Cardiac biomarkers and clinical scores for risk stratification in elderly patients with non-high-risk pulmonary embolism.

OBJECTIVE: To determine the prognostic accuracy of cardiac biomarkers alone and in combination with clinical scores in elderly patients with non-high-risk pulmonary embolism (PE). DESIGN: Ancillary analysis of a Swiss multicentre prospective cohort study. SUBJECTS: A total of 230 patients aged ≥65 years with non-high-risk PE. MAIN OUTCOME MEASURES: The study end-point was a composite of PE-related complications, defined as PE-related death, recurrent venous thromboembolism or major bleeding during a follow-up of 30 days. The prognostic accuracy of the Pulmonary Embolism Severity Index (PESI), the Geneva Prognostic Score (GPS), the precursor of brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) was determined using sensitivity, specificity, predictive values, receiver operating characteristic (ROC) curve analysis, logistic regression and reclassification statistics. RESULTS: The overall complication rate during follow-up was 8.7%. hs-cTnT achieved the highest prognostic accuracy [area under the ROC curve: 0.75, 95% confidence interval (CI): 0.63-0.86, P < 0.001). At the predefined cut-off values, the negative predictive values of the biomarkers were above 95%. For levels above the cut-off, the risk of complications increased fivefold for hs-cTnT [odds ratio (OR): 5.22, 95% CI: 1.49-18.25] and 14-fold for NT-proBNP (OR: 14.21, 95% CI: 1.73-116.93) after adjustment for both clinical scores and renal function. Reclassification statistics indicated that adding hs-cTnT to the GPS or the PESI significantly improved the prognostic accuracy of both clinical scores. CONCLUSION: In elderly patients with nonmassive PE, NT-proBNP or hs-cTnT could be an adequate alternative to clinical scores for identifying low-risk individuals suitable for outpatient management.

Risk of falls and bleeding in elderly patients with acute venous thromboembolism.

OBJECTIVE: Whether or not a high risk of falls increases the risk of bleeding in patients receiving anticoagulants remains a matter of debate. METHODS: We conducted a prospective cohort study involving 991 patients ≥ 65 years of age who received anticoagulants for acute venous thromboembolism (VTE) at nine Swiss hospitals between September 2009 and September 2012. The study outcomes were as follows: the time to a first major episode of bleeding; and clinically relevant nonmajor bleeding. We determined the associations between the risk of falls and the time to a first episode of bleeding using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS: Four hundred fifty-eight of 991 patients (46%) were at high risk of falls. The mean duration of follow-up was 16.7 months. Patients at high risk of falls had a higher incidence of major bleeding (9.6 vs. 6.6 events/100 patient-years; P = 0.05) and a significantly higher incidence of clinically relevant nonmajor bleeding (16.7 vs. 8.3 events/100 patient-years; P < 0.001) than patients at low risk of falls. After adjustment, a high risk of falls was associated with clinically relevant nonmajor bleeding [subhazard ratio (SHR) = 1.74, 95% confidence interval (CI) = 1.23-2.46], but not with major bleeding (SHR = 1.24, 95% CI = 0.83-1.86). CONCLUSION: In elderly patients who receive anticoagulants because of VTE, a high risk of falls is significantly associated with clinically relevant nonmajor bleeding, but not with major bleeding. Whether or not a high risk of falls is a reason against providing anticoagulation beyond 3 months should be based on patient preferences and the risk of VTE recurrence.

[Age-adjusted D-dimers and pulmonary embolism]. / D-dimères et suspicion d'embolie pulmonaire: seuil adapté à l'age.

Plasma D-dimer measurement is the first diagnostic test performed in patients with a non-high or an unlikely clinical probability of pulmonary embolism (PE) but its clinical usefulness is limited in elderly patients due to a low specificity in this subgroup. PE can be excluded based on D-dimers and clinical probability only in about 5% of patients over 80 years when using the conventional cut-off. Age-adjusted D-dimer cut-off (adjusted cut-off value = age x 10 in patients over 50) increases the specificity of the test without significantly reducing its sensitivity. Using the age-adjusted D-dimer cut-off markedly reduces the need for further diagnostic studies such as computed tomography pulmonary angiography (CTPA). The age-adjusted cut-off has been widely validated in retrospective cohorts, and more recently in a prospective management study.

[Diagnosing pulmonary embolism during pregnancy: how should we do?]. / Diagnostic de l'embolie pulmonaire chez la femme enceinte: comment faire?

