Bernard Tardy

A Clinical Trial of Vena Caval Filters in the Prevention of Pulmonary Embolism in Patients with Proximal Deep-Vein Thrombosis

BACKGROUND The efficacy and safety of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis is still a matter of debate. METHODS Using a two-by-two factorial design, we randomly assigned 400 patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients). The rates of recurrent venous thromboembolism, death, and major bleeding were analyzed at day 12 and at two years. RESULTS At day 12, two patients assigned to receive filters (1.1 percent), as compared with nine patients assigned to receive no filters (4.8 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). At two years, 37 patients assigned to the filter group (20.8 percent), as compared with 21 patients assigned to the no-filter group (11.6 percent), had had recurrent deep-vein thrombosis (odds ratio, 1.87; 95 percent confidence interval, 1.10 to 3.20). There were no significant differences in mortality or the other outcomes. At day 12, three patients assigned to low-molecular-weight heparin (1.6 percent), as compared with eight patients assigned to unfractionated heparin (4.2 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.38; 95 percent confidence interval, 0.10 to 1.38). CONCLUSIONS In high-risk patients with proximal deep-vein thrombosis, the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis, without any difference in mortality. Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism.

Prognostic factors for pulmonary embolism: the prep study, a prospective multicenter cohort study.

RATIONALE The short-term prognosis of pulmonary embolism (PE) depends on hemodynamic status and underlying disease. The prognostic value of right ventricular dysfunction and injury is less well established. OBJECTIVES To evaluate prognostic factors of PE in a multicenter prospective cohort study. METHODS Echocardiography, brain natriuretic peptide (BNP), N-terminal-proBNP and cardiac troponin I measurements were done on admission of 570 consecutive patients with an acute PE. A predictive model was based on independent predictors of 30-day adverse events defined as death, secondary cardiogenic shock, or recurrent venous thromboembolism. MEASUREMENTS AND MAIN RESULTS At 30 days, 42 patients (7.4%; 95% confidence interval [CI], 5.5-9.8%) had adverse events. On multivariate analysis, altered mental state (odds ratio [OR] 6.8; 95% confidence interval [CI], 2.0-23.3), shock on admission (OR 2.8; 95% CI, 1.1-7.5), cancer (OR 2.9; 95% CI, 1.2-6.9), BNP (OR 1.3 for an increase of 250 ng/L; 95% CI, 1.1-1.6) and right to left ventricle diameter ratio (OR 1.2 for an increase of 0.1; 95% CI, 1.1-1.4) were associated with 30-days of adverse events. The predictive performance of the model was good (area under receiver operating characteristics curve 0.84 [95% CI, 0.78-0.90]), making it possible to develop a bedside prognostic score. CONCLUSIONS BNP and echocardiography may be useful determinants of the short-term outcome for patients with PE, together with clinical findings. Patients with PE can be stratified according to the initial risk of adverse outcome, using a simple score based on clinical, echocardiographic, and biochemical variables.

High Sensitivity and Specificity of Serum Procalcitonin Levels in Adults with Bacterial Meningitis

It was shown in children that serum procalcitonin was the best marker to use to differentiate bacterial from viral meningitis. To evaluate procalcitonin in the diagnosis of acute bacterial and viral meningitis, we conducted a prospective study including adult patients who were suspected of having meningitis and who were admitted to an emergency department. Cerebrospinal fluid (CSF) and serum levels of procalcitonin were measured in 105 consecutive patients. The diagnosis of meningitis was based on clinical findings, gram staining, culture, and chemical analysis of CSF. Twenty-three patients had bacterial meningitis, 57 had viral meningitis, and 25 did not have meningitis. Bacteriologic and chemical analysis of CSF did not allow correct differentiation of viral from bacterial meningitis. On the other hand, a serum procalcitonin level >0.2 ng/mL had a sensitivity and specificity of up to 100% in the diagnosis of bacterial meningitis. Serum procalcitonin levels seem to be the best marker in differentiating between bacterial and viral meningitis in adults.

