. A similar evolution was reflected in the therapeutic methods, from lung recruitment and protective ventilation, to noninvasive ventilation, to extracorporeal membrane oxygenation.\u003c/p\u003e \u003cp\u003eTo perform the co-citation clustering analysis, we selected the Web of Science as our final literature source, which may have excluded some studies. Valuable articles can also be found in evidence-based medicine databases such as the Cochrane Library and citation databases such as Scopus. When constructing the retrieval strategy, we listed a large number of technical terms related to ARDS treatment, and limited the scope to treatment, possibly ignoring the literature related to diagnosis, prevention and control of ARDS, which may influence treatment. We selected as many search terms as possible, to cover as much of the relevant literature as we could. Research topics that are deemed exciting are often pursued intensively during a given period and result in multiple publications, but the findings may not be clinically valuable with the passage of time and further investigation, weakening the value of the research topic. Finally, we did not include conference abstracts in our search, which may have influenced the weighting of results.\u003c/p\u003e "},{"header":"Conclusions","content":" \u003cp\u003eOn the basis of the bibliographic analysis of the literature in the last 20 years, the research into ARDS treatment has been receiving continuous attention. Extracorporeal membrane oxygenation is currently a topic of active research, and it and oxidative stress are likely to be the research interests in the near future. Meta-analysis of original studies will still be a popular research method in this field.\u003c/p\u003e "},{"header":"List of Abbreviations","content":" \u003cp\u003eARDS, acute respiratory distress syndrome; PEEP, positive end-expiratory pressure; ECMO, extracorporeal membrane oxygenation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe supporting data are provided in the online supplementary material.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone declared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the National Science and Technology Major Project (grant number 2018ZX10101004), the National Natural Science Foundation of China (grant number 81372043), Beijing Natural Science Foundation (grant number 7162199), and Peking University Third Hospital Foundation (grant number Y76478-01).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZ.Y.W. designed the study and manuscript content and contributed to drafting the manuscript. Z.C.Z. contributed to the manuscript content, collected and analyzed the data, and drafted the manuscript. J.Z. and Z.K.C. contributed to the manuscript content. X.Z. contributed to the study concept and critical evaluation of the manuscript. All authors approved the submission of this version for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eX.Z. takes responsibility for the content of the manuscript, including the data and analysis.\u003c/p\u003e\n\u003cp\u003eThe authors appreciate the contribution of Wei Li to the study concept and the contribution of Yuan Zhang to coordinating cooperation. We thank Hugh McGonigle and Claire Barnes, PhD, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016;315:788\u0026ndash;800.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAshbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet (London, England). 1967;2:319\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAshbaugh DG, Petty TL, Bigelow DB, Harris TM. Continuous positive-pressure breathing (CPPB) in adult respiratory distress syndrome. The Journal of thoracic and cardiovascular surgery. 1969;57:31\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKing EG, Jones RL, Patakas DA. Evaluation of positive end-expiratory pressure therapy in the adult respiratory distress syndrome. Canadian Anaesthetists' Society journal. 1973;20:546\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAcute RDSN, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The New England journal of medicine. 2000;342:1301\u0026ndash;08.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBorges JB, Okamoto VN, Matos GFJ, Caramez MPR, Arantes PR, Barros F, et al. Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome. Am J Resp Crit Care. 2006;174:268\u0026ndash;78.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWriting GFTA, Cavalcanti AB, Suzumura \u0026Eacute;A, Laranjeira LN, Paisani DDM, Damiani LP, et al. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2017;318:1335\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFan E, Brodie D, Slutsky AS. Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment. JAMA. 2018;319:698.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePapazian L, Aubron C, Brochard L, Chiche J, Combes A, Dreyfuss D, et al. Formal guidelines: management of acute respiratory distress syndrome. Ann Intensive Care. 2019;9:69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuler AT, Waaijer CJF, Palmblad M. Scientific workflows for bibliometrics. Scientometrics. 2016;107:385\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen C. CiteSpace II: Detecting and visualizing emerging trends and transient patterns in scientific literature. Journal of the American Society for Information Science \u0026amp; Technology. 2006;57:359\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang D, Wang X, Wang Z, Yang Z, Bian X. A scientometric analysis on hepatocellular carcinoma magnetic resonance imaging research from 2008 to 2017. Quant Imag Med Surg. 2019;9:465\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen C. Science Mapping: A Systematic Review of the Literature. Journal of Data and Information Science. 2017;2:1\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShibata N, Kajikawa Y, Takeda Y, Matsushima K. Detecting emerging research fronts based on topological measures in citation networks of scientific publications. Technovation. 2008;28:775.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen C, Fidelia I, Jianhua H. The structure and dynamics of cocitation clusters: A multiple-perspective cocitation analysis. Journal of the American Society for Information Science \u0026amp; Technology. 2010;61:1386\u0026ndash;409.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarth\u0026eacute;lemy M. Betweenness centrality in large complex networks. Eur Phys J B. 2004;38:163\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGm\u0026uuml;r M. Co-citation analysis and the search for invisible colleges: A methodological evaluation. Scientometrics. 2003;57:27\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKleinberg J. Bursty and Hierarchical Structure in Streams. Data Min Knowl Disc. 2003;7:373\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArshad, Rahman, Fabeha, Fazal. Blocking NF-κB: an inflammatory issue. Proceedings of the American Thoracic Society. 2011;8:497\u0026ndash;503.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet (London, England). 