Photosynthesis and crop productivity are enhanced by glucose-functionalised carbon dots.

From global food security to textile production and biofuels, the demands currently made on plant photosynthetic productivity will continue to increase. Enhancing photosynthesis using designer, green and sustainable materials offers an attractive alternative to current genetic-based strategies and promising work with nanomaterials has recently started to emerge. Here we describe the in planta use of carbon-based nanoparticles produced by low-cost renewable routes that are bioavailable to mature plants. Uptake of these functionalised nanoparticles directly from the soil improves photosynthesis and also increases crop production. We show for the first time that glucose functionalisation enhances nanoparticle uptake, photoprotection and pigment production, unlocking enhanced yields. This was demonstrated in Triticum aestivum 'Apogee' (dwarf bread wheat) and resulted in an 18% increase in grain yield. This establishes the viability of a functional nanomaterial to augment photosynthesis as a route to increased crop productivity.

Clinical chemistry score versus high-sensitivity cardiac troponin I and T tests alone to identify patients at low or high risk for myocardial infarction or death at presentation to the emergency department.

BACKGROUND: Testing for high-sensitivity cardiac troponin (hs-cTn) may assist triage and clinical decision-making in patients presenting to the emergency department with symptoms of acute coronary syndrome; however, this could result in the misclassification of risk because of analytical variation or laboratory error. We sought to evaluate a new laboratory-based risk-stratification tool that incorporates tests for hs-cTn, glucose level and estimated glomerular filtration rate to identify patients at risk of myocardial infarction or death when presenting to the emergency department. METHODS: We constructed the clinical chemistry score (CCS) (range 0-5 points) and validated it as a predictor of 30-day myocardial infarction (MI) or death using data from 4 cohort studies involving patients who presented to the emergency department with symptoms suggestive of acute coronary syndrome. We calculated diagnostic parameters for the CCS score separately using high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT). RESULTS: For the combined cohorts (n = 4245), 17.1% of participants had an MI or died within 30 days. A CCS score of 0 points best identified low-risk participants: the hs-cTnI CCS had a sensitivity of 100% (95% confidence interval [CI] 99.5%-100%), with 8.9% (95% CI 8.1%-9.8%) of the population classified as being at low risk of MI or death within 30 days; the hs-cTnT CCS had a sensitivity of 99.9% (95% CI 99.2%-100%), with 10.5% (95% CI 9.6%-11.4%) of the population classified as being at low risk. The CCS had better sensitivity than hs-cTn alone (hs-cTnI < 5 ng/L: 96.6%, 95% CI 95.0%-97.8%; hs-cTnT < 6 ng/L: 98.2%, 95% CI 97.0%-99.0%). A CCS score of 5 points best identified patients at high risk (hs-cTnI CCS: specificity 96.6%, 95% CI 96.0%-97.2%; 11.2% [95% CI 10.3%-12.2%] of the population classified as being at high risk; hs-cTnT CCS: specificity 94.0%, 95% CI 93.1%-94.7%; 13.1% [95% CI 12.1%-14.1%] of the population classified as being at high risk) compared with using the overall 99th percentiles for the hs-cTn assays (specificity of hs-cTnI 93.2%, 95% CI 92.3-94.0; specificity of hs-cTnT 73.8%, 95% CI 72.3-75.2). INTERPRETATION: The CCS score at the chosen cut-offs was more sensitive and specific than hs-cTn alone for risk stratification of patients presenting to the emergency department with suspected acute coronary syndrome. Study registration: ClinicalTrials.gov, nos. NCT01994577; NCT02355457.

Rule-In and Rule-Out of Myocardial Infarction Using Cardiac Troponin and Glycemic Biomarkers in Patients with Symptoms Suggestive of Acute Coronary Syndrome.

