Exclusion Of Pulmonary Embolism Research Articles

Clinical observation of the long-term course of COVID- 19 infection in a patient with an immunodeficiency condition

The new coronavirus infection caused by the SARS-CoV-2 virus has become a real challenge for the world’s population. Despite the fact that vaccines have been developed and the effectiveness of antiviral drugs has been demonstrated, COVID-19 continues to be an urgent problem. SARS-CoV-2 is genetically modified due to the accumulation of mutations, new strains with high virulence appear that distort the immune response. In addition, it has been shown that the virus can persist in the body for a long time, which ensures the maintenance of an inflammatory response and causes the persistence and recurrence of symptoms after acute infection, especially in certain groups of patients. The article presents a clinical case of a long-term course of new coronavirus infection with predominant lung damage in the form of interstitial changes and persistent inflammation for 7 months from the moment of diagnosis against the background of an immunodeficiency condition due to the patient’s lymphoma in remission after polychemotherapy, exclusion of pulmonary embolism and progression of lymphoproliferative disease. The article highlights the difficulties of determining the criteria for a post-COVID and the features of its treatment using long-term therapy with systemic glucocorticosteroids, inhalation administration of tauractant (Surfactant-BL) in comparison with the dynamic assessment of total ventilation disorders and dynamic control of MSCT of the chest organs. Thus, the importance of identifying risk factors for the progression of COVID-19-associated conditions in patients with different comorbid backgrounds and identifying criteria for the development of new long-COVID treatment strategies is emphasized.

Cost-effectiveness of modified diagnostic strategy to safely rule-out pulmonary embolism in the emergency department: a non-inferiority cluster crossover randomized trial (MODIGLIA-NI)

BackgroundThe aim of this trial-based economic evaluation was to assess the incremental costs and cost-effectiveness of the modified diagnostic strategy combining the YEARS rule and age-adjusted D-dimer threshold compared with the control (which used the age-adjusted D-dimer threshold only) for the diagnosis of pulmonary embolism (PE) in the Emergency Department (ED).MethodsEconomic evaluation from a healthcare system perspective alongside a non-inferiority, crossover, and cluster-randomized trial conducted in 16 EDs in France and two in Spain with three months of follow-up. The primary endpoint was the additional cost of a patient without failure of the diagnostic strategy, defined as venous thromboembolism (VTE) diagnosis at 3months after exclusion of PE during the initial ED visit. Mean differences in 3-month failure and costs were estimated using separate generalized linear-regression mixed models, adjusted for strategy type, period, and the interaction between strategy and period as fixed effects and the hospital as a random effect. The incremental cost-effectiveness ratio (ICER) was obtained by dividing the incremental costs by the incremental frequency of VTE.ResultsOf the 1,414 included patients, 1,217 (86%) were analyzed in the per-protocol analysis (648 in the intervention group and 623 in the control group). At three months, there were no statistically significant differences in total costs (€-46; 95% CI: €-93 to €0.2), and the failure rate was non inferior in the intervention group (-0.64%, one-sided 97.5% CI: -∞ to 0.21%, non-inferiority margin 1.5%) between groups. The point estimate of the incremental cost-effectiveness ratio (ICER) indicating that each undetected VTE averted in the intervention group is associated with cost savings of €7,142 in comparison with the control group. There was a 93% probability that the intervention was dominant. Similar results were found in the as randomized population.ConclusionsGiven the observed cost decrease of borderline significance, and according to the 95% confidence ellipses, the intervention strategy has a potential to lead to cost savings as a result of a reduction in the use of chest imaging and of the number of undetected VTE averted. Policy-makers should investigate how these monetary benefits can be distributed across stakeholders.ClinicaltrialsTrial registration number ClinicalTrials.gov Identifier: NCT04032769; July 25, 2019.

Using an age and fibrinogen levels adjusted D-dimer cutoff significantly improves the specificity of two equivalent D-dimer assays for excluding pulmonary embolism

ObjectivesOur single-center prospective study compared two methods of D-dimer determination used in the exclusion of pulmonary embolism: bioMérieux method, VIDAS® D-Dimer Exclusion™ II, and Diagnostica Stago method, STA®-Liatest® D-Di Plus. For each of these two methods, we calculated optimized variable cutoffs based on fibrinogen and/or age to improve the specificity of the methods. Patients – methods2530 patients admitted to the Emergency Department of the Brest University Hospital for suspected pulmonary embolism were included in this study. The comparison of the two methods was performed by calculating their different characteristics: sensitivity, specificity and negative predictive value for different cutoffs systems: fixed or age-adjusted according to Douma et al. An optimization of the variable cutoff according to age and fibrinogen was then performed. ResultsThe two methods VIDAS and STAGO are approximately equivalent in terms of performance even if the STAGO method presents a better specificity (57.1 %) at the fixed cutoff of 0.5 μg/mL. The adoption of age-adjusted, fibrinogen-adjusted or doubly-adjusted (age and fibrinogen) cutoffs, significantly improves the specificity of the tests without affecting their excellent sensitivity. These specificities peak respectively at 75.8 % and 76 % for the VIDAS and STAGO tests when using a doubly-adjusted, age and fibrinogen, cutoff, i.e. a gain in specificity of approximately 10 % compared with the age-adjusted cutoff of Douma et al. and of approximately 20 % compared with the fixed cutoff of 0.5 μg/mL. ConclusionAdopting an optimized variable cutoff based on fibrinogen and/or age significantly improves specificity of D-dimer methods for pulmonary embolism exclusion.