2009;374:1351\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAustralia ANZE, Davies A, Jones D, Bailey M, Beca J, Bellomo R, et al. Extracorporeal Membrane Oxygenation for 2009 Influenza A(H1N1) Acute Respiratory Distress Syndrome. JAMA. 2009;302:1888\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBein T, Weber-Carstens S, Goldmann A, M\u0026uuml;ller T, Staudinger T, Brederlau J, et al. Lower tidal volume strategy (\u0026asymp; 3 ml/kg) combined with extracorporeal CO2 removal versus 'conventional' protective ventilation (6 ml/kg) in severe ARDS: the prospective randomized Xtravent-study. Intens Care Med. 2013;39:847\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchmidt M, Zogheib E, Roz\u0026eacute; H, Repesse X, Lebreton G, Luyt C, et al. The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. Intens Care Med. 2013;39:1704\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCombes A, Hajage D, Capellier G, Demoule A, Lavou\u0026eacute; S, Guervilly C, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2018;378:1965\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper DJ, et al. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008;299:637\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMercat A, Richard JM, Vielle B, Jaber S, Osman D, Diehl J, et al. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008;299:646\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNational Heart LABI, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, et al. Comparison of two fluid-management strategies in acute lung injury. The New England journal of medicine. 2006;354:2564\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D, Labarta V, et al. Effect of prone positioning on the survival of patients with acute respiratory failure. The New England journal of medicine. 2001;345:568\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBriel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, et al. Higher vs Lower Positive End-Expiratory Pressure in Patients With Acute Lung Injury and Acute Respiratory Distress Syndrome: Systematic Review and Meta-analysis. JAMA. 2010;303:865\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGu\u0026eacute;rin C, Reignier J, Richard J, Beuret P, Gacouin A, Boulain T, et al. Prone positioning in severe acute respiratory distress syndrome. New Engl J Med. 2013;368:2159\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSlutsky AS, Ranieri VM. Ventilator-induced lung injury. New Engl J Med. 2013;369:2126\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCalfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014;2:611\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmato MBP, Meade MO, Slutsky AS, Brochard L, Costa ELV, Schoenfeld DA, et al. Driving Pressure and Survival in the Acute Respiratory Distress Syndrome. New Engl J Med. 2015;372:747\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372:2185\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePapazian L, Forel J, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. The New England journal of medicine. 2010;363:1107\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eARDS DTF, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307:2526\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L, Austin P, et al. High-frequency oscillation in early acute respiratory distress syndrome. New Engl J Med. 2013;368:795\u0026ndash;805.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoung D, Lamb SE, Shah S, MacKenzie I, Tunnicliffe W, Lall R, et al. High-frequency oscillation for acute respiratory distress syndrome. New Engl J Med. 2013;368:806\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, et al. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. The New England journal of medicine. 2004;351:327\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, et al. Incidence and outcomes of acute lung injury. The New England journal of medicine. 2005;353:1685\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"acute respiratory distress syndrome, treatment, visualization analysis, bibliometrics, reference co-citation analysis","lastPublishedDoi":"10.21203/rs.3.rs-128479/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-128479/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eAcute respiratory distress syndrome (ARDS) is a common and extensively researched condition, and treatment modalities are continuously being developed and improved. Although the literature on ARDS treatment is vast, there have not been any bibliographic analyses examining trends in this area. We aimed to systematically evaluate the literature on ARDS treatments published between 2000 and 2019, from the perspective of bibliometrics.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eLiterature retrieval was performed in PubMed and in the Web of Science Core Collection, and analyzed for publication and temporal trends. CiteSpace was used to perform co-occurrence analysis for institutions, and reference co-citation analysis for research topics. Burst keyword detection was used to predict future areas of research interest in the field.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eA total of 13,933 articles were retrieved. The journal \u003cem\u003eCritical Care Medicine\u003c/em\u003e published the largest number of articles (956, 6.86%). The University of Toronto was affiliated with the most publications (574, 4.28%) and had the highest degree of betweenness centrality, indicating extensive inter-institution collaboration. The papers on ARDS treatment published between 2000 and 2019 were grouped into 10 major clusters, 3 of which indicated recent activity (“acute lung injury,” “long-term outcome” and “extracorporeal membrane oxygenation”). Fifteen burst keywords/terms were identified, including extracorporeal membrane oxygenation, meta-analysis and oxidative stress.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eOn the basis of the literature published in the preceding 20 years, the exploration of ARDS treatment is an ongoing concern. Extracorporeal membrane oxygenation was an active focus of research in this field. It and oxidative stress are likely to become major topics of research interest in the near future. Meta-analysis will be a popular method in analyzing the efficacy of ARDS treatments.\u003c/p\u003e","manuscriptTitle":"Bibliometric Analysis of Literature on Acute Respiratory Distress Syndrome Treatments Published Between 2000 and 2019","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-12-22 21:45:34","doi":"10.21203/rs.3.rs-128479/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ac61f53d-305f-4ea9-a64c-364e94790a06","owner":[],"postedDate":"December 22nd, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":1593382,"name":"Health Economics \u0026 Outcomes Research"},{"id":1593383,"name":"Pulmonology"}],"tags":[],"updatedAt":"2021-04-27T12:59:12+00:00","versionOfRecord":[],"versionCreatedAt":"2020-12-22 21:45:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-128479","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-128479","identity":"rs-128479","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}