BACKGROUND: Early rule-in/rule-out of myocardial infarction (MI) in patients presenting to the emergency department (ED) is important for patient care and resource allocation. Given that dysglycemia is a strong risk factor for MI, we sought to explore and compare different combinations of cardiac troponin (cTn) cutoffs with glycemic markers for the early rule-in/rule-out of MI. METHODS: We included ED patients (n = 1137) with symptoms suggestive of acute coronary syndrome (ACS) who had cTnI, high-sensitivity cTnI (hs-cTnI), hs-cTnT, glucose, and hemoglobin A1c (Hb A1c) measurements. We derived rule-in/rule-out algorithms using different combinations of ROC-derived and literature cutoffs for rule-in and rule-out of MI within 7 days after presentation. These algorithms were then tested for MI/cardiovascular death and ACS/cardiovascular death at 7 days. ROC curves, sensitivity, specificity, likelihood ratios, positive and negative predictive values (PPV and NPV), and CIs were determined for various biomarker combinations. RESULTS: MI was diagnosed in 133 patients (11.7%; 95% CI, 9.8-13.8). The algorithms that included cTn and glucose produced the greatest number of patients ruled out/ruled in for MI and yielded sensitivity ≥99%, NPV ≥99.5%, specificity ≥99%, and PPV ≥80%. This diagnostic performance was maintained for MI/cardiovascular death but not for ACS/cardiovascular death. The addition of hemoglobin A1c (Hb A1c) (≥6.5%) to these algorithms did not change these estimates; however, 50 patients with previously unknown diabetes may have been identified if Hb A1c was measured. CONCLUSIONS: Algorithms incorporating glucose with cTn may lead to an earlier MI diagnosis and rule-out for MI/cardiovascular death. Addition of Hb A1c into these algorithms allows for identification of diabetes. Future studies extending these findings are needed for ACS/cardiovascular death. ClinicalTrials.gov identifier: NCT01994577.

Economic Considerations of Early Rule-In/Rule-Out Algorithms for The Diagnosis of Myocardial Infarction in The Emergency Department Using Cardiac Troponin and Glycemic Biomarkers.

BACKGROUND: We have previously demonstrated the utility of a rule-in/rule-out strategy for myocardial infarction (MI) using glycemic biomarkers in combination with cardiac troponin in the emergency department (ED). Given that the cost of assessing patients with possible MI in the ED is increasing, we sought to compare the health services cost of our previously identified early rule-in/rule-out approaches for MI among patients who present to the ED with symptoms suggestive of acute coronary syndrome (ACS). METHODS: We compared the cost differences between different rule-in/rule-out strategies for MI using presentation cardiac troponin I (cTnI), high-sensitivity cTnI (hs-cTnI), high-sensitivity cardiac troponin T (hs-cTnT), glucose, and/or hemoglobin A1c (Hb A1c) in 1137 ED patients (7-day MI n = 133) as per our previously defined algorithms and compared them with the European Society of Cardiology (ESC) 0-h algorithm-cutoffs. Costs associated with each decision model were obtained from site-specific sources (length of stay) and provincial sources (Ontario Case Costing Initiative). RESULTS: Algorithms incorporating cardiac troponin and glucose for early rule-in/rule-out were the most cost effective and clinically safest methods (i.e., ≤1 MI missed) for early decision making, with hs-cTnI and glucose yielding lower costs compared to cTnI and glucose, despite the higher price for the hs-cTnI test. The addition of Hb A1c to the algorithms increased the cost of these algorithms but did not miss any additional patients with MI. Applying the ESC 0-h algorithm-cutoffs for hs-cTnI and hs-cTnT were the most costly. CONCLUSIONS: Rule-in/rule-out algorithms incorporating presentation glucose with high-sensitivity cardiac troponin are the safest and most cost-effective options as compared to the ESC 0-h algorithm-cutoffs.

BNP and NT-proBNP as prognostic markers in persons with acute decompensated heart failure: a systematic review.

