[Legionella spp: An update]. / Actualités sur les infections à Legionella.

Legionella-related disease is caused by an intracellular bacteria mainly living in water. Contamination results from inhalation of Legionella sp containing aerosolized water. Main risk factors are tobacco, immunodeficiency, and advanced age. Antigenuria is the cornerstone of the diagnosis. Immunocompromised patients, more commonly infected with non pneumophilaLegionella, present negative antigenuria, and culture and PCR are essential for the diagnosis. Legionnaires' disease may be severe, especially in elderly and/or immunocompromised patients. Mortality rate varies from 10 % in the general population to 50 % in intensive care. Treatment is based on macrolides or fluoroquinolones. Antibiotic resistance is very rare.

Reduction of radiation exposure associated with renewal of the radiologic systems in coronary interventions.

PURPOSE: Interventional coronary procedures are an important source of radiation. This study sought to evaluate the effect of the renewal of the radiologic system on patient exposure during diagnostic coronary angiography (DCA) and percutaneous coronary interventions (PCIs). METHODS: DCA and PCIs were obtained from three centres, which renewed their radiologic systems during their participation in the multicentre prospective observational RAY'ACT-2 study. Data were analysed from the months before and after the radiologic system was changed. The primary outcomes were the dose reduction estimated by the kerma.area product (KAP in Gy·cm2) and the ratio of the KAP to fluoroscopy time (Gy·cm2·min-1). RESULTS: A total of 2148 patients underwent DCA (1575 before and 573 after the system change), and 1563 underwent PCI (1196 before and 367 after). A change in the radiologic system was associated with a KAP reduction of 43% for DCA (median [interquartile range]: 18.1Gy·cm2 [10.2-34.0] versus 31.5 [19.0-49.0], P<0.0001), and 38% for PCI (42.2Gy·cm2 [23.8-81.7] versus 70.1 [42.0-109.0], P<0.0001). Fluoroscopy time did not vary significantly, and the ratio KAP to fluoroscopy time significantly decreased by 54%. The dose reduction was homogeneous between the three centres and between different manufacturer's systems. CONCLUSIONS: In this multicentre study, the renewal of the radiologic system was associated with a highly significant 40%-50% reduction in radiation dose, irrespective of the manufacturer. A close interaction between manufacturers and operators is needed to optimise the use of new equipment and the effectiveness of radiation reduction tools and techniques.

Eclipsed mitral regurgitation: an unusual cause of acute heart failure.

AIMS: So far, a total of five patients with eclipsed mitral regurgitation (MR) have been reported in the literature by three different teams. The aim of this article was to detail clinical and echocardiographic characteristics, and outcome of patients presenting eclipsed MR. METHODS AND RESULTS: We defined eclipsed MR as spontaneous appearance, at rest, from 1 min to the next of an acute restriction in the motion of mitral leaflets preventing coaptation and leading to massive MR in patients with normal left ventricular end-diastolic diameter, left ventricular ejection fraction >45%, and baseline MR ≤2. Spontaneous regression occurred within 30 min, and no obvious trigger such as acute hypertension, new-onset arrhythmia, or myocardial ischaemia is present. Clinical data, ECG, echocardiographic data, surgery report, and follow-up status of six patients with eclipsed MR are reported: all were post-menopausal women with median age of 74 [57-80] years presenting hypertension (4/6), chronic kidney disease (5/6), or chronic anaemia (4/6). Five out of six patients experienced acute pulmonary oedema requiring hospitalization and underwent mitral valve replacement because of heart failure recurrence. Two patients died in the first days after surgery while the three others are free of symptoms at, respectively, 56, 18, and 10 months follow-up. CONCLUSION: Eclipsed MR is a clinical and echocardiographic syndrome responsible for heart failure with preserved EF. It is presently underdiagnosed and should be evoked in cases of recurrent acute pulmonary oedema without obvious trigger, in particular in patients presenting discordant evaluation of MR severity over time.

[Evaluation of patients' knowledge regarding counsels provided in case of chest pain after an acute myocardial infarction]. / Evaluation des conseils assimilés par les patients sur l'attitude recommandée en cas de douleur thoracique au décours d'un infarctus aigu du myocarde. Conseils ou patient après un infarctus du myocarde.

