The Effects of Sepsis on Mitochondria Garrabou, Glòria; Morén, Constanza; López, Sònia ...
The Journal of infectious diseases,
02/2012, Letnik:
205, Številka:
3
Journal Article
Recenzirano
Background. Sepsis is associated with mitochondrial dysfunction and impaired oxygen consumption, which may condition clinical outcome independent of tissue oxygénation. However, mitochondrial role in ...sepsis severity remains unknown. We aimed to characterize mitochondrial function in sepsis, establish its origin and cellular consequences, and determine its correlation with clinical symptoms and outcome. Methods. Different markers of mitochondrial activity, nitrosative and oxidative stress, apoptosis, and inflammation were measured in peripheral blood mononuclear cells (PBMCs) and plasma of 19 septic patients and 20 controls. Plasma capacity to induce mitochondrial dysfunction was assessed in muscle mitochondria from 5 healthy individuals incubated with plasma of septic patients or controls. Results. Despite unaltered mitochondrial mass and protein synthesis, enzymatic mitochondrial complexes I, III, and IV and oxygen consumption were significantly inhibited in sepsis. Septic plasma tended to reduce oxygen consumption of healthy mitochondria and showed significantly increased amounts of extracellular mitochondrial DNA and inflammatory cytokines, especially in patients presenting adverse outcome. Active nuclear factor kappa-light-chain enhancer of activated B cells (NFKB) was also significantly increased, together with nitric oxide, oxidative stress and apoptosis. Additionally, sepsis severity significantly correlated with complex I inhibition, NFKB activation and intercellular adhesion molecule expression. Conclusions. A plasmatic factor such as nitric oxide, increased in inflammation and able to induce mitochondrial dysfunction, oxidative stress and apoptosis, may be responsible for cell damage in sepsis. Together with bacterial infection, leakage of mitochondrial DNA from damaged cells into circulation could contribute to systemic inflammatory response syndrome. Mitochondrial dysfunction and inflammation correlate with sepsis severity and outcome, becoming targets for supporting therapies.
Lung ultrasound is a useful tool for the assessment of patients with both acute and chronic heart failure, but the use of different image acquisition methods, inconsistent reporting of the technique ...employed and variable quantification of ‘B‐lines,’ have all made it difficult to compare published reports. We therefore need to ensure that future studies utilizing lung ultrasound in the assessment of heart failure adopt a standardized approach to reporting the quantification of pulmonary congestion. Strategies to improve patient care by use of lung ultrasound in the assessment of heart failure have been difficult to develop. In the present document, key aspects of standardization are discussed, including equipment used, number of chest zones assessed, the method of quantifying B‐lines, the presence and timing of additional investigations (e.g. natriuretic peptides and echocardiography) and the impact of therapy. This consensus report includes a checklist to provide standardization in the preparation, review and analysis of manuscripts. This will serve as a guide for investigators and clinicians and enhance the quality and transparency of lung ultrasound research.
Physicians in the emergency department (ED) need additional tools to stratify patients with acute heart failure (AHF) according to risk.
To predict mortality using data that are readily available at ...ED admission.
Prospective cohort study.
34 Spanish EDs.
The derivation cohort included 4867 consecutive ED patients admitted during 2009 to 2011. The validation cohort comprised 3229 patients admitted in 2014.
88 candidate risk factors and 30-day mortality.
Thirteen independent risk factors were identified in the derivation cohort and were combined into an overall score, the MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF) score. This score predicted 30-day mortality with excellent discrimination (c-statistic, 0.836) and calibration (Hosmer-Lemeshow P = 0.99) and provided a steep gradient in 30-day mortality across risk groups (<2% for patients in the 2 lowest risk quintiles and 45% in the highest risk decile). These characteristics were confirmed in the validation cohort (c-statistic, 0.828). Multiple sensitivity analyses did not find important amounts of confounding or bias.
The study was confined to a single country. Participating EDs were not selected randomly. Many patients had missing data. Measurement of some risk factors was subjective.
This tool has excellent discrimination and calibration and was validated in a different cohort from the one that was used to develop it. Physicians can consider using this tool to inform clinical decisions as further studies are done to determine whether the tool enhances physician decision making and improves patient outcomes.