A systematic review was undertaken to examine the evidence for B-type natriuretic peptides (BNP and NT-proBNP) as independent predictors of mortality, morbidity, or combined mortality and morbidity outcomes in persons with acute decompensated heart failure (ADHF). Electronic databases (Medline(®), Embase™, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL) were searched from 1989 to June 2012. Reference lists of included articles, systematic reviews, and the gray literature were also searched. English language studies were eligible if they included subjects with ADHF and measured BNP/NT-proBNP using FDA approved assays. Standardized forms were used to select studies, extract data, and assess risk of bias. Seventy-nine studies, ranging over followup intervals from 14 days to 7 years, evaluating levels of BNP (n = 38), NT-proBNP (n = 35), or both (n = 6) were eligible. The majority of studies predicted mortality outcomes for admission BNP/NT-proBNP levels, with fewer studies evaluating serial, change from admission, or discharge levels. In general, higher levels of admission BNP or NT-proBNP predicted greater risk for all outcomes. Decreased levels post-admission predicted decreased risk. Overall, these studies were rated as having moderate risk of bias. This systematic review shows that BNP and NT-proBNP are independent predictors of mortality (all-cause and cardiovascular) in ADHF despite different cutpoints, time intervals, and prognostic models. Findings for morbidity and composite outcomes were less frequently evaluated and showed inconsistency. Further research is required to assess cutpoints for admission, serial measurements, change following admission, and discharge levels to assist clinical decision-making.

Incremental predictive value of natriuretic peptides for prognosis in the chronic stable heart failure population: a systematic review.

The aim of this study was to determine whether measurement of natriuretic peptides independently adds incremental predictive value for mortality and morbidity in patients with chronic stable heart failure (CSHF). We electronically searched Medline®, Embase™, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL from 1989 to June 2012. We also searched reference lists of included articles, systematic reviews, and the gray literature. Studies were screened for eligibility criteria and assessed for methodological quality. Data were extracted on study design, population demographics, assay cutpoints, prognostic risk prediction model covariates, statistical methods, outcomes, and results. One hundred and eighty-three studies were identified as prognostic in the systematic review. From these, 15 studies (all NT-proBNP) considered incremental predictive value in CSHF subjects. Follow-up varied from 12 to 37 months. All studies presented at least one estimate of incremental predictive value of NT-proBNP relative to the base prognostic model. Using discrimination or likelihood statistics, these studies consistently showed that NT-proBNP increased model performance. Three studies used re-classification and model validation computations to establish incremental predictive value; these studies showed less consistency with respect to added value. Although there were differences in the base risk prediction models, assay cutpoints, and lengths of follow-up, there was consistency in NT-proBNP adding incremental predictive value for prognostic models in chronic stable CSHF patients. The limitations in the literature suggest that studies designed to evaluate prognostic models should be undertaken to evaluate the incremental value of natriuretic peptide as a predictor of mortality and morbidity in CSHF.

B-type natriuretic peptide-guided therapy: a systematic review.

BNP/NT-proBNP measurement has not gained widespread use for the management of patients with heart failure (HF) despite several randomized controlled trials. A systematic review addressing the question of whether patients with HF benefit from BNP-assisted therapy or intensified therapy compared with usual care was undertaken. Relevant randomized controlled trial (RCTs) were selected by searching Medline, Embase, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL for English-language articles published from 1980 to 2012. Selected studies required patients to be treated for chronic HF with medical therapy based on BNP/NT-proBNP or usual care. There were no restrictions except that BNP/NT-proBNP measurement had to be done by an FDA approved method. Nine RCTs were identified with 2,104 patients with study duration that ranged from 3 to 18 months. Overall, there was a wide variation in study design and how parameters were reported including patient selection, baseline characteristics, therapy goals, BNP/NT-proBNP cutpoint, and outcome types. Meta-analysis was not appropriate given this study heterogeneity. The strength of evidence for the outcome of mortality, reported in seven studies, was found to be low due to inconsistency and imprecision. This systematic review showed that the evidence is of low quality and insufficient to support the use of BNP/NT-proBNP to guide HF therapy. Further trials with improved design are needed.