Does bicarbonate therapy improve the management of severe diabetic ketoacidosis

OBJECTIVE The use of bicarbonates in the treatment of severe diabetic ketoacidosis remains controversial, especially regarding the benefit/risk ratio. The aim of this study was to assess the efficacy of bicarbonate therapy during severe diabetic ketoacidosis (pH <7.10). DESIGN Retrospective study. SETTING The emergency unit of a teaching hospital. PATIENTS The records of 39 patients consecutively admitted for severe diabetic ketoacidosis were analyzed (pH <7.10). The patients were divided into two groups: group 1 (n = 24; patients with bicarbonate treatment) and group 2 (n = 15; patients without bicarbonate treatment). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We compared two groups of patients presenting with severe diabetic ketoacidosis (pH values between 6.83 and 7.08) treated with or without bicarbonate. A group of 24 patients received 120+/-40 mmol sodium bicarbonate. The two groups were similar at admission with regard to clinical and biological parameters. No difference could be demonstrated between the two groups concerning the clinical parameters or the normalization time of biochemical parameters. If the number of patients with hypokalemia was comparable between the two groups, the potassium supply was significantly more important in group 1 compared with group 2 (366+/-74 mmol/L vs. 188+/-109 mmol/L, respectively; p < .001). CONCLUSIONS Data from the literature and this study are not in favor of the use of bicarbonate in the treatment of diabetic ketoacidosis with pH values between 6.90 and 7.10.

Superficial vein thrombosis: risk factors, diagnosis, and treatment

Superficial vein thrombosis (SVT) risk factors are close to those of venous thromboembolism (VTE). Diagnosis is made in a clinical setting but ultrasonography is useful to eliminate concomitant deep vein thrombosis (DVT). For SVT of the lower limbs, which is the main location, varicose veins represent the principal cause but underlying conditions (e.g.: autoimmune diseases, malignancy or thrombophilia) must be sought in idiopathic, migrant or recurrent SVT and in the absence of varicose veins. Concomitant DVT and pulmonary embolism can occur in approximately 15% and 5% respectively. Historical treatments consist of anti-inflammatory agents plus elastic stockings and, in case of varicose veins, thrombectomy and stripping. Other treatments (anticoagulants, vein ligation) were assessed to limit the VTE risk. A one-month prophylactic dose of low molecular weight heparin plus elastic stockings could be the appropriate strategy in most cases. Other studies are needed before definitive conclusions can be drawn.

Serum and ascitic procalcitonin levels in cirrhotic patients with spontaneous bacterial peritonitis: diagnostic value and relationship to pro-inflammatory cytokines.

Objective: To assess the potential role of procalcitonin and pro-inflammatory cytokines, TNF-α, and IL-6, in the diagnosis of spontaneous bacterial peritonitis (SBP). Design: Prospective study. Setting: The emergency unit of a teaching hospital. Patients: We included 21 patients with SBP and 40 patients with sterile ascitic fluid. Interventions: None. Measurements and main results: For the diagnosis of SBP, the best markers were serum levels of procalcitonin with a cut-off value of 0.75 ng/ml, a sensitivity of 95 %, a specificity of 98 %, and ascitic fluid levels of IL-6 with a cut-off value of 5000 ng/ml, a sensitivity of 100 %, and a specificity of 88 %. C-reactive protein and serum polymorphonuclear count have low sensitivity/specificity at 62/92 % and 57/90 %, respectively. From 21 patients with SBP, ascitic fluid to serum ratio of TNF-α and IL-6 was greater than to 2 in all cases with a mean at 6.2 ± 6.5 and 34 ± 31, respectively. By contrast, this ratio for procalcitonin was less than 1 in all cases with a mean at 0.31 ± 0.25. We found no correlation between procalcitonin levels and cytokine levels in either ascitic fluid or serum. Conclusions: Serum procalcitonin level may become a useful marker for the diagnosis of SBP in cirrhotic patients. The low ratio of ascitic fluid to serum procalcitonin supports the hypothesis that procalcitonin is not produced intraperitoneally.