Development of a Machine Learning Model Using Electrocardiogram Signals to Determine Acute Pulmonary Embolism

Background. Patients with acute pulmonary embolism (PE) benefit from immediate initiation of anticoagulation but similar symptoms can come from clinical conditions for which anticoagulation can be detrimental. A method for immediate, bedside diagnosis or exclusion of PE is not available. Objective. To develop an artificial intelligence (AI) model enabling analysis of 12-lead electrocardiogram (ECG) to detect the presence of acute PE and the categories of acute PE with right ventricular strain (RVS). Methods. One cohort of patients was selected by using a newly developed highly accurate natural language processing (NLP) model to analyze radiology reports of CT angiogram (CTA) and ECG within 6 hours before or after CTA from Mayo Clinic enterprise sites consisting of three tertiary referral centers (Rochester, MN, Phoenix, AZ, and Jacksonville, FL) and regional Mayo Clinic Health System sites in MN, WI, and IA. We identified patients with acute PE, acute PE with RVS, acute saddle PE, and patients with no PE on the CTA. Another cohort consisted of consecutive patients with acute PE who were enrolled into the Mayo Thrombophilia Clinic Registry (TCR) between March 1, 2013 and May 31, 2022 and prospectively followed. For this group, AHA criteria were used to classify PE as massive, submassive, and low risk PE category which for this study was described as PE with no right ventricular dysfunction (NRVD). For this cohort, ECG performed within 24 hours before or after CTA was analyzed. We allocated patients with positive PE testing and negative PE to the training, internal validation, and testing datasets in a 7:1:2 ratio to develop and validate an AI-enabled algorithm using a convolutional neural network to detect the ECG signature of any acute PE, PE with RVS or saddle PE (RVS/SPE) and massive/submassive PE. We calculated the area under the curve of the receiver operating characteristic curve (AUROC) for the internal validation dataset to select a probability threshold, which we applied to the testing dataset. We evaluated model performance on the testing dataset by calculating the AUROC, accuracy, sensitivity, and specificity. Results. NLP identified a total of 80,432 patients with ECG performed within 6 hours before or after CTA who were not a part of the TCR. This cohort was subdivided into 79,894 consisting of acute PE and no PE and another group of 73,609 consisting of either acute PE with RVS/SPE, and no PE. In the former group, 7,423 (9.29%) had acute PE (mean age 63.7±15.9, 46.1% female), and in the latter group, 1,138 (1.55%) had acute PE with RVS/SPE (mean age 65.6±14.1, 45.7% female). Both groups had the same number of negative studies (72,471) for any PE (mean age 60.5±17.6, 52.3% female). Within the group of 4,818 TCR patients with acute venous thromboembolism, 1,007 had acute PE and ECG 24 hours before or after CTA (mean age 62.7±14.6, 43.8% female) including 44 with massive, 317 submassive, 508 NRVD, and 138 with subsegmental PE. For the TCR cohort, we created a control group from NLP identified cases with CTA negative for PE by selecting 6,774 patients that were matched (by age, sex) with acute PE cases from the TCR. The deep neural network prediction of acute PE in patients identified by NLP from Mayo Clinic sites to those without any PE was modest (AUROC 0.6929, see Figure 1). The sensitivity was 63.54% and specificity of 64.66%. This was associated with the positive predictive value (PPV) of 15.55% and high negative predictive value (NPV) of 94.54%. The performance of the deep neural network prediction for the presence of RVS/SPE to the group with negative testing for any PE was better (AUROC 0.8041). The sensitivity was 68.42% and specificity of 74.77%. This was associated with the PPV of 4.07% and NPV as high as 99.34%. The deep neural network prediction of any acute PE from TCR patients was similar to the NLP selected cohort from Mayo Clinic sites (AUROC 0.6756). The sensitivity was 54.95% and specificity of 69.70%. This was associated with the PPV of 21.18% and NPV of 91.26%. Prediction of massive or submassive PE from the TCR group was very well demonstrated within the TCR group (Figure 2). Conclusions. The AI-based analysis of 12-lead ECG shows modest detection power for acute PE, but is accurate for high risk PE detection. Moreover, it provides a fast and very reliable way to exclude the presence of severe PE and therefore the need for immediate anticoagulation and fibrinolytic therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID‐19: The Swiss COVID‐HEP randomized clinical trial