Incremental value of natriuretic peptide measurement in acute decompensated heart failure (ADHF): a systematic review.

The aim of this systematic review was to determine whether B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) independently add incremental value for predicting mortality and morbidity in patients with acute decompensated heart failure (ADHF). Medline(®), Embase™, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL were searched from 1989 to June 2012. We also searched reference lists of included articles, systematic reviews, and the gray literature. Studies were screened for eligibility criteria and assessed for risk of bias. Data were extracted on study design, population demographics, assay cutpoints, prognostic risk prediction model covariates, statistical methods, outcomes, and results. From 183 citations, only seven studies (5 BNP and 2 NT-proBNP) considered incremental value in ADHF subjects admitted to acute care centers. Admission assay levels and length of follow-up varied for BNP studies (31 days to 12 months) and for NT-proBNP studies (25-82 months). All studies presented at least one estimate of incremental value of BNP/NT-proBNP relative to the base prognostic model. Using discrimination or likelihood statistics, these studies consistently showed that BNP or NT-proBNP increased model performance. Three studies used reclassification and model validation computations to establish incremental value; these studies showed less consistency with respect to added value. In conclusion, the literature assessing incremental value of BNP/NT-proBNP in ADHF populations is limited to seven studies evaluating only mortality outcomes and at moderate risk of bias. Although there were differences in the base risk prediction models, assay cutpoints, and lengths of follow-up, there was consistency in BNP/NT-proBNP adding incremental value in prediction models in ADHF patients.

Prediction of clinical outcomes using B-type natriuretic peptides in the general population: a systematic review.

The use of B-type natriuretic peptides to predict outcomes in general populations has been investigated in a number of primary studies. A previous systematic review considering natriuretic peptides in cardiovascular disease included a subgroup of general population studies, which suggested an association with a number of clinical outcomes. We electronically searched Medline, Embase, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL for English-language articles published between 1989 and mid-2012. We utilized trained reviewers and standardized forms to screen articles for inclusion and extract data from included articles. All included studies (n = 7) were summarized in narrative and tabular form. A general population was defined as one that was randomly selected from a community setting where no specific inclusion or exclusion criteria were specified. The seven included studies all used FDA approved assays for NT-proBNP. The range of clinical outcomes and heterogeneity did not allow for meta-analysis. The hazard ratios for predicting outcomes in the included studies ranged from 1.0 to 4.1 (all p values <0.05). The discrimination statistics reported in four studies all demonstrated statistically significant improvements in predicting outcomes. NT-proBNP is associated with heart failure, all-cause and cardiovascular mortality, and other combined cardiovascular events in a general unselected population. The discrimination statistics suggest modest improvements in risk stratification. No prospective studies exist to demonstrate the clinical utility of using B-type natriuretic peptides to predict clinical outcomes in a general population.

Use of BNP and NT-proBNP for the diagnosis of heart failure in the emergency department: a systematic review of the evidence.

Our purpose was to determine the test performance characteristics of BNP and NT-proBNP in the diagnosis of heart failure for patients presenting to an emergency department or urgent care center. We searched Medline, Embase, AMED, Cochrane, Cochrane Database of Systematic Reviews, and CINAHL for English-language articles published between 1989 and June 2012. Studies were limited to those using FDA-approved assays. We examined test performance at three pre-specified cutpoints (manufacturers' suggested, researchers' optimal, and lowest) and considered the effect of age, gender, ethnicity and renal function. We used the QUADAS-2 tool to examine risk of bias and applicability, and the AHRQ Methods Guide to assess the strength of evidence. Seventy-six articles met our inclusion criteria, 37 examined BNP, 25 examined NT-proBNP, and 14 examined both. Pooled sensitivity and specificity for BNP at the three pre-specified cutpoints were 95, 91, and 95 % (sensitivity) and 55, 80, and 67 % (specificity), respectively. For NT-proBNP, sensitivity and specificity at the same cutpoints were 91, 90, and 96 % (sensitivity) and 67, 74, and 55 % (specificity). Both BNP and NT-proBNP perform well to rule out, but less well to rule in, the diagnosis of heart failure among persons presenting to emergency departments or urgent care centers. Both BNP and NT-proBNP levels are positively associated with age and negatively associated with renal function. However, the effect of these factors with respect to selecting optimal cutpoints is unclear. For BNP, 100 pg/mL appears to be a consensus cutpoint. No clear consensus has emerged for NT-proBNP, but the age-adjusted cutpoints of 450 pg/mL for <50 years, 900 pg/mL for 50-75 years and 1,800 pg/mL for >75 years appear promising and merit greater scrutiny and validation.

