Caen University Hospital Center

Caen, France

Caen University Hospital Center

Caen, France

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Bernier M.,Caen University Hospital Center
Journal of Immunotherapy | Year: 2017

The anti-programmed cell-death-1 antibody, nivolumab, has been recently approved for the treatment of advanced non–small cell lung cancer. Although, today, immune-related adverse effects such as dermatologic, digestive, hepatic, and endocrine toxicities are well-known with immune checkpoint inhibitors, rheumatic diseases are less well described. Herein, we report the case of a patient without a history of arthritis who developed polymyalgia rheumatica after 13 cycles of nivolumab used for the treatment of advanced non–small cell lung cancer. Laboratory evidence of inflammatory syndrome, articular echography, and clinical presentation with classical symptoms and also distal manifestations were suggestive of this chronic inflammatory disorder. Because of a relevant pain, clinicians were forced to suspend immunotherapy. Nevertheless, due to glucocorticoid therapy, the patient’s symptoms have decreased progressively. Moreover, nivolumab was reintroduced 8 weeks later, whereas prednisone (10 mg) was continued, without any recurrence symptoms. To conclude, our case suggests that polymyalgia rheumatica might be a very disabling anti-programmed cell-death-1 immune-related adverse effect. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-15-2015 | Award Amount: 6.34M | Year: 2015

Stroke is the second leading cause of death in the world population. When not fatal, stroke often results in disability, due to motor and cognitive impairments, and secondary health problems affecting not only patients but also their families. Building on emerging preclinical and pilot clinical evidences, RESSTORE will focus on the clinical assessment of regenerative cell therapy to improve stroke recovery and patients quality of life. RESSTORE European multicentre randomised phase IIb will explore, for the first time, the efficacy (functional recovery) and safety of intravenous infusion of allogenic adipose tissue derived mesenchymal stem cells (ADMSCs) in 400 stroke patients. Therapeutic effects of ADMSCs will be assessed and monitored in patients using clinical rating scales, multimodal MRI and novel blood biomarkers. Additionally, the societal value and cost-effectiveness of ADMSCs-based regenerative therapy will be evaluated through health economics and predictive in silico simulations. Complementary ancillary animal studies will support the clinical trial by defining i) if the treatment response can be further enhanced by intensive rehabilitation, ii) the contribution of co-morbidities and iii) the mechanism(s) underlying the therapeutic effect. The European regenerative therapy capacities (France, Spain, Finland, United Kingdom and Czech Republic), developed in RESSTORE will cover the full value chain in the field (large scale GMP cell production, clinical testing, biomarkers discovery, understanding of the restoring mechanisms, modelling, biobanking, economic studies, exploitation and communication plan). RESSTORE will thus surely contribute, together with the workforce trained in the context of the programme, to improve its public and private (SME) competitiveness and increase the attractiveness of Europe as a reference location to develop and clinically assess new innovative therapeutic options for brain diseases.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2013.5.2 | Award Amount: 5.03M | Year: 2013

Heart failure (HF) is one of the major health issues in Europe affecting 6 million patients and growing substantially because of the ageing population and improving survival following myocardial infarction. The poor short to medium term prognosis of these patients means that, treatments such as cardiac re-synchronisation therapy and mitral valve repair can have substantial impact. However, these therapies, are ineffective in up to 50% of the treated patients and involve significant morbidity and substantial cost. The primary aim of VP2HF is to bring together image and data processing tools with statistical and integrated biophysical models mainly developed in previous VPH projects, into a single clinical workflow to improve therapy selection and treatment optimisation in HF. The tools will be tested and validated in 200 patients (including 50 historical datasets) across 3 clinical sites, including a prospective clinical study in 50 patients in the last year of the project. The key innovations in VP2HF that make it likely that the project results will be commercially exploited and have major clinical impact are; 1) all tools to process images and signals, and obtain the statistical and biophysical models will be integrated into one clinical software platform that can be easily and intuitively used by clinicians and tried out in the prospective clinical study and 2) by utilising a decision tree stratification approach, only the appropriate parts of the tool chain, that will add maximum value to the predictions will be used in individual patients, so that the more resource intensive parts will be used when they will add real value. We expect that the study results of substantial improved efficacy of decision making over current guidelines, and an integrated package that is used as part of clinical workflow will ensure the industrial project partners, in particular Philips, will develop project outputs into dedicated products that will have significant clinical impact.


