Diagnostic performance of a point of care high-sensitivity cardiac troponin I assay and single measurement evaluation to rule out and rule in acute coronary syndrome.

OBJECTIVES: About 10 million individuals in USA presented annually in the emergency department (ED) with chest pain or with signs and symptoms of acute coronary syndrome (ACS). The advent of point of care (POC) devices, able to measure high sensitivity troponin, are a very interesting tool in the ED setting for its rapid turnaround time (<10 min). METHODS: The present study evaluates the diagnostic performance of the Atellica VTLi (Siemens) in real life setting using the clinical data derived from integrated diagnoses of emergency room staff and cardiologist and in comparison with standard laboratory hs-cTnT assay (Cobas 8000, Elecsys, Roche). 966 patients admitted to the emergency department of "G. Mazzini Hospital" in Teramo, Italy, from July 27, 2022, through June 09, 2023, were enrolled. RESULTS: The diagnostic performance of POC hs-cTnI was evaluated. An appropriate POC hs-cTnI threshold values <4 ng/L supplied a sensitivity and an NPV of 100 % (95 % CI: 99.5-100) in order to achieve rapid rule out for MI through a single measurement at patient presentation in the ED. Furthermore, a derivation POC hs-cTnI concentration >54 ng/L provided a specificity of 97.2 % (95 % CI: 95.9-98.1) and a PPV of 43.5 % (95 % CI: 40.3-46.7) for ruling in MI. CONCLUSIONS: This platform showed comparable diagnostic performance for myocardial infarction to the central laboratory. Our data suggest the possible use of the Atellica VTLi hs-cTnI POC assay either in emergency department of urban medical centre, either in rural hospital for triage and patient management.

Accelerated -Rule-Out of acute Myocardial Infarction using prehospital copeptin and in-hospital troponin: The AROMI study.

AIMS: The present acute myocardial infarction (AMI) rule-out strategies are challenged by the late temporal release of cardiac troponin. Copeptin is a non-specific biomarker of endogenous stress and rises early in AMI, covering the early period where troponin is still normal. An accelerated dual-marker rule-out strategy combining prehospital copeptin and in-hospital high-sensitivity troponin T could reduce length of hospital stay and thus the burden on the health care systems worldwide. The AROMI trial aimed to evaluate if the accelerated dual-marker rule-out strategy could safely reduce length of stay in patients discharged after early rule-out of AMI. METHODS AND RESULTS: Patients with suspected AMI transported to hospital by ambulance were randomized 1:1 to either accelerated rule-out using copeptin measured in a prehospital blood sample and high-sensitivity troponin T measured at arrival to hospital or to standard rule-out using a 0 h/3 h rule-out strategy. The AROMI study included 4351 patients with suspected AMI. The accelerated dual-marker rule-out strategy reduced mean length of stay by 0.9 h (95% confidence interval 0.7-1.1 h) in patients discharged after rule-out of AMI and was non-inferior regarding 30-day major adverse cardiac events when compared to standard rule-out (absolute risk difference -0.4%, 95% confidence interval -2.5 to 1.7; P-value for non-inferiority = 0.013). CONCLUSION: Accelerated dual marker rule-out of AMI, using a combination of prehospital copeptin and first in-hospital high-sensitivity troponin T, reduces length of hospital stay without increasing the rate of 30-day major adverse cardiac events as compared to using a 0 h/3 h rule-out strategy.

Assessment, Management and Quality of Care of Patients Presenting with Non-Traumatic Acute Chest Pain in the Emergency Room who had Acute Coronary Syndrome.