BackgroundHospitalized patients with COVID‐19 suffered initially from high rates of venous thromboembolism (VTE), with possible associations between therapeutic anticoagulation and better clinical outcomes in observational studies. ObjectiveTo test whether therapeutic anticoagulation improves clinical outcomes in severe COVID‐19. Patients/MethodsIn this multicenter, open‐label, randomized controlled trial, we recruited acutely ill medical COVID‐19 patients with D‐dimer >1000 ng/ml or critically ill COVID‐19 patients in four Swiss hospitals, from April 2020 until June 2021, with a 30‐day follow‐up. Participants were randomized to in‐hospital therapeutic anticoagulation versus low‐dose anticoagulation in acutely ill participants/intermediate‐dose anticoagulation in critically ill participants, with enoxaparin or unfractionated heparins. The primary outcome was a centrally adjudicated composite of 30‐day all‐cause mortality, VTE, arterial thrombosis, and disseminated intravascular coagulopathy (DIC), with screening for proximal deep vein thrombosis. ResultsAmong 159 participants, 55.3% were critically ill and 94.3% received corticosteroids. Before study inclusion, pulmonary embolism had been excluded in 71.7%. The primary outcome occurred in 4/79 participants randomized to therapeutic anticoagulation and 4/80 to low/intermediate anticoagulation (5.4% vs. 5.0%; risk difference +0.4%; adjusted hazard ratio 0.76, 95% confidence interval 0.18–3.21), including three deaths in each group. All primary outcomes and major bleeding (n = 3) occurred in critically ill participants. There was no asymptomatic proximal deep vein thrombosis and no difference in major bleeding. ConclusionsAmong patients with severe COVID‐19 treated with corticosteroids and with exclusion of pulmonary embolism at hospital admission for most, risks of mortality, thrombotic outcomes, and DIC were low at 30 days. The lack of benefit of therapeutic anticoagulation was too imprecise for definite conclusions.

ОСОБЕННОСТИ ЛАБОРАТОРНЫХ ПОКАЗАТЕЛЕЙ ВОСПАЛЕНИЯ И ТРОМБОЗА У ПАЦИЕНТОВ С НОВОЙ КОРОНАВИРУСНОЙ ИНФЕКЦИЕЙ SARS-COV-2 И ТРОМБОЭМБОЛИЕЙ ЛЕГОЧНОЙ АРТЕРИИ

Introduction. The COVID-19 pandemic continues with over 600 million cases and over 6 million deaths worldwide according to WHO. The state of hypercoagulation is a key feature of the course of COVID-19 which often leads to the development of serious cardiovascular events and adverse outcomes. There is a higher risk of all-cause mortality in the COVID-19 cohort with thrombotic complications, and mortality among patients with COVID-19 and PE is significantly higher than in patients with either condition alone, indicating a life-threatening additive effect of the combination of COVID-19 and PE. Thus, it is necessary to study further the features of inflammation and thrombosis parameters in patients with COVID-19 given the high prevalence of thrombotic complications among this group of patients. Objective. To define features of inflammation and thrombosis laboratory markers in patients with COVID-19 and pulmonary embolism. Materials and Methods. The study included n = 116 patients with COVID-19 hospitalized in 4-th city clinical hospital of Minsk named after N.E.Sauchenko in whom a thrombotic event – pulmonary embolism (PE) – was developed. The mean age of the patients was 64.7 ± 11.3 years, with 53 (45.7%) male and 63 (54.3%) female patients, respectively. The study group consisted of patients with COVID-19 and confirmed diagnosis of PE (n = 37) and the comparison group consisted of patients with COVID-19 without PE (n = 79). Patients in the groups were comparable by sex, age, presence of traditional risk factors, and COVID-19 severity. The parameters associated with thrombosis were analyzed in general blood count, hemostasiogram, biochemical blood analysis at the moment of confirmation or exclusion of PE using computer tomographic angiography of the pulmonary arteries. Results. Intergroup comparison of laboratory parameters in the group of patients with COVID-19 and confirmed diagnosis of PE in comparison with the group of patients with COVID-19 without PE showed a significantly higher mean group leukocyte count: 10,59 (6,75-12,6)×109/L versus 7,12 (4,50-9,08)×109/L (U = 96,5; p < 0,05); significantly higher mean group level of C-reactive protein: 120.09 (45.08-164.38) mg/L versus 54.89 (31.14-96.86) mg/L (U = 101.0; p < 0.05); group mean fibrinogen and D-dimer were significantly higher: 7.03 (5.89-8.28) g/L versus 5.98 (4.25-6.80) g/L (U = 99.0; p < 0.05) and 2058.5 (826.0-4026.0) ng/mL versus 982.5 (656.5-1936.0) ng/mL (U = 141.5; p < 0.05) respectively. A higher proportion of individuals with increased prothrombin time was identified: 75.5% (n = 28) versus 32.9% (n = 26) (χ2 = 6.31; p < 0.05). In patients with COVID-19 and PE there was a direct moderate relationship between CRP and D-dimer values (ρ = 0.66; p < 0.05), a direct moderate relationship between CRP and fibrinogen values (ρ = 0.61; p < 0.05). Conclusion. Patients with new coronavirus infection COVID-19 and PE had a marked increase of inflammatory and thrombotic markers (leukocyte count, CRP, fibrinogen, D-dimer). The relationship between the values of CRP, fibrinogen, D-dimer indicates the association of inflammation with the thrombosis markers level.

