Elevated high-sensitivity troponin (hsTnT) after noncardiac surgery is associated with higher mortality, but the temporal relationship between early elevated troponin and the later development of ...noncardiac morbidity remains unclear.
Prospective observational study of patients aged ≥45 yr undergoing major noncardiac surgery at four UK hospitals (two masked to hsTnT). The exposure of interest was early elevated troponin, as defined by hsTnT >99th centile (≥15 ng L−1) within 24 h after surgery. The primary outcome was morbidity 72 h after surgery, defined by the Postoperative Morbidity Survey (POMS). Secondary outcomes were time to become morbidity-free and Clavien–Dindo ≥grade 3 complications.
Early elevated troponin (median 21 ng L−1 16–32) occurred in 992 of 4335 (22.9%) patients undergoing elective noncardiac surgery (mean standard deviation, sd age, 65 11 yr; 2385 54.9% male). Noncardiac morbidity was more frequent in 494/992 (49.8%) patients with early elevated troponin compared with 1127/3343 (33.7%) patients with hsTnT <99th centile (odds ratio OR=1.95; 95% confidence interval CI, 1.69–2.25). Patients with early elevated troponin had a higher risk of proven/suspected infectious morbidity (OR=1.54; 95% CI, 1.24–1.91) and critical care utilisation (OR=2.05; 95% CI, 1.73–2.43). Clavien–Dindo ≥grade 3 complications occurred in 167/992 (16.8%) patients with early elevated troponin, compared with 319/3343 (9.5%) patients with hsTnT <99th centile (OR=1.78; 95% CI, 1.48–2.14). Absence of early elevated troponin was associated with morbidity-free recovery (OR=0.44; 95% CI, 0.39–0.51).
Early elevated troponin within 24 h of elective noncardiac surgery precedes the subsequent development of noncardiac organ dysfunction and may help stratify levels of postoperative care in real time.
Abstract Objectives: Use of cumulative mortality adjusted for case mix in patients with acute myocardial infarction for early detection of variation in clinical practice. Design: Observational study. ...Setting: 20 hospitals across the former Yorkshire region. Participants: All 2153 consecutive patients with confirmed acute myocardial infarction identified during three months. Main outcome measures: Variable life-adjusted displays showing cumulative differences between observed and expected mortality of patients; expected mortality calculated from risk model based on admission characteristics of age, heart rate, and systolic blood pressure. Results: The performance of two individual hospitals over three months was examined as an example. One, the smallest district hospital in the region, had a series of 30 consecutive patients but had five more deaths than predicted. The variable life-adjusted display showed minimal variation from that predicted for the first 15 patients followed by a run of unexpectedly high mortality. The second example was the main tertiary referral centre for the region, which admitted 188 consecutive patients. The display showed a period of apparently poor performance followed by substantial improvement, where the plot rose steadily from a cumulative net lives saved of −4 to 7. These variations in patient outcome are unlikely to have been revealed during conventional audit practice. Conclusions: Variable life-adjusted display has been integrated into surgical care as a graphical display of risk-adjusted survival for individual surgeons or centres. In combination with a simple risk model, it may have a role in monitoring performance and outcome in patients with acute myocardial infarction. What is already known on this topic The national service framework for coronary artery disease requires minimal standards of care and audit of patients with acute myocardial infarction but does not integrate clinical status into the audit tool Predictive models using only a few factors to adjust for case mix are easy to use and may be as accurate as more complicated methods Early identification of variations in patient outcome is not revealed by block audit, and, instead, a continuous monitoring process is required What this study adds Using just patients' age, blood pressure, and heart rate to adjust for case mix, a continuous plot can be derived to compare observed and expected outcome for patients with acute myocardial infarction This method of monitoring outcome over time can be used as an early warning system to allow more detailed audit to be performed
Recent studies have demonstrated that RANTES, a member of the CC chemokine family affecting monocytes, T cells, basophils, and eosinophils, is expressed by several cell types. To investigate whether ...human bronchial epithelial cells can also express this chemokine, we investigated human bronchial epithelial cells for their ability to synthesize RANTES, both in vitro and in vivo. Additionally, we investigated the effect of treatment for 4 mo with inhaled corticosteroids on the expression of RANTES in these cells in vivo. Human bronchial epithelial cells cultured from surgical tissue expressed the mRNA for RANTES and synthesized RANTES, as demonstrated by polymerase chain reaction and immunocytochemical staining and enzyme-linked immunosorbent assay, respectively. Incubation of the cultures with 50 ng/ml of tumor necrosis factor-alpha (TNF-alpha) significantly increased the release of RANTES into culture medium after 18 to 48 h of incubation, an effect that was abolished by treatment of the cultures with anti-TNF-alpha antibody. RANTES was also expressed in the bronchial epithelium in vivo, as indicated by positive immunocytochemical staining of bronchial biopsy tissues obtained from mild asthmatic patients before and after treatment with 500 micrograms of inhaled beclomethasone dipropionate (BDP) twice daily or matched placebo for 4 mo. Quantitation, by color image analysis, of the percentage of epithelium staining for RANTES showed that treatment with BDP decreased the expression of RANTES in the bronchial epithelium from 17.12% to 4.22% (P < 0.05). The numbers of EG2-staining cells in the epithelium were also reduced, from 790.1/mm2 to 203.3/mm2 (geometric mean; P < 0.01), after BDP treatment. These results suggest that human bronchial epithelial cells are capable of synthesizing RANTES and may therefore play an important role in the development of inflammation in allergic airways disease. Furthermore, corticosteroids may prevent airway inflammation by downregulating the expression of proinflammatory cytokines in the bronchial epithelium.
