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NEWTON, Mass., May 18, 2017 (GLOBE NEWSWIRE) -- Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, today announced that interim clinical data from the ongoing Phase 2b SADAL study evaluating lead product candidate, selinexor (KPT-330), an oral Selective Inhibitor of Nuclear Export / SINE™ compound, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will be featured in an oral presentation at the 22nd Congress of the European Hematology Association (EHA) taking place June 22-25, 2017 in Madrid, Spain. “DLBCL is the most common type of non-Hodgkin lymphoma among adults and there remains a high unmet medical need, particularly in the relapsed and refractory setting for patients who are not eligible for stem cell transplant or who relapse afterward,” said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm.  “Previously reported data from the ongoing Phase 2b SADAL study showed that treatment with single-agent oral selinexor resulted in robust response rates with prolonged durability in patients with heavily pretreated DLBCL, including against both GCB and non-GCB (ABC) subtypes.  We look forward to sharing some further detail from the SADAL study with the medical community at EHA and ICML this year.” In addition, Karyopharm’s Phase 2b SADAL data were also selected for a poster presentation at the 14th International Conference on Malignant Lymphoma (ICML) being held June 14-17, 2017 in Lugano, Switzerland. Details for the Oral Presentation at EHA 2017: Title: Single Agent Oral Selinexor Exhibits Durable Responses in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) of Both GCB and Non-GCB Subtypes: The Phase 2b SADAL Study Presenter: Marie Maerevoet, Institute Jules Bordet, Brussels, Belgium Abstract code: S469 Topic: Aggressive Non-Hodgkin lymphoma – Clinical Session: Aggressive Non-Hodgkin lymphoma – Relapsed/refractory Location: Hall C Date and Time: Saturday, June 24, 2017 from 14:45 - 17:00 CET Details for the Poster Presentation at ICML 2017: Title: A Phase 2b Randomized Study of Single Agent Selinexor in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Presenter: Rene-Olivier Casanovas, Hematologie Clinique, CHU Dijon, France Poster #: 193 Location: Marquee Parco Ciani Date and Time: From Wednesday, June 14, 2017 at 12:00 CET through Friday, June 16, 2017 at 18:30 CET Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE™ compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,000 patients have been treated with selinexor and it is currently being evaluated in several mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Karyopharm plans to initiate a pivotal randomized Phase 3 study of selinexor in combination with bortezomib (Velcade®) and low-dose dexamethasone (BOSTON) in patients with multiple myeloma in May 2017. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform the Company's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov. Karyopharm Therapeutics Inc. (Nasdaq:KPTI) is a clinical-stage pharmaceutical company focused on the discovery and development of novel first-in-class drugs directed against nuclear transport and related targets for the treatment of cancer and other major diseases. Karyopharm's SINE™ compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). In addition to single-agent and combination activity against a variety of human cancers, SINE™ compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm, which was founded by Dr. Sharon Shacham, currently has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com. This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, including the timing of initiation of certain trials and of the reporting of data from such trials. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company's current expectations. For example, there can be no guarantee that any of Karyopharm's SINE™ compounds, including selinexor (KPT-330), will successfully complete necessary preclinical and clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for diseases in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended March 31, 2017, which was filed with the Securities and Exchange Commission (SEC) on May 4, 2017, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.


