University of Lausanne

About: University of Lausanne is a education organization based out in Lausanne, Switzerland. It is known for research contribution in the topics: Population & Poison control. The organization has 20508 authors who have published 46458 publications receiving 1996655 citations. The organization is also known as: Université de Lausanne & UNIL.

Extracellular matrix remodelling: the role of matrix metalloproteinases.

Abstract: Matrix metalloproteinases (MMPs) are a growing family of metalloendopeptidases that cleave the protein components of the extracellular matrix and thereby play a central role in tissue remodelling. For many years following their discovery, MMPs were believed to function primarily as regulators of ECM composition and to facilitate cell migration simply by removing barriers such as collagen. It is becoming increasingly clear, however, that MMPs are implicated in the functional regulation of a host of non-ECM molecules that include growth factors and their receptors, cytokines and chemokines, adhesion receptors and cell surface proteoglycans, and a variety of enzymes. MMPs therefore play an important role in the control of cellular interactions with and response to their environment in conditions that promote tissue turnover, be they physiological, such as normal development, or pathological, such as inflammation and cancer. This review summarizes some of the recent discoveries that have shed new light on the role of MMPs in physiology and disease.

Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial

Abstract: Summary Background Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma. Methods Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m 2 on days 1–5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34·0 Gy administered in 3·4 Gy fractions over 2 weeks), or standard radiotherapy (60·0 Gy administered in 2·0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623. Findings 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8·3 months [95% CI 7·1–9·5; n=93] vs 6·0 months [95% CI 5·1–6·8; n=100], hazard ratio [HR] 0·70; 95% CI 0·52–0·93, p=0·01), but not with hypofractionated radiotherapy (7·5 months [6·5–8·6; n=98], HR 0·85 [0·64–1·12], p=0·24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8·4 months [7·3–9·4; n=119] vs 7·4 months [6·4–8·4; n=123]; HR 0·82, 95% CI 0·63–1·06; p=0·12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0·35 [0·21–0·56], p vs standard radiotherapy 0·59 [95% CI 0·37–0·93], p=0·02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9·7 months [95% CI 8·0–11·4] vs 6·8 months [5·9–7·7]; HR 0·56 [95% CI 0·34–0·93], p=0·02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0·97 [95% CI 0·69–1·38]; p=0·81). As expected, the most common grade 3–4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3–5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed. Interpretation Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide. Funding Merck, Lion's Cancer Research Foundation, University of Umea, and the Swedish Cancer Society.

Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin.

Abstract: Toxic epidermal necrolysis (TEN, Lyell's syndrome) is a severe adverse drug reaction in which keratinocytes die and large sections of epidermis separate from the dermis. Keratinocytes normally express the death receptor Fas (CD95); those from TEN patients were found to express lytically active Fas ligand (FasL). Antibodies present in pooled human intravenous immunoglobulins (IVIG) blocked Fas-mediated keratinocyte death in vitro. In a pilot study, 10 consecutive individuals with clinically and histologically confirmed TEN were treated with IVIG; disease progression was rapidly reversed and the outcome was favorable in all cases. Thus, Fas-FasL interactions are directly involved in the epidermal necrolysis of TEN, and IVIG may be an effective treatment.

Real estimates of mortality following COVID-19 infection.

Abstract: Materno-fetal and Obstetrics Research Unit, Department Woman-Mother-Child, Lausanne University Hospital, 1011 Lausanne, Switzerland (DB, LP, GF); CHESS Center, The First Hospital of Lanzhou University, Lanzhou, Gansu, China (XQ); Division of Pediatric Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA (KN-S); Aix Marseille Université, Institut de Recherche pour le Développement, Assistance Publique–Hôpitaux de Marseille, Service de Santé des Armées, Vecteurs— Infections Tropicales et Méditerranéennes (VITROME), Institut Hospitalo-Universitaire– Méditerranée Infection, Marseille, France (DM); and Laboratoire Eurofins—Labazur Guyane, French Guiana, France (DM)

2016 updated EULAR evidence-based recommendations for the management of gout

Abstract: Background New drugs and new evidence concerning the use of established treatments have become available since the publication of the first European League Against Rheumatism (EULAR) recommendations for the management of gout, in 2006. This situation has prompted a systematic review and update of the 2006 recommendations. Methods The EULAR task force consisted of 15 rheumatologists, 1 radiologist, 2 general practitioners, 1 research fellow, 2 patients and 3 experts in epidemiology/methodology from 12 European countries. A systematic review of the literature concerning all aspects of gout treatments was performed. Subsequently, recommendations were formulated by use of a Delphi consensus approach. Results Three overarching principles and 11 key recommendations were generated. For the treatment of flare, colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), oral or intra-articular steroids or a combination are recommended. In patients with frequent flare and contraindications to colchicine, NSAIDs and corticosteroids, an interleukin-1 blocker should be considered. In addition to education and a non-pharmacological management approach, urate-lowering therapy (ULT) should be considered from the first presentation of the disease, and serum uric acid (SUA) levels should be maintained at<6 mg/dL (360 µmol/L ) and <5 mg/dL (300 µmol/L ) in those with severe gout. Allopurinol is recommended as first-line ULT and its dosage should be adjusted according to renal function. If the SUA target cannot be achieved with allopurinol, then febuxostat, a uricosuric or combining a xanthine oxidase inhibitor with a uricosuric should be considered. For patients with refractory gout, pegloticase is recommended. Conclusions These recommendations aim to inform physicians and patients about the non-pharmacological and pharmacological treatments for gout and to provide the best strategies to achieve the predefined urate target to cure the disease.