Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. METHODS: Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. RESULTS: Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). CONCLUSIONS: There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.
ISSN: 1058-4838

hal-00875143
https://hal.archives-ouvertes.fr/hal-00875143
DOI : 10.1093/cid/cis878
PUBMED : 23074311

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: In Guadeloupe and Martinique, two French Overseas Departments, colorectal cancer (CRC) has become an essential public health issue. However, little is known about CRC characteristics and the p53 status in these populations, particularly in Guadeloupe, whereas certification of a cancer registry has been recently validated. METHODS: This was a descriptive retrospective study of 201 patients who, between 1995 and 2000, underwent surgery for CRC in the Guadeloupe Teaching Hospital (GlpeTH; 83 patients) and in the Martinique Teaching Hospital (MqueTH; 118 patients). The clinicopathological features and the p53 expression, evaluated with immunohistochemistry, were compared at the time of diagnosis. A relationship between these parameters and the p53 expression was also studied. Data were analysed, using the SPSS computer software version 17.0. RESULTS: No statistical difference was found between the two groups of patients regarding age (p = 0.60), percentage of young patients (<=50 years; p = 0.94)), sex (p = 0.47), histological type (p = 0.073) and tumour sites (p = 0.65), although the GlpeTH patients were diagnosed with more distal colon cancers (54.2%) than the Mque TH patients (47.4%). By contrast, a significant difference was found regarding the tumour grade (p < 0.0001), the pTNM stage (p = 0.045) and the pT stage (p < 0.0001). Regarding p53 expression, solely for the MqueTH patients, nuclear expression was associated with pTNM, the percentage of p53 negative tumours increasing with the progression of the pTNM stages (p = 0.029). CONCLUSIONS: For the first time, this study reveals discrepancies in clinicopathological features and in the p53 status between the two groups of patients. The GlpeTH patients were diagnosed with more moderated CRCs but with few CRCs at pTNM IV stage. By contrast, the MqueTH patients were diagnosed with more differentiated tumours, but with many more CRCs at pTNM IV stage. This paradox may be due to differences in tumour location (distal vs proximal), multiplicity of the genetic profiles of patients, or patients getting treatment elsewhere. Although our study is limited due to its small size, it emphasizes the originality of our results.
ISSN: 1472-6890

inserm-00971313
http://www.hal.inserm.fr/inserm-00971313
http://www.hal.inserm.fr/inserm-00971313/document
http://www.hal.inserm.fr/inserm-00971313/file/1472-6890-14-12.pdf
DOI : 10.1186/1472-6890-14-12

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Aims: The aims of this study were to compare short-and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy.Methods: Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short-and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics.Results: No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short-or long-term outcomes.Conclusion: The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery.
ISSN: 0959-8049

hal-01666517
https://hal.univ-lorraine.fr/hal-01666517
DOI : 10.1016/j.ejca.2015.11.024

Éditeur(s) : HAL CCSD Oxford University Press (OUP): Policy B
Résumé : International audience
AIMS: Indications for surgery in acute infective endocarditis (IE) are detailed in guidelines, but their application is not well known. We analysed the agreement between the patient's attending physicians and European Society of Cardiology guidelines regarding indications for surgery. We also assessed whether surgery was performed in patients who had an indication. METHODS AND RESULTS: From the 2008 prospective population-based French survey on IE, 303 patients with definite left-sided native IE were identified. For each case, we prospectively recorded (i) indication for surgery according to the attending physicians and (ii) indication for surgery according to guidelines. Surgery was indicated in 194 (65%) patients according to attending physicians and in 221 (73%) according to guidelines, while 139 (46%) underwent surgery. Agreement was moderate between attending physicians and guidelines (kappa 0.41-0.59) and between indication according to guidelines and the performance of surgery (kappa 0.38). Of the 90 (30%) patients not operated despite indication, contraindication to surgery was reported by the attending physicians in 42 (47%), and indication was not identified in 48 (53%). One-year survival was 76% in patients with indication and surgery performed (n = 131), 69% in patients without indication and no surgery (n = 74), 56% in patients with identified indication and contraindication to surgery (n = 42), and 60% in patients with no identified indication (n = 48; P = 0.059). CONCLUSION: Cardiac surgery during acute IE was recommended in almost three out of four patients, although fewer than half were actually operated. Indication was not acknowledged by the attending physicians in one out of six patients
ISSN: 0195-668X

hal-01255874
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01255874
DOI : 10.1093/eurheartj/ehv650
PUBMED : 26685134