BACKGROUND: Non-traumatic Acute Chest pain (NTACP) is a common presentation in the emergency services of many hospitals and a key presenting symptom of acute coronary syndrome (ACS). However, there is a dearth of data on the system of care of ACS patients in our facilities. OBJECTIVE: Our objective was to evaluate the process of care of patients presenting with NTACP at a Tertiary Hospital emergency department (ED) in sub-Saharan Africa, using quality indicators of a universal chain of survival to identify any care gaps in the diagnosis and management of those with life-threatening ACS. METHODS: This was a retrospective cross-sectional study of adult patients ≥18 years of age, seen between July 2020 and June 2023 at the ED of the University College Hospital (UCH), Ibadan, Nigeria. We used this information to determine the frequency of ACS amongst those presenting with NTACP. From this subset, we assessed the main domains of quality indicators of the universal chain of survival in ACS care. These were, early symptom recognition and call for help; emergency medical service (EMS) evaluation and treatment; ED evaluation and treatment; and reperfusion therapy. RESULTS: We assessed a total of 4,306 patients who presented to the ED during the study period. Of these, 225 patients presented with NTACP. The mean ± SD age of these patients was 45.9 ± 18.4 years, with most between the ages of 40-49 years (20.9%) and males (50.7%). More than 80% of the patients presented to ED 12 hours after the onset of chest pain. Only 4.0% presented via an ambulance service which offered no prehospital guideline-directed medical treatment, and 70.7% were non-referred patients. Only 37.3%, 57.8%, 12.4%, and 8.9% had ECG, chest x-ray, echocardiography, and cardiac enzyme evaluation, respectively, in the acute phase of care. There were 29 (12.9%) patients who had a diagnosis of ACS. Two (6.9%) had medical revascularization with thrombolytic agents, while 8 (27.6%) and 19 (65.5%) were referred for primary and secondary PCI respectively. CONCLUSION: We found a high burden of late presentation and significant barriers to recommended guideline management of ACS patients, presenting with clinical features of NTACP in our hospital's ED.

CONTEXTE: La douleur thoracique aiguë non traumatique (NTACP) est une présentation courante dans les services d'urgence de nombreux hôpitaux et un symptôme clé du syndrome coronarien aigu (SCA). Cependant, il y a peu de données sur le système de soins des patients atteints de SCA dans nos établissements. OBJECTIF: Notre objectif était d'évaluer le processus de prise en charge des patients présentant une NTACP dans un service d'urgence d'un hôpital tertiaire en Afrique subsaharienne, en utilisant des indicateurs de qualité de la chaîne universelle de survie pour identifier les lacunes dans le diagnostic et la gestion de ceux présentant un SCA potentiellement mortel. MÉTHODES: Il s'agit d'une étude rétrospective transversale sur des patients adultes âgés de ≥18 ans, vus entre juillet 2020 et juin 2023 aux urgences de l'Hôpital Universitaire de l'Université d'Ibadan (UCH), Nigeria. Nous avons utilisé ces informations pour déterminer la fréquence du SCA parmi ceux présentant une NTACP. À partir de ce sous-ensemble, nous avons évalué les principaux domaines des indicateurs de qualité de la chaîne universelle de survie dans les soins du SCA. Ces domaines comprenaient la reconnaissance précoce des symptômes et l'appel à l'aide, l'évaluation et le traitement par les services médicaux d'urgence (SMU), l'évaluation et le traitement aux urgences, et la thérapie de reperfusion. RÉSULTATS: Nous avons évalué un total de 4 306 patients qui se sont présentés aux urgences au cours de la période d'étude. Parmi eux, 225 patients présentaient une NTACP. L'âge moyen ± écart-type de ces patients était de 45,9 ± 18,4 ans, la plupart ayant entre 40 et 49 ans (20,9%) et étant des hommes (50,7%). Plus de 80% des patients se sont présentés aux urgences 12 heures après le début de la douleur thoracique. Seulement 4,0% sont arrivés via un service d'ambulance qui n'a pas offert de traitement médical préhospitalier dirigé par des lignes directrices, et 70,7% étaient des patients non référés. Seuls 37,3%, 57,8%, 12,4% et 8,9% ont eu un ECG, une radiographie thoracique, une échocardiographie et une évaluation des enzymes cardiaques, respectivement, dans la phase aiguë des soins. Vingt-neuf patients (12,9%) ont été diagnostiqués avec un SCA. Deux (6,9%) ont subi une revascularisation médicale avec des agents thrombolytiques, tandis que 8 (27,6%) et 19 (65,5%) ont été référés pour une ICP primaire et secondaire, respectivement. CONCLUSION: Nous avons constaté une forte prévalence de présentation tardive et des obstacles significatifs à la gestion recommandée par les lignes directrices des patients atteints de SCA, se présentant avec des caractéristiques cliniques de NTACP dans les urgences de notre hôpital. MOTS CLÉS: Qualité des soins, Douleur thoracique non traumatique, Syndrome coronarien aigu, Troponines, Reperfusion, Intervention coronarienne percutanée, Département/salle d'urgence, Protocoles de diagnostic, Assurance santé.

Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain using Point of Care Testing (WESTCOR-POC): study design.

OBJECTIVES: Patients presenting with symptoms suggestive of acute coronary syndrome (ACS) contribute to a high workload and overcrowding in the Emergency Department (ED). Accelerated diagnostic protocols for non-ST-elevation myocardial infarction have proved challenging to implement. One obstacle is the turnaround time for analyzing high-sensitivity cardiac troponin (hs-cTn). In the WESTCOR-POC study (Clinical Trials number NCT05354804) we aim to evaluate safety and efficiency of a 0/1 h hs-cTn algorithm utilizing a hs-cTnI point of care (POC) instrument in comparison to central laboratory hs-cTnT measurements. DESIGN: This is a prospective single-center randomized clinical trial aiming to include 1500 patients admitted to the ED with symptoms suggestive of ACS. Patients will receive standard investigations following the European Society of Cardiology 0/1h protocols for centralized hs-cTnT measurements or the intervention using a 0/1h POC hs-cTnI algorithm. Primary end-points are 1) Safety; death, myocardial infarction or acute revascularization within 30 days 2) Efficiency; length of stay in the ED, 3) Cost- effectiveness; total episode cost, 4) Patient satisfaction, 5) Patient symptom burden and 6) Patients quality of life. Secondary outcomes are 12-months death, myocardial infarction or acute revascularization, percentage discharged after 3 and 6 h, total length of hospital stay and all costs related to hospital contact within 12 months. CONCLUSION: Results from this study may facilitate implementation of POC hs-cTn testing assays and accelerated diagnostic protocols in EDs, and may serve as a valuable resource for guiding future investigations for the use of POC high sensitivity troponin assays in outpatient clinics and prehospital settings.

Separation sign: novel ultrasound sign for ruling out diagnosis of placenta accreta spectrum.

OBJECTIVE: To assess the performance of the 'separation sign' as a predictor of normal placental separation in a large cohort of women at risk for placenta accreta spectrum (PAS) and in a high-risk subgroup with placenta previa or anterior low-lying placenta and at least one previous Cesarean delivery. METHODS: This was a prospective study of women at risk for PAS referred to a specialist clinic at between 22 and 38 weeks' gestation. All women underwent ultrasound assessment for the presence of the separation sign, which detects the difference in elasticity between the myometrium and the placenta, characterized by different rates of rebound after an ultrasound probe is used to apply pressure over the uteroplacental interface. When the sign is positive, the placenta appears to move relative to the myometrium, leading to the appearance or enhancement of the clear zone. The predictive performance of the separation sign for normal spontaneous placental separation at delivery was assessed. RESULTS: Of the 194 included women, 163 had a positive separation sign, all of whom went on to have normal placental separation at delivery. Of the 24 women with a negative separation sign, three (12.5%) had normal placental separation and 21 (87.5%) were diagnosed with PAS. This yielded a sensitivity of 98.2% (95% CI, 94.8-99.6%) and specificity of 100% (95% CI, 83.9-100%). In the high-risk cohort (n = 35), a positive separation sign remained a reliable predictor of normal placental separation, with a positive predictive value of 100%, sensitivity of 88.9% (95% CI, 65.3-98.6%) and specificity of 100% (95% CI, 80.5-100%). CONCLUSIONS: The separation sign could be a useful tool in women considered to be at risk for PAS, as it can facilitate the prediction of normal placental separation at delivery. This may prevent overtreatment, the associated iatrogenic morbidity and unnecessary allocation of clinical resources. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Validation of an artificial intelligence solution for acute triage and rule-out normal of non-contrast CT head scans.