NEWTON, Mass., May 18, 2017 (GLOBE NEWSWIRE) -- Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, today announced that interim clinical data from the ongoing Phase 2b SADAL study evaluating lead product candidate, selinexor (KPT-330), an oral Selective Inhibitor of Nuclear Export / SINE™ compound, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will be featured in an oral presentation at the 22nd Congress of the European Hematology Association (EHA) taking place June 22-25, 2017 in Madrid, Spain. “DLBCL is the most common type of non-Hodgkin lymphoma among adults and there remains a high unmet medical need, particularly in the relapsed and refractory setting for patients who are not eligible for stem cell transplant or who relapse afterward,” said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm.  “Previously reported data from the ongoing Phase 2b SADAL study showed that treatment with single-agent oral selinexor resulted in robust response rates with prolonged durability in patients with heavily pretreated DLBCL, including against both GCB and non-GCB (ABC) subtypes.  We look forward to sharing some further detail from the SADAL study with the medical community at EHA and ICML this year.” In addition, Karyopharm’s Phase 2b SADAL data were also selected for a poster presentation at the 14th International Conference on Malignant Lymphoma (ICML) being held June 14-17, 2017 in Lugano, Switzerland. Details for the Oral Presentation at EHA 2017: Title: Single Agent Oral Selinexor Exhibits Durable Responses in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) of Both GCB and Non-GCB Subtypes: The Phase 2b SADAL Study Presenter: Marie Maerevoet, Institute Jules Bordet, Brussels, Belgium Abstract code: S469 Topic: Aggressive Non-Hodgkin lymphoma – Clinical Session: Aggressive Non-Hodgkin lymphoma – Relapsed/refractory Location: Hall C Date and Time: Saturday, June 24, 2017 from 14:45 - 17:00 CET Details for the Poster Presentation at ICML 2017: Title: A Phase 2b Randomized Study of Single Agent Selinexor in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Presenter: Rene-Olivier Casanovas, Hematologie Clinique, CHU Dijon, France Poster #: 193 Location: Marquee Parco Ciani Date and Time: From Wednesday, June 14, 2017 at 12:00 CET through Friday, June 16, 2017 at 18:30 CET Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE™ compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,000 patients have been treated with selinexor and it is currently being evaluated in several mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Karyopharm plans to initiate a pivotal randomized Phase 3 study of selinexor in combination with bortezomib (Velcade®) and low-dose dexamethasone (BOSTON) in patients with multiple myeloma in May 2017. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform the Company's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov. Karyopharm Therapeutics Inc. (Nasdaq:KPTI) is a clinical-stage pharmaceutical company focused on the discovery and development of novel first-in-class drugs directed against nuclear transport and related targets for the treatment of cancer and other major diseases. Karyopharm's SINE™ compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). In addition to single-agent and combination activity against a variety of human cancers, SINE™ compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm, which was founded by Dr. Sharon Shacham, currently has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com. This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, including the timing of initiation of certain trials and of the reporting of data from such trials. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company's current expectations. For example, there can be no guarantee that any of Karyopharm's SINE™ compounds, including selinexor (KPT-330), will successfully complete necessary preclinical and clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for diseases in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended March 31, 2017, which was filed with the Securities and Exchange Commission (SEC) on May 4, 2017, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.


