Manterola L.,Hospital Universitario Donostia |
Guruceaga E.,Center for Applied Medical Research |
Perez-Larraya J.G.,University of Navarra |
Gonzalez-Huarriz M.,University of Navarra |
And 21 more authors.
Neuro-Oncology | Year: 2014
Background. Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults, and its prognosis remains dismal despite intensive research and therapeutic advances. Diagnostic biomarkers would be clinically meaningful to allow for early detection of the tumor and for those cases in which surgery is contraindicated or biopsy Results. are inconclusive. Recent findings show that GBM cells release microvesicles that contain a select subset of cellular proteins and RNA. The aim of this hypothesis-generating study was to assess the diagnostic potential of miRNAs found in microvesicles isolated from the serum of GBM patients. Methods. To control disease heterogeneity, we used patients with newly diagnosed GBM. In the discovery stage, PCR-based TaqMan Low Density Arrays followed by individual quantitative reverse transcriptase polymerase chain reaction were used to test the differences in the miRNA expression levels of serum microvesicles among 25 GBM patients and healthy controls paired by age and sex. The detected noncoding RNAs were then validated in another 50 GBM patients. Results. We found that the expression levels of 1 small noncoding RNA (RNU6-1) and 2 microRNAs (miR-320 and miR-574-3p) were significantly associated with a GBM diagnosis. In addition, RNU6-1 was consistently an independent predictor of a GBM diagnosis. Conclusions. Altogether our Results. uncovered a small noncoding RNA signature in microvesicles isolated from GBM patient serum that could be used as a fast and reliable differential diagnostic biomarker. © 2014 © The Author(s) 2014.
PubMed | University of Limoges, Paoli Calmettes, Montpellier University, Center Henri Becquerel and 12 more.
Type: Journal Article | Journal: Bone marrow transplantation | Year: 2016
Poly-chemotherapy plus rituximab followed by autologous stem cell transplantation (auto-SCT) is standard care for untreated young patients with mantle cell lymphoma (MCL). Despite this intensive treatment, transplant patients remain highly susceptible to relapse over time. The French SFGM-TC performed a national survey on reduced-intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) for fit relapsed/refractory patients who failed after auto-SCT (n=106). Median times of relapse after auto-SCT, and from auto-SCT to RIC-allo-SCT were 28 months and 3.6 years, respectively. Sixty per cent of patients received at least three lines of treatment before RIC-allo-SCT. Conditioning regimens for RIC-allo-SCT were heterogeneous. Twenty patients experienced grade III/IV aGvHD, extensive cGvHD was reported in 28 cases. Median follow-up after RIC-allo-SCT was 45 months. Median PFS after RIC-allo-SCT was 30.1 months and median overall survival was 62 months. Treatment-related mortality (TRM) at 1 year and 3 years were estimated at 28% and 32%, respectively. A total of 52 patients died; major causes of death were related to toxicity (n=34) and MCL (n=11). Patients in good response before RIC-allo-SCT experienced a better PFS and OS. Our work highlights the need for new RIC-allo-SCT MCL-tailored approaches to reduce TRM, and early and late relapse.
Masson-Lecomte A.,Pitie Salpetriere |
Masson-Lecomte A.,University Paris - Sud |
Bensalah K.,Reims University Hospital Center |
Bensalah K.,University Of Reims Champagnes Ardenne |
And 17 more authors.
BJU International | Year: 2013
What's known on the subject? and What does the study add? Nephron-sparing surgery has become the standard of care for small renal masses because it allows for the same oncological control as radical nephrectomy and achieves better overall survival, while lowering the risk of subsequent chronic renal failure. Mini-invasive surgical approaches have also been developed, e.g. laparoscopic partial nephrectomy (LPN) and robot-assisted laparoscopic PN (RAPN), which result in less bleeding, reduced postoperative pain, shorter length of stay (LOS) and shorter recovery time. LPN requires advanced surgical skill, has a longer learning curve and requires perseverance, which limits its large diffusion. From this prospective comparative study, we can now claim that RAPN is not inferior to pure LPN in terms of perioperative outcomes (i.e. blood loss, operative duration, warm ischaemia time, LOS). Objective To prospectively compare the surgical and pathological outcomes obtained with robot-assisted laparoscopic partial nephrectomy (RAPN) or laparoscopic PN (LPN) for renal cell carcinoma in a multicentre cohort. Patients and Methods Between 2007 and 2011, 265 nephron-sparing surgeries were performed at six French urology departments. The patients underwent either RAPN (n = 220) or LPN (n = 45) procedures. The operative data included operative duration, warm ischaemia time (WIT) and estimated blood loss (EBL). The postoperative outcomes included length of stay (LOS), creatinine variation (Modification of Diet in Renal Disease group), Clavien complications and pathological results. The complexity of the renal tumour was classified using the R.E.N.A.L. nephrometry scoring system. Student's t-test and chi-squared tests were used to compare variables. Results The median follow-ups for the RAPN and LPN groups were 7 and 18 months, respectively (P < 0.001). Age and American Society of Anesthesiology score were significantly higher in the LPN group (P = 0.02 and P = 0.004, respectively). These variables were lower in the RAPN group: WIT [mean (sd) 20.4 (9.7) vs 24.3 (15.2) min; P = 0.03], operative duration [mean (sd) 168.1 (55.5) vs 199.7 (51.2) min; P < 0.001], operating room occupation time [mean (sd) 248.3 (66.7) vs 278.2 (71.3) min; P = 0.008], EBL [mean (sd) 244.8 (365.4) vs 268.3 (244.9) mL; P = 0.01], use of haemostatic agents [used in 78% of RAPNs and 100% of LPNs; P < 0.001] and LOS [mean (sd) 5.5 (4.3) vs 6.8 (3.2) days; P = 0.05). There were no significant differences between pre- and postoperative creatinine levels, pathology report or complication rates between the groups. The main limitation was due to the study's non-randomised design. Conclusion RAPN is not inferior to pure LPN for perioperative outcomes (i.e. EBL, operative duration, WIT, LOS). Only a randomised study with a longer follow-up can now provide further insight into oncological outcomes. © 2012 BJU International.