Safety and Efficiency of Diagnostic Strategies for Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups : A Systematic Review and Individual-Patient Data Meta-analysis.

How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. MEDLINE from 1 January 1995 until 1 January 2021. 16 studies assessing at least 1 diagnostic strategy. Individual-patient data from 20553 patients. Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE considered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probability-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresholds, with failure rates varying between 2% and 4% in the predefined patient subgroups. Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verification bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds. Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds. Dutch Research Council. (PROSPERO: CRD42018089366).

Diagnostic Accuracy of D-Dimer for Pulmonary Embolism and Lower Limb Deep Vein Thrombosis Testing in People with Cancer: A Meta-Analysis

IntroductionThere are evidence-based protocols for the diagnosis and exclusion of pulmonary embolism (PE) and deep vein thrombosis (DVT) which include clinical probability scoring along with selective D-dimer testing and diagnostic imaging. D-dimer assessment in VTE (venous thromboembolism) testing tends to be omitted in patients with cancer, partly because of perceived D-dimer lack of sensitivity and specificity. The aim of this systematic review and meta-analysis was to report the diagnostic accuracy of D-dimer for PE and lower limb DVT in patients with cancer. This study was part of a research program to set International Society of Thrombosis and Haemostasis standards for VTE testing in patients with cancer.MethodsThis systematic review and meta-analysis followed the MOOSE guidelines and was registered in PROSPERO, CRD42020181007. We searched Medline via OVID from conception to 12 th March 2020 for diagnostic PE and DVT studies reporting on people with cancer, or a subgroup of people with cancer. Researchers in the field were contacted for information on unpublished studies. All languages were included. Two researchers screened the titles and abstracts. Four researchers reviewed the selected full texts to determine which studies fulfilled inclusion criteria. Two researchers assessed risk of bias using QUADAS-2, extracted data on the true positive, false positive, true negative and false negative results for D-dimer alone, and D-dimer combined with clinical probability estimation. We used the bivariate random effects method to meta-analyze sensitivity and specificity values. We used a random effects model to estimate pooled false negative rates and efficiency for combining a negative D-dimer (manufacturer recommended cutoff) with a low clinical probability to exclude PE or DVT in patients with cancer. Results were displayed on a Forest plot. Heterogeneity was assessed using I 2.ResultsFrom 7947 titles and abstracts, we reviewed 49 full text manuscripts, including 13 studies for analysis. Risk of bias was low across all domains for only 5/13 studies. Figures 1 shows the Forest plots grouped by sensitivity and specificity for PE and DVT. The pooled estimates for D-dimer in the diagnosis of VTE in cancer patients (regardless of clinical probability) were 96.4% (95% confidence interval (CI) 94.8 to 97.5%) sensitivity and 26.4% (95% CI 18.1 to 37.0%) specificity. For PE, D-dimer was 96.9% (96.1 to 97.5%) sensitive (I 2 0%, N=2,299) and 14.0% (12.1 to 16.0%) specific, (I 2 69%, N=11,455). For DVT, D-dimer was 94.3% (89.8 to 97.6%) sensitive, (I 2 61%, N=546) and 46.4% (39.8 to 53.3%) specific, (I 2 59%, N=724). The efficiency of combining a low D-dimer (using the manufacturer recommended cutoff) and low clinical probability to exclude DVT or PE was 9.3%, (95% CI 6.9 to 11.9%), N=1,347. There were only 122 patients in the false negative rate analysis of whom 1 patient was diagnosed with VTE in follow up. A pooled analysis was not performed for the false negative rate.ConclusionsD-dimer is a sensitive test for both PE and lower limb DVT in people who have cancer. Approximately 10% of patients with cancer and suspected VTE can have VTE excluded with D-dimer and clinical probability prior to ordering diagnostic imaging. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Excluding Pulmonary Embolism with End-tidal Carbon Dioxide: Accuracy, Cost, and Harm Avoidance.