NEWTON, Mass., May 18, 2017 (GLOBE NEWSWIRE) -- Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, today announced that interim clinical data from the ongoing Phase 2b SADAL study evaluating lead product candidate, selinexor (KPT-330), an oral Selective Inhibitor of Nuclear Export / SINE™ compound, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will be featured in an oral presentation at the 22nd Congress of the European Hematology Association (EHA) taking place June 22-25, 2017 in Madrid, Spain. “DLBCL is the most common type of non-Hodgkin lymphoma among adults and there remains a high unmet medical need, particularly in the relapsed and refractory setting for patients who are not eligible for stem cell transplant or who relapse afterward,” said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm.  “Previously reported data from the ongoing Phase 2b SADAL study showed that treatment with single-agent oral selinexor resulted in robust response rates with prolonged durability in patients with heavily pretreated DLBCL, including against both GCB and non-GCB (ABC) subtypes.  We look forward to sharing some further detail from the SADAL study with the medical community at EHA and ICML this year.” In addition, Karyopharm’s Phase 2b SADAL data were also selected for a poster presentation at the 14th International Conference on Malignant Lymphoma (ICML) being held June 14-17, 2017 in Lugano, Switzerland. Details for the Oral Presentation at EHA 2017: Title: Single Agent Oral Selinexor Exhibits Durable Responses in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) of Both GCB and Non-GCB Subtypes: The Phase 2b SADAL Study Presenter: Marie Maerevoet, Institute Jules Bordet, Brussels, Belgium Abstract code: S469 Topic: Aggressive Non-Hodgkin lymphoma – Clinical Session: Aggressive Non-Hodgkin lymphoma – Relapsed/refractory Location: Hall C Date and Time: Saturday, June 24, 2017 from 14:45 - 17:00 CET Details for the Poster Presentation at ICML 2017: Title: A Phase 2b Randomized Study of Single Agent Selinexor in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Presenter: Rene-Olivier Casanovas, Hematologie Clinique, CHU Dijon, France Poster #: 193 Location: Marquee Parco Ciani Date and Time: From Wednesday, June 14, 2017 at 12:00 CET through Friday, June 16, 2017 at 18:30 CET Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE™ compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,000 patients have been treated with selinexor and it is currently being evaluated in several mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Karyopharm plans to initiate a pivotal randomized Phase 3 study of selinexor in combination with bortezomib (Velcade®) and low-dose dexamethasone (BOSTON) in patients with multiple myeloma in May 2017. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform the Company's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov. Karyopharm Therapeutics Inc. (Nasdaq:KPTI) is a clinical-stage pharmaceutical company focused on the discovery and development of novel first-in-class drugs directed against nuclear transport and related targets for the treatment of cancer and other major diseases. Karyopharm's SINE™ compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). In addition to single-agent and combination activity against a variety of human cancers, SINE™ compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm, which was founded by Dr. Sharon Shacham, currently has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com. This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, including the timing of initiation of certain trials and of the reporting of data from such trials. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company's current expectations. For example, there can be no guarantee that any of Karyopharm's SINE™ compounds, including selinexor (KPT-330), will successfully complete necessary preclinical and clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for diseases in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended March 31, 2017, which was filed with the Securities and Exchange Commission (SEC) on May 4, 2017, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.


Habib G.,Marseille University Hospital Center | Charron P.,University Pierre and Marie Curie | Eicher J.-C.,CHU Dijon | Giorgi R.,La Timone Hospital | And 7 more authors.
European Journal of Heart Failure | Year: 2011

Aims The clinical features, prognosis, and even definition of left ventricular non-compaction (LVNC) are still the subject of much debate. The aim of this registry was to describe the clinical, echocardiographic, and prognostic features of LVNC in France. The main endpoint was to assess clinical and echocardiographic predictors of adverse outcome, defined as death or heart transplantation. Methods and resultsBetween 2004 and 2006, 154 suspected cases of LNVC were identified from a nationwide survey in France. The diagnosis of LVNC was confirmed in 105 cases by echocardiographic evaluation in a core laboratory. Clinical and echocardiographic data for the 105 cases of LVNC are presented. Left ventricular non-compaction was first detected from heart failure symptoms in 45 patients, rhythm disorders in 12, and familial screening in 8. Left ventricular ejection fraction (LVEF) was <30 in 46 of patients, but ≥50 in 16. The latter had less symptoms of severe heart failure (11 vs. 54%, P = 0.001), but similar extension of the NC zone. During 2.33 ± 1.47 years of follow-up, several complications occurred, including severe heart failure in 33 patients, transplantation in 9, ventricular arrhythmia in 7, embolic events in 9, and death in 12. Factors associated with death or heart transplantation were NYHA 3 or 4 (HR = 6.69; P = 0.0007), high LV filling pressures (HR = 7.59; P = 0.001), LVEF (HR = 0.93; P = 0.006), and hospitalization for heart failure (HR = 13.55; P < 0.0001). Conclusion In this large reported series of LVNC, we observed that: (i) Left ventricular non-compaction was detected by familial screening in asymptomatic patients in 8% of cases. (ii) Left ventricular non-compaction was frequently over-diagnosed by echocardiography. (iii) Patients identified as LVNC presented with a high risk of severe complications, transplantation or death and needed close follow-up. © 2010 The Author.