Instituto de Salud Carlos III, Spanish Ministry of Health; Fundació La Marató de TV3; and Catalonia Govern.
The safety of the European Society of Cardiology (ESC) 0/1-h algorithm for rapid rule-out and rule-in of non–ST-segment elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac ...troponin (hs-cTn) has been questioned.
This study aimed to validate the diagnostic performance of the 0/1-h algorithm in a large multicenter study.
The authors prospectively enrolled unselected patients in 6 countries presenting to the emergency department with symptoms suggestive of NSTEMI. Final diagnosis was centrally adjudicated by 2 independent cardiologists. Hs-cTnT and hs-cTnI blood concentrations were measured at presentation and after 1 h. Safety of rule-out was quantified by the negative predictive value (NPV) for NSTEMI, accuracy of rule-in by the positive predictive value (PPV), and overall efficacy by the proportion of patients triaged towards rule-out or rule-in within 1 h.
Prevalence of NSTEMI was 17%. Among 4,368 patients with serial hs-cTnT measurements available, safety of rule-out (NPV 99.8%, 2,488 of 2,493), accuracy of rule-in (PPV 74.5%, 572 of 768), and overall efficacy were high by assigning three-fourths of patients either to rule-out (57%, 2,493 to 4,368) or rule-in (18%, 768 to 4,368). Similarly, among 3,500 patients with serial hs-cTnI measurements, safety of rule-out (NPV 99.7%, 1,528 of 1,533), accuracy of rule-in (PPV 62.3%, 498 of 800), and overall efficacy were high by assigning more than two-thirds of patients either to rule-out (44%, 1,533 of 3,500) or rule-in (23%, 800 of 3,500). Excellent safety was confirmed in multiple subgroup analyses including patients presenting early (≤3 h) after chest pain onset.
The ESC 0/1-h algorithm using hs-cTnT and hs-cTnI is very safe and effective in triaging patients with suspected NSTEMI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation APACE; NCT00470587; and Biomarkers in Acute Cardiac Care BACC; NCT02355457)
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Wine lovers: their interests in tourist experiences Crespi-Vallbona, Montserrat; Mascarilla-Miró, Oscar
International journal of culture, tourism and hospitality research,
04/2020, Letnik:
14, Številka:
2
Journal Article
Recenzirano
Purpose
The purpose of this paper is to explore the intrinsic components of wine tourism products that satisfy the consumers and analyze the economic development of wine regions, away from ...consolidated tourist destinations.
Design/methodology/approach
The objective of the study is fulfilled by reviewing the literature on culture and gastronomy as tourism-driving forces of hinterland development and the needs of wine lovers in their tourism experiences and then using it to design appropriate research tools to collect empirical data through a survey within the context of a single case study. Thus, the specific case of wine origin certification, denomination of origin (DO) in the Catalan regional area of Pla de Bages (Barcelona) is the successful case analyzed, through 210 valid questionnaires.
Findings
Wine tourism has a long history, although it may appear to be quite recent and innovative. Today’s visitors are well travelled and seek new experiences, authentic contexts and particular or exceptional activities. The findings show that the intrinsic components of wine tourism products that satisfy these consumers are critical to develop wine regions, focusing on the design of activities with significant dose of local identity and wine and gastronomic pairing. Definitely, participation, hedonism, significance, knowledge, nostalgia, tasting, novelty and local culture are the basic ingredients of a memorable and satisfying wine tourism experience.
Research limitations/implications
The present study has several limitations that need to be mentioned. First, this research is a single case study; the Pla de Bages DO serves as the case, focusing on one cultural heritage experience, the large wine vats walking visits. This fact can put the study’s validity in question. Another limitation is that this study is not a longitudinal one, the latter could lead to more accurate findings. It would be interesting to ad in-depth interviews to advance the understanding about how to enhance visits according to the analyzed components.
