Acute lung injury (ALI) remains a significant source of morbidity and mortality in the critically ill patient population. Defined by a constellation of clinical criteria (acute onset of bilateral pulmonary infiltrates with hypoxemia without evidence of hydrostatic pulmonary edema), ALI has a high incidence (200,000 per year in the US) and overall mortality remains high. Pathogenesis of ALI is explained by injury to both the vascular endothelium and alveolar epithelium. Recent advances in the understanding of pathophysiology have identified several biologic markers that are associated with worse clinical outcomes. Phase III clinical trials by the NHLBI ARDS Network have resulted in improvement in survival and a reduction in the duration of mechanical ventilation with a lung-protective ventilation strategy and fluid conservative protocol. Potential areas of future treatments include nutritional strategies, statin therapy, and mesenchymal stem cells.

Acute Lung Injury: Epidemiology, Pathogenesis, and Treatment

Sepsis is generally viewed as a disease aggravated by an inappropriate immune response encountered in the afflicted individual. As an important organ system frequently compromised by sepsis and always affected by septic shock, the cardiovascular system and its dysfunction during sepsis have been studied in clinical and basic research for more than 5 decades. Although a number of mediators and pathways have been shown to be associated with myocardial depression in sepsis, the precise cause remains unclear to date. There is currently no evidence supporting global ischemia as an underlying cause of myocardial dysfunction in sepsis; however, in septic patients with coexistent and possibly undiagnosed coronary artery disease, regional myocardial ischemia or infarction secondary to coronary artery disease may certainly occur. A circulating myocardial depressant factor in septic shock has long been proposed, and potential candidates for a myocardial depressant factor include cytokines, prostanoids, and nitric oxide, among others. Endothelial activation and induction of the coagulatory system also contribute to the pathophysiology in sepsis. Prompt and adequate antibiotic therapy accompanied by surgical removal of the infectious focus, if indicated and feasible, is the mainstay and also the only strictly causal line of therapy. In the presence of severe sepsis and septic shock, supportive treatment in addition to causal therapy is mandatory. The purpose of this review is to delineate some characteristics of septic myocardial dysfunction, to assess the most commonly cited and reported underlying mechanisms of cardiac dysfunction in sepsis, and to briefly outline current therapeutic strategies and possible future approaches.

Sepsis and the Heart

Mevalonate pathway: a review of clinical and therapeutical implications.

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular 'reactive oxygen species' (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation.

/pdf/iron-behaving-badly-inappropriate-iron-chelation-as-a-major-229l082exr.pdf

Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

Background In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS. Methods We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a doubleblind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure–free days to day 14. Results The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P = 0 .21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P = 0 .96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was assoc iated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P = 0 .01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P = 0 .003). Rosuvas tatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range. Conclusions Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis a ssociated ARDS and may have contributed to hepatic and renal organ dysfunction. (Funded by the National Heart, Lung, and Blood Institute and the Investigator-Sponsored Study Program of AstraZeneca; ClinicalTrials.gov number, NCT00979121.)

/pdf/rosuvastatin-for-sepsis-associated-acute-respiratory-3dz7d4qeph.pdf

Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome

Background— Statins have anti-inflammatory properties that are independent of their lipid-lowering abilities. We hypothesized that statin therapy before the onset of an acute bacterial infection may have a protective effect against severe sepsis. The aim of this study was to determine whether patients treated with statins develop severe sepsis less frequently. Methods and Results— In this prospective observational cohort study, consecutive patients admitted with presumed or documented acute bacterial infection were enrolled. The primary outcomes were the rate of severe sepsis and intensive care unit (ICU) admission. Of the 361 patients enrolled, 82 (22.7%) were treated with statins before their admission. Both groups had a similar severity of illness on admission. Severe sepsis developed in 19% of patients in the no-statin group and in only 2.4% of the statin group (P<0.001). Statin treatment was associated with a relative risk of developing severe sepsis of 0.13 (95% CI, 0.03 to 0.52) and an absolute ris...

Prior Statin Therapy Is Associated With a Decreased Rate of Severe Sepsis

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Miruna Eizinger

Author Tools

Chat about Author

Papers

Prior Statin Therapy Is Associated With a Decreased Rate of Severe Sepsis