No diagnostic strategy for pulmonary embo- lism (PE) during pregnancy is based on strong evidence and unanimously accepted. Clinical scores are not validated. The diagnostic yield of the non radiating tests is low: D-dimer is rarely negative in pregnant women and lower limb venous compression ultrasonography is poorly sensitive. Nevertheless, they are still recommended as first line exams. The radia- ting exams (ventilation-perfusion scintigra- phy and thoracic angio-CT) have an equiva- lent diagnostic yield (more than 90%). But both raise the risk of cancer: any childhood cancer for the fetus (scintigraphy), and breast cancer for the mother (angio-CT). However, the diagnosis of PE in the pregnant woman has a major impact and must be established with certainty, even if this requires performing radiation imaging.

[Usefulness of preemptive anticoagulation in patients with suspected pulmonary embolism]. / Utilité d'une anticoagulation avant le diagnostic définitif d'embolie pulmonaire.

The usefulness of anticoagulation in patients with suspected non-massive pulmonary embolism (PE) is uncertain. We recently published a decision analysis model suggesting a benefit for preemptive anticoagulation in patients with an intermediate or high probability of PE, even with short diagnostic delays (0-3 h). In case of a low probability of PE, the decision to treat or not could partly rely on the expected diagnostic delay. Once the diagnosis is confirmed, achieving rapidly therapeutic anticoagulation levels decreases future thrombotic complications.

Diagnosis of and treatment for symptomatic carotid stenosis: an updated review.

Carotid stenoses of ≥50% account for about 15-20% of strokes. Their degree may be moderate (50-69%) or severe (70-99%). Current diagnostic methods include ultrasound, MR- or CT-angiography. Stenosis severity, irregular plaque surface, and presence of microembolic signals detected by transcranial Doppler predict the early recurrence risk, which may be as high as 20%. Initial therapy comprises antiplatelets and statins. Benefit of revascularization is greater in men, in older patients, and in severe stenosis; patients with moderate stenoses may also profit particularly if the plaque has an irregular aspect. An intervention should be performed within <2 weeks. In large randomized studies comparing endarterectomy and stenting, endovascular therapy was associated with a higher risk of periprocedural stroke, yet in some studies, with a lower risk of myocardial infarction and of cranial neuropathy. These trials support endarterectomy as the first choice treatment. Risk factors for each of the two therapies have been indentified: coronary artery disease, neck radiation, contralateral laryngeal nerve palsy for endarterectomy, and, elderly patients (>70 years), arch vessel tortuosity and plaques with low echogenicity on ultrasound for carotid stenting. Lastly, in direct comparisons, a contralateral occlusion increases the risk of periprocedural complications in both types of treatment.

[Bleeding risk in patients with venous thromboembolism]. / Evaluation du risque hémorragique en cas de maladie thromboembolique veineuse: état des lieux en 2012.

About 2 to 2,5% of patients with venous thromboembolism suffer from a major bleed in the first 90 days of treatment with anticoagulation. Many predictors of hemorrhages have been identified, and include the stability of INRs, a bleeding history, cancer, chronic kidney disease and an advanced age. This knowledge may help care-providers to identify high-risk situations and to determine the best duration of treatment for their patients. Bleeding prediction rules for prevalent users of warfarin have not been validated for patients in venous thromboembolism, and their usefulness remains to be determined.

Medullary sponge kidney: unusual finding in kidney transplant recipient.

BACKGROUND: Medullary sponge kidney is generally considered a benign condition, gold standard for the diagnosis is urography but it has almost been replaced by UroCT that did not present the same sensibility. Although it is really rare, our sonography's findings were consistent with medullary sponge kidney in the transplanted kidneys. CASE PRESENTATION: A 45-year-old woman with a long history of double-kidney transplantation complained of frequent urinary tract infections, a history of vague loin pain and came to our attention for sonography follow-up. Her kidney function was normal, we did not find signs of infections in the transplanted kidneys and urinary findings were normal. Curiously, the transplanted kidneys came from a newborn and the patient received a double-kidney transplantation in order to guarantee a satisfactory renal function. CONCLUSIONS: Despite a long history of kidney transplantation, genetic disease should not be forgotten when symptoms and images recall to specific inherited alterations. Sonography has to be considered in diagnostic path of kidney cystic disease.

MR Brain Screening in ADPKD Patients : To Screen or not to Screen?