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
To analyze the characteristics and outcome of infective endocarditis (IE) according to the time interval between IE first symptoms and diagnosis.
Among the IE cases of a French population-based epidemiological survey, patients having early-diagnosed IE (diagnosis of IE within 1 month of first symptoms) were compared with those having late-diagnosed IE (diagnosis of IE more than 1 month after first symptoms).
Among the 486 definite-IE, 124 (25%) had late-diagnosed IE whereas others had early-diagnosed IE. Early-diagnosed IE were independently associated with female gender (OR = 1.8; 95% CI [1.0-3.0]), prosthetic valve (OR= 2.6; 95% CI [1.4-5.0]) and staphylococci as causative pathogen (OR = 3.7; 95% CI [2.2-6.2]). Cardiac surgery theoretical indication rates were not different between early and late-diagnosed IE (56.3% vs 58.9%), whereas valve surgery performance was lower in early-diagnosed IE (41% vs 53%; p = .03). In-hospital mortality rates were higher in early-diagnosed IE than in late-diagnosed IE (25.1% vs 16.1%; p < .001).
The time interval between IE first symptoms and diagnosis is closely related to the IE clinical presentation, patient characteristics and causative microorganism. Better prognosis reported in late-diagnosed IE may be related to a higher rate of valvular surgery. KEY MESSAGES Infective endocarditis, which time interval between first symptoms and diagnosis was less than one month, were mainly due to Staphylococcus aureus in France. Staphylococcus aureus infective endocarditis were associated with septic shock, transient ischemic attack or stroke and higher mortality rates than infective endocarditis due to other bacteria or infective endocarditis, which time interval between first symptoms and diagnosis was more than one month. Infective endocarditis, which time interval between first symptoms and diagnosis was more than one month, were accounting for one quarter of all infective endocarditis in our study and were associated with vertebral osteomyelitis and a higher rate of cardiac surgery performed for hemodynamic indication than other infective endocarditis.
ISSN: 0785-3890

hal-01509563
https://hal.archives-ouvertes.fr/hal-01509563
PUBMED : 27607562

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Whilst it used to affect mostly intravenous drug users and patients who underwent valvular surgery with suboptimal infection control procedures, fungal endocarditis is now mostly observed in patients with severe immunodeficiency (onco-haematology), in association with chronic central venous access and broad-spectrum antibiotic use. The incidence of fungal endocarditis has probably decreased in most developed countries with access to harm-reduction policies (i.e. needle exchange programmes) and with improved infection control procedures during cardiac surgery. Use of specific blood culture bottles for diagnosis of fungal endocarditis has decreased due to optimisation of media and automated culture systems. Meanwhile, the advent of rapid techniques, including fungal antigen detection (galactomannan, mannan/anti-mannan antibodies and β-1,3-d-glucans) and PCR (e.g. universal fungal PCR targeting 18S rRNA genes), shall improve sensitivity and reduce diagnostics delays, although limited data are available on their use for the diagnosis of fungal endocarditis. New antifungal agents available since the early 2000s may represent dramatic improvement for fungal endocarditis: (i) a new class, the echinocandins, has the potential to improve the management of Candida endocarditis owing to its fungicidal effect on yeasts as well as tolerability of increased dosages; and (ii) improved survival in patients with invasive aspergillosis with voriconazole compared with amphotericin B, and this may apply to Aspergillus sp. endocarditis as well, although its prognosis remains dismal. These achievements may allow selected patients to be cured with prolonged medical treatment alone when surgery is considered too risky.
ISSN: 0924-8579

hal-01118441
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118441
DOI : 10.1016/j.ijantimicag.2014.07.003
PUBMED : 25178919

