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Biomedical subjects

Gabriel Thabut

Publications and source records attributed to Gabriel Thabut.

At least 19 recordsLinked to original sources

Hair versus plasma concentrations as indicator of indinavir exposure in HIV-1-infected patients treated with indinavir/ritonavir combination.

Large intra-individual variability in plasma levels may limit the interest of therapeutic drug monitoring based on a single determination. Indinavir concentrations were determined both in plasma and hair samples, and correlated with concomitant plasma HIV-RNA in 43 HIV-infected patients. In multivariate analysis, significant association was found between HIV-RNA below 50 copies/ml and indinavir concentrations in hair but not in plasma, suggesting that hair concentrations gave more extensive information on drug exposure than a single plasma sample.

Antiretroviral Therapy, Highly Active↗

Biomarker-based strategy for screening right ventricular dysfunction in patients with non-massive pulmonary embolism.

OBJECTIVE: To evaluate the usefulness of B-type natriuretic peptide and troponin I measurements in predicting right ventricular dysfunction (RVD) in non-massive pulmonary embolism. DESIGN: Prospective observational study. SETTING: University-affiliated emergency unit, cardiology and pneumology departments. PATIENTS: Sixty-seven patients admitted because of acute pulmonary embolism, without shock on admission, completed the study. INTERVENTIONS: Blood samples and echocardiography were obtained on admission for subsequent and independent assessment of B-type natriuretic peptide (BNP) and troponin I levels as well as RVD. MEASUREMENTS AND RESULTS: Echocardiographic RVD was diagnosed in 36 patients and was severe in 13 on admission. BNP and troponin I levels were higher in patients with RVD than in those with no RVD [62 (27-105) vs. 431 (289-556) pg/ml for BNP, p<0.001; 0.01 (0-0.09) vs. 0.16 (0.03-0.32) microg/l for troponin I, p=0.005]. The area under the receiving operating characteristic curve (AUC) for diagnosing RVD was 0.93 for BNP and 0.72 for troponin I. The troponin I level increased further when RVD was severe, compared with moderate, and the AUC was 0.91 for identifying severe RVD. Diagnoses of RVD and severe RVD were ruled out by BNP 100 pg/ml and troponin I >0.10 microg/l. CONCLUSION: In hemodynamically stable pulmonary embolism, BNP/troponin I measurement is helpful on admission, especially for ruling out RVD, i.e. patients with in-hospital high-risk.

Aged↗

Diagnosis of aortic valvular stenosis by multislice cardiac computed tomography.

AIMS: Current improvements in spatial, temporal, and contrast resolution of multislice computed tomography (CT) could be useful in the assessment of valvular diseases. We evaluated the diagnostic accuracy of multislice CT for the identification and quantification of aortic valvular stenosis (AS), compared with echography. METHODS AND RESULTS: Consecutive patients, referred for coronary CT, were evaluated for AS, by the use of standard electrocardiography-gated 16-slice CT protocol. Multiplanar reformat was applied to systolic phases of the cardiac cycle, with projection on thick slices for measuring the aortic valvular area (AVA). CT results were compared with echocardiographic-based measurement of the AVA. Among 107 enrolled patients, CT analysis of the AVA was feasible in 103. Among the 30 patients with AS, Bland-Altman analysis showed good agreement between the two methods [mean difference -7 mm(2) (-40-25 mm(2))]. CONCLUSION: CT analysis of aortic valve is feasible in most cases and allows for reliable diagnosis and quantification of AS.

Aged↗

Pulmonary vascular lesions in end-stage idiopathic pulmonary fibrosis: Histopathologic study on lung explant specimens and correlations with pulmonary hemodynamics.