PURPOSE: Non-contrast CT head scans provide rapid and accurate diagnosis of acute head injury; however, increased utilisation of CT head scans makes it difficult to prioritise acutely unwell patients and places pressure on busy emergency departments (EDs). This study validates an AI algorithm to triage patients presenting with Intracranial Haemorrhage (ICH) or Acute Infarct whilst also identifying a subset of patients as Normal, with the potential to function as a rule-out test. METHODS: In total, 390 CT head scans were collected from 3 institutions in the UK, US and India. Ground-truth labels were assigned by 3 FRCR consultant radiologists. AI performance, as well as the performance of 3 independent radiologists, was measured against ground-truth labels. RESULTS: The algorithm showed AUC values of 0.988 (0.978-0.994), 0.933 (0.901-0.961) and 0.939 (0.919-0.958) for ICH, Acute Infarct and Normal, respectively. Sensitivity/specificity for ICH and Acute Infarct were 0.988/0.925 and 0.833/0.927, respectively, compared to 0.907/0.991 and 0.618/0.977 for radiologists. AI rule-out of Normal scans achieved 0.93% negative predictive value (NPV) for the removal of 54.3% of Normal cases, compared to 86.8% NPV for radiologists. CONCLUSION: We show our algorithm can provide effective triage of ICH and Acute Infarct to prioritise acutely unwell patients. AI can also benefit clinical accuracy, with the algorithm identifying 91.3% of radiologist false negatives for ICH and 69.1% for Acute Infarct. Rule-out of Normal scans has huge potential for workload management in busy EDs, in this case removing 27.4% of all scans with no acute findings missed.

Improving the ACS Triage-Using High Sensitivity TroponinI and Copeptin for Early 'Rule-Out' of AMI.

Rule-out of acute myocardial infarction (AMI) in patients presenting with acute chest pain at the emergency department (ED) is a major challenge across the globe. Patients presenting very early with chest pain may provide a diagnostic challenge even when using a cardiac necrosis specific biomarker, high sensitivity troponin (hs-Tn) as they are elevated at 3-6 h after the symptom onset. Copeptin is a marker of acute hemodynamic stress which is released within few minutes of the occurrence of MI and is elevated immediately at the presentation of patients with AMI. This indicates a complementary pathophysiology and kinetics of these two biomarkers. Hence, we evaluated whether or not a protocol with combined testing of copeptin and hs-TnI at admission in patients presenting with chest pain within 6 h in low to intermediate risk and suspected ACS leads to an earlier diagnosis of AMI and thereby, aids to prevent a higher proportion of major adverse cardiac events than the current standard protocol followed in ED. A total of 148 patients as per the inclusion criterion were recruited for the study. The dual biomarker copeptin and hs-TnI allows a rule-out of AMI at presentation with a sensitivity of 100% and NPV of 99.8%. Hence, the use of dual biomarker in conjunction with clinical assessment may obviate the need for a prolonged stay in the ED and retesting hs-TnI after 2 h (for delta check) in more than two-thirds of the patients. The inclusion of these tests could have an impact on the economic burden of the ED without jeopardizing the outcome for the patient.

Whats new in 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST segment elevation?

The article sumarizes the 2020 ESC Guidelines for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation. The diagnostics of ACS consists in assessment of chest pain, EKG and cardiac troponin. Troponin should be evaluated by high sensitivity assay. 0h/1h algorithms should be used to rule-in or rule-out ACS. Patients with a positive troponin have higher risk of cardivascular events and mortality and the early invasive treatment should be applied in these patients. In the guidelines several antithrombotic stretegies for different clinical conditions are mentioned, where the cornerstone for the length and intensity of antithrombotic treatment is the evaluation of bleeding risk. Further on the revascularization aspects and strategies are debated in the guidelines. Finally there are mentioned two specific conditions of ACS - Myocardioal infarction with non-obstructive coronary arteries and Spontaneous coronary artery dissection.

Early Rule-Out Strategies in the Emergency Department Utilizing High-Sensitivity Cardiac Troponin Assays.