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: To better select for patients who most likely will benefit from cardiac surgery among those with infective endocarditis (IE), we aimed to identify preoperative markers associated with poor outcome after cardiac surgery for IE, and to evaluate the accuracy of European System for Cardiac Operative Risk Evaluation (EuroSCORE) II to predict mortality. METHODS: We enrolled all adult patients who underwent cardiac surgery during the acute phase of definite IE (Duke Criteria) in two referral centres for cardiac surgery. Patients were identified through intensive care unit (ICU) electronic databases, and data were collected from medical charts on standardized questionnaire. RESULTS: Between 2002 and 2013, 149 patients (117 males), with a median age of 64 years [interquartile range 52-73], fulfilled the inclusion criteria. Main complications before surgery were left ventricular dysfunction (23%), central nervous system symptomatic events (34%) and septic shock (24%). Most patients (95%) presented with valve regurgitation, and 49% had perivalvular abscess. Surgery was performed with a median delay of 12 days [5-24] after IE diagnosis, and mean EuroSCORE II was 15.8 (13.4-18.1). In-hospital mortality was 21%. Preoperative variables associated with mortality in multivariate analysis were obesity [odds ratio (OR) 3.67 [1.10-12.19], P = 0.03], vegetation extgreater15 mm (OR 6.72 [1.46-30.98], P = 0.01), septic shock (OR 4.87 [1.67-14.28], P = 0.004) and mechanical prosthetic valve IE (OR 4.99 [1.72-28.57], P = 0.007). EuroSCORE II underestimated mortality in patients with predicted mortality over 10%. CONCLUSION: Factors independently predictive of mortality after cardiac surgery for IE are obesity, septic shock, large vegetation and a mechanical prosthetic valve IE. EuroSCORE II underestimates post-cardiac surgery mortality in patients with IE
ISSN: 1010-7940

hal-01169802
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01169802
DOI : 10.1093/ejcts/ezv223
PUBMED : 26116921

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.
ISSN: 0001-6322

hal-00875723
https://hal.archives-ouvertes.fr/hal-00875723
DOI : 10.1007/s00401-013-1084-y
PUBMED : 23400299

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: In the context of recent guidelines on invasive candidiasis (IC), how French intensive care units (ICUs) are managing IC? METHODS: This is a prospective observational multicenter cohort study. During 1 year (2012-2013), 87 French ICUs enrolled consecutive patients with suspected or proven IC (SIC or PIC) and receiving systemic antifungal therapy (SAT). Data were collected up to 28 days after inclusion. RESULTS: We studied 835 patients, 291 with PIC and 544 with SIC. At SAT initiation, patients with SIC were significantly more severe (SAPS II 50.1 ± 18.7 vs. 46.2 ± 18.0). Severe sepsis or septic shock prompted to initiate empiric SAT in 70 % of SIC. Within 4 days in median, the initial SAT was modified in 49 % of patients with PIC vs. 33 % patients with SIC. Modifications were most often motivated by mycological results, and de-escalation was the most frequent change. Regarding compliance to IC management guidelines, echinocandin was used for 182 (62.5 %) patients with PIC, and 287 (52.7 %) of those with SIC; central venous catheter was removed in 87 (54.3 %) of patients with candidaemia, and 43 of the remaining patients received echinocandin; and de-escalation was undertaken after 5 days of SAT in 142 patients, after 10 days in 13 patients. As 20.6 % of SIC were secondarily documented, 403/835 (48 %) patients had finally a proven IC. Candida albicans was the main pathogen (65.3 %), then Candida glabrata (15.9 %). The 28-day mortality rates were 40.0 % in candidaemia, 25.4 % in cIAI, and 26.7 % in deep-seated candidiasis. In the overall population of patients with proven IC, four independent prognostic factors were identified: immunosuppression (Odds Ratio (OR) = 1.977: 1.03-3.794 95 % confidence interval (CI), p = 0.04), age (OR = 1.035; 1.017-1.053 95 % CI; p  extless 0.001), SAPS extgreater46 on ICU admission (OR = 2.894; 1.81-4.626 95 % CI; p  extless 0.001), and surgery just before or during ICU stay (OR = 0.473; 0.29-0.77 95 % CI; p  extless 0.001). CONCLUSION: When SAT is initiated in French ICUs, the IC is ultimately proven for 48 % of patients. Empiric SAT is initiated in severely ill ICU patients. The initial SAT is often adapted, with de-escalation to fluconazole when possible. Mortality rate remains high
ISSN: 2110-5820

hal-01259216
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259216
DOI : 10.1186/s13613-015-0103-7
PUBMED : 26743881