In patients presenting with idiopathic pulmonary fibrosis (IPF), modifications of pulmonary vessels are well defined in fibrotic areas but have not been accurately assessed in the intervening patches of preserved lung. Moreover, the relation between pulmonary vessel lesions and pulmonary hemodynamics is not well known. We therefore designed a retrospective study on lung explant specimens from 26 patients with a firm diagnosis of IPF who had undergone lung transplantation. Our aim was to (1) describe the vascular lesions, especially in preserved lung areas, and (2) correlate them with pulmonary hemodynamics. In dense fibrotic zones, thickening of the arterial and venous wall with severe luminal narrowing was present in each patient. In architecturally preserved lung zones, occlusion of venules and small pulmonary veins was observed in 65% of the patients, although there were only mild changes of muscular pulmonary arteries. We found a significant positive correlation between the macroscopic extent of lung fibrosis and mean pulmonary artery pressure, but we failed to find a relation between mean pulmonary artery pressure and venous/venular lesions in nonfibrotic areas. Our study points out that in many patients with IPF, nonfibrotic lung areas demonstrate an occlusive venopathy, the signification of which remains undetermined.

Adult↗

Prognostic value of cardiopulmonary exercise variables in chronic heart failure patients with or without beta-blocker therapy.

The prognostic value of exercise-derived variables in the prediction of mortality in patients with chronic heart failure treated by beta blockers continues to be debated. A total of 402 patients with chronic heart failure, including 255 treated with beta blockers, were included and followed for 26 +/- 20 months after the exercise test. On univariate analysis, and in contrast to peak exercise oxygen consumption, the prognostic value of the minute ventilation/carbon dioxide production slope was increased in patients receiving beta-blocker therapy. On multivariate analysis, no independent prognostic variable emerged in patients not on beta-blocker therapy. However, the model that included the circulatory power (peak oxygen uptake x systolic blood pressure), in addition to age, New York Heart Association class, and left ventricular ejection fraction, was the best 1 for patients on beta-blocker therapy. In conclusion, in patients with chronic heart failure, the circulatory power is the exercise variable with the greatest independent prognostic value, compared with the peak exercise oxygen consumption and minute ventilation/carbon dioxide production slope.

Adrenergic beta-Antagonists↗

Lung transplantation for pulmonary langerhans' cell histiocytosis: a multicenter analysis.

BACKGROUND: Lung transplantation (LT) may represent a therapeutic option in case of advanced pulmonary Langerhans' cell histiocytosis (PLCH). Little is known however about the characteristics of the patients considered for LT or its results. METHODS: We conducted a retrospective multicenter study by questionnaire on 39 patients who underwent LT for end-stage PLCH at seven centers in France. RESULTS: Of the 39 patients, 15 received single lung transplantation, 15 double lung transplantation and 9 heart-lung transplantation. At evaluation, extrapulmonary involvement was present in 31% of the patients, pulmonary hypertension (PAPm>25 mm Hg) was observed in 92% of cases and was moderate-to-severe (PAPm> or =35 mm Hg) in 72.5%. The survival was 76.9% at 1 year, 63.6% at 2 years, 57.2% at 5 years, and 53.7% at 10 years. Recurrence of the disease occurred in eight cases (20.5%) with no impact on the survival rate. The sole risk factor for recurrence of the disease was the presence of preoperative extrapulmonary involvement. CONCLUSION: Severe pulmonary hypertension is a common feature in patients with end-stage PLCH. Given the good postransplant survival rate and despite a recurrence rate of the disease of approximately 20% after LT, we conclude that LT is a therapeutic option in this setting.

Adolescent↗

Needle aspiration as first-line management of primary spontaneous pneumothorax.

BACKGROUND: Initial management of primary spontaneous pneumothorax (PSP) remains a topic of debate. Recent guidelines recommend needle aspiration as the initial strategy for large PSP, but chest tube drainage is still widely used. METHODS: Over a six-year period, we used needle aspiration in all cases of large PSP at our center to assess this technique's efficacy in real-life clinical practice. Our prospective study in the pulmonary intensive care unit of a 680-bed university hospital included patients with a PSP greater than 20%, as estimated by the Light's index. Needle aspiration, performed after local anesthesia, used a plastic intravenous catheter. If it failed, we performed thoracic drainage. RESULTS: The study included 35 patients. The initial success rate of needle aspiration was 69% (n=24/35), the one-week success rate 63% (n=22/35), and the one-year rate 51% (n=18/35). Tolerance of needle aspiration was good except for transient vagal reaction in four patients. No risk factors (age, body mass index, delay before hospitalization, previous pneumothorax, or Light index at inclusion) predicted initial failure of needle aspiration. CONCLUSION: Our results confirmed that needle aspiration is an attractive therapeutic option for patients with large PSP: success was observed in approximately two thirds of cases.