Luporsi E.,Nancy University Hospital Center |
Andre F.,Institute Gustave Roussy |
Spyratos F.,Institute Curie Hopital Rene Huguenin |
Martin P.-M.,Translational Laboratory Biological Oncology |
And 21 more authors.
Breast Cancer Research and Treatment | Year: 2012
Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER?) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cutpoints used for treatment decision. Data describing study design, patients' characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05-1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for longterm follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6-13/20 vs. 10-18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use. © Springer Science+Business Media, LLC. 2011.
Annane D.,Raymond Poincare Hospital |
Siami S.,CH dEtampes |
Jaber S.,CHU Montpelier |
Martin C.,AP HM Hopital Nord |
And 18 more authors.
JAMA - Journal of the American Medical Association | Year: 2013
IMPORTANCE: Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear. OBJECTIVE: To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit (ICU) with hypovolemic shock. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized clinical trial stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma). Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial was open label but outcome assessment was blinded to treatment assignment. Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France, Belgium, North Africa, and Canada; follow-up ended in November 2012. INTERVENTIONS: Colloids (n = 1414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) or crystalloids (n = 1443; isotonic or hypertonic saline or Ringer lactate solution) for all fluid interventions other than fluid maintenance throughout the ICU stay. MAIN OUTCOMES AND MEASURES: The primary outcomewas death within 28 days. Secondary outcomes included 90-day mortality; and days alive and not receiving renal replacement therapy, mechanical ventilation, or vasopressor therapy. RESULTS: Within 28 days, there were 359 deaths (25.4%) in colloids group vs 390 deaths (27.0%) in crystalloids group (relative risk [RR], 0.96 [95% CI, 0.88 to 1.04]; P = .26). Within 90 days, there were 434 deaths (30.7%) in colloids group vs 493 deaths (34.2%) in crystalloids group (RR, 0.92 [95% CI, 0.86 to 0.99]; P = .03). Renal replacement therapy was used in 156 (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI, 0.83 to 1.03]; P = .19). There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1 vs 1.8 days, respectively; mean difference, 0.30 [95% CI, 0.09 to 0.48] days; P = .01) and by 28 days (mean: 14.6 vs 13.5 days; mean difference, 1.10 [95% CI, 0.14 to 2.06] days; P = .01) and alive without vasopressor therapy by 7 days (mean: 5.0 vs 4.7 days; mean difference, 0.30 [95% CI, -0.03 to 0.50] days; P = .04) and by 28 days (mean: 16.2 vs 15.2 days; mean difference, 1.04 [95% CI, -0.04 to 2.10] days; P = .03). CONCLUSIONS AND RELEVANCE: Among ICU patients with hypovolemia, the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy.
Oehler E.,French Polynesia Tertiary Hospital |
Fournier E.,Pitie Salpetriere |
Leparc-Goffart I.,French National Reference Center for Arboviruses |
Larre P.,French Polynesia Tertiary Hospital |
And 4 more authors.
Eurosurveillance | Year: 2015
During the recent chikungunya fever outbreak in French Polynesia in October 2014 to March 2015, we observed an abnormally high number of patients with neurological deficit. Clinical presentation and complementary exams were suggestive of Guillain–Barré syndrome (GBS) for nine patients. All nine had a recent dengue-like syndrome and tested positive for chikungunya virus (CHIKV) in serology or RT-PCR. GBS incidence was increased four- to nine-fold during this period, suggesting a link to CHIKV infection. © 2015, European Centre for Disease Prevention and Control (ECDC). All rights reserved.