INTRODUCTION: an early call to the department of urgent medical assistance--Center 15 (SAMU-centre 15) is associated to shortest delays of reperfusion in case of myocardial infarction. However, patients are not always aware of this. OBJECTIVE: to assess the assimilated counsels by patients after an acute myocardial infarction. METHODS: from January 1998 to June 2004, patients managed by SAMU 93 and having benefited from thrombolytic therapy prior to hospitalization and/or primary angioplasty for a ST+ acute coronary syndrome with a confirmation of acute myocardial infarction during their hospital stay were prospectively enrolled into this study. A questionnaire was administered by phone from december 2003 to july 2005, assessing the knowledge about the necessity to alert SAMU-center 15 in case of chest pain and availability of medical files data. RESULTS: among the 976 patients: 111 (11%) were lost during follow-up, 162 (19%) were deceased when phone contact and 119 (12%) could not be interrogated. Among the 584 (60%) remaining subjects interrogated with a median follow-up period of 985 days (413-1596), 290 (50%) patients answered they received counseling, including 156 (27%) for taking nitrates, 19 (29%) stated they know that they should call SAMU-center 15. Patients with a high level of education and those treated by thrombolytic therapy prior to hospitalization were better informed; 464 (79%) patients declared having a prescription, 392 (67%) a hospital report, 406 (69%) an electrocardiogram, 227 (39%) a CD with their coronary angiography, and 79(14%) their medical file. CONCLUSION: the level of knowledge regarding the recommended attitude in case of chest pain is poor. The availability of medical data was better. Arch Mal Cceur

[Transient left ventricular apical ballooning syndrome or Takotsubo cardiomyopathy. About 11 cases]. / Ballonisation apicale transitoire du ventricule gauche ou syndrome de tako-tsubo. a propos de 11 cas et revue de la littérature.

Takotsubo cardiomyopathy is a clinical entity mimicking an ST elevation myocardial infarction recently identified. Are associated a chest pain, electrocardiographics abnormalities, minor elevation of enzyme biomarkers in patients who don't have any significant angiographic stenosis on the coronary angiography and where left ventricle angiography shows apical regional wallmotion abnormalities with a characteristic apical ballooning aspect. Between march 2003 and march 2005, we included 11 patients for whom this syndrom was suspected. Mean age was 70, 3 years old. Electrocardiogram was abnormal in all cases. Biological markers show for all patients an elevation of troponin I. All patients had a coronary angiography and coronary arteries were normal. Left ventricle angiography showed in all cases wall-motion abnormalities in the apex with a ballooning aspect. A psychological or physical inducing factor has been found for 8 patients. The evolution was simple for all patients with no complications noted and no recurrence with a mean follow up of 15 months. Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrom have a good long-term prognosis even if serious complications sometimes deathly can be seen. The cause of this syndrom is unknown but it must be considered as a possible diagnosis of ST elevation myocardial infarction with normal coronary arteries.

[Measurement of fractional flow reserve in patients with severe aortic stenosis: A valid test?] / Sténose aortique et lésions coronaires : la fractional flow reserve (FFR) est-elle valide ?

A 54-year-old woman was hospitalized for an acute pulmonary oedema revealing a severe aortic stenosis (AS) associated with an aortic aneurysm and a left ventricular hypertrophy (LVH). The coronary angiography found an equivocal left main lesion. Fractional flow reserve (FFR) showed hemodynamic significance (FFR=0.78) and optical coherence tomography confirmed this result with a minimal lumen area of 4.9mm2. FFR-guided percutaneous intervention is reported to improve outcome in patients with stable coronary disease. However, only few data are available in cases of AS. In this condition, secondary LVH is associated with microcirculatory dysfunction, which interferes with optimal hyperemia. An elevated right atrial pressure could also modify FFR measurement. This risk of underestimation of a coronary lesion in patients with severe AS has to be taken into consideration in clinical practice.

[Free floating thrombus in right cardiac chambers and thrombolysis]. / Thrombus flottant dans les cavités droites.

