R. Azarian

A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism

BACKGROUND Low-molecular-weight heparin appears to be at least as effective and safe as standard, unfractionated heparin for the treatment of deep-vein thrombosis, but only limited data are available on the use of low-molecular-weight heparin to treat acute symptomatic pulmonary embolism. METHODS We randomly assigned 612 patients with symptomatic pulmonary embolism who did not require thrombolytic therapy or embolectomy to either subcutaneous low-molecular-weight heparin (tinzaparin) given once daily in a fixed dose or adjusted-dose, intravenous unfractionated heparin. Oral anticoagulant therapy was begun between the first and the third day and was given for at least three months. We compared the treatments at day 8 and day 90 with respect to a combined end point of recurrent thromboembolism, major bleeding, and death. RESULTS In the first eight days of treatment, 9 of 308 patients assigned to receive unfractionated heparin (2.9 percent) reached at least one of the end points, as compared,with 9 of 304 patients assigned to low-molecular-weight heparin (3.0 percent; absolute difference, 0.1 percentage point; 95 percent confidence interval, -2.7 to 2.6). By day 90, 22 patients assigned to unfractionated heparin (7.1 percent) and 18 patients assigned to low-molecular-weight heparin (5.9 percent) had reached at least one end point (P=0.54; absolute difference, 1.2 percentage points; 95 percent confidence interval, -2.7 to 5.1). The risk of major bleeding was similar in the two treatment groups throughout the study. CONCLUSIONS Under the conditions of this study, initial subcutaneous therapy with the low-molecular-weight heparin tinzaparin appeared to be as effective and safe as intravenous unfractionated heparin in patients with acute pulmonary embolism.

Pulmonary hypertension in patients with human immunodeficiency virus infection. Comparison with primary pulmonary hypertension.

BACKGROUND Previously reported cases of patients with pulmonary hypertension (PH) and human immunodeficiency virus (HIV) infection are poorly documented regarding baseline hemodynamics and potential for pulmonary vasodilatation. The purpose of this report was to compare HIV-infected patients who had PH with non-HIV-infected patients who had primary pulmonary hypertension (PPH) in terms of (1) clinical characteristics, (2) hemodynamics in baseline conditions and during a short-term vasodilator trial with epoprostenol, and (3) survival. METHODS AND RESULTS Between April 1987 and August 1992, 20 HIV-infected patients with PH and 93 non-HIV-infected patients with PPH were referred to our department. At the time of referral, baseline right-side heart hemodynamics were obtained in addition to demographic variables and medical history. A short-term vasodilator trial with epoprostenol was performed in 19 of 20 HIV-infected and 86 of 93 non-HIV-infected patients. Outcome and survival were analyzed and compared for both groups (22 transplant recipients were excluded from the group of patients with PPH). At the time of diagnosis of PH, HIV-infected patients significantly differed from non-HIV-infected patients in age (32 +/- 5 versus 42 +/- 13 years; P < .05) and degree of disability (New York Heart Association functional class III or IV, 50% versus 75%; P < .01). The proportion of disease states known to be associated with PPH (Raynauds phenomenon, migraine, collagen disease without overt symptoms and signs, or a positive family history of PPH) was similar in the two groups. HIV-infected patients had a severe but significantly lower level of PH than patients with PPH. The percentage of responders to epoprostenol and the level achieved in pulmonary vasodilatation were similar in the two groups. PH was the cause of death in 8 of the 10 HIV-infected patients who died within 1 year after the diagnosis of PH. Overall survival was poor and not significantly different between the two groups. Pathological findings in lung tissue obtained from 3 HIV-infected patients were close to those seen in most of the lung specimens available from 27 patients with PPH and resembled plexogenic pulmonary arteriopathy. CONCLUSIONS These results support the view that HIV infection may now be regarded as another common disease state that can be associated with PPH development. The lower initial severity in HIV-infected patients may be due to the close medical attention usually devoted to such patients, who may account for an earlier diagnosis. However, the overall survival rate of HIV-infected patients with PH appeared to be as poor as in non-HIV-infected patients with PPH.