Adolescent↗

Determination of exercise training heart rate in patients on beta-blockers after myocardial infarction.

BACKGROUND: In patients with coronary artery disease, the target intensity-level of exercise training is usually based on a training heart rate that aims to be close to the upper level of metabolic aerobic exercise. AIM: We intended to evaluate whether a training heart rate calculated with the Karvonen formula after a conventional exercise test is comparable with the heart rate at the anaerobic threshold in patients after myocardial infarction treated with beta-blockers and if not to propose a new formula. METHODS AND RESULTS: In this multicenter prospective study, 115 consecutive beta-blocked patients recovering from myocardial infarction performed a cardiopulmonary exercise test to determine the anaerobic threshold. The training heart rate determined by the Karvonen formula was compared with the heart rate at the anaerobic threshold in a derivation sample (n=58) and a validation sample (n=57) of patients. The Karvonen training heart rate was significantly lower than the heart rate at the anaerobic threshold (91+/-5 versus 102+/-17 bpm, P<0.0001) in the first sample of patients and this difference was clinically relevant in 40% of patients. Thus, a 'modified Karvonen training heart rate', equal to 0.8xx(maximum heart rate-resting heart rate)+resting heart rate, was calculated by linear regression in the derivation sample and prospectively assessed in the validation sample. The modified Karvonen training heart rate was closer to the heart rate at the anaerobic threshold than the Karvonen training heart rate, and the difference between the modified Karvonen training heart rate and the heart rate at the anaerobic threshold was clinically relevant in only 5% of patients. CONCLUSION: The Karvonen formula underestimates the heart rate at the anaerobic threshold in beta-blocked patients, which may lead to undertraining of patients with coronary artery disease; we propose another formula more adapted to these patients.

Adrenergic beta-Antagonists↗

Liver stiffness measurement versus clinicians' prediction or both for the assessment of liver fibrosis in patients with chronic hepatitis C.

OBJECTIVES: The goal of this study was to estimate the additional value of liver stiffness measurement (LSM) with physicians' assessment of fibrosis based on epidemiological, clinical, and biological parameters. METHODS: One hundred forty-two unselected patients with chronic hepatitis C were included. Liver biopsy and LSM were performed simultaneously. First, four physicians (two junior residents with limited experience in hepatology and two senior hepatologists) independently predicted the stage of fibrosis according to the METAVIR classification, using clinical, epidemiological, and biological data. For the second step, they were informed of LSM values and could modify their first evaluation if necessary. Finally, the two successive evaluations were compared with the histological fibrosis score. RESULTS: Providing LSM values improved agreement between physicians and resulted in a better correlation between clinical impression and histological liver fibrosis. The diagnostic performances were only significantly improved with transient elastography for the diagnosis of cirrhosis where assessment improved in three of the four physicians (AUROC [area under receiver operating characteristic curve]: 0.76 vs 0.87, 0.80 vs 0.87, and 0.83 vs 0.89, all p < 0.05). Moreover, these performances were nearly similar for junior and senior physicians when LSM was provided with the AUROC ranging from 0.69 to 0.72 for significant fibrosis and 0.87 to 0.90 for cirrhosis. CONCLUSIONS: Providing LSM values to physicians results in a better estimation of liver fibrosis and a more accurate diagnosis of cirrhosis. Moreover, it allows physicians with limited experience to predict liver fibrosis as well as experienced hepatologists.

Adult↗

Methodological issues in trials assessing primary prophylaxis of venous thrombo-embolism.