Background: Recent studies have demonstrated that some antihistamines can attenuate histamine-induced release of inflammatory mediators from bronchial epithelial cells.
Objective: The purpose of ...study was to test the hypothesis that loratadine may influence pollution-induced inflammation of the airways by modulating epithelial membrane integrity and the synthesis and/or release of inflammatory mediators from airway epithelial cells.
Methods: We have cultured human bronchial epithelial cell (HBEC) cultures from surgical explants and investigated the effect of loratadine on NO
2 –induced changes in both electrical resistance of HBEC cultures and release of IL-8, RANTES, and soluble intercellular adhesion molecule-1 (sICAM-1) from these cells after exposure for 6 hours to either air or 400 ppb NO
2.
Results: Exposure for 6 hours to NO
2 significantly decreased the electrical resistance of HBEC cultures by 18.1% from baseline (
P < .05). Incubation with 0.25 to 25 μmol/L loratadine did not alter the NO
2 –induced decrease in the electrical resistance of HBEC cultures. NO
2 also significantly increased the release of IL-8 from a control value of 52.5 pg/μg cellular protein to 81.9 pg/μg cellular protein (
P < .05), RANTES from a control value of 0.023 pg/μg cellular protein to 0.062 pg/μg cellular protein (
P < .05), and sICAM-1 from a control value of 7.7 pg/μg cellular protein to 16.3 pg/μg cellular protein (
P < .05). The NO
2 –induced release of all 3 mediators was significantly attenuated by incubation of HBECs with 25 μmol/L loratadine. Incubation with 2.5 μmol/L loratadine also significantly attenuated the NO
2 –induced release of RANTES and sICAM-1, but not IL-8.
Conclusions: These results suggest that loratadine has the potential to reduce airway inflammation by modulating the release of inflammatory cytokines from airway epithelial cells. (J Allergy Clin Immunol 1999;104:93-9.)
Biological invasions are a major driver of ecosystem change but causes of variation in their environmental impacts over space and time remain poorly understood. Most approaches used to quantify the ...impacts of non‐native species assume there are interactions among per capita (i.e. individual level) effects, species abundance and the area occupied by the species. However, studies rarely evaluate these factors and their interactions and often fail to recognize that the magnitude of impacts can be highly context dependent. Understanding what drives the context dependence of non‐native species impacts can improve our understanding and predictions of ecosystem change and better inform options for mitigation.
Conifers, especially pines, are among the most problematic non‐native plant species globally. We use Pinaceae to illustrate how context dependence in biodiversity and environmental impacts of non‐native plant species can be generated by at least four processes: nonlinear density effects; intraspecific variation in functional traits; shifts in impacts over time; and persistence of impacts as biological or ecosystem legacies following non‐native species removal. Using this understanding, we develop a framework to better quantify interactions of impacts along environmental gradients (e.g. soil fertility, climate, ecosystem age).
We demonstrate how impacts of non‐native species can occur at both low and high density, and that failing to account for intraspecific variation in effect traits can lead to significant errors in the prediction of impacts. By incorporating context dependence in regard to density and functional traits, we can measure how the interaction of this context dependence will shift along environmental gradients. Moreover, disentangling the roles of species and abundance along such gradients will provide new insights into the net effects of both the native and non‐native components of communities. We use a working example of our framework that incorporates all four processes to demonstrate how to measure fire risk impacts of Pinus contorta.