Free-floating thrombi in the right heart chambers is a rare phenomenon. Nearly 99% of detected cases are associated with the presence of proven pulmonary embolism. Its presence is associated with a poor outcome with a mortality between 27 to 44% according to studies. Despite the emergency of treatment, optimal management of free floating right heart thrombus remains controversial with no clear consensus. We present the case of a 84-year-old man hospitalised for acute decompensated heart failure. After an initial favourable evolution, a degradation of respiratory occurred with dyspnea and desaturation. A bedside transthoracic echocardiography showed a mobile serpiginous thrombus, 7cm size, moving to and across the tricuspid valve. A computed tomography of the chest demonstrated massive bilateral pulmonary embolism. After persistence of the thrombus and seven days of heparinotherapy, thrombolysis therapy was initiated. The thrombus disappeared 24h after thrombolysis. Without contra-indication, thrombolysis is a faster, readily available treatment for the management of floating thrombus in the right heart chambers associated with pulmonary embolism.

Modulation of functional connectivity following visual adaptation: homeostasis in V1.

Sensory neurons exhibit remarkable adaptability in acquiring new optimal selectivity to unfamiliar features when a new stimulus becomes prevalent in the environment. In conventionally prepared adult anesthetized cats, we used visual adaptation to change the preferred orientation selectivity in V1 neurons. Cortical circuits are dominated by complex and intricate connections between neurons. Cross-correlation of cellular spike-trains discloses the putative functional connection between two neurons. We sought to investigate changes in these links following a 12 min uninterrupted application of a specific, usually non-preferred, orientation. We report that visual adaptation, mimicking training, modulates the magnitude of crosscorrelograms suggesting that the strength of inter-neuronal relationships is modified. While individual cell-pairs exhibit changes in their response correlation strength, the average correlation of the recorded cell cluster remains unchanged. Hence, visual adaptation induces plastic changes that impact the connectivity between neurons.

One-month results of coronary stenting in patients > or = 75 years of age.

Coronary artery bypass operations are associated with increased morbidity and mortality in the elderly. Similarly, it has been shown that coronary angioplasty is associated with a higher risk of complications in the elderly than in younger patients. The purpose of this study was to evaluate the 1-month outcome of elderly patients (>75 years old) who were included in the Stenting without Coumadin French Registry. From December 1992 to March 1995, 2,900 patients (mean age 61+/-11 years) were included in this registry. All patients were treated with ticlopidine (250 to 500 mg/day) for 1 month from the day of percutaneous transluminal angioplasty, aspirin (100 to 250 mg/day) for >6 months, and low-molecular-weight heparin (antiXa 0.5 to 1 IU/ml) for 1 month in phase II, 15 days in phase III, and 7 days in phase IV. No heparin was given in phase V. The study group included 233 patients (8.0%) > 75 years old (mean age 79+/-4), 44 (18%) of whom were women. All patients underwent dilatation of a native coronary vessel. One hundred seventeen had unstable angina (50.2%), 20 had postmyocardial infarction ischemia (8.6%), and 6 had acute myocardial infarction (2.6%). Indications for stenting were de novo lesion in 63 patients (27.0%), restenosis in 38 (16.3%), suboptimal result in 48 (20.6%), nonocclusive dissection in 56 (24.0%), and occlusive dissection in 28 (12.0%), respectively. Stented coronary arteries were the left anterior descending in 109 (46.8%), the right in 80 (34.3%), the left circumflex in 40 (17.2%), and the left main in 4 (1.7%). Palmaz-Schatz stents were used in 228 patients (82.0%), AVE microstents in 38 (13.7%), and other stents in 12 (4.3%). More than 1 stent was used in 48 patients (17.3%). The mean diameter of the balloon used for stenting was 3.31+/-0.38 mm and maximal inflation pressure was 12.2+/-2.9 atm. At one-month follow-up, vascular complications occurred in 5 patients, requiring surgery in 2 (1.3%), acute closure occurred in 1 (0.4%), subacute closure in 3 (1.3%), emergency or planned coronary artery bypass graft surgery in none, acute myocardial infarction in 4 (1.7%), stroke in 1 (0.4%), and death in 8 (3.4%). The composite end point of a major cardiac event was observed in 13 cases (5.6%). Coronary stenting using ticlopidine and aspirin appears to be a particularly safe approach in this high-risk subset.

Predictive factors of outcome of intensive intravenous treatment for attacks of ulcerative colitis.