Performance of BNP and NT-proBNP for diagnosis of heart failure in primary care patients: a systematic review.

National and international guidelines have been published recommending the use of natriuretic peptides as an aid to the diagnosis of heart failure (HF) in acute settings; however, few specific recommendations exist for governing the use of these peptides in primary care populations. To summarize the available data relevant to the diagnosis of HF in primary care patient population, we systematically reviewed the literature to identify original articles that investigated the diagnostic accuracy of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in primary care settings. The search yielded 25,864 articles in total: 12 investigating BNP and 20 investigating NT-proBNP were relevant to our objective and included in the review. QUADAS-2 and GRADE were used to assess the quality of the included articles. Diagnostic data were pooled based on three cutpoints: lowest and optimal, as chosen by study authors, and manufacturers' suggested. The effect of various determinants (e.g., age, gender, BMI, and renal function) on diagnostic performance was also investigated. Pooled sensitivity and specificity of BNP and NT-proBNP using the lowest [0.85 (sensitivity) and 0.54 (specificity)], optimal (0.80 and 0.61), and manufacturers' (0.74 and 0.67) cutpoints showed good performance for diagnosing HF. Similar performance was seen for NT-proBNP: lowest (0.90 and 0.50), optimal (0.86 and 0.58), and manufacturers' (0.82 and 0.58) cutpoints. Overall, we rated the strength of evidence as high because further studies will be unlikely to change the estimates diagnostic performance.

Three-dimensional visualization of predatory gastropod feeding teeth with synchrotron scanning.

Several families of neogastropod mollusks independently evolved the ability to drill through mineralized prey skeletons using their own mineralized feeding teeth, sometimes with shell-softening chemical agents produced by an organ in the foot. Teeth with more durable tooth shapes should extend their use and improve predator performance, but past studies have described only the cusped-side of teeth, mostly overlooking morphologies related to functional interactions between teeth. Here, we describe the three-dimensional morphology of the central drilling tooth (rachidian) from four species of the neogastropod family Muricidae using synchrotron tomographic microscopy and assemble a three-dimensional model of a multitooth series in drilling position for two of them to investigate their dynamic form. We find two new types of articulating surfaces, including a saddle joint at either end of the rachidian and a large tongue-and-groove joint in the center. The latter has a shape that maximizes contact surface area between teeth as they rotate away from each other during drilling. Articulating joints have not been described in Neogastropod radula previously, but they are consistent with an earlier hypothesis that impact forces on individual teeth during predatory drilling are dispersed by tooth-tooth interactions.

Applicability of the AGREE II instrument in evaluating the development process and quality of current National Academy of Clinical Biochemistry guidelines.