We show that ecosystem impacts of non‐native tree species are not fixed but rather vary predictably along major environmental gradients. Moreover, removal of non‐native species through management provides an important tool for revealing biological and ecosystem legacy effects. Although we focus here on relatively well‐documented Pinaceae, the new insights into context dependence of impacts can be widely applied across species, environments and regions.
A free Plain Language Summary can be found within the Supporting Information of this article.
A free Plain Language Summary can be found within the Supporting Information of this article.
Diabetes mellitus (DM) is an established adverse prognostic factor in patients sustaining myocardial infarction (MI). However, its impact on long-term survival remains less clear. The aim of this ...observational study was to quantify lifetime mortality and years of life lost after MI in patients with and without DM.
In 1995, 2153 individuals with MI were recruited from 20 adjacent hospitals within Yorkshire, UK. Median survival, all-cause mortality at 20years and lost years of life when compared to actuarial predictions were compared in patients with and without DM. Landmark analyses were conducted to define the ongoing impact of DM beyond specified time points.
13% (279/2153) had known DM. They experienced higher mortality at 30days (33.1% vs 24.6%; p<0.0001) and at 20years (84.9% vs 75.7%; p<0.0001). Overall, there was a 48% increased risk of death (p<0.0001), which persisted after adjustment for potential confounders. There was no interaction between DM and prior MI in predicting mortality (p=0.67). Median survival decreased by 3.3years (p<0.0001). The adverse impact of DM persisted in sequential landmark analyses at 1, 5 and 10years. Presence of DM conferred 2 extra years of life lost when compared with actuarial predictions (8 vs 6years; p<0.0001).
DM remains an independent adverse prognostic factor in the long-term after MI. Persistently diverging survival curves support enduring efforts to reduce mortality late after MI.
Although studies have suggested that exposure to cigarette smoke (CS) may be associated with the development of atopy, the mechanisms underlying this are not clearly understood. It has been suggested ...that CS impairs the barrier function of the airway epithelium, leading to increased access of allergens such as those of the house dust mite (HDM) Dermatophagoides pteronyssinus (Der p) to antigen-presenting cells, with subsequent allergic sensitization. In order to test this hypothesis, we established primary explant cultures of human bronchial epithelial cells (HBEC) in cell culture inserts, and exposed these for 20 min, 1 h, 3 h, and 6 h to CS or air in the absence or presence of 300 ng/ml Der p, and then further incubated the cultures over a period of 24 h. The HBEC cultures were assessed for changes in permeability as measured by changes in: (1) electrical resistance (ER); and (2) passage of 14C-labeled bovine serum albumin (14C-BSA) and Der p allergens across the HBEC cultures. We also assessed the effects of protease inhibitors and the antioxidant glutathione (GSH) in this experimental system. Damage to HBEC cultures was assessed by the release of 51Crsodium chromate from prelabeled cells, and by release of lactate dehydrogenase (LDH). Twenty minutes of exposure to CS as compared with exposure to air did not significantly alter either the ER or passage of 14C-BSA across the HBEC cultures. In contrast, incubation with Der p led to a significant increase in the permeability of HBEC cultures, an effect that was enhanced by exposure to CS but was abrogated by the specific protease inhibitors and GSH. Passage of Der p was also increased by exposure to CS. Exposure of HBEC cultures to CS led to a significant release of 51Cr and LDH from these cells as compared with cells exposed to air. This effect was augmented further when HBEC cultures were incubated with Der p. Exposure of HBEC cultures for 1 h, 3 h, and 6 h to CS led to a markedly significant dose- and time-dependent increase in the permeability of these cells. These results suggest that exposure to CS significantly enhances Der p-induced decreases in electrical resistance and the increased passage across HBEC cultures of 14C-BSA and of the Der p allergen itself.
Although major bleeding is among the most common and prognostically important perioperative complications, the relative timing of bleeding events is not well established. This information is critical ...for preventing bleeding complications and for informing the timing of pharmacologic thromboprophylaxis.
To determine the timing of postoperative bleeding among patients undergoing surgery for up to 30 days after surgery.