BACKGROUND: Adult polycystic kidney disease (ADPKD) still represents a major cause of renal failure and intracranial aneurisms (IA) have a higher prevalence in ADPKD than in the general population. Current guidelines suggest performing brain MRI only in the subjects with a positive familiar history of IAs or subarachnoid hemorrhage (SAH). This is a retrospective case-control analysis to evaluate the usefulness of a MR screening program in ADPKD patients. METHODS: We retrospectively analyzed all ADPKD patients followed in our outpatient clinic between 2016 and 2019 who underwent a brain MRI screening. We evaluated the presence of IAs and others brain abnormalities and compared our results with a non-ADPKD population (n = 300). We performed univariate and multivariate regression analysis to evaluate if general and demographic features, laboratory findings, clinical parameters and genetic test results correlated with IAs or other brain abnormalities presence. RESULTS: Among the patients evaluated 17 out of 156 (13.6%) ADPKD patients had IAs, compared to 16 out of 300 (5.3%) non-ADPKD controls (p < 0.005). Considering ADPKD patients presenting IAs, 12 (70.6%) had no family history for IAs or SAH. Genetic analysis was available for 97 patients: in the sub-population with IAs, 13 (76.5%) presented a PKD1 mutation and none a PKD2 mutation. We found that arachnoid cysts (AC) (p < 0.001) and arterial anatomical variants (p < 0.04) were significantly more frequent in ADPKD patients. CONCLUSION: In our population ADPKD patients showed a higher prevalence of IAs, AC and arterial variants compared to non-ADPKD. Most of the IAs were found in patients presenting a PKD1 mutation. We found a significant number of alterations even in those patients without a family history of IAs or SAH. The practice of submitting only patients with familial IAs or kidney transplantation candidates to MRI scan should be re-evaluated.

Prognostic value of the Geneva prediction rule in patients in whom pulmonary embolism is ruled out.

OBJECTIVES: The prognosis of patients in whom pulmonary embolism (PE) is suspected but ruled out is poorly understood. We evaluated whether the initial assessment of clinical probability of PE could help to predict the prognosis for these patients. DESIGN: Retrospective analysis of data obtained during a prospective multicentre management study. SETTING: Six general and teaching hospitals in Belgium, France and Switzerland. SUBJECTS: In 1334 patients in whom PE was ruled out, 3-month mortality data were available (hospital readmission status was unknown for three patients) and clinical probability was evaluated with the revised Geneva score (RGS). MAIN OUTCOME MEASURES: Three-month mortality and readmission rates. RESULTS: Three-month mortality and readmissions rates were 3% and 19%, respectively and differed significantly depending on the RGS-determined PE probability group (P<0.001). When compared with patients presenting with a low probability, the risk of death after 3 months was higher in cases of intermediate or high RGS-based probability {odds ratio: 8.7 [95% confidence interval (CI): 2.7-28.5] and 22.6 (95%CI: 2.1-241.2), respectively}. The readmission risk increased with PE probability group (P<0.001). The main causes of death were cancer, respiratory failure and cardiovascular failure. In total, 86% of patients with low RGS-based probability were alive and had not been readmitted to hospital, whereas other patients had a twofold increased risk of death or readmission during the 3-month follow-up. The simplified Geneva score, calculated a posteriori, gave similar results. CONCLUSIONS: Initial assessment of clinical probability may help to stratify prognosis of patients in whom PE has been ruled out. Patients with a low probability of PE have a good prognosis. Whether patients with higher probability might benefit from more vigilant care should be evaluated.

Nano-optical trapping of Rayleigh particles and Escherichia coli bacteria with resonant optical antennas.

Immobilizing individual living microorganisms at designated positions in space is important to study their metabolism and to initiate an in situ scrutiny of the complexity of life at the nanoscale. While optical tweezers enable the trapping of large cells at the focus of a laser beam, they face difficulties in maintaining them steady and can become invasive and produce substantial damage that prevents preserving the organisms intact for sufficient time to be studied. Here we demonstrate a novel optical trapping scheme that allows us to hold living Escherichia coli bacteria for several hours using moderate light intensities. We pattern metallic nanoantennas on a glass substrate to produce strong light intensity gradients responsible for the trapping mechanism. Several individual bacteria are trapped simultaneously with their orientation fixed by the asymmetry of the antennas. This unprecedented immobilization of bacteria opens an avenue toward observing nanoscopic processes associated with cell metabolism, as well as the response of individual live microorganisms to external stimuli, much in the same way as pluricellular organisms are studied in biology.

[Diagnosis of pulmonary embolism]. / Diagnostic de l'embolie pulmonaire.