A non-randomized single center prospective, descriptive, correlational design was used to determine what end-tidal carbon dioxide (EtCO2) level provided the best sensitivity, specificity, and negative predictive value to exclude pulmonary embolism (PE) diagnosis in hemodynamically stable hospitalized adults (n = 111). The financial impact and harm avoidance of adding EtCO2 to the PE diagnostic process also were examined. PE diagnosis was determined by computed tomography pulmonary angiography (CTPA). PE prevalence was 18.9%. Mean±SD EtCO2 was lower for PE positive than negative participants (28 ± 7.8 to 33 ± 8.1 mmHg respectively 95% CI: 1.22-8.96; P = .01). For PE exclusion, an EtCO2 cutoff ≥42 mmHg yielded 100% sensitivity, 12.2% specificity, and 100% negative predictive value. For every six inpatients assessed with EtCO2, one could be saved from unnecessary CTPA. Eliminating unnecessary CTPA removes the potential harm associated with radiation and intravenous contrast exposure. Additionally, an EtCO2 cutoff ≥42 mmHg could eliminate ~$88,000/year in healthcare waste at this institution.

Update of national diagnostic reference levels for adult CT in Switzerland and assessment of radiation dose reduction since 2010.

To update the national diagnostic reference levels (DRLs) for adult CT in Switzerland using dose management software and to compare them to the previous Swiss DRLs from 2010. CT dose data from 14 radiological institutes with a total of 50 CT scanners were collected with locally installed dose management software between 2014 and 2017. Data were assigned to 15 defined master protocols. Data cleaning steps were developed and adjusted individually for each participating institute and protocol. The DRLs for each master protocol were calculated as the 75th percentile of the distribution of the median volume computed tomography dose index (CTDIvol) and dose-length product (DLP) values per CT scanner. In total, 220,269 CT exams were available after data cleaning. Updated DRLs showed a clear trend towards lower doses compared with previous DRLs. The average relative change in the DRLs for CTDIvol was - 30% (0 to - 47%) and - 22% for DLP (+ 20 to - 40%). The largest relative decrease in the DRL for DLP was observed for the cervical spine protocol (- 40%), the two chest protocols (chest, - 37%; and exclusion of pulmonary embolism, - 33%), and the two neck protocols (neck, - 32%; and carotid angiography, - 28%). The DRLs for other protocols, for example the head and the abdomen-pelvis protocol, showed smaller relative changes (- 11% and - 17%). The updated national DRLs are substantially lower than the previous values from 2010, demonstrating technological progress and the efforts of the radiological community to lower CT radiation exposure. • Dose management software allows the establishment of DRLs based on big data. • Updated Swiss DRLs for adult CT are substantially lower compared with those from 2010. • Swiss DRLs are low compared with other national DRLs.

P5019Derivation and validation of a new probability score in pulmonary embolism suspicion allowing safely reduction of imaging testing: PEPS (Pulmonary Embolism Probability Score)