BACKGROUND: Over the past decade, intense collaboration between academic investigators and the diagnostic industry have allowed the integration of high-sensitivity cardiac troponin (hs-cTn) assays into clinical practice worldwide. The hs-cTn assays, with their increased diagnostic accuracy for acute myocardial infarction (AMI), have facilitated the maturation of early rule-out strategies. The first iteration was complex and required the combination of a biomarker panel, the electrocardiogram, and a clinical risk score and allowed the safe rule-out of AMI in only 10% of patients with acute chest pain. In contrast, the latest iterations, including the European Society of Cardiology (ESC) 0/1-h algorithm, are simple. They are based on hs-cTn concentrations only and allow the safe rule-out or rule-in of AMI in up to 75% of patients. CONTENT: The purposes of this minireview are (a) to describe the best validated hs-cTn-based strategies for early rule-out of AMI, (b) to discuss the advantages and limitations of the different strategies, (c) to identify patient subgroups requiring particular attention, (d) to recognize challenges for widespread clinical implementation, and (e) to provide guidance on strategies for their safe and effective clinical implementation. SUMMARY: Physicians and institutions may choose among several well-validated rule-out algorithms. The ESC 0/1-h algorithm for hs-cTnT or hs-cTnI seems to be the most attractive option today. It best balances safety and efficacy, and it has been derived and validated for all currently available hs-cTnT/I assays, facilitating widespread clinical implementation.

A neonate with metabolic acidosis: Intentional ethylene glycol poisoning.

We present a rare case of the intentional poisoning of a neonate. An 8-day old child presented to an academic pediatric emergency department (ED) with respiratory distress and decreased intake. In the ED the patient was stabilized, and workup uncovered an anion gap metabolic acidosis. Blood, urine, and CSF cultures were negative at 48 h and a metabolic screen revealed elevated glycine. Calcium oxalate crystals were later found in the urinalysis, raising concern for ethylene glycol poisoning. The patient's father admitted to mixing antifreeze with the child's formula. The workup of an ill or distressed neonate should be methodical, ruling out sepsis, inborn errors of metabolism, cardiac disease, trauma, and less common etiologies such as intestinal catastrophes, renal or hepatic disease, neurologic disease, drug withdrawal, non-accidental trauma, formula mixing errors, and poisoning.

The triple rule out CT in acute chest pain: a challenge for emergency radiologists?

PURPOSE: To evaluate the feasibility of triple rule out computed tomography (TRO-CT) in an emergency radiology workflow by comparing the diagnostic performance of cardiovascular and general radiologists in the interpretation of emergency TRO-CT studies in patients with acute and atypical chest pain. METHODS: Between July 2017 and December 2019, 350 adult patients underwent TRO-CT studies for the assessment of atypical chest pain. Three radiologists with different fields and years of expertise (a cardioradiologist-CR, an emergency senior radiologist-SER, and an emergency junior radiologist-JER) retrospectively and independently reviewed all TRO-CT studies, by trans-axial and multiplanar reconstruction only. Concordance rates were then calculated using as reference blinded results from a different senior cardioradiologist, who previously evaluated studies using all available analysis software. RESULTS: Concordance rate was 100% for acute aortic syndrome (AAS) and pulmonary embolism (PE). About coronary stenosis (CS) for non-obstructive (<50%), CS concordance rates were 97.98%, 90.91%, and 97.18%, respectively, for CR, SER, and JER; for obstructive CS (>50%), concordance rates were respectively 88%, 85.7%, and 71.43%. Moreover, it was globally observed a better performance in the evaluation of last half of examinations compared with the first one. CONCLUSIONS: Our study confirm the feasibility of the TRO-CT even in an Emergency Radiology department that cannot rely on a 24/7 availability of a dedicated skilled cardiovascular radiologist. The "undedicated" radiologists could exclude with good diagnostic accuracy the presence of obstructive stenosis, those with a clinical impact on patient management, without needing time-consuming software and/or reconstructions.

An evaluation of the real world use and clinical utility of the Cxbladder Monitor assay in the follow-up of patients previously treated for bladder cancer.