The diagnosis of pulmonary embolism (PE) is nowadays based on the sequential use of several diagnostic tests rather than on a single test. These diagnostic strategies are safe and have been prospectively validated. The first step after identifying patients with suspicion of PE is to establish the pre-test clinical probability. Several scores are available in order to make a standardised and reproducible assessment of the clinical probability, and therefore represent precious diagnostic tools. Indeed, clinical probability guides further investigations. Indeed, in patients with a low or an intermediate clinical probability or an "unlikely" probability, PE can be safely ruled out by negative D-dimers in approximately one third of outpatients without additional imaging. In case of positive D-dimers and a high clinical probability or a "likely" clinical probability, CT pulmonary angiography is now the recommended imaging technique. However, lower limb venous compression ultrasound and ventilation/perfusion scans remain useful in patients with contra-indications to CT, mainly those with renal insufficiency. Finally, some novel diagnostic tests seem promising. For example, V/Q SPECT has arisen as a highly accurate test and a potential alternative to CTPA. However, prospective management outcome studies are still lacking and are warranted before its implementation in routine clinical practice.

Comparison of the revised Geneva score with the Wells rule for assessing clinical probability of pulmonary embolism.

BACKGROUND: The revised Geneva score, a standardized clinical decision rule in the diagnosis of pulmonary embolism (PE), was recently developed. The Wells clinical decision is widely used but lacks full standardization, as it includes subjective clinician's judgement. We have compared the performance of the revised Geneva score with the Wells rule, and their usefulness for ruling out PE in combination with D-dimer measurement. METHODS: In 300 consecutive patients, the clinical probability of PE was assessed prospectively by the Wells rule and retrospectively using the revised Geneva score. Patients comprised a random sample from a single center, participating in a large prospective multicenter diagnostic study. The predictive accuracy of both scores was compared by area under the curve (AUC) of receiver operating characteristic (ROC) curves. RESULTS: The overall prevalence of PE was 16%. The prevalence of PE in the low-probability, intermediate-probability and high-probability categories as classified by the revised Geneva score was similar to that of the original derivation set. The performance of the revised Geneva score as measured by the AUC in a ROC analysis did not differ statistically from the Wells rule. After 3 months of follow-up, no patient classified into the low or intermediate clinical probability category by the revised Geneva score and a normal D-dimer result was subsequently diagnosed with acute venous thromboembolism. CONCLUSIONS: This study suggests that the performance of the revised Geneva score is equivalent to that of the Wells rule. In addition, it seems safe to exclude PE in patients by the combination of a low or intermediate clinical probability by the revised Geneva score and a normal D-dimer level. Prospective clinical outcome studies are needed to confirm this latter finding.

Venous thromboembolism: contemporary diagnostic and therapeutic aspects.

To discuss new features that were published during the past few years on diagnosis and treatment of venous thromboembolism (VTE). Progress has been made in assessing clinical probability of pulmonary embolism (PE), in addressing the particular aspects of PE diagnosis in the elderly, in evaluating the diagnostic performance of single- and multi-detector row helical computed tomography (hCT), and in looking at the role of D-dimer measurement and lower limb venous compression ultrasonography in the diagnostic work-up of PE. New therapeutic options have also been proposed. Diagnosing VTE depends upon several, mainly non-invasive diagnostic tools that must be used sequentially, depending on the clinical situation and the local expertise. In the vast majority of patients, a noninvasive work-up is feasible and the diagnostic algorithms are becoming simpler. We focused on new developments of clinical probability assessment, PE in the elderly, potential new uses of D-dimer measurement, advent of multidetector row helical computed tomography and utility of ultrasonography to detect deep vein thrombosis in PE suspected patients. Treatment of acute venous thromboembolism consists of parenteral administration of heparin (usually low-molecular-weight heparin or, more recently, fondaparinux) overlapped and followed by oral vitamin K antagonists that will be administered for a certain period of time (usually 3 to 12 months), depending upon the estimated risks of recurrence and bleeding in each individual patient. Contemporary features include the controversial possibility of reducing the intensity of oral anticoagulant treatment (INR 1.5-2) after an initial full-intensity treatment (INR 2-3) period of 3 to 12 months, and the emergence of new anticoagulant drugs such as direct oral synthetic inhibitors of thrombin or factor Xa.

[D-dimers measurement to predict the risk of thromboembolic recurrence]. / Dosage des D-dimères et risque de récidive thromboembolique veineuse.