Clinical Significance of the Pulmonary Vasodilator Response During Short-term Infusion of Prostacyclin in Primary Pulmonary Hypertension

BACKGROUND The short-term vasodilator response to prostacyclin (PGI2) in patients with primary pulmonary hypertension (PPH) is not only unpredictable but also extremely variable in magnitude. In this retrospective study, we attempted to evaluate in a nonselected population of patients with PPH the degree of vasodilatation achieved during short-term infusion of PGI2 and to investigate whether patients with PPH differed in terms of baseline characteristics and prognoses, according to the level of vasodilatation achieved during initial testing with PGI2. METHODS AND RESULTS Between 1984 and 1992, 91 consecutive patients with PPH underwent catheterization of the right side of the heart with a short-term vasodilator trial with PGI2 (5 to 10 ng.kg-1.min-1). According to the level of vasodilatation achieved during PGI2 infusion, patients were divided into three groups: nonresponding (NR, n = 40), moderately responding (MR, n = 42), and highly responding (HR, n = 9) patients. All three groups were defined by a decrease in total pulmonary resistance index (TPRi) of < 20%, between 20% and 50%, and > 50%, respectively, relative to control values. Prolonged oral vasodilator therapy was subsequently started only in MR and HR patients. All patients had long-term oral anticoagulant therapy. The survival rate at 2 years (transplant recipients excluded) was significantly higher in HR patients compared with NR and MR patients (62% versus 38% and 47% survivors, respectively; P < .05). Comparisons between groups showed no significant differences in baseline hemodynamics or clinical characteristics except for a longer time between onset of symptoms and diagnosis (ie, first catheterization) of PPH in HR patients than in NR and MR patients (71 +/- 61 versus 35 +/- 34 and 21 +/- 21 months, respectively; P < .05). CONCLUSIONS In this study, patients with PPH exhibiting a decrease in TPRi > 50% during short-term PGI2 challenge at the time of diagnosis had longer disease evolutions and better prognoses than patients with a lower vasodilator response.

Cancer bronchique du sujet âgé : Performance Status et/ou indices gériatriques ?

Resume Introduction Le vieillissement demographique pose le probleme de la prise en charge plus specifique du CBP chez le sujet âge (SA) de plus de 65 ans. Le performance status (PS) est un indice d’activite globale, conditionnant pour une part le traitement. Les indices geriatriques permettent d’apprehender de facon multifactorielle le SA. Le but de notre etude est d’evaluer si le PS est correle aux indices geriatriques chez les SA porteurs d’un CBP. Methodes Il s’agit d’une etude prospective, monocentrique. Le PS, les indices geriatriques (ADL, IADL, PINI, MMS) et le score de Charlson (SC) etaient recueillis avant traitement. Resultats Quarante et un patients âges de 75,7 ± 6,6 ans ont ete inclus. Un PS 3-4 etait note chez 15% des patients et 44% etaient stade IV. La moitie etait dependante pour l’ADL et 95% etaient dependants pour l’IADL. Un MMS 20. Le SC etait de 2,7 ± 2,1. Il existait une correlation entre le PS et les parametres geriatriques etudies mais il n’existait pas de correlation entre le PS et le SC. Conclusion Le PS est correle aux indices geriatriques; il apparait comme un bon indice d’activite globale chez le SA atteint d’un CBP.

Longs survivants de cancers bronchiques non à petites cellules stades IIIB-IV: Caractéristiques et facteurs pronostiques à partir d'une série rétrospective

Resume Introduction L’evolution des patients atteints de cancers bronchiques non a petites cellules localement avances ou metastasiques (CBav) est heterogene. Certains vont presenter une survie superieure a 2 ans : ce sont des « longs survivants » (LS). Peu d’etudes leur sont consacrees. Le but de notre etude etait de definir le taux de LS dans une population de CBNPC stades IIIB-IV et de comparer leurs caracteristiques aux patients non LS. Methode Etude retrospective menee dans un service de pneumologie de centre hospitalier general. Resultats 169 patients (43 femmes) ont ete inclus avec un taux de LS de 13,6%. Deux tiers des patients avaient un PS 0-1 et les stades IIIB pleuraux (IIIBw) et IV representaient 84,6% des cas. L’adenocarcinome (ADK) etait l’histologie predominante. En analyse univariee, les facteurs associes a une survie prolongee etaient un score de Charlson inferieur ou egal a 2, un PS 0-1, une leucocytose normale, l’ADK, la reponse (RP) au traitement de 1 re ligne, avoir recu un inhibiteur de tyrosine kinase (TKI). En analyse multivariee, seuls le PS 0-1, la RP et avoir recu un TKI etaient des facteurs independants de survie prolongee. Conclusion Les LS de CBav existent. L’avenement des TKI apparait ouvrir de nouvelles perspectives pour ces patients.