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: The effects of pressure-controlled (PC) ventilation on the ventilatory and haemodynamic parameters during laparoscopy procedures had not been carefully assessed. This prospective cross-over study was undertaken to compare how volume-controlled (VC) and PC modes could affect pulmonary mechanics, gas exchange, and cardiac function in patients undergoing laparoscopy. METHODS: Twenty-one patients undergoing laparoscopic urological procedures had their lungs ventilated at the beginning with VC ventilation. PC ventilation was instituted at the end of the VC sequence. Ventilator settings were adjusted to keep tidal volume, respiratory rate, and Fi(o(2)) constant in every mode. A complete set of ventilatory, haemodynamic, and gas exchange parameters was obtained under VC after 40 min of pneumoperitoneum and 20 min after switching for PC. Transoesophageal echocardiography was performed in order to evaluate systolic and diastolic function of the heart. RESULTS: When VC was switched to PC, peak airway pressure decreased [mean (sd) 32 (6) vs 27 (6) cm H(2)O; P < 0.0001], peak inspiratory flow increased [17 (3) vs 48 (8) litre min(-1); P < 0.0001), and dynamic compliance improved [+15 (8)%]. No difference was noted for static airway pressure, static compliance, and arterial oxygenation. No significant change could be demonstrated in the systolic [left ventricular end-systolic wall stress 66 (16) vs 63 (14) x 10(3) dyn cm(-2) m(-2)] or diastolic function [early diastolic velocity 10.3 (2.5) vs 10.5 (2.7) cm s(-1)]. CONCLUSIONS: In this study, no short-term beneficial effect of PC ventilation could be demonstrated over conventional VC ventilation in patients with pneumoperitoneum.
BJA

hal-00689758
https://hal.archives-ouvertes.fr/hal-00689758
DOI : 10.1093/bja/aem166
PUBMED : 17626027

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Cancer is the main complication of transplantation surgery. The literature concerning renal transplant recipients among the Afro-Caribbean population is scant. The aim of this study was to determine the incidence of cancer in these patients, with the secondary objective being to identify predisposing factors for cancer. This was an epidemiological and retrospective study that included all Guadeloupians of phototype V-VI undergoing renal transplantation from 01/01/2004 to 31/12/2011. Skin cancer screening was performed before transplantation and during an annual dermatological consultation following transplantation. Screening for non-cutaneous cancers was guided by clinical symptoms or by the results of the screening examinations recommended in the current guidelines. At the study time-point (31/12/2011), all patients were examined by a dermatologist. One hundred and two patients were included : 42 women and 60 men (mean age: 52.1±11.6 years at transplantation). Eight cancers were diagnosed. The cumulative incidence of cancer was 7.8% at 3 years. Three factors were associated with more rapid onset of cancer: personal history or familial history of cancer, and genital lesion induced by HPV. Our results suggest a low incidence of cancer in Afro-Caribbean renal transplant patients. Personal or family history of cancer and HPV-induced genital lesions would appear to accelerate the onset of cancer in this population.
ISSN: 0151-9638

hal-01260468
https://hal.archives-ouvertes.fr/hal-01260468
https://hal.archives-ouvertes.fr/hal-01260468/document
https://hal.archives-ouvertes.fr/hal-01260468/file/2015%2C%20Ameline.pdf
https://hal.archives-ouvertes.fr/hal-01260468/file/14%20148%20Fig%201%20ap.pdf

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
TMPRSS2/ERG fusion resulting in ERG overexpression occurs in 30 to 50% of prostate cancer (PCa) in Caucasian patients, but its prognostic relevance remains controversial. In the present study, we investigated ERG expression in all stages of PCa progression, and evaluated the prognostic impact of ERG status in clinically localized PCa (CLC) and in castration resistant disease (CRPC). ERG and AR expressions were evaluated by immunohistochemistry on tissue microarrays containing samples of high grade PIN (n = 57), CLC surgically treated (n = 299, including 185 Caucasians and 114 African-Caribbeans), metastases (n = 17), and CRPC (n = 41). In Caucasians, ERG expression significantly increased from high grade PIN (17.5%) to pT2 (27%) and pT3 CLC (43%), then to metastases (53%). In CLC, stainings for ERG and AR were correlated, and ERG expression was less frequent in African-Caribbeans compared to Caucasians (11.5% vs. 33%). In Caucasians CLC, ERG was associated with longer recurrence free survival, after adjusting for classical prognostic markers. In CRPC, ERG was expressed in 29% of cases, and was associated with a longer overall survival. Our results confirm that ERG expression is less frequent in PCa from patients of African descent. Although ERG expression increases during PCa natural history, positive ERG status is associated with better outcome in both CLC and CRPC. This paradox could be explained in part by the fact that ERG expression is AR dependant, then ERG positive cancers are likely to progress in a rich androgen environment, with a better response to androgen suppression.
ISSN: 0270-4137

hal-01118555
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118555
DOI : 10.1002/pros.22863
PUBMED : 25175352

