Factors influencing survival after surgery of pure non-ischemic mitral insufficiency

Uni and multifactorial (Cox) statistical analysis of the results of surgery in a series of 247 patients operated between 1969 and 1988 for pure, non-ischaemic mitral regurgitation was undertaken to determine the factors influencing operative and late mortality. All but 3 cases were adults, average age 51 years, and very symptomatic (75 per cent Class III et IV of NYHA Classification). Dystrophic or degenerative lesions were responsible for 53 per cent of cases of regurgitation whilst rheumatic valvular disease was only observed in 30 per cent of cases. Mitral valve replacement was performed in 137 patients (96 mechanical and 41 bioprostheses) and conservative surgery was possible in 110 cases. There were 12 operative deaths (4.9%); the operative risk increased with age and with the practice of valve replacement. Eleven of the 235 survivors (4.7%) were lost to follow-up. During the follow-up period (average 58 months) there were 37 late deaths of which nearly a half were due to left ventricular dysfunction. Multifactorial analysis identified cardiothoracic ratio and atrial fibrillation as predictive factors of late mortality whilst left ventricular ejection fraction and the type of surgery were related to the development of left ventricular dysfunction. The postoperative left ventricular ejection fraction was significantly lower after valve replacement than after valvuloplasty (11 +/- 13% vs 3 +/- 13%; p less than 0.01). These results are therefore in favour of early correction of severe mitral regurgitation by conservative surgery whenever possible.     

Preoperative Measurement of Thickness of Cutaneous Melanoma Using High-Resolution 20 MHz Ultrasound Imaging: A Monocenter Prospective Study and Systematic Review of the Literature

Histologic measurement of the thickness of melanoma is a major prognostic factor and governs the size of the surgical excision (1cm for melanomas less than 1 mm thick, 2 cm for melanomas thicker than 2 mm and 3 cm beyond 4 mm). To determine whether high-resolution ultrasound can be used to predict surgical margins and, thus, to operate on patients in a single procedure avoiding further re-excision, we performed a systematic review of studies published from January 1987 to June 2007 and a prospective study. The systematic review selected 14 studies comparing histologic and ultrasound measurements and showing correlation coefficients generally greater than 0.9. Data available from 7 of the 14 studies (total 869 patients) showed predictive values of adequate margins in at least 72% of lesions using preoperative measurement of ultrasound thickness. The prospective study included 31 patients referred with a primary melanoma from March 2005 to March 2007. Ultrasound measurement of thickness was possible except for thin melanomas (<0.4 mm) in areas with marked photoaging, in the plantar zone, and in the case of very thick melanomas exceeding the explored depth (7.6 mm). The average thickness was 1.96 mm measured by ultrasound (SD: 2.15) and 1.95 mm by histology (SD: 2.62) and the Bland and Altman graph showed moderate agreement between ultrasound and histology. Limits of agreement were estimated at –1.4 and +1.8, corresponding to relative limits of agreement of –40 to +80%. Ultrasound predicted appropriate margins (1, 2 or 3 cm wide according to sonometric thickness) in 26 of the 31 subjects (84%, 95% CI 66–95). Preoperative high-resolution ultrasound is a noninvasive examination that can help in choosing appropriate surgical margins and should reduce the need of partial or excisional biopsy before surgery, and the need for further re-excision. (E-mail: machet@univ-tours.fr)     

Les multiples facettes du déficit en ADA2, vascularite,maladie auto-inflammatoire et immunodéficit : mise au point à partir des 135 cas de la littérature

Deficiency of adenosine deaminase 2 (DADA2) is a recently described auto-inflammatory disorder. It is an autosomal recessive inherited disease, caused by mutations in the ADA2 gene (formerly known as CECR1) encoding ADA2 enzyme. Besides its role in the purine metabolism, it has been postulated that ADA2 may act as a growth factor for endothelial cells and in the differenciation of monocytes. Thus, deficiency of ADA2 would lead to endothelial damage and a skewing of monocytes into M1 pro-inflammatory macrophage, causing DADA2 manifestations. Three core clinical features have been described: inflammatory-vascular signs, hematologic abnormalities and immunodeficiency. Clinically, patients display intermittent fever, cutaneous vascular manifestations, such as livedo, ischemic strokes, arthralgia and abdominal pain crisis. Corticosteroids and immunosuppressive agents (i.e. cyclophosphamide, azathioprine, ciclosporin, methotrexate) appear to be poorly effective. Although the mechanism has not been elucidated, anti-TNF agents have been proven efficient in DADA2 and should therefore be used as first line therapy for vasculitis. Role of anti-platelet and anticoagulant therapies in stroke-prophylaxis remains to be discussed, as those patients display a high risk of intracranial bleeding.     

