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Sepsis: From Pathophysiology to Individualized Patient Care.

ABSTRACT: Sepsis has become a major health economic issue, with more patients dying in hospitals due to sepsis related complications compared to breast and colorectal cancer together. Despite extensive research in order to improve outcome in sepsis over the last few decades, results of large multicenter studies were by-and-large very disappointing. This fiasco can be explained by several factors, but one of the most important reasons is the uncertain definition of sepsis resulting in very heterogeneous patient populations, and the lack of understanding of pathophysiology, which is mainly based on the imbalance in the host-immune response. However, this heroic research work has not been in vain. Putting the results of positive and negative studies into context, we can now approach sepsis in a different concept, which may lead us to new perspectives in diagnostics and treatment. While decision making based on conventional sepsis definitions can inevitably lead to false judgment due to the heterogeneity of patients, new concepts based on currently gained knowledge in immunology may help to tailor assessment and treatment of these patients to their actual needs. Summarizing where we stand at present and what the future may hold are the purpose of this review.

SUBMITTER: Laszlo I

PROVIDER: S-EPMC4518174 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Sepsis: From Pathophysiology to Individualized Patient Care.

László Ildikó I Trásy Domonkos D Molnár Zsolt Z Fazakas János J

Journal of immunology research 20150715

Sepsis has become a major health economic issue, with more patients dying in hospitals due to sepsis related complications compared to breast and colorectal cancer together. Despite extensive research in order to improve outcome in sepsis over the last few decades, results of large multicenter studies were by-and-large very disappointing. This fiasco can be explained by several factors, but one of the most important reasons is the uncertain definition of sepsis resulting in very heterogeneous pa ...[more]

PMID: 26258150

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Project description:Background. Few Americans obtain all 41 guideline-recommended preventive services for nonpregnant adults. We assessed patient interest in prioritizing their preventive care needs. Methods. We conducted a mixed-methods study, with 4 focus groups (N = 28) at a single institution and a nationwide survey (N = 2,103). Participants were middle-aged and older adults with preventive care needs. We obtained reactions to written materials describing the magnitude of benefit from major preventive services, including both absolute and relative benefits. Recommendations were individualized for patient risk factors ("individualized preventive care recommendations"). Focus groups assessed patient interest, how patients would want to discuss individualized recommendations with their providers, and potential for individualized recommendations to influence patient decision making. Survey content was based on focus groups and analyzed with logistic regression. Results. Patients expressed strong interest in individualized recommendations. Among survey respondents, an adjusted 88.2% (95% confidence interval [CI] = 86.7% to 89.7%) found individualized recommendations very easy to understand, 77.2% (95% CI = 75.3% to 79.1%) considered them very useful, and 64.9% (95% CI = 62.8% to 67.0%) highly trustworthy (each ≥6/7 on Likert scale). Three quarters of participants wanted to receive their own individualized recommendations in upcoming primary care visits (adjusted proportion = 77.5%, 95% CI = 75.6% to 79.4%). Both focus group and survey participants supported shared decision making and reported that individualized recommendations would improve motivation to obtain preventive care. Half of survey respondents reported that they would be much more likely to visit their doctor if they knew individualized recommendations would be discussed, compared with 4.2% who would not be more likely to visit their doctor. Survey respondents already prioritized preventive services, stating they were most likely to choose quick/easy preventive services and least likely to choose expensive preventive services (adjusted proportions, 63.8% and 8.5%, respectively). Results were consistent in sensitivity analyses. Conclusions. Individualized preventive care recommendations are likely to be well received in primary care and might motivate patients to improve adherence to evidence-based care.