Cattoir V.,Caen University Hospital Center | Cattoir V.,University of Caen Lower Normandy
Journal of Infection | Year: 2012

Actinobaculum schaalii is a facultative anaerobic, Gram-positive rod-shaped species phylogenetically related to Actinomyces that is likely part of the commensal flora of the human genitourinary tract. Because of its fastidious growth under aerobic conditions and its resemblance to bacteria of the resident flora, A. schaalii is frequently overlooked or considered as a contaminant. It is also difficult to identify phenotypically, still requiring molecular identification. Note that the recent technology of matrix-assisted laser desorption/ionisation time-of-flight-mass spectrometry could be a promising tool for its identification. Recent studies using sensitive PCR assays showed that its clinical significance was largely underestimated. Since its first description in 1997, A. schaalii has been responsible for numerous urinary tract infections (UTIs), mainly in elderly (usually >60 years) and patients with underlying urological conditions. Infected urines usually show many Gram-positive rods with significant leukocyturia and a negative test for nitrites. Numerous cases of severe infections have also been described, such as urosepsis, bacteremia, cellulitis, spondylodiscitis, and endocarditis. Invitro, A. schaalii is highly susceptible to β-lactams but it is resistant to ciprofloxacin and cotrimoxazole, first-choice antimicrobials for the oral treatment of UTIs. A penicillin (e.g. amoxicillin) or a cephalosporin (e.g. cefuroxime, ceftriaxone) should be the preferred treatment. © 2012 The British Infection Association.


Continuous subcutaneous insulin infusion (CSII) using an external pump is widely used for the treatment of type 1 diabetes, but has been less evaluated in type 2 diabetes. This review analyzes the open-label as well as randomized controlled studies performed in type 2 diabetic patients. The efficacy of CSII is compared with multiple daily injections (MDI) in terms of glycaemic control, weight variation, insulin requirements, treatment satisfaction and hypoglycaemic events. CSII may be offered as an alternative treatment to type 2 diabetic patients with poor glycaemic control despite high-dose insulin requirements administered through MDI. L'administration sous-cutanée continue d'insuline par pompe externe est largement utilisée pour le traitement du diabète de type 1, mais son usage dans le diabète de type 2 est moins bien évalué. Cette revue analyse les études ouvertes et controlées réalisées dans cette indication, études qui à ce jour sont peu nombreuses. L'efficacité de la pompe à insuline est comparée aux multi-injections sous-cutanées, en termes d'équilibre glycémique, de variation pondérale, de besoins en insuline, de satisfaction du traitement et d'incidence des hypoglycémies. La pompe à insuline pourrait être une alternative intéressante chez les patients diabétiques de type 2 dont l'équilibre glycémique reste médiocre en dépit de l'administration de fortes doses d'insuline en injections sous-cutanées discontinues. © 2010 Elsevier Masson SAS.


Churg A.,University of British Columbia | Galateau-Salle F.,Caen University Hospital Center
Archives of Pathology and Laboratory Medicine | Year: 2012

The separation of benign from malignant mesothelial proliferations is crucial to patient management but is often a difficult problem for the pathologist. Objective.-To review the pathologic features that allow separation of benign from malignant mesothelioma proliferations, with an emphasis on new findings. Data Sources.-Literature review and experience of the authors. Conclusions.-Invasion is still the most reliable indicator of malignancy. The distribution and amount of proliferating mesothelial cells are important in separating benignity from malignancy, and keratin stains can be valuable because they highlight the distribution of mesothelial cells. Hematoxylin-eosin examination remains the gold standard, and the role of immunochemistry is extremely controversial; we believe that at present there is no reliable immunohistochemical marker of malignancy in this setting. Mesothelioma in situ is a diagnosis that currently cannot be accurately made by any type of histologic examination. Desmoplastic mesotheliomas are characterized by downward growth of keratin-positive spindled cells between S100-positive fat cells; some cases of organizing pleuritis can mimic involvement of fat, but these fatlike spaces are really S100-negative artifacts aligned parallel to the pleural surface. Fluorescence in situ hybridization on tissue sections to look for homozygous p16 gene deletions is occasionally useful, but many mesotheliomas do not show homozygous p16 deletions. Equivocal biopsy specimens should be diagnosed as atypical mesothelial hyperplasia and another biopsy requested if the clinicians believe the process is malignant. Copyright © 2012 College of American Pathologists.


Tavernier M.,Caen University Hospital Center
Journal of visceral surgery | Year: 2013

In primary Crohn's disease (CD), laparoscopic ileocolic resection has been shown to be both feasible and safe, and is associated with improved outcomes in terms of postoperative morbidity and length of hospital stay. At this time, it is unclear whether the laparoscopic approach can be routinely proposed as a safe procedure for patients with complex CD involving localized abscess, fistula or recurrent disease. The aim of this systematic literature review was to assess the feasibility and safety of laparoscopic surgery for complex or recurrent CD. In the current literature, there are nine non-randomized cohort studies, two of which were case-matched. The mean rate of conversion to open laparotomy reported in these series ranged from 7% to 42%. Morbidity rate and hospital stay following laparoscopic resection for complex CD were similar to those for initial resection or for non-complex CD. In summary, even though strong evidence is lacking and more contributions with larger size are needed, the limited experiences available from the literature confirm that the laparoscopic approach for complex CD is both feasible and safe in the hands of experienced IBD surgeons with extensive expertise in laparoscopic surgery. Further studies are required to confirm these results and determine precisely patient selection criteria. Copyright © 2013 Elsevier Masson SAS. All rights reserved.