AIMS: Many trials have been conducted to assess the efficacy of various strategies in the prevention of venous thrombo-embolism (VTE). Some of these trials have been subject to methodological criticisms. We aimed to assess the methodological issues raised by VTE trials. METHODS AND RESULTS: We searched MEDLINE and the Cochrane Central Register of Controlled Trials for articles assessing primary thromboprophylaxis published between 1994 and 2003 in 60 general medical and specialty journals. A total of 77 articles were analysed by two independent reviewers using a list of items. No primary endpoint was defined in 20% of trials. Although the primary endpoint was collected before day 15 in 75% of trials, there were >/=20% missing data in 56% of articles and >/=30% in 24.2% of articles. The rate of missing data was 23.7+/-9.7% in studies using venography-detected deep-vein thrombosis as an endpoint compared with 5.6+/-6.0% in studies using other endpoints. Among the 47 superiority trials, 27 (57.4%) reported an intention-to-treat (ITT) analysis, but only 10 (21.3%) reported an analysis that complied with this principle. These results were consistent when limiting the analysis to articles published in high-impact journal (impact factor more than 5). CONCLUSION: Recent randomized controlled trials assessing prophylactic regimens in VTE have important methodological limitations in terms of primary endpoints, missing data, and compliance with the ITT principle. These methodological shortcomings should be addressed when planning future trials.

Humans↗

Graft ischemic time and outcome of lung transplantation: a multicenter analysis.

RATIONALE: The effect of graft ischemic time on early graft function and long-term survival of patients who underwent lung transplantation remains controversial. Consequently, graft ischemic time has not been incorporated in the decision-making process at the time of graft acceptance. OBJECTIVES: To investigate the relationship between graft ischemic time and (1) early graft function and (2) long-term survival after lung transplantation. MEASUREMENTS AND MAIN RESULTS: The data from 752 patients who underwent single lung transplantation (n = 258), bilateral lung transplantation (n = 247), and heart-lung transplantation (n = 247) in seven French transplantation centers during a 12-year period were reviewed. Independent data quality control was done to ensure the quality of the collected variables. Mean graft ischemic time was 245.8 +/- 96.4 minutes (range 50-660). After adjustment on 11 potential confounders, graft ischemic time was associated with the recipient Pa(O2)/FI(O2) ratio recorded within the first 6 hours and with long-term survival in patients undergoing single or double lung transplantation but not in patients undergoing heart-lung transplantation. The relationship between graft ischemic time and survival appears to be of cubic form with a cutoff value of 330 minutes. These results were unaffected by the preservation fluid employed. CONCLUSIONS: The results of this large cohort of patients suggest a close relationship between graft ischemic time and both early gas exchange and long-term survival after single and double lung transplantation. Such relationship was not found in patients undergoing heart-lung transplantation. The expected graft ischemic time should be incorporated in the decision-making process at the time of graft acceptance.

Adult↗

Influence of donor characteristics on outcome after lung transplantation: a multicenter study.

BACKGROUND: The liberalization of lung-donor criteria and the use of marginal donors have been advocated to face the current shortage of donors in lung transplantation. However, the impact of donor characteristics on the outcome of lung transplantation is still largely unknown. We aimed to determine, on a large cohort of patients, the effect of donors characteristics on short- and long-term outcome of lung transplantation METHODS: Between 1988 and 1998, a total of 785 adult patients underwent single-lung transplantation (n = 270), bilateral-lung transplantation (n = 251), and heart-lung transplantation (n = 264) in 7 centers in France. We constructed several multivariate models to assess the relationship between donor characteristics and early gas exchange, duration of mechanical ventilation, and long-term survival after lung transplantation. RESULTS: Among donor characteristics, donor gas exchange before harvest was found to be significantly associated with recipient early gas exchange, duration of mechanical ventilation, and long-term survival after adjustment for potential confounding variables. Moreover, nonlinear modeling showed a steep increase in the relative risk of death when donor PaO2/FiO2 before harvest was below 350 (hazard ratio 1.43; 95% confidence interval 1.10-1.85; p = 0.01). Donor and recipient sex mismatch were also found to be significantly associated with long-term survival. CONCLUSIONS: Although liberalization of lung-donor criteria may be considered to overcome the shortage of lung donors, our data suggest that the violation of the gas-exchange criterion should be avoided.

Adult↗

Analysis of the different histologic lesions observed in transbronchial biopsy for the diagnosis of acute rejection. Clinicopathologic correlations during the first 6 months after lung transplantation.