Abstract Background In pulmonary embolism (PE) suspicion, several strategies based on clinical criteria and D-dimer (Dd) measurement have been developed in order to reduce resource utilization. However, they used different clinical probability (CP) assessment methods limiting their combination. Purpose To develop and validate a unique probability score integrating most of previous proposals to allow safely reduction of imaging testing. Methods 4 CP levels were previously defined in order to obtain a false negative rate <1.9%: 1) without Dd test: very low CP (PE prevalence <1.9%), 2) with Dd <1000 μg/L: low CP (<15%), 3) with Dd <500 or age x10μg/L: moderate CP (<60%) and 4) precluding PE exclusion on Dd: high CP. We used individual data from 4 prospective cohorts of suspected PE patients in Europe and America (n=11 066) for derivation and internal validation. The variables significantly associated with PE in univariate analysis were included in a multivariate logistic regression model. Points were assigned according to the regression coefficients. The score was validated in two external independent cohorts (n=1554, n=1669). Results PEPS comprised 13 variables: age <50 years (−2), age 50–64 years (−1), heart rate <80 beats/min (−1), chronic lung disease (−1), chest pain and recent dyspnea (+1), syncope (+1), male sex (+1), previous venous thromboembolism (+2), medical or orthopaedic immobilization (+2), estrogenic treatment (+2), oxygen saturation <95% (+3), unilateral lower limb pain (+3) and PE is the most likely diagnosis (+ 5). The rates of false negative and avoidable imaging tests if the PEPS strategy would have been applied were 0.6% [95% CI: 0.3–1.1] and 22.7% [20.2–25.3] in the first external validation cohort, and 0.85 [0.5–1.45] and 26.6% [23.5–29.9] in the second one. Applied retrospectively, PEPS strategy compared favourably with other strategies and combinations. Derivation Int. validation Ext. validation 1 Ext. validation 2 nPE/N % [95% CI] nPE/N % [95% CI] nPE/N % [95% CI] nPE/N % [95% CI] TOTAL 615/5588: 11.0% [10.2–11.9] 432/3726: 11.6% [10.6–12.7] 327/1546: 21.2% [19.2–23.2] 196/1669: 11.7% [10.3–13.4] Very low CP PEPS<0 16/1445: 1.1% [0.7–1.8] 16/946: 1.7% [1.0–2.7] 3/118: 2.5% [0.7–6.8] 5/347: 1.4% [0.6–3.3] Low CP 0≤PEPS<5 127/2620: 4.9% [4.1–5.7] 106/1805: 5.9% [4.9–7.1] 49/611: 8.0% [6.1–10.4] 61/647: 7.2% [5.7–9.1] Moderate CP 5≤PEPS<12 347/1334: 26.0% [23.7–28.4] 243/867: 28.0% [25.1–31.1] 206/715: 28.8% [25.6–32.2] 107/430: 24.9% [21.0–29.2] High CP 12≤PEPS 125/179:69.8% [62.8–76.1] 67/108: 62.0% [52.6–70.6] 69/102: 67.7% [58.1–76.2] 23/45: 51.1% [37.0–65.0] AUC 0.84 [0.83–0.86] 0.82 [0.80–0.84] 0.79 [0.76–0.82] 0.77 [0.74–0.80] CP: Clinical probability; PEPS: Pulmonary Embolism Probability Score. Conclusions A strategy based on the proposed score may lead to a safely substantial reduction of imaging testing. It should now be tested in an outcome interventional study.

Diagnosis of Pulmonary Embolism During Pregnancy: A Multicenter Prospective Management Outcome Study.

Data on the optimal diagnostic management of pregnant women with suspected pulmonary embolism (PE) are limited, and guidelines provide inconsistent recommendations on use of diagnostic tests. To prospectively validate a diagnostic strategy in pregnant women with suspected PE. Multicenter, multinational, prospective diagnostic management outcome study involving pretest clinical probability assessment, high-sensitivity D-dimer testing, bilateral lower limb compression ultrasonography (CUS), and computed tomography pulmonary angiography (CTPA). (ClinicalTrials.gov: NCT00740454). 11 centers in France and Switzerland between August 2008 and July 2016. Pregnant women with clinically suspected PE in emergency departments. Pulmonary embolism was excluded in patients with a low or intermediate pretest clinical probability and a negative D-dimer result. All others underwent lower limb CUS and, if results were negative, CTPA. A ventilation-perfusion (V/Q) scan was done if CTPA results were inconclusive. Pulmonary embolism was excluded if results of the diagnostic work-up were negative, and untreated pregnant women had clinical follow-up at 3 months. The primary outcome was the rate of adjudicated venous thromboembolic events during the 3-month follow-up. 441 women were assessed for eligibility, and 395 were included in the study. Among these, PE was diagnosed in 28 (7.1%) (proximal deep venous thrombosis found on ultrasonography [n= 7], positive CTPA result [n= 19], and high-probability V/Q scan [n= 2]) and excluded in 367 (clinical probability and negative D-dimer result [n= 46], negative CTPA result [n= 290], normal or low-probability V/Q scan [n= 17], and other reason [n= 14]). Twenty-two women received extended anticoagulation during follow-up, mainly for previous venous thromboembolic disease. The rate of symptomatic venous thromboembolic events was 0.0% (95% CI, 0.0% to 1.0%) among untreated women after exclusion of PE on the basis of negative results on the diagnostic work-up. There were several protocol deviations, reflecting the difficulty of performing studies in pregnant women with suspected PE. A diagnostic strategy based on assessment of clinical probability, D-dimer measurement, CUS, and CTPA can safely rule out PE in pregnant women. Swiss National Foundation for Scientific Research, Groupe d'Etude de la Thrombose de Bretagne Occidentale, and International Society on Thrombosis and Haemostasis.