PURPOSE: The optimal duration of anticoagulant therapy after a first episode of venous thromboembolism (VTE) is still matter of debate. Currently, the duration of anticoagulation is recommended on the basis of the clinical characteristics of the index event. In particular, the seventh ACCP conference on antithrombotic and thrombolytic therapy suggests that events secondary to a reversible risk factor should anticoagulated for shorter period of time than idiopathic VTE. Recently, D-dimer measurement has been used to predict the risk of recurrence and to tailor anticoagulant therapy on an individual basis. CURRENT KNOWLEDGE AND KEY POINTS: Four studies used various D-dimer tests at various cut-off to predict the risk of recurrence after a first VTE event. Overall, these studies confirmed that D-dimer measurement has a high negative predictive value (>92%) to predict the risk of a recurrent VTE event. One intervention randomized study confirmed that in patients who stopped anticoagulation, the adjusted hazard ratio for a recurrent event among those with an abnormal D-dimer test, as compared with those with a normal test was of 2.27 (95% CI:1.15-4.46). FUTURE PROSPECTS AND PROJECTS: The missing gap remains to find a test able to detect patients at high risk of recurrence in whom maintaining anticoagulation would be beneficial. The limited positive predictive value of D-dimer reported in all studies suggests that the D-dimer test will have limited value in this field. Moreover, standardization of the cut-off and of the time of blood sampling in relation to cessation of anticoagulation is warranted.

[Distal deep-venous thrombosis: diagnostic and therapeutic issues]. / Les thromboses veineuses distales: problématique de leur diagnostic et de leur traitement.

PURPOSE: Compression ultrasonography is the reference test for the diagnosis of distal deep venous thrombosis of lower limbs. However, the ways it is performed and the related treatments are very heterogeneous between various countries. CURRENT KNOWLEDGE AND KEY POINTS: In USA, Canada and Netherlands, compression ultrasonography is restricted to proximal limbs considering that this test is inadequate to explore the distal veins. The strategy consisting of a clinical approach, including the clinical probability and/or a follow-up ultrasonography has demonstrated its efficacy and safety (extension rate to proximal veins of 1.2% at three months and absence of fatal pulmonary embolism). In France, Italy and Spain, lower limb ultrasonography testing includes the examination of calf veins in a so called "complete testing". This procedure leads to the diagnosis of a large number of distal deep venous thrombosis (45-56%) among the 14 to 36% of deep vein thrombosis diagnosed in the setting of clinical suspicion. Recent diagnosis strategy studies have shown that both strategies are effective, but the complete ultrasound strategy doubles the number of anticoagulation treatments. Justification of inappropriate anticoagulation is not evident owing to the relatively low risk of proximal venous-thrombosis extension, the rate of severe hemorrhagic events at three months and the cost excess. FUTURE PROSPECTS AND PROJECTS: Prospective comparative clinical trials are necessary in distal-venous thrombosis and ongoing Cactus study addresses this therapeutic dilemma.

Impending paradoxical embolism. When and how to treat?

Impending paradoxical embolism (IPDE) is the presence of an entrapped thrombus through the patent foramen ovale (PFO). Usually IPDE are diagnosed by echocardiography or thoracic CT-scan performed during the evaluation of patient presenting with a suspicion of pulmonary embolism (PE). We report the case of a 73-year-old patient presenting with a very large IPDE successfully treated with cardiac surgery and we focus our discussion on the treatment modalities of this rare entity (anticoagulation alone, fibrinolytic regimens, cardiac surgery, percutaneous thrombectomy) and on PFO management after IPDE.

[Clinical probability of PE: should we use a clinical prediction rule?]. / Apport de la clinique : faut-il utiliser un score ?

The determination of the clinical pretest probability using clinical prediction models is an important step in the assessment of patients with suspected pulmonary embolism (PE). It helps establish which test or sequence of tests can effectively corroborate or safely rule out PE. For example, it has been demonstrated that it is safe to withhold anticoagulant therapy in patients with negative d-dimer results and low pretest probability at initial presentation. Clinical probability will also increase the diagnostic yield of ventilation perfusion lung scan. Compared with clinical gestalt, clinical prediction rules provide a standardized and more reproducible estimate of a patient's probability of having a PE. Clinical prediction models combine aspects of the history and physical examination to categorize a patient's probability of having a disease. The models classify patients as having a low, moderate, or high likelihood of having PE. Clinical prediction models have been validated and are well established for the diagnosis of PE in symptomatic patients. They allow all physicians, whatever their expertise, to reliably determine the clinical pretest probability of PE, and thus safely manage their patients using diagnostic and therapeutic algorithms.