Acute rejection is an extremely common complication of lung transplantation. (1) To appreciate the interobserver variation in the interpretation of histologic findings and (2) to assess the efficacy of transbronchial biopsy (TBB) for acute rejection diagnosis and associated diseases, particularly infection, we performed a retrospective study including 53 consecutive patients who underwent at least one clinically indicated TBB during the first 6 months after lung transplantation. A total of 94 TBB was obtained. The following histologic features observed in TBB specimens-perivascular mononuclear infiltrates, lymphocytic bronchitis/bronchiolitis, and alveolar lesions, were reliably reproduced by 2 pathologists from the same transplant center, with kappa values ranging from 0.79 to 0.82. For identifying perivascular mononuclear infiltrates, discordance between the 2 observers was significantly associated with moderate/severe alveolar lesions. For the diagnosis of acute rejection, perivascular mononuclear infiltrates had a specificity of 96.5%, a positive predictive value of 97.5%, and a sensitivity of 67.7%, whereas lymphocytic bronchitis/bronchiolitis had a specificity of 56.3% and a sensitivity of 19.4%. Interestingly, there was a positive independent correlation between infection and moderate/severe alveolar histologic lesions ( P < .01). In conclusion, the interobserver agreement between experienced pathologists in TBB interpretation is good. Perivascular mononuclear infiltrates remain the cornerstone for acute rejection diagnosis. The presence of moderate/severe alveolar lesions should prompt to search for infection.

Adult↗

Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation.

STUDY OBJECTIVES: To assess the pulmonary hemodynamic characteristics in COPD candidates for lung volume reduction surgery (LVRS) or lung transplantation (LT). DESIGN: Retrospective study. SETTING: One center in France. PATIENTS: Two hundred fifteen patients with severe COPD who underwent right-heart catheterization before LVRS or LT. RESULTS: Mean age was 54.6 years. Pulmonary function test results were as follows: FEV(1), 24.3% predicted; total lung capacity, 128.3% predicted; residual volume, 259.7% predicted. Mean pulmonary artery pressure (PAPm) was 26.9 mm Hg. Pulmonary hypertension (PAPm > 25 mm Hg) was present in 50.2% and was moderate (PAPm, 35 to 45 mm Hg) or severe (PAPm > 45 mm Hg) in 9.8% and in 3.7% of patients, respectively. Cardiac index was low normal. PAPm was related to Pao(2) and alveolar-arterial oxygen gradient in multivariate analysis. Cluster analysis identified a subgroup of atypical patients (n = 16, 7.4%) characterized by moderate impairment of the pulmonary mechanics (mean FEV(1), 48.5%) contrasting with high level of pulmonary artery pressure (PAPm, 39.8 mm Hg), and severe hypoxemia (mean Pao(2), 46.2 mm Hg). CONCLUSION: While pulmonary hypertension is observed in half of the COPD patients with advanced disease, moderate-to-severe pulmonary hypertension is not a rare event in these patients. We individualized a subgroup of patients presenting with a predominant vascular disease that could potentially benefit from vasodilators.

Adult↗

Recurrence of pulmonary emphysema in an alpha-1 proteinase inhibitor-deficient lung transplant recipient.

Several types of primary disease may recur after lung transplantation, but recurrence of pulmonary emphysema has so far never been published. We report the case of a 49-year-old white male who underwent single lung transplantation for emphysema related to alpha-1 antitrypsin deficiency and to superimposed smoking. The postoperative course was complicated by several rejection episodes. Subsequently, the patient remained stable without evidence of graft dysfunction for more than 10 years, but he resumed light smoking at 8 years after transplant. At 11 years after transplant, although the patient was still asymptomatic and had a stable lung function, recurrence of emphysema on the grafted side was diagnosed on computerized tomography of the thorax. One year later, the patient began to experience a moderate decline in lung function. Two separate bronchoalveolar lavages performed after the onset of the recurrence disclosed a significant elastolytic activity related to neutrophil serine-elastase in lavage fluid. In summary, we describe a case of recurrence of pulmonary emphysema in a patient with alpha-1 antitrypsin deficiency. The resumption of smoking has probably played a central role in the presence of elastolytic activity in lavage fluid and in the recurrence of emphysema.

Acute Disease↗