Samson M.,French Institute of Health and Medical Research | Samson M.,University of Burgundy | Audia S.,French Institute of Health and Medical Research | Audia S.,University of Burgundy | And 13 more authors.
Arthritis and Rheumatism | Year: 2012

Objective From an immunologic standpoint, the mechanisms by which treatment with tocilizumab (TCZ), a humanized anti-interleukin-6 (anti-IL-6) receptor antibody, results in improvement in rheumatoid arthritis (RA) patients are still not fully understood. In vitro studies and studies in mouse models have demonstrated the critical role of IL-6 in Th17 cell differentiation. Th17 lymphocytes have been shown to be strongly involved in RA pathogenesis, and the purpose of this study was to investigate the effect of IL-6 blockade on the balance between Th17 cells and Treg cells in patients with active RA. Methods Patients with active RA for whom TCZ had been prescribed by a rheumatologist were enrolled in this study. Phenotypic analyses of T cell populations were performed, and the Disease Activity Score in 28 joints (DAS28) was assessed. Serum cytokine levels and other parameters of inflammation were measured before the first infusion and after the third infusion of TCZ (8 mg/kg). Results Compared to controls, levels of Th17 cells (CD4+IL-17+) were increased and Treg cells (CD4+CD25highFoxP3+) were decreased in the peripheral blood of patients with active RA. The suppressive function of circulating Treg cells was not impaired in patients with active RA. TCZ treatment induced a significant decrease in the DAS28 associated with a significant decrease in the percentage of Th17 cells (from a median of 0.9% to 0.45%; P = 0.009) and an increase in the percentage of Treg cells (from a median of 3.05% to 3.94%; P = 0.0039) in all patients. Conclusion This study demonstrates for the first time that inhibition of IL-6 function by TCZ corrects the imbalance between Th17 cells and Treg cells in patients with RA. Copyright © 2012 by the American College of Rheumatology.


Sabia S.,University College London | Dumurgier J.,National Health Research Institute | Dumurgier J.,University Paris - Sud | Dumurgier J.,Fernand Widal Hospital | And 5 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2014

Background: Walking speed (WS) predicts mortality. However, it is unclear if decline in WS increases prior to death. We examined whether (a) WS declined faster in persons who died during the follow-up compared with those who remained alive and (b) adding change in WS to a model including age, sex, and baseline WS improved prediction of mortality. Methods: Data are from 4,016 participants of the Dijon center of the Three-City study (France), aged 65-85 years. Fast WS (FWS) was measured up to five times over a 12-year period. Mortality was ascertained until 2012. Results: Linear mixed models using a backward time scale showed that FWS declined faster in 908 participants who died during the follow-up (annual change = -0.031 m/s) than in those who survived (-0.021 m/s), corresponding to a difference of -0.009 (95% confidence interval = -0.013 to -0.005) m/s. Compared with "normal" change in FWS (annual change ≥-0.04 m/s), "substantial" decline (<-0.08 m/s) was associated with a 1.4-fold greater risk of mortality (hazards ratio = 1.40, confidence interval = 1.02-1.92) and small decline (-0.08 to -0.04 m/s) with a 1.2-fold greater risk (hazards ratio = 1.18, confidence interval = 0.89-1.57). The net reclassification index when adding these categories of change in FWS to the model adjusted for age, sex, and baseline FWS was 19.0% (0.6, 36.8%). Conclusion. Participants who died during the follow-up had a steeper decline in FWS than the others. Both baseline FWS and FWS decline predict mortality. © The Author 2013.