Adult first generalized seizure: Etiology, biological tests, EEG, CT scan, in an ED

The purpose of this study was to evaluate adult first seizures in an emergency department by analyzing etiologic and epidemiological data and studying the usefulness of biological screening, electroencephalogram (EEG), and cerebral computed tomography (CT) scan. This was a retrospective study of a 3-year period during which 247 patients were admitted to an emergency department for a first generalized seizure. A CT scan had been performed in 247 patients and an EEG in 209. Etiologies were found to be (1) unknown, (2) alcohol abuse, (3) stroke, and (4) tumor. Early recurrence rate was 18.5%. EEG was of low interest in emergency. The rate of cerebral focal lesions on CT scan was significantly lower when both examination results and EEG were normal. The rate of metabolic abnormalities was 4.9%. It was concluded that (1) a short hospitalization is advisable because of recurrences, (2) recurrence rate does not increase significantly in patients with focal cerebral lesion, (3) metabolic screening is necessary, and (4) CT scan will be an outpatient procedure for most patients.

Limited screening with versus without (18)F-fluorodeoxyglucose PET/CT for occult malignancy in unprovoked venous thromboembolism: an open-label randomised controlled trial.

BACKGROUND Clear guidelines for the investigation of occult malignancy after unprovoked venous thromboembolism are not yet available. (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT could serve as a comprehensive screening strategy for occult malignancy in this context. We aimed to compare a screening strategy based on (18)F-FDG PET/CT with a limited screening strategy for detection of malignant disease in patients with unprovoked venous thromboembolism. METHODS In an open-label, multicentre, randomised study we enrolled patients from four French university hospitals. Patients aged 18 years or older, diagnosed with unprovoked venous thromboembolism (not provoked by a major inherited or acquired risk factor) were invited to participate. Patients were randomly assigned in a 1:1 ratio to a limited screening strategy (physical examination, usual laboratory tests, and basic radiographs) or a screening strategy consisting of the limited strategy plus an (18)F-FDG PET/CT scan. Randomisation was done with a dedicated central web-based randomisation system, in block sizes of six, stratified by centre, and concealed from the investigators. Patients and investigators were not masked to study group assignment. Patients were followed up for 2 years. The primary outcome was the proportion of patients with a cancer diagnosis in each group after the initial screening assessment. Analyses were conducted in modified intention-to-test and per-protocol populations. This trial is completed and registered with ClinicalTrials.gov, number NCT00964275. FINDINGS Between March 3, 2009, and Aug 18, 2012, we enrolled and randomly assigned 399 patients; five withdrew consent, leaving 197 in each group for the modified intention-to-test analysis. After initial screening assessment, cancer was diagnosed in 11 (5·6%) patients in the (18)F-FDG PET/CT group and four (2·0%) patients in the limited screening group (absolute risk difference 3·6%, 95% CI -0·4 to 7·9; p=0·07). At the initial screening assessment, seven (64%) of the 11 cancers diagnosed in the (18)F-FDG PET/CT group were early-stage compared with two of four cancers diagnosed in the limited screening group (p=1·00). One (0·5%) occult malignancy was detected in 186 patients who had negative initial screening in the (18)F-FDG PET/CT group, compared with nine (4·7%) in 193 patients in the limited screening group (absolute risk difference 4·1%, 95% CI 0·8 to 8·4, p=0·01). Overall, five (42%) of the 12 cancers diagnosed in the (18)F-FDG PET/CT group were advanced stage, compared with seven (54%) of the 13 cancers diagnosed in the limited screening group (p=0·70). 16 patients died during follow-up, eight (4·1%) in each group. Two (1·0%) patients in the (18)F-FDG PET/CT group and five (2·5%) in the limited screening group had cancer-related deaths. INTERPRETATION A strategy including limited screening and a (18)F-FDG PET/CT was not associated with a significantly higher rate of cancer diagnosis after unprovoked venous thromboembolism. The risk of subsequent cancer diagnosis was, however, lower in patients who had negative initial screening that included (18)F-FDG PET/CT than in patients who had negative initial limited screening. Whether or not (18)F-FDG PET/CT might be useful in a more selected population of patients with a high risk of cancer remains to be determined. FUNDING Programme Hospitalier de Recherche Clinique (French Department of Health).

