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Ryvlin P.,French Institute of Health and Medical Research | Nashef L.,King's College | Lhatoo S.D.,Case Western Reserve University | Bateman L.M.,Columbia University | And 24 more authors.
The Lancet Neurology | Year: 2013

Background: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy. Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology. The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide. Methods: Between Jan 1, 2008, and Dec 29, 2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence. Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms. An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available. Findings: 147 (92%) of 160 units responded to the survey. 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported. Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18-50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction. Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest. SUDEP incidence in adult epilepsy monitoring units was 5·1 (95% CI 2·6-9·2) per 1000 patient-years, with a risk of 1·2 (0·6-2·1) per 10000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal. Interpretation: SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest. Improved supervision is warranted in epilepsy monitoring units, in particular during night time. Funding: Commission of European Affairs of the International League Against Epilepsy. © 2013 Elsevier Ltd.


Rajkumar S.V.,Mayo Medical School | Dimopoulos M.A.,National and Kapodistrian University of Athens | Palumbo A.,University of Turin | Merlini G.,University of Pavia | And 29 more authors.
The Lancet Oncology | Year: 2014

This International Myeloma Working Group consensus updates the disease definition of multiple myeloma to include validated biomarkers in addition to existing requirements of attributable CRAB features (hypercalcaemia, renal failure, anaemia, and bone lesions). These changes are based on the identification of biomarkers associated with near inevitable development of CRAB features in patients who would otherwise be regarded as having smouldering multiple myeloma. A delay in application of the label of multiple myeloma and postponement of therapy could be detrimental to these patients. In addition to this change, we clarify and update the underlying laboratory and radiographic variables that fulfil the criteria for the presence of myeloma-defining CRAB features, and the histological and monoclonal protein requirements for the disease diagnosis. Finally, we provide specific metrics that new biomarkers should meet for inclusion in the disease definition. The International Myeloma Working Group recommends the implementation of these criteria in routine practice and in future clinical trials, and recommends that future studies analyse any differences in outcome that might occur as a result of the new disease definition. © 2014 Elsevier Ltd.


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.


Bosmans J.M.,University of Antwerp | Kefer J.,UCLouvain | De Bruyne B.,OLV Ziekenhuis | Herijgers P.,University Hospital Leuven | And 4 more authors.
Interactive Cardiovascular and Thoracic Surgery | Year: 2011

We report clinical outcomes following transcatheter aortic valve implantation (TAVI), using the CoreValve revalving system (18 Fr transfemoral or subclavian) or the Edwards Sapien valve (22 Fr transfemoral or 24 Fr transapical) as part of a Belgian prospective nonrandomized multicentre registry. All 15 Belgian centres performing TAVI participated to this registry (seven exclusively Edwards Sapien, eight exclusively CoreValve). All consecutive high-risk symptomatic patients with severe aortic stenosis were evaluated by a heart team and screened for eligibility for TAVI. Three hundred and twenty-eight patients underwent TAVI with CoreValve (n=141; eight subclavian and 133 transfemoral) or Edwards Sapien (n=187; 99 transfemoral and 88 transapical) up to April 2010. Procedural success was 97%. Onemonth survival was 88% for the Edwards and 89% for the CoreValve treated patients. One-month mortality was both related to cardiac and non-cardiac reasons. Overall one-year survival was 78% in the CoreValve transfemoral treated patients, 100% in the CoreValve subclavian treated patients, 82% in the Edwards transfemoral treated patients and 63% in the Edwards transapical treated patients. This mid-term mortality was mainly related to age-related, non-cardiac complications. © 2011 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.