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Glioblastoma (GB) is the most frequent and aggressive type of primary brain tumor. Recurrences are mostly located at the margin of the resection cavity in the peritumoral brain zone (PBZ). Although it is widely believed that infiltrative tumor cells in this zone are responsible for GB recurrence, few studies have examined this zone. In this study, we analyzed PBZ left after surgery with a variety of techniques including radiology, histopathology, flow cytometry, genomic, transcriptomic, proteomic, and primary cell cultures. The resulting PBZ profiles were compared with those of the GB tumor zone and normal brain samples to identify characteristics specific to the PBZ. We found that tumor cell infiltration detected by standard histological analysis was present in almost one third of PBZ taken from an area that was considered normal both on standard MRI and by the neurosurgeon under an operating microscope. The panel of techniques used in this study show that the PBZ, similar to the tumor zone itself, is characterized by substantial inter-patient heterogeneity, which makes it difficult to identify representative markers. Nevertheless, we identified specific alterations in the PBZ such as the presence of selected tumor clones and stromal cells with tumorigenic and angiogenic properties. The study of GB-PBZ is a growing field of interest and this region needs to be characterized further. This will facilitate the development of new, targeted therapies for patients with GB and the development of approaches to refine the per-operative evaluation of the PBZ to optimize the surgical resection of the tumor.
ISSN: 0167-594X

hal-01117083
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117083
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117083/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117083/file/Characterizing%20the%20Peritumoral%20Brain%20Zone_accepted.pdf
DOI : 10.1007/s11060-014-1695-8

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
UNLABELLED: ABSTRACT: BACKGROUND: Genomics, transcriptomics and proteomics of glioblastoma multiforme (GBM) have recently emerged as possible tools to discover therapeutic targets and biomarkers for new therapies including immunotherapy. It is well known that macroscopically complete surgical excision, radiotherapy and chemotherapy have therapeutic limitations to improve survival in these patients. In this study, we used a differential proteomic-based technique (2D-Difference Gel Electrophoresis) coupled with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry to identify proteins that may serve as brain tumor antigens in new therapeutic assays. Five samples of patients presenting a GBM and five samples of microscopically normal brain tissues derived from brain epileptic surgery specimen were labeled and run in 2D-PAGE (Two-Dimensional Polyacrylamide Gel Electrophoresis) with an internal pool sample on each gel. Five gels were matched and compared with DIA (Difference In-gel Analysis) software. Differential spots were picked, in-gel digested and peptide mass fingerprints were obtained. RESULTS: From 51 protein-spots significantly up-regulated in GBM samples, mass spectrometry (MS) identified twenty-two proteins. The differential expression of a selected protein set was first validated by western-blotting, then tested on large cohorts of GBM specimens and non-tumor tissues, using immunohistochemistry and real-time RT-PCR. CONCLUSIONS: Our results confirmed the importance of previously described proteins in glioma pathology and their potential usefulness as biological markers but also revealed some new interesting targets for future therapies.
ISSN: 1477-5956

inserm-00585020
http://www.hal.inserm.fr/inserm-00585020
http://www.hal.inserm.fr/inserm-00585020/document
http://www.hal.inserm.fr/inserm-00585020/file/1477-5956-9-16.pdf
DOI : 10.1186/1477-5956-9-16

Éditeur(s) : HAL CCSD American Medical Association (AMA)
Résumé : International audience
IMPORTANCE Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome. OBJECTIVE To determine whether empirical micafungin reduces invasive fungal infection (IFI)-free survival at day 28. DESIGN, SETTING, AND PARTICIPANTS Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs. INTERVENTIONS Empirical treatment with micafungin (100mg, once daily, for 14 days) (n = 131) vs placebo (n = 129). MAIN OUTCOMES AND MEASURES The primary end pointwas survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-beta-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia. RESULTS Among 260 patients (mean age 63 years; 91 [35%] women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-beta-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a (1-3)-beta-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI, 0.85-2.33]). Day-28 IFI-free survival in patients with a high SOFA score (> 8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients [12%]) (P =.008). CONCLUSIONS AND RELEVANCE Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection-free survival at day 28.
ISSN: 0098-7484

hal-01405822
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01405822
DOI : 10.1001/jama.2016.14655
PUBMED : 27706483