BACKGROUND: Surveilling recurrent urothelial carcinoma (UC) requires frequent cystoscopy, which is invasive, expensive and time-consuming. An accurate urinary biomarker has the potential to reduce the number of cystoscopies required during post-treatment surveillance. OBJECTIVE: To audit the clinical utility of a new surveillance protocol incorporating the Cxbladder Monitor (CxbM) test in real-world practice. METHODS: Three hospitals implemented a new surveillance protocol. Patients were risk stratified, and then provided urine samples for CxbM testing. Low-risk CxbM-positive patients and all high-risk patients had cystoscopy at 2-3 months. Low-risk CxbM-negative patients had cystoscopy at ~ 12 months. RESULTS: 443 CxbM tests were conducted on samples from 309 patients: 257 (83.2%) low-risk and 52 (16.8%) high-risk. No pathology-confirmed recurrences were seen in low-risk CxbM-negative patients (n = 108) during the first post-CxbM cystoscopy undertaken a mean ± SD 10.3 ± 3.9 months after testing. Three recurrences were detected during cystoscopy at 2.7 ± 3.4 months in 53 low-risk CxbM-positive patients. In 49 high-risk patients, 39 (79.6%) were CxbM-negative with no pathology-confirmed recurrences. Ten high-risk patients (20.4%) were CxbM-positive with four confirmed recurrences; 2 high-grade and 2 low-grade. The median time to first cystoscopy was 12.13 (95% CI: 11.97-12.4) months in patients with a CxbM-negative result versus 1.63 (95% CI: 1.13-2.3) months in patients with a CxbM-positive result (p < 0.00001). No positive cases were missed, no patients progressed to invasive or metastatic disease, and no patient died of cancer over 35 months of follow-up. CONCLUSIONS: CxbM accurately identified a high proportion of patients (77.8%) who were safely managed with only one cystoscopy per year. Including CxbM in the protocol for patient surveillance provided clinical utility by reducing the average number of annual cystoscopies by approximately 39%, thereby sparing patients the potential discomfort and anxiety, without compromising detection rates. No advantage was observed for risk stratification prior to CxbM.

Early identification of patients with chest pain at very low risk of acute myocardial infarction using clinical information and ECG only.

BACKGROUND: A considerable proportion of patients with angina-like symptoms in an emergency department have very low pretest probability for acute myocardial infarction (AMI). Numerous algorithms exist for the exclusion of AMI, usually including laboratory tests. We aimed to investigate whether patients with very low risk can safely be identified by ECG and clinical information without biomarker testing, contributing to saving time and costs. METHODS: Prospective diagnostic test accuracy study. We included all consecutive patients presenting with angina at the department of emergency medicine of a tertiary care hospital during a 1-year period. Using clinical information without biomarker testing and ECG, the "Mini-GRACE score," based on the well-established GRACE-score without using laboratory parameters was calculated. In a cohort design we compared the index test Mini-GRACE to AMI as reference standard in the final diagnosis using standard measures of diagnostic test accuracy. RESULTS: We included 2755 patients (44% female, age 44 ± 17 years). AMI was diagnosed in 103 (4%) patients, among those 44% with STEMI. Overall 2562 patients (93%) had a negative "Mini-GRACE," four (0.2%) of these patients had myocardial infarction, and this results in a sensitivity of 96.1% (95% CI 90.4%-98.9%), specificity 96.5% (95.7%-97.1%), positive predictive value 51.3% (46.3%-56.3%) and negative predictive value 99.8% (99.6%-99.9%). Model performance according to C statistic (0.90) and Brier score (0.0045) was excellent. In rule-out patients 30-day mortality was 0.3% and 1-year mortality was 0.8%. CONCLUSIONS: Patients with very low risk of AMI can be identified with high certainty using clinical information without biomarker testing and ECG. Cardiac biomarkers might be avoided in such cases, potentially leading to a significant cost reduction.

Soluble fms-like tyrosine kinase-1 to placental growth factor ratio: ruling out pre-eclampsia for up to 4 weeks and value of retesting.