Daculsi G.,French Institute of Health and Medical Research |
Pascal-Moussellard H.,Pitie Salpetriere
Key Engineering Materials | Year: 2013
The objective of the study was to compare clinical efficiency of the fusion after reconstruction with an anatomically shaped PEEK cage associated with a iliac crest autograft or MBCP in the treatment of cervical disc disease in randomized clinical trial. A multicente randomized, comparative and prospective study on 58 patients, with a 12 months follow up are reported. They underwent anterior cervical decompression and fusion being randomized for autologous graft or MBCP. Patients presenting purely degenerative disc disease were implanted with a PEEK cage filled with iliac crest autograft or MBCP. Pain and functionality as well as patient's satisfaction were assessed through VAS, Neck Disability Index (NDI) and Patient Satisfaction index were recorded until 24 month follow-up. Radiological evaluation included plain and dynamic short X-rays at each stage of the follow up. The patient's satisfaction rates was of 82% in the autograft group versus 96% in the MBCP group. Pain at the donor site was significantly more important in the autograft group at 3 weeks, 3 months and 1 year follow-up. No implant failures were recorded. Previously goat preclinical study was performed. Micro CT, light microscopy and shistomorphometry were related to the high performance of the MBCP insert for filling cage fusion, completing the clinical assessment of our clinical study. The use of MBCP insert is safe and avoids potential graft site morbidity and pain in comparison with an autologous graft procedure. © (2013) Trans Tech Publications, Switzerland.
Dupin C.,Institute Bergonie |
Lang P.,Pitie Salpetriere |
Dessard-Diana B.,Hopital Europeen Georges Pompidou |
Simon J.-M.,Pitie Salpetriere |
And 3 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2014
Purpose To retrospectively assess the outcomes of radiation therapy in patients with head and neck paragangliomas. Methods and Materials From 1990 to 2009, 66 patients with 81 head and neck paragangliomas were treated by conventional external beam radiation therapy in 25 fractions at a median dose of 45 Gy (range, 41.4-68 Gy). One case was malignant. The median gross target volume and planning target volume were 30 cm3 (range, 0.9-243 cm 3) and 116 cm3 (range, 24-731 cm3), respectively. Median age was 57.4 years (range, 15-84 years). Eleven patients had multicentric lesions, and 8 had family histories of paraganglioma. Paragangliomas were located in the temporal bone, the carotid body, and the glomus vagal in 51, 18, and 10 patients, respectively. Forty-six patients had exclusive radiation therapy, and 20 had salvage radiation therapy. The median follow-up was 4.1 years (range, 0.1-21.2 years). Results One patient had a recurrence of temporal bone paraganglioma 8 years after treatment. The actuarial local control rates were 100% at 5 years and 98.7% at 10 years. Patients with multifocal tumors and family histories were significantly younger (42 years vs 58 years [P=.002] and 37 years vs 58 years [P=.0003], respectively). The association between family predisposition and multifocality was significant (P<.001). Two patients had cause-specific death within the 6 months after irradiation. During radiation therapy, 9 patients required hospitalization for weight loss, nausea, mucositis, or ophthalmic zoster. Two late vascular complications occurred (middle cerebral artery and carotid stenosis), and 2 late radiation-related meningiomas appeared 15 and 18 years after treatment. Conclusion Conventional external beam radiation therapy is an effective and safe treatment option that achieves excellent local control; it should be considered as a first-line treatment of choice for head and neck paragangliomas. © 2014 Elsevier Inc. All rights reserved.
Izzedine H.,Pitie Salpetriere |
Gueutin V.,Pitie Salpetriere |
Gharbi C.,Pitie Salpetriere |
Mateus C.,French Institute of Health and Medical Research |
And 5 more authors.
Investigational New Drugs | Year: 2014
Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) have been investigated in metastatic melanoma and other cancers and have shown promising results. Inhibition of CTLA-4 characteristically induces well-known side effects called "immune-related adverse events" (irAEs). IrAEs mainly include colitis, dermatitis, hepatitis, endocrinopathies; uveitis, iridocyclitis, neuropathies, and inflammatory myopathy have occasionally been reported. Kidney involvement is rare. We report 2 cases of acute granulomatous interstitial nephritis and present, based on literature review, renal disorders related to Ipilimumab therapy. Autoimmune symptoms have to be carefully checked for patients treated with CTLA-4 inhibitors. In order to reduce the risk of sequelae, early recognition of irAEs and treatment initiation are crucial. © 2014 Springer Science+Business Media.
PubMed | Pitie Salpetriere
Type: | Journal: Virology journal | Year: 2013
Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia.A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated.Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected.Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments to further optimize clinical management and to promote vaccination in HIV-infected patients.