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
RATIONALE: Optimal management of complicated parapneumonic effusions (CPPE) remains controversial. OBJECTIVES: to assess safety and efficacy of iterative therapeutic thoracentesis (ITTC), the first-line treatment of CPPE in Rennes University Hospital. METHODS: Patients with CPPE were identified through our computerized database. We retrospectively studied all cases of CPPE initially managed with ITTC in our institution between 2001 and 2010. ITTC failure was defined by the need for additional treatment (i.e. surgery or percutaneous drainage), or death. RESULTS: Seventy-nine consecutive patients were included. The success rate was 81% (n = 64). Only 3 patients (4%) were referred to thoracic surgery. The one-year survival rate was 88%. On multivariate analysis, microorganisms observed in pleural fluid after Gram staining and first thoracentesis volume ≥450 mL were associated with ITTC failure with adjusted odds-ratios of 7.65 [95% CI, 1.44-40.67] and 6.97 [95% CI, 1.86-26.07], respectively. The main complications of ITTC were iatrogenic pneumothorax (n = 5, 6%) and vasovagal reactions (n = 3, 4%). None of the pneumothoraces required chest tube drainage, and no hemothorax or re-expansion pulmonary edema was observed. CONCLUSIONS: Although not indicated in international recommendations, ITTC is safe and effective as first-line treatment of CPPE, with limited invasiveness.
ISSN: 1932-6203

hal-00945622
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00945622
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00945622/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00945622/file/fetchObject.pdf
PUBMED : 24400113

Éditeur(s) : HAL CCSD Centers for Disease Control and Prevention
Résumé : International audience
We report 20 cases of extensively drug-resistant tuberculosis managed in France. Treatment was individualized and included bedaquiline and linezolid for most patients and surgery in 8 patients. At last follow-up (22 months), 19 patients had achieved conversion from positive to negative on culture testing. These promising results of comprehensive management obtained in a small series deserve confirmation.
ISSN: 1080-6040

hal-01294307
http://hal.upmc.fr/hal-01294307
http://hal.upmc.fr/hal-01294307/document
http://hal.upmc.fr/hal-01294307/file/15-1130.pdf
DOI : 10.3201/eid2203.151130

Éditeur(s) : HAL CCSD
Résumé : International audience
OBJECTIVE: To analyze complications of endoscopic transsphenoidal surgery (ETS) for nonfunctioning pituitary macroadenomas (NFPAs).ăMETHODS: A retrospective study of 300 NFPAs was performed. Complications and factors that could influence these complications were analyzed.ăRESULTS: Visual and pituitary functions worsened in 2.4% and 13.7% of cases, respectively. Postoperative diabetes insipidus was permanent in 6.2% of cases. Postoperative meningitis occurred in 3.3% of patients. Meningitis was strongly associated with intraoperative cerebrospinal fluid (CSF) leaks (P = 0.01), postoperative CSF leaks (P = 0.0001), and operation times longer than 1 hour (P = 0.023). Detection of Staphylococcus aureus and preoperative treatment with mupirocin in the nostrils did not impact the occurrence of meningitis. Two patients with meningitis died (unique causes of death). Postoperative CSF leaks occurred in 2.7% of cases and were associated with intraoperative CSF leaks (P = 0.007) and permanent diabetes insipidus (P = 0.028). The rate of CSF leak decreased from 4% to 0.8% (P = 0.048) after we moved from a soft to hard reconstruction of the sella. The rate of postoperative epistaxis decreased from 6.7% to 1.25% after we stopped using monopolar coagulation (P = 0.013).ăCONCLUSIONS: ETS permits a wide view, allowing good conditions for a satisfactory resection in the majority of NFPAs. Some pitfalls of endoscopy can lead to complications that improve with modification of the operative technique (i.e., CSF leak and postoperative epistaxis). This study confirms an acceptable rate of complications associated with ETS.
World Neurosurgery

hal-01474296
https://hal.archives-ouvertes.fr/hal-01474296
DOI : 10.1016/j.wneu.2016.02.059
PUBMED : 26902781