BACKGROUND: Laboratory medicine practice guidelines (LMPGs) are an important part of clinical laboratory medicine. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument has been developed to evaluate the process of practice-guideline development and the quality of reporting. We assessed the applicability of AGREE II in assessing the National Academy of Clinical Biochemistry (NACB) LMPGs. METHODS: The NACB website was searched for all available LMPGs up to December 2011. Two independent appraisers used the AGREE II instrument to assess each LMPG identified by the search. Quality was assessed across 6 domains (scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence), comprising a total of 23 items and 2 overall assessments, each scored on a 7-point scale (1, strongly disagree, to 7, strongly agree). All scores were expressed as AGREE II calculated percentages (100% indicates that all items scored 7 by all appraisers). RESULTS: Eleven LMPGs were identified. All of the LMPGs provided some information seen as applicable to clinical practice by the appraisers. Only 5 of the LMPGs had overall scores ≥50%, with a median score of 42% (range: 8%-92%). Individual domain scores varied considerably from 0% to 100%. One guideline achieved a very high score on the instrument. CONCLUSIONS: The AGREE II instrument is applicable and useful to evaluate LMPGs. All domains were evaluated as being useful to assess LMPGs, some were addressed well (e.g., clarity of presentation), whereas others could be improved (e.g., applicability).

Biomarkers for predicting serious cardiac outcomes at 72 hours in patients presenting early after chest pain onset with symptoms of acute coronary syndromes.

BACKGROUND: Most outcome studies of patients presenting early to the emergency department with potential acute coronary syndromes have focused on either the index diagnosis of myocardial infarction (MI) or a composite end point at a later time frame (30 days or 1 year). We investigated the performance of 9 biomarkers for an early serious outcome. METHODS: Patients (n=186) who presented to the emergency department within 6 h of chest pain onset had their presentation serum sample measured for the following analytes: creatine kinase, creatine kinase isoenzyme MB, enhanced AccuTnI troponin I (Beckman Coulter), high-sensitivity cardiac troponin T (hs-cTnT), ischemia-modified albumin, interleukin-6, investigation use only hs-cTnI (Beckman Coulter), N-terminal pro-B-type natriuretic peptide, and cardiac troponin I (Abbott AxSym). We followed patients until 72 h after presentation and determined whether they experienced the following serious cardiac outcomes: MI, heart failure, serious arrhythmia, refractory ischemic cardiac pain, or death. ROC curves were analyzed to determine the area under the ROC curve (AUC) and optimal cutoffs for the biomarkers. RESULTS: The AUCs for the hs-cTnI assay (0.86; 95% CI, 0.76-0.96), the AccuTnI assay (0.86; 95% CI, 0.78-0.95), and the hs-cTnT assay (0.82; 95% CI, 0.71-0.94) assays were significantly higher than those for the other 6 assays (AUC values≤0.71 for the rest of the biomarkers, P<0.05). The ROC curve-derived optimal cutoffs were ≥19 ng/L (diagnostic sensitivity, 80%; specificity, 88%), ≥0.018 µg/L (diagnostic sensitivity, 75%; specificity, 86%), and ≥32 ng/L (diagnostic sensitivity, 68%; specificity, 92%) for the hs-cTnI, AccuTnI, and hs-cTnT assays, respectively. CONCLUSIONS: The optimal cutoffs for predicting serious cardiac outcomes in this low-risk population are different from the published 99th percentiles. Larger studies are required to verify these findings.

Clinical evaluation of Ortho Clinical Diagnostics high-sensitivity cardiac Troponin I assay in patients with symptoms suggestive of acute coronary syndrome.