BACKGROUND: Intensive intravenous treatment remains the first line therapy of severe, uncomplicated attacks of ulcerative colitis. AIM: To predict the failure of intensive intravenous treatment by combining clinical and laboratory parameters with endoscopy findings. METHODS: Retrospective study conducted in a tertiary care referral centre. Failure of intensive intravenous treatment was defined as colectomy before day 30, intravenous cyclosporin, or death. Predictive factors of outcome were assessed using univariate and multivariate prognostic analysis. RESULTS: Between January 1990 and May 1997, 85 consecutive patients were treated with intensive intravenous treatment for non-response to oral corticosteroids (n=59) and/or severe attack of ulcerative colitis (n=26). There were 41 successes and 44 failures (including 1 death, 13 cyclosporin and 30 colectomies before day 30). Multivariate prognostic analysis found that the presence of Truelove and Witts' criteria (P=0.018), an attack that had lasted more than 6 weeks (P=0.001), and severe endoscopic lesions (P=0.007) were associated with an increased risk of failure. Patients with severe endoscopic lesions and Truelove and Witts' criteria, or an attack of more than 6 weeks had a failure rate of 85-86%. CONCLUSION: Clinical, laboratory and endoscopic findings can predict the risk of failure of intensive intravenous treatment. A prospective study is required to confirm these results.

Effects of current and former cigarette smoking on the clinical course of Crohn's disease.

BACKGROUND: Cigarette smoking is associated with a more severe course of Crohn's disease, but individual factors determining this effect are poorly known and it is not clear whether smoking cessation is associated with an improvement in the disease activity. AIM: To assess the factors determining the harmful effect of smoking in individuals with Crohn's disease. METHODS: A total of 622 consecutive patients with Crohn's disease and Crohn's disease activity index <200 were enrolled in a prospective 12-18 month cohort study. Patients were classified as current smokers, former smokers, or non-smokers. Alcohol consumption, oral contraceptive use, body mass index, and blood lipid levels were also recorded. The main outcome measure was the rate of flare-up. RESULTS: A total of 139 current smokers (46%) developed a flare-up, vs. 79 non-smokers (30%) and 13 former smokers (23%). The relative risk of flare-up adjusted for confounding factors was 1.35 (1.03-1.76) in current smokers. This risk was increased in patients with previously inactive disease and in those who had no colonic lesions. It became significant above a threshold of 15 cigarettes per day. Former smokers behaved like non-smokers. Obesity, dyslipidaemia, and alcohol consumption had no significant effect. CONCLUSIONS: Current smoking, particularly heavy smoking, markedly increases the risk of flare-up in Crohn's disease. Former smokers have a risk similar to that of non-smokers.

Hepatocellular carcinoma and focal hepatic glycogenosis after prolonged azathioprine therapy.

A 22-year-old woman without predisposing liver disease developed focal hepatic glycogenosis and hepatocellular carcinoma after 6 years of azathioprine therapy for Crohn's disease. Hepatocellular carcinoma without cirrhosis has previously been described during immunosuppression, but this is the first report of disseminated focal hepatic glycogenosis after long-term azathioprine therapy.

Crohn's disease clinical course and severity in obese patients.

BACKGROUND AND AIMS: Obesity is unusual in Crohn's disease and the particularities of the disease in obese patients have not been studied. METHODS: 2065 patients were studied retrospectively. Obesity was defined by a BMI value >25.0 at disease onset and >30.0 at any time during the course of the disease. Disease characteristics, therapeutic needs, and year-by-year disease activity were determined in patients with and without obesity. RESULTS: 62 patients (3%) were obese. When compared with non-obese patients, obese patients did not show differences regarding sex, intestinal disease location, and disease behavior, but at diagnosis they were older (32 vs 28 years, P = 0.01) and a larger proportion had anoperineal disease (35 vs 24%, P = 0.03). When the 62 obese patients were paired for sex, location of disease at onset, date of birth, and date of diagnosis with 124 non-obese patients, the disease severity assessed by the importance of medical therapy and excisional surgery did not differ in the two groups but time to development of anoperineal abscess or fistula was shorter in obese patients, and obese patients were more prone to develop an active disease (OR 1.50, 95% CI 1.07-2.11) and to require hospitalization (OR 2.35, 95% CI 1.56-3.52) CONCLUSION: Obesity in Crohn's disease is associated with more frequent anoperineal complications and a more marked year-by-year disease activity, but does not alter significantly the long-term course of the disease.