OBJECTIVES: The soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is generally elevated some time before and at the clinical onset of pre-eclampsia. The PROGNOSIS study validated a sFlt-1/PlGF ratio cut-off of ≤ 38 to rule out the onset of pre-eclampsia within 1 week of testing in women with suspected disease. The aim of this study was to assess the predictive value of the sFlt-1/PlGF ratio to rule out the onset of pre-eclampsia for up to 4 weeks, and to assess the value of repeat measurements. METHODS: This was an exploratory post-hoc analysis of data from the PROGNOSIS study performed in pregnant women aged ≥ 18 years with suspected pre-eclampsia, who were at 24 + 0 to 36 + 6 weeks' gestation at their first clinic visit. Serum samples were collected at the first visit and weekly thereafter. sFlt-1 and PlGF levels were measured using Elecsys® sFlt-1 and PlGF immunoassays. Whether the sFlt-1/PlGF ratio cut-off of ≤ 38 used to rule out the onset of pre-eclampsia within 1 week could predict the absence of pre-eclampsia 2, 3, and 4 weeks post-baseline was assessed. The value of repeat sFlt-1/PlGF testing was assessed by examining the difference in sFlt-1/PlGF ratio 2 and 3 weeks after the first measurement in women with, and those without, pre-eclampsia or adverse fetal outcome. RESULTS: On analysis of 550 women, sFlt-1/PlGF ratio ≤ 38 ruled out the onset of pre-eclampsia 2 and 3 weeks post-baseline with high negative predictive values (NPV) of 97.9% and 95.7%, respectively. The onset of pre-eclampsia within 4 weeks was ruled out with a high NPV (94.3%) and high sensitivity and specificity (66.2% and 83.1%, respectively). Compared with women who did not develop pre-eclampsia, those who developed pre-eclampsia had significantly larger median increases in sFlt-1/PlGF ratio at 2 weeks (∆, 31.22 vs 1.45; P < 0.001) and at 3 weeks (∆, 48.97 vs 2.39; P < 0.001) after their initial visit. Women who developed pre-eclampsia and/or adverse fetal outcome compared with those who did not had a significantly greater median increase in sFlt-1/PlGF ratio over the same period (∆, 21.22 vs 1.40; P < 0.001 at 2 weeks; ∆, 34.95 vs 2.30; P < 0.001 at 3 weeks). CONCLUSION: The Elecsys® immunoassay sFlt-1/PlGF ratio can help to rule out the onset of pre-eclampsia for 4 weeks in women with suspected pre-eclampsia. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain-the WESTCOR study: study design.

Objectives. The main aim of the Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain (WESTCOR-study) (Clinical Trials number NCT02620202) is to improve diagnostic pathways for patients presenting to the Emergency department (ED) with acute chest pain. Design. The WESTCOR-study is a two center, cross-sectional and prospective observational study recruiting unselected patients presenting to the ED with suspected non-ST elevation acute coronary syndrome (NSTE-ACS). Patient inclusion started September 2015 and we plan to include 2250 patients, finishing in 2019. The final diagnosis will be adjudicated by two independent cardiologists based on all available information including serial high sensitivity cardiac troponin measurements, coronary angiography, coronary CT angiography and echocardiography. The study includes one derivation cohort (N = 985) that will be used to develop rule out/rule in algorithms for NSTEMI and NSTE-ACS (if possible) using novel troponin assays, and to validate established NSTEMI algorithms, with and without clinical scoring systems. The study further includes one subcohort (n = 500) where all patients are examined with coronary CT angiography independent of biomarker status, aiming to assess the associations between biomarkers and the extent and severity of coronary atherosclerosis. Finally, an external validation cohort (N = 750) will be included at Stavanger University Hospital. Prospective studies will be based on the merged cohorts. Conclusion. The WESTCOR study will provide new diagnostic algorithms for early inclusion and exclusion of NSTE-ACS and insights in the associations between cardiovascular biomarkers, CT-angiographic findings and short and long-term clinical outcomes.

Low-grade squamous intraepithelial lesion, cannot rule out high-grade lesion: Diagnosis, histological outcomes and human papillomavirus results.