BACKGROUND: As more companies obtain regulatory approval for high-sensitivity cardiac troponin (hs-cTn) assays there is an urgent need for independent analytical and clinical evaluations. To this end, we have evaluated Ortho Clinical Diagnostics' hs-cTnI assay and compared it to their contemporary cTnI-ES assay in emergency department (ED) patients with suspected acute coronary syndrome (ACS). METHODS: The study cohort consisted of ED patients (n = 906) with symptoms suggestive of ACS who had Ortho hs-cTnI and cTnI-ES results at presentation and 3 h (with calculated delta (0-3 h) defined as the absolute concentration difference between paired results). The primary composite outcome was 7-day myocardial infarction (MI) or cardiovascular death, with secondary analyses performed for 7-day MI and index-MI. Analytical imprecision testing (i.e., coefficient of variation; CV), receiver-operating characteristic (ROC) curve analyses with area under the curve (AUC), and diagnostic parameters (sensitivity/specificity/predictive values) were calculated. RESULTS: The hs-cTnI assay had superior precision compared to the cTnI-ES assay below 5 ng/L in EDTA plasma (hs-cTnI CV ≤ 15% versus cTnI-ES CV ≥ 85%). The AUCs were higher for hs-cTnI as compared to cTnI-ES at 0 h (0.88 vs. 0.85), 3 h (0.94 vs. 0.92), and the delta (0-3 h) value (0.91 vs. 0.85) for the primary composite outcome (p < 0.05). At 3 h, the sensitivity/specificity for index-MI was ≥97%/≥82%, for 7-day MI was ≥89%/≥84%, and for the primary composite outcome was ≥90%/≥85% using the manufacturer's sex-specific 99th-percentile cutoffs. CONCLUSION: The Ortho hs-cTnI assay has superior analytical and clinical performance over their contemporary cTnI-ES assay in evaluating ED patients with symptoms suggestive of ACS.

Comparison of two biomarker only algorithms for early risk stratification in patients with suspected acute coronary syndrome.

BACKGROUND: We developed a biomarker algorithm encompassing the clinical chemistry score (CCS; which includes the combination of a random glucose concentration, an estimated glomerular filtration rate and high-sensitivity cardiac troponin; hs-cTn) with the Ortho Clinical Diagnostics hs-cTnI assay (CCS-serial) and compared it to the cutoffs derived from Ortho Clinical Diagnostics 0/1 h (h) algorithm for 7-day myocardial infarction (MI) or cardiovascular (CV)-death. METHODS: The study cohort was an emergency department (ED) population (n = 906) with symptoms suggestive of acute coronary syndrome (ACS) who had two Ortho hs-cTnI results approximately 3 h apart. Diagnostic parameters (sensitivity/specificity/negative predictive value; NPV/positive predictive value; PPV) were derived for the CCS-serial and the 0/1 h algorithm for 7-day MI/CV-death. A safety analysis was performed for patients in the rule-out arms of the algorithms for 30-day MI/death. RESULTS: The CCS-serial algorithm yielded 100% sensitivity/NPV (32% low-risk) and 95.7% specificity/65% PPV (11% high-risk). The 0/1 h algorithm-cutoffs yielded sensitivity/NPV/specificity/PPV of 97.8%/99.4%/91.3%/50%, which classified 38% of patients as low-risk and 16% of patients as high-risk. Four patients (1.2%) in the 0/1 h algorithm-cutoff rule-out arm had a 30-day MI/death outcome as compared to zero patients in the CCS-serial rule-out arm (p = 0.06). CONCLUSION: Both the CCS-serial and 0/1 h algorithm cutoffs yield high NPVs with a similar proportion of patients identified as low-risk. These data may be useful for sites who are unable to collect samples at 0/1 h in the emergency department.

Using the clinical chemistry score in the emergency department to detect adverse cardiac events: a diagnostic accuracy study.