This is a secondary analysis of a prospective cohort study. Patients aged 45 years or older who underwent inpatient noncardiac surgery were recruited in 14 countries between 2007 and 2013, with follow-up until December 2014. Data analysis was performed from June to July 2023.
Noncardiac surgery requiring overnight hospital admission.
The primary outcome (postoperative major bleeding) was a composite of the timing of the following bleeding outcomes: (1) bleeding leading to transfusion, (2) bleeding leading to a postoperative hemoglobin level less than 7 g/dL, (3) bleeding leading to death, and (4) bleeding associated with reintervention. Each of the components of the composite primary outcome (1-4) and bleeding independently associated with mortality after noncardiac surgery, which was defined as a composite of outcomes 1 to 3, were secondary outcomes.
Among 39 813 patients (median IQR age, 63.0 54.8-72.5 years; 19 793 women 49.7%), there were 5340 major bleeding events (primary outcome) in 4638 patients (11.6%) within the first 30 days after surgery. Of these events, 42.7% (95% CI, 40.9%-44.6%) occurred within 24 hours after surgery, 77.7% (95% CI, 75.8%-79.5%) by postoperative day 7, 88.3% (95% CI, 86.5%-90.2%) by postoperative day 14, and 94.6% (95% CI, 92.7%-96.5%) by postoperative day 21. Within 48 hours of surgery, 56.2% of major bleeding events, 56.2% of bleeding leading to transfusion, 56.1% of bleeding independently associated with mortality after noncardiac surgery, 51.8% of bleeding associated with hemoglobin less than 7 g/dL, and 51.8% of bleeding associated with reintervention had occurred.
In this cohort study, of the major postoperative bleeding events in the first 30 days, more than three-quarters occurred during the first postoperative week. These findings are useful for researchers for the planning future clinical research and for clinicians in prevention of bleeding-related surgical complications and in decision-making regarding starting of pharmacologic thromboprophylaxis after surgery.
Background: Recent studies have suggested that asthmatic patients may be more susceptible to the adverse effects of air pollutants, including diesel exhaust particles (DEP). The underlying ...mechanisms, however, are not clear.
Methods: We cultured bronchial epithelial cells from bronchial biopsy specimens of well-characterized groups of nonatopic, nonasthmatic individuals and atopic patients with mild asthma and compared the ciliary beat frequency (CBF) and release of IL-8, GM-CSF, regulated on activation, normal T-cell expressed and secreted (RANTES), and soluble intercellular adhesion molecule-1 (sICAM-1) from these cells both before and after exposure for 24 hours to 10 to 100 μg/mL DEP in vitro.
Results: The baseline CBF was not found to be significantly different in the bronchial epithelial cell cultures of nonasthmatic and asthmatic individuals. Incubation with DEP significantly attenuated the CBF of both the nonasthmatic and asthmatic bronchial epithelial cell cultures at all concentrations of DEP investigated and were maximal (55.5% and 45.2%, respectively) after incubation with 100 μg/mL DEP. The bronchial epithelial cell cultures of asthmatic patients constitutively released significantly greater amounts of IL-8, GM-CSF, and sICAM-1 than bronchial epithelial cell cultures of nonasthmatic subjects. The cultures of only asthmatic patients additionally released RANTES. Incubation of the asthmatic cultures with 10 μg/mL DEP significantly increased the release of IL-8 (from 102.0 to 167.8 pg/μg cellular protein;
P < .01), GM-CSF (from 0.43 to 1.87 pg/μg cellular protein;
P < .01), and sICAM-1 (from 14.7 to 38.1 pg/μg cellular protein;
P < .02) after 24 hours. Incubation with 50 to 100 μg/mL DEP, however, significantly decreased the release of IL-8 and RANTES from these cultures. In contrast, only the higher concentrations of 50 to 100 μg/mL DEP significantly increased release of IL-8 (from 37.9 to 71.5 pg/μg cellular protein;
P < .05) and GM-CSF (from 0.06 to 0.34 pg/μg cellular protein;
P < .05) from the bronchial epithelial cells of nonasthmatic individuals.
Conclusions: These results suggest that bronchial epithelial cells of asthmatic subjects are different from bronchial epithelial cells of nonasthmatic subjects with regard to the amounts and types of proinflammatory mediators they can release and that the increased sensitivity of bronchial epithelial cells of asthmatic subjects to DEP may possibly result in exacerbation of their disease symptoms. (J Allergy Clin Immunol 1998;102:771-82.)
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