Cognard C.,Toulouse University Hospital Center | Pierot L.,Reims University Hospital Center | Anxionnat R.,Nancy University Hospital Center | Ricolfi F.,CHU Dijon
Neurosurgery | Year: 2011

Background: The International Subarachnoid Aneurysm Trial (ISAT) showed that for ruptured aneurysms suitable for both techniques, coiling should be the first-choice treatment. Only a small proportion of patients (22%) with ruptured aneurysms were included in that trial. Operators were selected on their experience. One could then criticize the impact of the ISAT on clinical practice as a result of recruitment biases and operators' selection. Objective: To evaluate the morbidity and mortality of coiling when used as first-choice treatment in a consecutive population of patients with ruptured aneurysms treated by nonselected operators. Methods: Thirty-four operators from 19 French centers treated 405 patients with GDC coils from November 2006 to July 2007. The method of treatment was not prespecified. Results: World Federation of Neurological Societies grade at admission was I/II in 65.7% and IV/V in 30.6% of patients. At the 3- to 6-month follow-up, 23.3% of patients were dependent or dead. Thromboembolic events and intraoperative rupture resulted in permanent deficit in 13 (3.2%) and 2 (0.5%), respectively, and death in 4 (1.0%) and 0. Early rebleeding occurred in 2 patients (0.5%) with 2 subsequent deaths. Permanent treatment morbidity and mortality were 3.7 % and 1.5 %, respectively. Conclusion: Clinical results of the multicenter prospective Clarity registry show that when coiling is performed as first-intention treatment in a consecutive series of nonselected ruptured aneurysms by nonselected operators, clinical results are similar to those of the ISAT. Copyright © 2011 by the Congress of Neurological Surgeons.


Pierot L.,Reims University Hospital Center | Cognard C.,Toulouse University Hospital Center | Ricolfi F.,CHU Dijon | Anxionnat R.,Nancy University Hospital Center
American Journal of Neuroradiology | Year: 2010

BACKGROUND AND PURPOSE: The efficacy of the endovascular treatment in providing stable occlusion of intracranial aneurysms is still controversial and should be precisely analyzed. A first step is to carefully study immediate anatomical results. CLARITY (Clinical and Anatomical Results in the Treatment of Ruptured Intracranial Aneurysms) is a prospective multicenter consecutive series including patients treated by coiling for ruptured aneurysms. Immediate anatomic results are presented. MATERIALS AND METHODS: Postoperative anatomic results were evaluated by DSA by the treating physician and anonymously and independently by 2 experienced neuroradiologists by using the 3-point Montreal Scale. Patients were divided into 2 groups: patients treated with GDC and those treated with Matrix detachable coils. RESULTS: A total of 773 patients (461 women, 312 men; 19-80 years of age; mean, 51.2 ± 13.2 years) with 773 ruptured aneurysms were included in the study. The rate of occlusion as determined by the treating physician was designated complete for 586 aneurysms (75.8%), neck remnant for 145 aneurysms (18.8%), and aneurysm remnant for 42 aneurysms (5.4%). The same evaluation as reported by the 2 independent reviewers was complete occlusion for 366 aneurysms (47.4%), neck remnant for 324 aneurysms (41.9%), and aneurysm remnant for 83 aneurysms (10.7%). Postoperative anatomic results were significantly linked to age but not to the technique of endovascular treatment or aneurysm characteristics (location, size, dome-to neck ratio). Results were not significantly different between the GDC and Matrix group. CONCLUSIONS: Endovascular treatment of ruptured intracranial aneurysms resulted in a high rate of satisfactory occlusion (complete occlusion and neck remnant in 89.3%). Patient age was the only factor associated with the rate of occlusion. The rate of aneurysm occlusion differed insignificantly between GDC and Matrix coils.