Beucher G.,Caen University Hospital Center
Diabetes & metabolism | Year: 2010

To estimate maternal outcome of treated or untreated gestational diabetes mellitus (GDM). French and English publications were searched using PubMed and the Cochrane library. The diagnosis of GDM includes a high risk population for preeclampsia and Caesarean sections (EL3). The risks are positively correlated with the level of hyperglycaemia in a linear way (EL2). Intensive treatment of mild GDM compared with routine care reduces the risk of pregnancy-induced hypertension (preeclampsia, gestational hypertension). Moreover, it does not increase the risk of operative vaginal delivery, Caesarean section and postpartum haemorrhage (EL1). Being overweight, obesity and maternal hyperglycaemia are independent risk factors for preeclampsia (EL2). Their association with GDM increases the risk of preeclampsia and Caesarean section compared to diabetic women with a normal body mass index (EL3). The association of several risk factors (such as advanced maternal age, pre-existing chronic hypertension, pre-existing nephropathy, obesity, suboptimal glycaemic control) increases the risk of preeclampsia. In that case, the classic follow-up (blood pressure measurement, proteinuria) should be more frequent than monthly (professional consensus). The risk of Caesarean section is increased by macrosomia, whether suspected prenatally or not, but this increased risk remains whatever the birth weight (EL3). Diagnosis and treatment of GDM do not reduce the risk of severe perineal lesions, operative vaginal delivery and postpartum haemorrhage (EL2). Some psychological symptoms, such as anxiety and alteration of self-perception, can occur upon diagnosis of GDM (EL3). The treatment of GDM appears to reduce the risk of postpartum depression symptoms (EL2). Most of the information published on GDM covers the risks of preeclampsia and Caesarean section; intensive care of GDM reduces these risks. Pregnancy care should be adjusted to the risk factors.


Cattoir V.,University of Caen Lower Normandy | Cattoir V.,Caen University Hospital Center | Leclercq R.,University of Caen Lower Normandy | Leclercq R.,Caen University Hospital Center
Journal of Antimicrobial Chemotherapy | Year: 2013

Twenty-five years ago, isolation of vancomycin-resistant Enterococcus faecium (VREm) was reported both in the UK and in France. Since then, VREm has spread worldwide in hospitals. Hospital outbreaks appeared to be related to the evolution since the end of 1980s of a subpopulation of E. faecium highly resistant to ampicillin and fluoroquinolones (the so-called clonal complex CC17) that later acquired resistance to vancomycin. CC17 isolates are presumably better adapted than other E. faecium isolates to the constraints of the hospital environment and most contain mobile genetic elements, phage genes, genes encoding membrane proteins, regulatory genes, a putative pathogenicity island and megaplasmids. Colonization and persistence are major features of VREm. Inherent characteristics of E. faecium including a remarkable genome plasticity, in part due to acquisition of IS elements, in particular IS16, have facilitated niche adaptation of this distinct E. faecium subpopulation that is multiply resistant to antibiotics. Quinupristin/dalfopristin and linezolid are licensed for the treatment of VREm infections, with linezolid often used as a first-line treatment. However, the emergence of plasmid-mediated resistance to linezolid by production of a Cfr methyltransferase in Enterococcus faecalis is worrying. Daptomycin has not been extensively evaluated for the treatment of VREm infections and resistant mutants have been selected under daptomycin therapy. Although control of VRE is challenging, a laissez-faire policy would result in an increased number of infections and would create an irreversible situation. Although so far unsuccessful, dissemination of glycopeptide-resistant Staphylococcus aureus with van genes acquired from resistant enterococci cannot be ruled out. © The Author 2012. Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Burdin G.,Caen University Hospital Center
Orthopaedics & traumatology, surgery & research : OTSR | Year: 2013

Tibial plateau fractures are serious articular fractures that are challenging to treat. Arthroscopy-assisted percutaneous fixation is the treatment of choice in Schatzker types 1, 2, 3, and 4 fractures, as it ensures optimal reduction and stable fixation consistent with early mobilisation. The most reliable fixation method seems to be percutaneous cannulated screw fixation, which is less invasive than open plate fixation. In complex proximal tibial fractures, arthroscopy may allow an evaluation of articular fracture reduction, thereby obviating the need for extensive arthrotomy. Complementary stable fixation is crucial and should allow early mobilisation to reap the benefits of the arthroscopic assistance. This article aims to review the technical points that are useful to the successful video-assisted management of tibial plateau fractures. Copyright © 2013. Published by Elsevier Masson SAS.

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