Retour veineux pulmonaire anormal révélé par un œdème pulmonaire localisé

Madame M. âgée de 69 ans, non fumeuse, sans antécédent patent, est hospitalisée pour une dyspnée rapidement progressive associée à une toux sèche, sans syndrome fébrile ou grippal, ni douleur thoracique. À l’examen clinique, la SaO2 en air ambiant est à 93 %, la TA à 129/98 mmHg, le pouls à 88 battements/min. Il n’y a pas de signes cardiaques droit ou gauche, les mollets sont souples. À l’auscultation, les bruits du cœur sont réguliers, sans souffle, il existe de rares sibilants sans crépitants. Le bilan biologique d’entrée montre : leucocytes = 6,6 G/l (PNN 52,8 % ; PNE 3 %), CRP 18 mg/l (N < 5 mg/l), troponine-Ic normale, D-dimères ELISA 1 152 ng/ml (N < 500 ng/ml). La gazométrie artérielle en air ambiant montre un pH à 7,48, une PaO2 à 60 mmHg, une PaCO2 à 37 mmHg et une SaO2 à 94 %. Le rythme est régulier sinusal avec un bloc de branche incomplet droit sans trouble de conduction ou de repolarisation à l’électrocardiogramme. La radiographie thoracique ne montre pas de foyer pleuro pulmonaire mais un discret infiltrat lobaire supérieur droit. L’index cardio-thoracique est normal. Un angioscanner thoracique est réalisé (fig. 1).

Pneumopathie aiguë à éosinophiles : rôle d’un tabagisme récemment débuté

La pneumopathie aiguë à éosinophiles (PAE) est une entité rare. Un début récent de tabagisme à la cigarette semble être un facteur déclenchant rapporté dans plusieurs cas cliniques en particulier chez des patients jeunes. Ses mécanismes et la susceptibilité individuelle des patients ne sont pas actuellement connus. Nous rapportons le cas de M. C., 23 ans, sans antécédent en dehors d’une schizophrénie traitée au long cours par Risperdal®, Tranxene®, Deroxat®. Il n’existait pas de terrain atopique, ni d’asthme, ni de toxicomanie. Alors que le patient était hospitalisé en psychiatrie, survenait brutalement en dehors de toute prise alimentaire deux épisodes de dyspnée aiguë motivant son transfert dans notre service. À l’entrée, le patient était apyrétique, cyanosé, polypnéique au repos, sans toux ni expectoration ni douleur thoracique. Le patient rapportait un tabagisme récent débuté 10 jours avant son admission en pneumologie, de 10 à 20 cigarettes par jour. Aucun nouveau traitement médicamenteux n’avait été instauré. L’auscultation cardio-pulmonaire était normale. La gazométrie artérielle en air ambiant objectivait une alcalose respiratoire avec une hypocapnie à 34 mmHg et une hypoxie à 60 mmHg. Le bilan biologique était le suivant : leucocytes : 15,7 G/l à prédominance de polynucléaires neutrophiles, polynucléaires éosinophiles : 0,15 G/l, CRP : 18 mg/l, bilans ioniques, rénaux et hépatiques : normaux, D-dimères : 1 003 ng/ml. L’électrocardiogramme était normal de même que la radiographie thoracique. La scintigraphie pulmonaire de ventilation-perfusion était de probabilité intermédiaire. Une anticoagulation à doses efficaces par héparine de bas poids moléculaire était débutée. Le lendemain de l’admission, apparaissait une fièvre à 39 °C avec à l’auscultation pulmonaire des crépitants des bases. La radiographie pulmonaire montrait l’apparition d’un comblement du cul-de-sac pleural gauche. L’angioscanner ne montrait pas d’obstruction vasculaire pulmonaire au moins jusqu’au niveau segmentaire ; les coupes tomodensitométriques hautes résolution (TDM-HR) parenchymateuses mettaient en évidence un épaississement des septas sous pleuraux, des images en verre dépoli au niveau des lobes supérieurs associé à un épanchement pleural bilatéRéception version princeps à la Revue : 19.02.2004. Retour aux auteurs pour révision : 08.04.2004. Réception 1ère version revisée : 28.05.2004. Acceptation définitive : 03.06.2004. cdujon@ch-versailles.fr

Anti-tumour effect of low molecular weight heparin in localised lung cancer: a phase III clinical trial

The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated. Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg−1 once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival. In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±sd age was 61.6±8.9 years, 190 (34.6%) patients had stage II−III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92–1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68–1.30; p=0.70). Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I−IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents. Whether the antimetastatic properties of heparins benefit patients with early-stage cancer is unknown. In this phase III trial, adjuvant tinzaparin in patients with resected lung cancer had no impact on overall survival and tumour recurrence. http://ow.ly/RZt030lpCuQ