BACKGROUND: The 2014 Bethesda System for Reporting Cervical Cytology classifies squamous intraepithelial lesions (SILs) of cervix into two main categories: low-grade SIL (LSIL) and high-grade SIL (HSIL). In some clinical practices, the LSIL cannot rule out high-grade lesion (LROH) interpretive category is used in cases with LSIL and findings that may raise the possibility of HSIL. Our purpose is to assess follow-up histopathology and high-risk human papillomavirus (hrHPV) results in patients with LROH, in comparison with LSIL, atypical squamous cells, cannot rule out HSIL (ASC-H), and HSIL in our institution. DESIGN: Cervical Papanicolaou tests with LROH, LSIL, ASC-H and HSIL interpretation, surgical follow-up, and hrHPV status were retrieved from the computer database from May 2014 to December 2016. RESULTS: Of 109 963 total Papanicolaou tests, LROH comprised 0.3%, LSIL 3.1%, ASC-H 0.2% and HSIL 0.4%. Only 3272 cases with surgical diagnoses were included in the study. The most common histological outcome for ASC-H was cervical intraepithelial neoplasia (CIN)2/3 (32.6%); LSIL was CIN 1 (45.7%); LROH was CIN 1 (46.7%) and HSIL was CIN 2/3 (64.4%). For LROH and LSIL, 31.1% and 7.5% respectively, had CIN 2/3. Approximately 79% of cases were hrHPV positive. Of LROH cases with surgical follow-up, 86.9% tested hrHPV positive, accounting for the second most common positive group after HSIL (92.6%). CONCLUSION: In our study cohort, LROH interpretation is associated with a higher number of CIN 2 or higher lesions on follow-up compared to patients with LSIL (P < 0.0001), and is associated with a significant percentage of positive other hrHPV, supporting LROH as a useful diagnostic category that triggers appropriate follow-up in affected women.

Direct Comparison of 4 Very Early Rule-Out Strategies for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin I.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 P=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 (P<0.01 for LOD versus each of the other strategies). CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.

The objective CORE score allows early rule out in acute chest pain patients.

OBJECTIVES: Chest pain is a common complaint in the emergency department (ED), and it is a challenge to identify low-risk chest pain patients eligible for early discharge. We aimed to develop a simple objective decision rule to exclude 30-day major adverse cardiac events (MACE) in ED chest pain patients. DESIGN: We analyzed prospectively included patients presenting with chest pain. Low risk patients were identified with the clinical objective rule-out evaluation (CORE). CORE was based on high sensitivity cardiac troponin T (hs-cTnT) tests at ED presentation (0 h) and 2 h later together with a simplified risk score consisting of four objective variables: age ≥65 years and a history of arterial disease, hypertension or diabetes. For the patient to be classified as low risk in the CORE rule, hs-cTnT had to be ≤14 ng/L both at 0 and 2 h, and the sum of the risk score had to be 0. The primary outcome was MACE within 30 days. RESULTS: Among the 751 patients in the final analysis, 90 (11.9%) had a MACE. CORE identified 248 (33%) of patients as low risk with a sensitivity of 98.9% (CI 93.1-99.9) and a negative predictive value of 99.6% (95% CI 97.4-100) for 30-day MACE. Adding the ED physician's interpretation of the ECG to CORE did not improve diagnostic performance. CONCLUSION: A simple objective decision rule (CORE) identified one-third of all patients as having a very low 30-day risk of MACE. These patients may potentially be discharged without additional investigations for acute coronary syndrome.

Role of Clinical Decision Tools in the Diagnosis of Pulmonary Embolism.

OBJECTIVE: The purpose of this article is to describe the importance of clinical decision rules for pretest assessment of the probability of the presence of pulmonary embolism (PE), the effect of use of the rules on the yield of pulmonary CT angiography, and obstacles to implementation of the rules in clinical practice. CONCLUSION: Pulmonary CT angiography is the imaging modality of choice for evaluating patients with suspected PE. Despite increased use of pulmonary CTA, the diagnostic yield for PE remains low. Study results suggest a potential benefit to the use of clinical decision tools in the diagnostic workup of suspected PE.