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Hepatocellular carcinoma (HCC) is a particularly severe disease characterized by a high rate of recurrence and death even after surgical resection. Molecular characterization of HCC helps refine prognosis and may facilitate the development of improved therapy. Phosphatidylinositol 4-kinases have recently been identified as cellular factors associated with cancer. Also, phosphatidylinositol 4-kinase type IIIα (PI4KA) is necessary for the propagation of the hepatitis C virus, a major etiological factor for HCC. METHODS: Reverse transcription, quantitative real-time PCR was used to assay PI4KA mRNA. The expression levels were investigated both in a collection of molecularly and clinically characterized hepatic tissues from 344 patients with diverse liver diseases and in human hepatocyte cell lines whose proliferative and differentiation status was controlled by specific culture conditions. Analytical microarray data for 60 HCC and six normal liver tissue samples were exploited to study correlations between PI4KA mRNA levels and cell proliferation markers in vivo. Postoperative disease-specific survival and time to recurrence in a set of 214 patients with HCC were studied by univariate and multivariate analyses. RESULTS: PI4KA mRNA was more abundant in HCC than normal healthy tissues. This upregulation correlated significantly with both poor differentiation and the active proliferation rate in HCC. These associations were confirmed with in vitro models. Moreover, patients with HCC who had been treated by surgical resection and had higher PI4KA mRNA concentrations in their tumor tissue exhibited a higher risk of tumor recurrence (median time: 20 months versus 49 months, P = 0.0012) and shorter disease-specific survival (first quartile time: 16 months versus 48 months, P = 0.0004). Finally, the abundance of PI4KA mRNA proved to be an independent prognostic marker of survival for cases of HCC (hazard ratio = 2.36, P = 0.0064). CONCLUSIONS: PI4KA mRNA could be used as a new molecular marker to improve established prognostic models for HCC. These findings also indicate possible new lines of research for the development of innovative therapeutic approaches targeting PI4KA.
ISSN: 1471-2407

inserm-00934294
http://www.hal.inserm.fr/inserm-00934294
http://www.hal.inserm.fr/inserm-00934294/document
http://www.hal.inserm.fr/inserm-00934294/file/1471-2407-14-7.pdf
DOI : 10.1186/1471-2407-14-7

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
UNLABELLED: Glioblastoma (GB) is the most frequent and aggressive tumor of the central nervous system. There is currently growing interest in proteomic studies of GB, particularly with the aim of identifying new prognostic or therapeutic response markers. However, comparisons between different proteomic analyses of GB have revealed few common differentiated proteins. The types of control samples used to identify such proteins may in part explain the different results obtained. We therefore tried to determine which control samples would be most suitable for GB proteomic studies. We used an isotope-coded protein labeling (ICPL) method followed by mass spectrometry to reveal and compare the protein patterns of two commonly used types of control sample: GB peritumoral brain zone samples (PBZ) from six patients and epilepsy surgery brain samples (EB) pooled from three patients. The data obtained were processed using AMEN software for network analysis. We identified 197 non-redundant proteins and 35 of them were differentially expressed. Among these 35 differentially expressed proteins, six were over-expressed in PBZ and 29 in EB, showing different proteomic patterns between the two samples. Surprisingly, EB appeared to display a tumoral-like expression pattern in comparison to PBZ. In our opinion, PBZ may be more appropriate control sample for GB proteomic analysis. BIOLOGICAL SIGNIFICANCE: This manuscript describes an original study in which we used an isotope-coded protein labeling method followed by mass spectrometry to identify and compare the protein patterns in two types of sample commonly used as control for glioblastoma (GB) proteomic analysis: peritumoral brain zone and brain samples obtained during surgery for epilepsy. The choice of control samples is critical for identifying new prognostic and/or diagnostic markers in GB.
ISSN: 1874-3919

inserm-00871494
http://www.hal.inserm.fr/inserm-00871494
http://www.hal.inserm.fr/inserm-00871494/document
http://www.hal.inserm.fr/inserm-00871494/file/ManuscritProt-accepted.pdf
DOI : 10.1016/j.jprot.2013.04.031