Aspects of pulmonary involvement in inflammatory bowel disease

The incidence of pulmonary manifestations of inflammatory bowel disease (IBD) appears to be much higher than previously assumed. In prospective studies, subclinical pulmonary interstitial infiltrates or pathological lung function were found in 40%-60% of IBD patients, both in children and adults. Pulmonary disorders can affect any part of the respiratory system, the most frequent pattern being inflammation of the large airways often associated with bronchiectasis. The differential diagnosis should include drug-related pulmonary disease and infectious causes when receiving immunosuppressive therapy. The diagnostic approach consists of athorough history and clinical status as well as lung function tests including body plethysmography and high-resolution computed tomography of the thorax. Bronchoscopy with broncheoalveolar lavage and sample collection for histology as well as exclusion of pulmonary embolism may be indicated. Pulmonary disease in association with IBD can develop at any time during the course of IBD: in rare cases, symptoms can evolve even before gastrointestinal symptoms appear. On the other hand, there are frequent reports on the occurrence of pulmonary inflammation after proctocolectomy in patients with ulcerative colitis. The pathophysiologic background is largely unknown, but there seems to be an interaction between gastrointestinal and pulmonary inflammation. The mainstay of therapy are inhaled or systemic corticosteroids. Most patterns of pulmonary involvement in IBD respond well to corticosteroid therapy. Rarely, serious and persisting complications occur, such as strictures or stenosis of the large airways.

Comparison of the age-adjusted and clinical probability-adjusted D-dimer to exclude pulmonary embolism in the ED

BackgroundDiagnosing pulmonary embolism (PE) in the emergency department (ED) can be challenging because its signs and symptoms are non-specific. ObjectiveWe compared the efficacy and safety of using age-adjusted D-dimer interpretation, clinical probability-adjusted D-dimer interpretation and standard D-dimer approach to exclude PE in ED patients. Design/methodsWe performed a health records review at two emergency departments over a two-year period. We reviewed all cases where patients had a D-dimer ordered to test for PE or underwent CT or VQ scanning for PE. PE was considered to be present during the emergency department visit if PE was diagnosed on CT or VQ (subsegmental level or above), or if the patient was subsequently found to have PE or deep vein thrombosis during the next 30 days. We applied the three D-dimer approaches to the low and moderate probability patients. The primary outcome was exclusion of PE with each rule. Secondary objective was to estimate the negative predictive value (NPV) for each rule. Results1163 emergency patients were tested for PE and 1075 patients were eligible for inclusion in our analysis. PE was excluded in 70.4% (95% CI 67.6–73.0%), 80.3% (95% CI 77.9–82.6%) and 68.9%; (95% CI 65.7–71.3%) with the age-adjusted, clinical probability-adjusted and standard D-dimer approach. The NPVs were 99.7% (95% CI 99.0–99.9%), 99.1% (95% CI 98.3–99.5%) and 100% (95% CI 99.4–100.0%) respectively. ConclusionThe clinical probability-adjusted rule appears to exclude PE in a greater proportion of patients, with a very small reduction in the negative predictive value.

Diagnosis and Exclusion of Pulmonary Embolism

BackgroundFailure to test for pulmonary embolism (PE) can be a lethal mistake, but PE and produces symptoms similar to many other diseases. Overtesting for PE has negative consequences. ObjectivesUse published evidence to create a rationale and safe diagnostic approach for ambulatory and emergency patients with suspected PE in 2017. FindingsPulmonary embolism need not be pursued in patients with no symptoms of PE in the present or recent history (dyspnea, chest pain, cough or syncope), and always normal vital signs. When clinicians have a low clinical suspicion for PE or a Wells score<2, they can reasonably exclude PE with the Pulmonary Embolism Rule out Criteria (PERC rule). For patients with a “PE-unlikely” pretest probability (Wells or simplified revised Geneva score<5), PE can be ruled out with a normal or age-adjusted D-dimer concentrations. Other patients should undergo pulmonary vascular imaging, and the choices are discussed, including computerized tomographic pulmonary angiography, planar and single-photon emission computed tomography (SPECT). ConclusionsA thoughtful algorithm for PE exclusion and diagnosis requires pretest probability assessment in all patients, followed by selective use of clinical criteria, the quantitative D-dimer, and pulmonary vascular imaging.

OC-7a: Imaging for the exclusion of pulmonary embolism in pregnancy – a Cochrane Systematic Review of diagnostic test accuracy

OC-7a: Imaging for the exclusion of pulmonary embolism in pregnancy – a Cochrane Systematic Review of diagnostic test accuracy

Volumetric capnography in the exclusion of pulmonary embolism at the emergency department: a pilot study