News Article | December 23, 2016
Site: www.prweb.com

Parathyroid hormone (PTH) is an 84 amino acid that plays a key role in phosphocalcic metabolism. Its measurement is essential to diagnose and treat primary hyperparathyroidism and to evaluate chronic kidney disease-mineral and bone disorders (CKD-MBD). PTH determination is not an easy task, mainly because of the many similar fragments that circulate in our blood. Because these fragments are recognized differently by the various assays, the values obtained are often very different between “intact” kits. Up to now, 3rd generation PTH assays have not demonstrated any clinical benefit over intact PTH assays. However, PTH standardization can be achieved only with 3rd generation and it will be impossible to standardize assays using the intact PTH kits, because of variable cross-reactivities to fragments. It is important to carefully select the “normal” subjects to establish reference ranges that allow the proper interpretation of the patient’s PTH results. These “normals” should not have secondary hyperparathyroidism and should have eGFR, 25(OH)D, calcium and phosphorus levels within a normal range. Unfortunately, manufacturers have not judiciously selected their “normals”, leading to falsely elevated PTH reference ranges. Using correctly established PTH reference ranges will assist physicians in correctly classifying HD patients in the appropriate bone turnover category. Participants of the webinar will better understand the importance of good reference range establishment for PTH and PTH standardization. They can also expect to learn how best to get up-to-date information regarding PTH stability. Dr. Etienne Cavalier, professor of clinical chemistry at the University of Liege and Head of the Department of Clinical Chemistry at the CHU de Liege, will be the presenter for this webinar. Cavalier earned both a Master of Sciences in pharmaceutical sciences and an Advanced Master in clinical biology from the University of Liege. He then went on to earn his PhD in Pharmaceutical and Biomedical Sciences from the same university. In his current role, Cavalier is the professor of clinical chemistry at the University of Liege and head of the Department of Clinical Chemistry at the CHU de Liege. His main research topics are linked with the phosphocalcic metabolism, renal function, frailty and sarcopenia. LabRoots will host the free webinar on February 15, 2017, beginning at 9:00 a.m. PT, 12 p.m. ET. To find out more on this event, learn about continuing education credits or to register for free, click here. About DiaSorin Headquartered in Italy and listed in the FTSE Italia Mid Cap Index, DiaSorin is a global leader in the In Vitro Diagnostics (IVD) field. For over 40 years the Company has been developing, producing and marketing reagent kits for IVD worldwide. Through constant investments in research and development, and using its own distinctive expertise in the field of immunodiagnostics to deliver a high level of innovation, DiaSorin offers today the broadest range of specialty tests available in the immunodiagnostics market and new tests in the molecular diagnostics markets, which identify DiaSorin Group as the IVD “diagnostics specialist.” About LabRoots LabRoots is the leading scientific social networking website and producer of educational virtual events and webinars. Contributing to the advancement of science through content sharing capabilities, LabRoots is a powerful advocate in amplifying global networks and communities. Founded in 2008, LabRoots emphasizes digital innovation in scientific collaboration and learning, and is a primary source for current scientific news, webinars, virtual conferences, and more. LabRoots has grown into the world’s largest series of virtual events within the Life Sciences and Clinical Diagnostics community.


De Brakeleer S.,Vrije Universiteit Brussel | De Greve J.,Vrije Universiteit Brussel | Loris R.,Vrije Universiteit Brussel | Janin N.,CHU de Liege | And 3 more authors.
Human Mutation | Year: 2010

Fifteen years ago BRCA1 and BRCA2 were reported as high penetrant breast cancer predisposing genes. However, mutations in these genes are found in only a fraction of high risk families. BARD1 is a candidate breast cancer gene, but only a limited number of missense mutations with rather unclear pathogenic consequences have been reported. We screened 196 high risk breast cancer families for the occurrence of BARD1 variants. All genetic variants were analyzed using clinical information as well as IN SILICO predictive tools, including protein modeling. We found three candidate pathogenic mutations in seven families including a first case of a protein truncating mutation (p.Glu652fs) removing the entire second BRCT domain of BARD1. In conclusion, we provide evidence for an increased breast cancer risk associated to specific BARD1 germline mutations. However, these BARD1 mutations occur in a minority of hereditary breast cancer families. ©2010 Wiley-Liss, Inc.


Radermecker R.P.,University of Liège | Saint Remy A.,CHU de Liege | Scheen A.J.,University of Liège | Bringer J.,Montpellier University Hospital Center | Renard E.,Montpellier University Hospital Center
Diabetes and Metabolism | Year: 2010