Practical implications
Sustainable governance of destinations implies the cooperation of private businesses, the public government and the support of the population of the territory, to develop creative and successful tourist products. Economic, social and cultural networks are necessary to create collaboration and innovation, following its mutual interests. The new governance approach based on networks that combines creative, sensorial and locally specific experiences is essential and offers many business opportunities and entrepreneurial options in hinterland regions, located near consolidated tourist destinations. Destination management organizations and private businesses should take into account the structure of the eight aforementioned components when they design oenological tourism activities.
Originality/value
The originality of the paper lies in the knowledge of the crucial components of memorable wine tourism experiences to satisfy visitor expectations. They have to include participation, hedonism, significance, knowledge, local culture, novelty, tasting and nostalgia.
Tourism is one of the activities most urgently in need of innovation and creativity to keep the boom going. This paper seeks to understand how mature destinations and tourism managers devise ...innovative and sustainable solutions in everyday practice. Current trends in demand call for active experiences that generate emotions, stir up feelings, present content, and provide a dose of pleasure. The case study presented here is an innovative street art project called Pinacoteca a Cel Obert (Open-Air Art Gallery), a clear example of reactivation, recovery and urban development that involves the local population and associations as part of the local government's drive to encourage community participation and empower change with regard to urban issues. The viability and sustainability of this commendable example are analysed through in-depth interviews with the respective project managers, the guides who run the tours and the visitors who have participated in the tour.
Four strategies for very early rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I (hs-cTnI) have been identified. It remains unclear which strategy is most attractive ...for clinical application.
We prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnI levels were measured at presentation and after 1 hour in a blinded fashion. We directly compared all 4 hs-cTnI-based rule-out strategies: limit of detection (LOD, hs-cTnI<2 ng/L), single cutoff (hs-cTnI<5 ng/L), 1-hour algorithm (hs-cTnI<5 ng/L and 1-hour change<2 ng/L), and the 0/1-hour algorithm recommended in the European Society of Cardiology guideline combining LOD and 1-hour algorithm.
Among 2828 enrolled patients, acute myocardial infarction was the final diagnosis in 451 (16%) patients. The LOD approach ruled out 453 patients (16%) with a sensitivity of 100% (95% confidence interval CI, 99.2%-100%), the single cutoff 1516 patients (54%) with a sensitivity of 97.1% (95% CI, 95.1%-98.3%), the 1-hour algorithm 1459 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%), and the 0/1-hour algorithm 1463 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%). Predefined subgroup analysis in early presenters (≤2 hours) revealed significantly lower sensitivity (94.2%, interaction
=0.03) of the single cutoff, but not the other strategies. Two-year survival was 100% with LOD and 98.1% with the other strategies (
<0.01 for LOD versus each of the other strategies).
All 4 rule-out strategies balance effectiveness and safety equally well. The single cutoff should not be applied in early presenters, whereas the 3 other strategies seem to perform well in this challenging subgroup.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.
Abstract
In acute heart failure (AHF) syndromes significant respiratory failure (RF) is essentially seen in patients with acute cardiogenic pulmonary oedema (ACPE) or cardiogenic shock (CS). ...Non-invasive ventilation (NIV), the application of positive intrathoracic pressure through an interface, has shown to be useful in the treatment of moderate to severe RF in several scenarios. There are two main modalities of NIV: continuous positive airway pressure (CPAP) and pressure support ventilation (NIPSV) with positive end expiratory pressure. Appropriate equipment and experience is needed for NIPSV, whereas CPAP may be administered without a ventilator, not requiring special training. Both modalities have shown to be effective in ACPE, by a reduction of respiratory distress and the endotracheal intubation rate compared to conventional oxygen therapy, but the impact on mortality is less conclusive. Non-invasive ventilation is also indicated in patients with AHF associated to pulmonary disease and may be considered, after haemodynamic stabilization, in some patients with CS. There are no differences in the outcomes in the studies comparing both techniques, but CPAP is a simpler technique that may be preferred in low-equipped areas like the pre-hospital setting, while NIPSV may be preferable in patients with significant hypercapnia. The new modality ‘high-flow nasal cannula’ seems promising in cases of AHF with less severe RF. The correct selection of patients and interfaces, early application of the technique, the achievement of a good synchrony between patients and the ventilator avoiding excessive leakage, close monitoring, proactive management, and in some cases mild sedation, may warrant the success of the technique.