Percutaneous transluminal angioplasty of stenotic lesions in dialysis vascular accesses.

Forty-five stenoses behind arteriovenous fistulas in 35' haemodialysed patients were treated with percutaneous transluminal angioplasty (PTA). Immediate stenoses dilatation results in relation to the AVF type were haemodynamically significant in 40 cases (88%), with poorer results on bovine heterograft stenoses. Dilatation results in relation to the site of the lesion showed haemodynamically efficient angioplasty on stenoses next to the anastomosis (67.5%) but a poor result on distal lesions (4 cases). We observed 4 cases of thrombosis but 2 recovered after treatment, one after local fibrinolytic perfusion one after surgical thrombectomy. Follow-up over a period of one to 18 months (mean 8 months) including angiography and appreciation of the dialysis quality were performed in 30 patients who had a successful dilatation. PTA appears to be a technically feasible and clinically effective method of treating stenoses lying on the venous limb fistula in patients on chronic haemodialysis.

[Methods of evaluating the treatment of unstable angina]. / Méthodologie de l'évaluation des traitements de l'angor instable.

Although unstable angina is an extremely common and often initial manifestation of coronary disease, few controlled studies of its treatment have been carried out. This relative dearth of information is due to the methodological problems raised by the evaluation of unstable angina. Unlike the definition of myocardial infarction, that of unstable angina--i.e. of a population of coronary patients who from time to time are at a high risk of myocardial infarction or death--is neither unequivocal nor easy to standardize. It follows that the patient population ultimately selected for controlled trials is but a small part of all unstable angina patients. The representativeness of patients involved in therapeutic trials is probably approximate. Moreover, the current criteria for assessment of effectiveness are either the clinical signs of angina in the short term or the incidence of myocardial infarction and changes in survival curves in the mid- and long terms. A more precise definition of criteria of inclusion, leading to an homogeneous population, and the development of a simple and reliable method for detecting and quantifying myocardial ischaemia, both being used as intermediate criteria of assessment, would undoubtedly improve the quality of therapeutic trials in unstable angina and, mostly, their applicability to daily therapeutic practice.

[Demonstration of reversible myocardial ischemia in necrotic akinetic areas using endocoronary ECG during angioplasty]. / Mise en évidence d'une ischémie myocardique réversible en territoire nécrosé akinétique par ECG endocoronaire per-angioplastie.

The presence of ischaemic myocardial tissues in necrotic territories and the usefulness of revascularizing these territories are controversial matters. We have determined the existence of this phenomenon by the per-angioplastic intracoronary ECG method, and we have compared the sensitivities of intracoronary ECG and surface ECG. Intracoronary EVG is achieved by using the mobile teflon-coated guide wire of coronary angioplasty as a unipolar epicardial electrode. Being epicardial and localized, the electrode explores a limited area of the myocardium, distal to the artery being dilated and momentarily occluded by the balloon during inflations. The study involved 12 patients (mean age 53.7 years) who presented with the following criteria of admission: transmural myocardial infarction, presence of a Q wave on two leads, akinetic segment at ventriculography and coronary stenosis or occlusion amenable to angioplasty. Patients with collateral circulation between the larger epicardial vessels were excluded. Intracoronary ECG recordings were taken before, during and after inflations. In 9 out of 12 patients the ST segments was elevated by 1.3 mV on average between inflations (S.D. 3.14 mV) and by 4.8 mV (S.D. 3.99 mV) during inflations. These high standard deviations were due to major inter- and intra-individual variations of ST. The difference was significant (p less than 0.05) at variance analysis. No variation of ST was observed in 3 patients. Only one of the 12 patients had elevated ST on both surface ECG and intracoronary ECG tracings. Thus, intracoronary ECG is a sensitive method to evaluate myocardial ischaemia during coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

[Paroxysmal ischemic mitral valve insufficiency]. / Insuffisance mitrale ischémique paroxystique.

The prognosis of patients with coronary artery disease may be threatened by ischaemic mitral regurgitation. Apart from rupture of a papillary muscle which requires rapid valve replacement. Chronic ischaemic papillary muscle dysfunction can often be a severe complication of ischaemic heart disease. The authors report the case of a patient with dyspnoea but no angina of effort. Cardiovascular investigations with right heart catheterisation demonstrated the occurrence of severe mitral regurgitation only during angioplasty of the left marginal artery.