Galectin-1 is highly expressed in human gliomas with relevance for modulation of invasion of tumor astrocytes into the brain parenchyma

Protein (lectin)-carbohydrate interaction is supposed to be relevant for tumor cell behavior. The aims of the present work are to investigate whether galectin-1 modulates migration/invasion features in human gliomas in vitro, whether it can be detected in human gliomas immunohistochemically, and whether its expression is attributable to certain glioma subgroups with respect to invasion and prognosis. For this purpose, we quantitatively determined (by computer-assisted microscopy) the immunohistochemical expression of galectin-1 in 220 gliomas, including 151 astrocytic, 38 oligodendroglial, and 31 ependymal tumors obtained from surgical resection. We also xenografted three human glioblastoma cell lines (the H4, U87, and U373 models) into the brains of nude mice in order to characterize the in vivo galectin-1 expression pattern in relation to tumor invasion of the normal brain parenchyma. In addition, we characterized the role in vitro of galectin-1 in U373 tumor astrocyte migration and kinetics. Our data reveal expression of galectin-1 in all human glioma types with no striking differences between astrocytic, oligodendroglial, and ependymal tumors. The level of galectin-1 expression correlated with the grade in the group of astrocytic tumors only. Furthermore, immunopositivity of high-grade astrocytic tumors from patients with short-term survival periods was stronger than that of tumors from patients with long-term survivals. In human glioblastoma xenografts, galectin-1 was preferentially expressed in the more invasive parts of these xenografts. In vitro experiments revealed that galectin-1 stimulates migration of U373 astrocytes.     

Neonatal screening for cystic fibrosis: France rises to the challenge

This paper describes the adjustments to the French neonatal screening programme required by the introduction of systematic screening for cystic fibrosis (CF), taking into account both the legal and statutory framework and the lessons of a pilot study carried out 10 years ago. The French association for the screening and prevention of infant handicaps (AFDPHE) has been mandated by its regulatory agencies to organize screening for CF in France (metropolitan and overseas territories). During the year 2001, expert groups (Technical Aspects, Information, Ethics and Genetics, Criteria for CF Centres, Protocol for the Care of a Newborn with CF) issued recommendations for the establishment of a national programme that would guarantee efficiency and adequate patient care from the time of diagnosis onward. The programme is based on a strategy combining immunoreactive trypsin (IRT) assay and the analysis of DNA mutations in dried blood samples obtained at 3 days of age. When an elevated IRT value is found, DNA analysis is performed on the same sample. Owing to the relative regional heterogeneity existing in France, 30 selected mutations are used, which provide 85% coverage. The Ethics and Genetics Committee recommended that, in order to avoid arousing anxiety by a recall, informed consent, according to the French legislation on bioethics, should be obtained for all neonates at birth by having the parents sign directly on the sampling paper. Information brochures for parents and health professionals have been designed. A new organization of patient care, involving the creation of CF centres recognized by the Ministry of Health, has been decided; all children diagnosed are to be referred to such centres, where they can be well cared for by a trained staff with sufficient means. The programme was implemented region by region in France, from the beginning of the year 2002 to early 2003. The expert groups still meet periodically to evaluate the implementation of the programme and to check that the terms of the agreement between the AFDPHE and the Social Security Agency are complied with.     

An overall strategy based on regression models to estimate relative survival and model the effects of prognostic factors in cancer survival studies

Relative survival provides a measure of the proportion of patients dying from the disease under study without requiring the knowledge of the cause of death. We propose an overall strategy based on regression models to estimate the relative survival and model the effects of potential prognostic factors. The baseline hazard was modelled until 10 years follow-up using parametric continuous functions. Six models including cubic regression splines were considered and the Akaike Information Criterion was used to select the final model. This approach yielded smooth and reliable estimates of mortality hazard and allowed us to deal with sparse data taking into account all the available information. Splines were also used to model simultaneously non-linear effects of continuous covariates and time-dependent hazard ratios. This led to a graphical representation of the hazard ratio that can be useful for clinical interpretation. Estimates of these models were obtained by likelihood maximization. We showed that these estimates could be also obtained using standard algorithms for Poisson regression.