Project description:BackgroundThe disruption of immune homeostasis after trauma is a major cause of post-traumatic organ dysfunction and/or sepsis. Recently, a variety of neutrophil phenotypes with distinct functions have been identified and suggested as involved in various clinical conditions. The association between neutrophil phenotypes and post-traumatic immunodeficiency has also been reported, yet the specific neutrophil phenotypes and their functional significance in post-traumatic sepsis have not been fully clarified. Therefore, we sought to investigate neutrophil phenotypic changes in a murine model, as these may hold prognostic value in post-traumatic sepsis.Materials and methodsThird-degree burns affecting 25% of the body surface area were used to establish trauma model, and sepsis was induced 24 h later through cecal ligation and puncture (CLP). The Burn/CLP post-traumatic sepsis model and the Sham/CLP control model were established to assess the immunological status after trauma. Histopathological evaluation was performed on the spleen, liver, kidneys, and lung tissues. Immunological evaluation included the assessment of neutrophil markers using mass cytometry as well as cytokine measurements in serum and ascitic fluid through multiplex analysis using LUMINEX®.ResultsThe Burn/CLP group had a lower survival rate than the Sham/CLP group. Histopathological examination revealed an impaired immune response and more advanced organ damage in the Burn/CLP group. Furthermore, the Burn/CLP group exhibited higher levels of transforming growth factor-beta 1 in the blood and generally lower levels of cytokines than the Sham/CLP group. CD11b, which is involved in neutrophil adhesion and migration, was highly expressed on neutrophils in the Burn/CLP group. The expression of CD172a, which is related to the inhibition of phagocytosis, was also upregulated on neutrophils in the Burn/CLP group. The expression of sialic acid-binding lg-like lectin F and CD68 also differed between the two groups.ConclusionDifferent neutrophil phenotypes were observed between Burn/CLP and Sham/CLP groups, suggesting that neutrophils are implicated in the immune imbalance following trauma. However, further studies are needed to prove the causal relationships between neutrophil phenotypes and outcomes, including survival rate and organ dysfunction.

Project description:ImportanceThis randomized clinical trial examines the feasibility and acceptability of a decision-making tool for increasing patient interest in individualized recommendations for preventive care services.ObjectiveTo pilot a tool to help patients compare life expectancy gains from evidence-based preventive services.Design, setting, and participantsThis randomized clinical trial examined patient and physician responses to a pilot decision tool incorporating personalized risk factors at 3 US primary care clinics between 2017 and 2020. Eligible patients were between ages 45 to 70 years with 2 or more high-risk factors. Patients were followed-up after 1 year.InterventionsThe gain in life expectancy associated with guideline adherence to each recommended preventive service was estimated. Personalized estimates incorporating risk factors in electronic health records were displayed in a physician-distributed visual aid. During development, physicians discussed individualized results with patients using shared decision-making (SDM). During the trial, patients were randomized to receive individualized recommendations or usual care (nonmasked, parallel, 1:1 ratio).Main outcomes and measuresPrimary outcome was patient interest in individualized recommendations, assessed by survey. Secondary outcomes were use of SDM, decisional comfort, readiness to change, and preventive services received within 1 year.ResultsThe study enrolled 104 patients (31 development, 39 intervention, 34 control), of whom 101 were included in analysis (mean [SD] age, 56.5 [5.3] years; 73 [72.3%] women; 80 [79.2%] Black patients) and 20 physicians. Intervention patients found the tool helpful and wanted to use it again, rating it a median 9 of 10 (IQR, 8-10) and 10 of 10 (8-10), respectively. Compared with the control group, intervention patients more often correctly identified the service least likely (18 [46%] vs 0; P = .03) to improve their life expectancy. A greater number of patients also identified the service most likely to improve their life expectancy (26 [69%] vs 10 [30%]; P = .07), although this result was not statistically significant. Intervention patients reported greater mean [SD] improvement in SDM (4.7 [6.9] points) and near-term readiness to change (13.8 points for top-3-ranked recommendations). Point estimates indicated that patients in the intervention group experienced greater, although non-statistically significant, reductions in percentage of body weight (-2.96%; 95% CI, -8.18% to 2.28%), systolic blood pressure (-6.42 mm Hg; 95% CI, -16.12 to 3.27 mm Hg), hemoglobin A1c (-0.68%; 95% CI, -1.82% to 0.45%), 10-year atherosclerotic cardiovascular disease risk score (-1.20%; 95% CI, -3.65% to 1.26%), and low-density lipoprotein cholesterol (-8.46 mg/dL; 95% CI, -26.63 to 9.70 mg/dL) than the control group. Nineteen of 20 physicians wanted to continue using the decision tool in the future.Conclusions and relevanceIn this clinical trial, an individualized preventive care decision support tool improved patient understanding of primary prevention and demonstrated promise for improved shared decision-making and preventive care utilization.Trial registrationClinicalTrials.gov Identifier: NCT03023813.

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Sepsis: From Pathophysiology to Individualized Patient Care.

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Sepsis: From Pathophysiology to Individualized Patient Care.

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