[Chronic obstructions of the left main and right coronary arteries]. / Occlusions chroniques du tronc coronaire gauche et de la coronaire droite.

The authors report a case of chronic occlusion of the left main coronary associated with occlusion of the second segment of the right coronary artery documented at coronary angiography carried out for effort angina without previous infarction. Myocardial perfusion was preserved mainly by a marginal branch of the right coronary arising immediately before the occluded second segment and by a small branch of the left main coronary artery.

[6-mercaptopurine levels and study of blood lymphocyte subsets during azathioprine treatment of Crohn's disease]. / Dosage de la 6-mercaptopurine et étude des sous-populations lymphocytaires sanguines au cours du traitement par l'azathioprine dans la malaide de Crohn.

OBJECTIVES: Our aim was to study the relationships between clinical efficacy of azathioprine, 6-mercaptopurine pharmacokinetics and changes in peripheral blood lymphocyte subpopulations induced by azathioprine treatment in Crohn's disease. METHODS: Twenty-three patients were prospectively followed up for 1 year. Peripheral blood counts, total lymphocytes, CD3+, CD4+, CD8+, CD25+, CD16+CD56+, CD57+ and CD19+ lymphocyte subpopulations were carried out, using flow cytometry, during azathioprine treatment. Pharmacokinetic studies were performed at day 8 and month 3 by measuring 6-mercaptopurine plasma concentration after an oral dose of azathioprine (2 mg/kg). Results were compared in responders (no activity and no steroids) and non-responders. RESULTS: The decrease in peripheral blood leukocytes and neutrophils was significant after 1 month, reaching 49% and 48% of the pre-treatment values at 1 year; the one of lymphocytes was significant after 6 months and reached 41% at 1 year. Percentages of CD3+, CD4+, CD8+, CD57+, CD16+CD56+ and CD19+ lymphocytes remained unchanged whereas percentage of CD25+ lymphocytes increased from 10% to 28% (P < 0.01). There was a high inter and intraindividual variability of 6-mercaptopurine peak plasma concentration and area under the curve. No significant difference was found between responders (n = 14) and non responders (n = 7) for pharmacokinetic parameters and lymphocyte subpopulations; there was no correlation between lymphocyte subpopulation changes and 6-mercaptopurine pharmacokinetics. CONCLUSION: Monitoring of 6-mercaptopurine plasma concentration and blood lymphocyte subpopulations is of little value in Crohn's disease patients treated with azathioprine.

[Contribution of telemedicine applied to digestive cancer]. / Apport de la télémédecine appliquée à la cancérologie digestive.

AIM OF THE STUDY: Telemedicine offers new possibilities for multidisciplinary care of cancer patients, allowing direct communications between different, complementary and geographically distant specialists. Thus, it is possible to form oncology committees in small hospitals where all specialties are not represented. The purpose of this study was to evaluate the medical and economic impact of visioconferences in the therapeutic management of cancer patients without access to oncology centers. MATERIALS: A telemedicine network was created in Paris between the General Surgery and Gastroenterology services of Rothschild Hospital and the services of Oncology at Saint-Antoine Hospital and Radiotherapy at Tenon Hospital. The three hospitals were connected simultaneously (multipoint) by visioconference and thus constituted a pluridisciplinary oncology committee of radiotherapy, chemotherapy and surgery. Eighty seven cases were evaluated in 27 staff conferences. In 48 cases, this consisted of re-evaluating therapeutic decisions made in surgery or gastroenterology, and in 39 cases opinions were requested by surgery (18), gastroenterology (14) or oncology departments (7). RESULTS: In only 34/87 cases therapeutic agreement was reached directly. The 53 other cases (60.9%) were debated. In fact, all 39 requests for opinion in difficult therapeutic decisions resulted in consensus. Among the 48 re-evaluations, disagreement persisted in one case between the surgeon in charge of the patient and the chemotherapist. Importantly, in 13 of 48 cases (27%), the discussion modified the therapeutic protocol initially proposed. The average cost was 118 French Francs per case and per center. Total initial investment was 334,762 French Francs, but the price of some equipment has already dropped from 30 to 60%. CONCLUSION: In our study, the visioconference improved management of cancer patients for a weak working cost.