Decrease in serum procalcitonin levels over time during treatment of acute bacterial meningitis

IntroductionThe aim of this study was to describe the change in serum procalcitonin levels during treatment for community-acquired acute bacterial meningitis.MethodsOut of 50 consecutive patients presenting with bacterial meningitis and infection at no other site, and who had received no prior antibiotic treatment, 48 had a serum procalcitonin level above 0.5 ng/ml on admission and were enrolled in the study.ResultsThe mean age of the patients was 55 years, and mean Glasgow Coma Scale score on admission was 13. The time from symptom onset to admission was less than 24 hours in 40% of the patients, 24–48 hours in 20%, and more than 48 hours in 40%. The median (interquartile) interval between admission and initial antibiotic treatment was 160 min (60–280 min). Bacterial infection was documented in 45 patients. Causative agents included Streptococcus pneumoniae (n = 21), Neisseria meningitidis (n = 9), Listeria monocytogenes (n = 6), other streptococci (n = 5), Haemophilus influenzae (n = 2) and other bacteria (n = 2). The initial antibiotic treatment was effective in all patients. A lumbar puncture performed 48–72 hours after admission in 34 patients showed sterilization of cerebrospinal fluid. Median (interquartile) serum procalcitonin levels on admission and at day 2 were 4.5 (2.8–10.8) mg/ml and 2 (0.9–5.0) mg/ml, respectively (P < 0.0001). The corresponding values for C-reactive protein were 120 (21–241) mg/ml and 156 (121–240) mg/ml, respectively. Five patients (10%) died from noninfectious causes during their hospitalization.ConclusionsSerum procalcitonin levels decrease rapidly with appropriate antibiotic treatment, diminishing the value of lumbar puncture performed 48–72 hours after admission to assess treatment efficacy.

Transient and Persistent Acute Kidney Injury and the Risk of Hospital Mortality in Critically Ill Patients: Results of a Multicenter Cohort Study

Objective:To assess the prognostic impact of transient and persistent acute kidney injury in critically ill patients. Design:Retrospective analysis of prospectively collected patient data Setting:Six hospital ICUs. Patients:Critically-ill patients with ICU stay longer than three days. Intervention:None. Measurements and Main Results:Assessment of hospital survival with respect to acute kidney injury duration. A total of 447 patients were included in this study, including 283 patients (63.3%) with an acute kidney injury at admission (175 and 108 patients with persistent and transient acute kidney injury, respectively). Patients with persistent acute kidney injury more frequently had stage 3 acute kidney injury (42.9% vs 30.6%; p = 0.04). Hospital survival was 76.2% (n = 125) in patients without acute kidney injury, 70.4% (n = 76) in patients with transient acute kidney injury, and 61.1% (n = 107) in patients with persistent acute kidney injury. After adjustment for confounding factors, the factors associated with lower hospital survival were the need for vasopressors (odds ratio, 0.65; 95% CI, 0.43–0.98) and the presence of persistent acute kidney injury (odds ratio, 0.58; 95% CI, 0.36–0.95). When included in the final model, stage 3 acute kidney injury was independently associated with a lower hospital survival (odds ratio, 0.83; 95% CI, 0.70–0.98), and persistent acute kidney injury was no longer associated with outcome. Conclusion:Two thirds of the critically ill patients with acute kidney injury have persistent acute kidney injury. Although mortality increased progressively with the duration of acute kidney injury, we found no independent association between this duration and patient outcome when the acute kidney injury severity is taken into account. Our results suggest that the classical “prerenal acute kidney injury” and “acute tubular necrosis” paradigm might be of limited interest from a pathophysiological or prognostic point of view.