Aims
Several clinical conditions may precipitate acute heart failure (AHF) and influence clinical outcome. In this study we hypothesized that precipitating factors are independently associated with ...90‐day risk of death in AHF.
Methods and results
The study population consisted of 15 828 AHF patients from Europe and Asia. The primary outcome was 90‐day all‐cause mortality according to identified precipitating factors of AHF acute coronary syndrome (ACS), infection, atrial fibrillation (AF), hypertension, and non‐compliance. Mortality at 90 days was 15.8%. AHF precipitated by ACS or by infection showed increased 90‐day risk of death compared with AHF without identified precipitants hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.44–1.97, P < 0.001; and HR 1.51, 95% CI 1.18–1.92, P = 0.001), while AHF precipitated by AF showed lower 90‐day risk of death (HR 0.56, 95% CI 0.42–0.75, P < 0.001), after multivariable adjustment. The risk of death in AHF precipitated by ACS was the highest during the first week after admission, while in AHF precipitated by infection the risk of death had a delayed peak at week 3. In AHF precipitated by AF, a trend toward reduced risk of death during the first weeks was shown. At weeks 5–6, AHF precipitated by ACS, infection, or AF showed similar risk of death to that of AHF without identified precipitants.
Conclusions
Precipitating factors are independently associated with 90‐day mortality in AHF. AHF precipitated by ACS or infection is independently associated with higher, while AHF precipitated by AF is associated with lower 90‐day risk of death.
Uncontrolled studies suggest that pulmonary embolism (PE) can be safely ruled out using the YEARS rule, a diagnostic strategy that uses varying D-dimer thresholds.
To prospectively validate the ...safety of a strategy that combines the YEARS rule with the pulmonary embolism rule-out criteria (PERC) rule and an age-adjusted D-dimer threshold.
A cluster-randomized, crossover, noninferiority trial in 18 emergency departments (EDs) in France and Spain. Patients (N = 1414) who had a low clinical risk of PE not excluded by the PERC rule or a subjective clinical intermediate risk of PE were included from October 2019 to June 2020, and followed up until October 2020.
Each center was randomized for the sequence of intervention periods. In the intervention period (726 patients), PE was excluded without chest imaging in patients with no YEARS criteria and a D-dimer level less than 1000 ng/mL and in patients with 1 or more YEARS criteria and a D-dimer level less than the age-adjusted threshold (500 ng/mL if age <50 years or age in years × 10 in patients ≥50 years). In the control period (688 patients), PE was excluded without chest imaging if the D-dimer level was less than the age-adjusted threshold.
The primary end point was venous thromboembolism (VTE) at 3 months. The noninferiority margin was set at 1.35%. There were 8 secondary end points, including chest imaging, ED length of stay, hospital admission, nonindicated anticoagulation treatment, all-cause death, and all-cause readmission at 3 months.
Of the 1414 included patients (mean age, 55 years; 58% female), 1217 (86%) were analyzed in the per-protocol analysis. PE was diagnosed in the ED in 100 patients (7.1%). At 3 months, VTE was diagnosed in 1 patient in the intervention group (0.15% 95% CI, 0.0% to 0.86%) vs 5 patients in the control group (0.80% 95% CI, 0.26% to 1.86%) (adjusted difference, -0.64% 1-sided 97.5% CI, -∞ to 0.21%, within the noninferiority margin). Of the 6 analyzed secondary end points, only 2 showed a statistically significant difference in the intervention group compared with the control group: chest imaging (30.4% vs 40.0%; adjusted difference, -8.7% 95% CI, -13.8% to -3.5%) and ED median length of stay (6 hours IQR, 4 to 8 hours vs 6 hours IQR, 5 to 9 hours; adjusted difference, -1.6 hours 95% CI, -2.3 to -0.9).
Among ED patients with suspected PE, the use of the YEARS rule combined with the age-adjusted D-dimer threshold in PERC-positive patients, compared with a conventional diagnostic strategy, did not result in an inferior rate of thromboembolic events.
ClinicalTrials.gov Identifier: NCT04032769.
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