Kerebel D.,French Army Hospital Sainte Anne | Joly L.-M.,CHU Rouen | Honnart D.,CHU Dijon | Schmidt J.,CHU Clermont Ferrand | And 4 more authors.
Critical Care | Year: 2013

Introduction: Prothrombin complex concentrates (PCC) are haemostatic blood preparations indicated for urgent anticoagulation reversal, though the optimal dose for effective reversal is still under debate. The latest generation of PCCs include four coagulation factors, the so-called 4-factor PCC. The aim of this study was to compare the efficacy and safety of two doses, 25 and 40 IU/kg, of 4-factor PCC in vitamin K antagonist (VKA) associated intracranial haemorrhage.Methods: We performed a phase III, prospective, randomised, open-label study including patients with objectively diagnosed VKA-associated intracranial haemorrhage between November 2008 and April 2011 in 22 centres in France. Patients were randomised to receive 25 or 40 IU/kg of 4-factor PCC. The primary endpoint was the international normalised ratio (INR) 10 minutes after the end of 4-factor PCC infusion. Secondary endpoints were changes in coagulation factors, global clinical outcomes and incidence of adverse events (AEs).Results: A total of 59 patients were randomised: 29 in the 25 IU/kg and 30 in the 40 IU/kg group. Baseline demographics and clinical characteristics were comparable between the groups. The mean INR was significantly reduced to 1.2 - and ≤1.5 in all patients of both groups - 10 minutes after 4-factor PCC infusion. The INR in the 40 IU/kg group was significantly lower than in the 25 IU/kg group 10 minutes (P = 0.001), 1 hour (P = 0.001) and 3 hours (P = 0.02) after infusion. The 40 IU/kg dose was also effective in replacing coagulation factors such as PT (P = 0.038), FII (P = 0.001), FX (P <0.001), protein C (P = 0.002) and protein S (0.043), 10 minutes after infusion. However, no differences were found in haematoma volume or global clinical outcomes between the groups. Incidence of death and thrombotic events was similar between the groups.Conclusions: Rapid infusion of both doses of 4-factor PCC achieved an INR of 1.5 or less in all patients with a lower INR observed in the 40 IU/kg group. No safety concerns were raised by the 40 IU/kg dose. Further trials are needed to evaluate the impact of the high dose of 4-factor PCC on functional outcomes and mortality.Trial registration: Eudra CT number 2007-000602-73. © 2013 Kerebel et al.; licensee BioMed Central Ltd.


Bernard A.,CHU Dijon | Rivera C.,Bordeaux University Hospital Center | Pages P.B.,CHU Dijon | Falcoz P.E.,CHU Strasbourg | And 2 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2011

Objectives: The estimation of risk-adjusted in-hospital mortality is essential to allow each thoracic surgery team to be compared with national benchmarks. The objective of this study is to develop and validate a risk model of mortality after pulmonary resection. Methods: A total of 18,049 lung resections for non-small cell lung cancer were entered into the French national database Epithor. The primary outcome was in-hospital mortality. Two independent analyses were performed with comorbidity variables. The first analysis included variables as independent predictive binary comorbidities (model 1). The second analysis included the number of comorbidities per patient (model 2). Results: In model 1 predictors for mortality were age, sex, American Society of Anesthesiologists score, performance status, forced expiratory volume (as a percentage), body mass index (in kilograms per meter squared), side, type of lung resection,extended resection, stage, chronic bronchitis, cardiac arrhythmia, coronary artery disease, congestive heart failure, alcoholism, history of malignant disease, and prior thoracic surgery. In model 2 predictors were age, sex, American Society of Anesthesiologists score, performance status, forced expiratory volume, body mass index, side, type of lung resection, extended resection, stage, and number of comorbidities per patient. Models 1 and 2 were well calibrated, with a slope correction factor of 0.96 and of 0.972, respectively. The area under the receiver operating characteristic curve was 0.784 (95% confidence interval, 0.76-0.8) in model 1 and 0.78 (95% confidence interval, 0.76-0.797) in model 2. Conclusions: Our preference is for the well-calibrated model 2 because it is easier to use in practice to estimate the adjusted postoperative mortality of lung resections for cancer. Copyright © 2011 by The American Association for Thoracic Surgery.

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