Aim: This study aimed to assess the effectiveness of continuous glucose monitoring (CGM) for glucose control in type 1 diabetic patients treated by continuous subcutaneous insulin infusion (CSII) and presenting with frequent hypoglycaemic episodes. Methods: Thirteen patients with type 1 diabetes (diabetes duration: 25±15 years; CSII duration: 5.5±7.0 years), with more than six recorded capillary blood glucose (CBG) values <60mg/dL, according to their metres for the past 14 days, were offered the permanent use of a CGM device (Guardian RT®, Medtronic) plus ongoing self-monitoring of blood glucose (SMBG) for 12 weeks, followed by a 12-week crossover period of SMBG only, or vice versa. Glucose control, determined by recorded 14-day CBG values <60mg/dL and HbA1c levels, and quality of life according to the Diabetes Quality of Life (DQOL) questionnaire, were assessed at baseline, and after 12- and 24-week follow-ups. Results: Four patients withdrew from the study during the first period (of whom three were using CGM). In the nine study completers, the number of low CBG values decreased significantly from 13.9±9.2 to 7.6±6.8 (P=0.011) when patients used CGM, in either the initial or final trial period, while a decrease in HbA1c from 8.3±0.7 to 7.7±0.6% (P=0.049) was also observed, in contrast to the absence of any significant differences during the SMBG-only period. DQOL scores were also essentially unaffected. Conclusion: This pilot observational study supports the hypothesis that CGM use can significantly improve overall glucose control while reducing hypoglycaemic episodes in hypoglycaemia-prone type 1 diabetic patients treated by CSII. © 2010 Elsevier Masson SAS.


De La Brassinne M.,CHU de Liege | Nikkels A.F.,CHU de Liege
Acta Clinica Belgica | Year: 2013

The treatment of psoriasis is mainly based on antiinflammatory and/or anti-hyperproliferative agents. The topical steroids appeared in the fifties and were the first therapeutic breakthrough for psoriasis, followed by methotrexate and phototherapy in the sixties, photochemotherapy (PUVA) in the seventies and acitretin and cyclosporine in the eighties. The targeted biologic therapies represent a whole new era of therapeutic possibilities with a highly beneficial safety record. The choice of treatment depends on a large series of factors, including the type and extend of the psoriasis, the patient's preferences, co-medications, comorbidities and drug tolerance. This overview presents the currently available topical and systemic agents for treating psoriasis, including topical corticosteroids, vitamin D derivatives, UV-light based therapies, methotrexate, cyclosporine, acitretin, and the biologic agents such as the TNF antagonists etanercept, adalimumab and infliximab, as well as the anti-p40 IL12/23 agent ustekinumab. Newer, very promising, agents aiming the Th17 pathway are under development for psoriasis.


Dresse C.,CHU de Liege | Joris J.L.,CHU de Liege | Hans G.A.,CHU de Liege
Trends in Anaesthesia and Critical Care | Year: 2012

Anaesthesia produces muscle relaxation and consequently reduces lung volumes, especially the functional residual capacity. This leads to repeated closure of small airways and constitution of atelectases. Repeated closure of small airways and atelectases not only alter gas exchanges but also contribute to ventilator-induced lung injury. Over the last decade, accumulating experimental and clinical data encourage to revise ventilation of anaesthetized patients. Alveolar collapse can be prevented as soon as the induction of anaesthesia by positioning the patient in head-up position, applying a continuous positive airway pressure, and lowering the inspired oxygen fraction. During mechanical ventilation, positive end-expiratory pressure becomes the cornerstone of the prevention of alveolar de-recruitment. Despite these measures, atelectases do develop in some circumstances and need to be reversed by recruitment manoeuvres. In addition, the extent of the tidal volume should be decreased to limit pulmonary overdistension and subsequently ventilator-induced lung injury. The extubation phase is also critical since hypoventilation and re-occurrence of atelectases secondary to the administration of pure oxygen can occur during the transition between controlled and spontaneous ventilation. The efficient measures recommended during the induction of anaesthesia should be also applied during extubation. An assisted mode of ventilation could be beneficial to smoothen this transition phase. © 2012 Elsevier Ltd.


Numerous patients with type 2 diabetes have renal impairment, especially in the elderly population. Metformin, the first choice oral glucose-lowering agent, is classically contraindicated in case of chronic kidney disease of stages 3-5 (creatinine clearance 60 ml/min/1.73 m), because of a risk of accumulation of the biguanide that may lead to lactic acidosis. Hence numerous patients with some degree of renal impairment are being treated with metformin in clinical practice, apparently without any harm. In contrast, several observational studies have shown that they may clinically bene-fit from this therapy, including with a significant reduction of all-cause mortality when compared to patients not receiving metformin. Thus, an increasing number of physicians plea for revisiting the official criteria of contraindication to the use of metformin in case of renal insufficiency. The present paper discusses this controversy and insists upon the mandatory cautions to be taken when using metformin in a diabetic patient with moderate (stage 3) chronic kidney disease (metformin being contraindicated in case of severe renal impairment - stages 4-5).

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