The analysis of the in expired air as a function of the exhaled volume (volumetric capnography) might result in a more specific exclusion tool for pulmonary embolism (PE) in addition to the Wells-score and D-dimer. A novel combination of volumetric capnography parameters () should be decreased in PE and could possibly be used to decrease the number of requested computed tomography pulmonary angiograms (CTPA). Volumetric capnography measurements were performed on consecutive patients seen in the emergency department for which, due to suspected PE (due to increased D-dimer level or Wells-score), a CTPA was ordered. A total of 30 subjects were included, of which in 13 PE was seen on CTPA. Median was 4.36 kPa (IQR 3.92–4.88) in the no PE group versus 4.07 kPa (IQR 3.37–4.39) in the PE group (p = 0.086). Median of the novel parameter was 1.85 min.kPa dl−1 (IQR 1.21–3.00) in the no PE group versus 1.18 min.kPa dl−1 (IQR 0.61–1.38) in the PE group (p = 0.006). Using a threshold for the new parameter of 1.90 min.kPa dl−1 or higher to exclude PE resulted in a negative predictive value of 100% (95% CI: 77%–100%) and would have potentially excluded PE in 47% (95% CI: 26%–69%) of the no PE group without the need for CTPA. This pilot study introduces a novel parameter which is significantly decreased in PE subjects. Future studies regarding validation and addressing aspects such as reproducibility and normalization after treatment are needed to confirm its usability in excluding PE in the emergency department.

Potential utility of a renal function adjusted D-dimer cut-off value for improving the exclusion of pulmonary embolism

To evaluate the potential utility of a renal function adjusted D-dimer cut-off value for improving the exclusion of pulmonary embolism. Retrospective analyses were performed for 1 784 inpatients and outpatients with low and moderate probability of pulmonary embolism at Anzhen Hospital from January 2011 to June 2013. The Well's score was used. The diagnoses of pulmonary embolism were confirmed by computed tomography pulmonary angiogram and ventilation-perfusion scan. Based upon estimated glomerular filtration rate (GFR), they were divided into three subgroups of normal renal function, mild renal impairment and moderate renal impairment. Negative D-dimer was defined as a level of age-standardized D-dimer value<500 µg/L. The proportions of patients with negative D-dimer and the utility of D-dimer for ruling out pulmonary embolism were compared between three subgroups. A new D-dimer cut-off point in patients with renal impairment was developed by receiver operating characteristics (ROC) curves and the effect of diagnostic efficiency of ruling out pulmonary embolism with renal function adjusted D-dimer cut-off was assessed. The medians of D-dimer of three subgroups with normal renal function, mild renal impairment and moderate renal impairment were 291.5, 995.5 and 1 901.5 µg/L (P<0.001) respectively. The sensitivity of negative D-dimer for ruling out pulmonary embolism was 99%-100% and the specificity 70%, 42% and 23% in three subgroups. The number of patients needed to test (NNT) for one negative test of D-dimer in three subgroups of different renal function was 3.32, 3.58 and 3.95 respectively. The new D-dimer cut-off value increased to 1.2 and 1.75 times of old one in patients with mild and moderate renal impairments and the proportion of patients with a negative D-dimer level rose from 48.7% to 53.0% as compared with old D-dimer cut-off value. The sensitivity and specificity of negative D-dimer for ruling out pulmonary embolism was 98% and 62% with the new cut-off value versus 99% and 57% with the old cut-off value and the NNT of D-dimer for ruling out pulmonary embolism declined from 3.52 to 3.34. The renal function adjusted D-dimer cut-off point can improve the diagnostic efficiency of D-dimer test for ruling out pulmonary embolism.

Use of pulmonary embolism rule-out criteria (PERC) in the emergency department

To assess the use of pulmonary embolism rule-out criteria (PERC) to exclude pulmonary embolism (PE) in the emergency department. An extensive literature review was carried out to evaluate the evidence base for the use of PERC scoring in the exclusion of PE. A retrospective study of case notes of

Accuracy of X-ray with perfusion scan in young patients with suspected pulmonary embolism

BackgroundComputed tomography pulmonary angiogram (CTPA) has become the standard test in the diagnostic workup of patients with suspected pulmonary embolism (PE). However, young patients may have an increased risk of cancer with CTPA. Perfusion scanning combined with chest X-ray (X/Q) may offer an adequate alternative, but has never been prospectively validated. We directly compared this strategy with CTPA in patients aged ≤50years with suspected PE. MethodsConsecutive patients with a likely clinical probability or an abnormal D-dimer level underwent both CTPA and X/Q. Two trained and experienced nuclear physicians independently analyzed the X/Q-scans. The accuracy of X/Q according to the PISAPED criteria was calculated in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). ResultsSeventy-six patients were included, with a PE rate of 33%. The inter-observer agreement for X/Q-scan reading was high (κ=0.89). After consensus reading, 21 patients (28%) were categorized as ‘PE present’, 53 (70%) as ‘PE absent’, and two (2.6%) as ‘non-diagnostic’. In 22%, there was a discrepancy between the X/Q-scan and CPTA for the diagnosis or exclusion of PE. The PPV and NPV were 71% and 83%, respectively. ConclusionIn patients with a high risk of PE, a diagnostic strategy of chest X-ray and perfusion scanning using the PISAPED criteria seems less safe than CTPA. Additional studies should further investigate this diagnostic algorithm.