BACKGROUND: The ability to rule out or in a major adverse cardiac event (MACE) in patients with suspected acute coronary syndrome at emergency department (ED) presentation would be beneficial to patient care and the health care system. The clinical chemistry score (CCS) was evaluated in this context. METHODS: This diagnostic accuracy study evaluated 2 different ED cohorts with suspected acute coronary syndrome. For patients in cohort 1, who presented to the ED of 3 hospitals in Hamilton, Ontario, between May and August 2013, retrospective measurements were taken using the Ortho Clinical Diagnostics high-sensitivity cardiac troponin I (hs-cTnI) assay; for patients in cohort 2, who presented to the ED of the same 3 hospitals in Hamilton between November 2012 and February 2013, an ED cardiac presentation blood test panel was performed with the Abbott Diagnostics hs-cTnI assay. The sensitivity and specificity of the CCS (cut-offs of ≥ 1 and 5) and hs-cTnI alone (published cut-offs) were compared for MACE (composite of death, myocardial infarction, unstable angina, revascularization) at 30 days for both cohorts and at 90 days for cohort 2. RESULTS: The incidence of MACE at 30 days was higher in cohort 1 (n = 1058) (19.4%, 95% confidence interval [CI] 16.8%-22.2%) than in cohort 2 (n = 5974) (14.6%, 95% CI 13.6%-15.6%). In cohort 1, a CCS of 1 or above yielded a sensitivity of 99.5% (95% CI 97.3%-99.9%). The sensitivity with an Ortho hs-cTnI cut-off of 1 ng/L or above was 91.2% (95% CI 86.5%-95.7%). The specificity of a CCS of 5 (97.8%, 95% CI 96.5%-98.7%) was higher than when the overall 99th-percentile cut-off for the Ortho hs-cTnI assay (> 11 ng/L; 90.1%, 95% CI 87.9%-92.0%) was used. A similar pattern was observed in cohort 2 at 30 days and persisted at 90 days with the Abbott hs-cTnI assay. INTERPRETATION: The CCS derived with 2 different hs-cTnI assays and ED populations yielded higher sensitivity and specificity estimates for MACE than hs-cTnI alone. An intervention study is needed to evaluate the impact of the CCS at both the patient and hospital levels. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01994577.

Utility of urine myoglobin for the prediction of acute renal failure in patients with suspected rhabdomyolysis: a systematic review.

BACKGROUND: Urine myoglobin continues to be used as a marker of rhabdomyolysis, particularly to assess risk of developing acute renal failure and evaluate treatment success. We sought to determine the predictive validity of urine myoglobin (uMb) for acute renal failure (ARF) in patients with suspected rhabdomyolysis. METHODS: We performed a broad systemic review of the literature from January 1980 to December 2006 using the search terms myoglobin$ AND (renal OR ARF OR kidney). Only primary studies published in English where uMb measurement was related to ARF were included. RESULTS: Of 1602 studies screened, 52 met all selection criteria. The studies covered a wide spectrum of etiologies for rhabdomyolysis, dissimilar diagnostic criteria for ARF and rhabdomyolysis, and various methods of uMb measurement and were mostly case series (n = 32). There was poor reporting on the uMb method, and 17 studies failed to provide any information about the method. The reporting of clinical criteria for ARF with respect to timing, description, performance, and interpretation also lacked adequate detail for replication. Eight studies (total 295 patients) had data for 2-by-2 tables. Sensitivity of the uMb test was 100% in 5 of the 8 studies, specificity varied widely (15% to 88%), and CIs around these measures were high. Pooling of data was not possible because of study heterogeneity. CONCLUSIONS: There is inadequate evidence evaluating the use of uMb as a predictor of ARF in patients with suspected rhabdomyolysis.

Selective photothermal killing of cancer cells using LED-activated nucleus targeting fluorescent carbon dots.

The development of effective theranostic probes in cancer therapy is hampered due to issues with selectivity and off-target toxicity. We report the selective LED-photothermal ablation of cervical (HeLa) cancer cells over human dermal fibroblasts (HDF) using a new class of green-emissive fluorescent carbon dots (FCDs). The FCDs can be easily prepared in one pot using cheap and commercial starting materials. Physico-chemical characterization revealed that a surface coating of 2,5-deoxyfructosazine on a robust amorphous core gives rise to the nanomaterial's unique properties. We show that intracellular uptake mostly involves passive mechanisms in combination with intracellular DNA interactions to target the nucleus and that cancer cell selective killing is likely due to an increase in intracellular temperature in combination with ATP depletion, which is not observed upon exposure to either the "naked" core FCDs or the surface components individually. The selectivity of these nanoprobes and the lack of apparent production of toxic metabolic byproducts make these new nanomaterials promising agents in cancer therapy.