Institute Central des Hopitaux Valaisans

Sion, Switzerland

Institute Central des Hopitaux Valaisans

Sion, Switzerland
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Kempers M.J.E.,Radboud University Nijmegen | Kuiper R.P.,Radboud University Nijmegen | Ockeloen C.W.,Radboud University Nijmegen | Chappuis P.O.,University of Geneva | And 40 more authors.
The Lancet Oncology | Year: 2011

Background: Lynch syndrome is caused by germline mutations in MSH2, MLH1, MSH6, and PMS2 mismatch-repair genes and leads to a high risk of colorectal and endometrial cancer. We previously showed that constitutional 3' end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of MSH2 in EPCAM-expressing tissues, resulting in tissue-specific MSH2 deficiency. We aim to establish the risk of cancer associated with such EPCAM deletions. Methods: We obtained clinical data for 194 carriers of a 3' end EPCAM deletion from 41 families known to us at the Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands and compared cancer risk with data from a previously described cohort of 473 carriers from 91 families with mutations in MLH1, MSH2, MSH6, or a combined EPCAM-MSH2 deletion. Findings: 93 of the 194 EPCAM deletion carriers were diagnosed with colorectal cancer; three of the 92 women with EPCAM deletions were diagnosed with endometrial cancer. Carriers of an EPCAM deletion had a 75% (95% CI 65-85) cumulative risk of colorectal cancer before the age of 70 years (mean age at diagnosis 43 years [SD 12]), which did not differ significantly from that of carriers of combined EPCAM-MSH2 deletion (69% [95% CI 47-91], p=0·8609) or mutations in MSH2 (77% [64-90], p=0·5892) or MLH1 (79% [68-90], p=0·5492), but was higher than noted for carriers of MSH6 mutation (50% [38-62], p<0·0001). By contrast, women with EPCAM deletions had a 12% [0-27] cumulative risk of endometrial cancer, which was lower than was that noted for carriers of a combined EPCAM-MSH2 deletion (55% [20-90], p<0·0001) or of a mutation in MSH2 (51% [33-69], p=0·0006) or MSH6 (34% [20-48], p=0·0309), but did not differ significantly from that noted for MLH1 (33% [15-51], p=0·1193) mutation carriers. This risk seems to be restricted to deletions that extend close to the MSH2 gene promoter. Of 194 carriers of an EPCAM deletion, three had duodenal cancer and four had pancreatic cancer. Interpretation: EPCAM deletion carriers have a high risk of colorectal cancer; only those with deletions extending close to the MSH2 promoter have an increased risk of endometrial cancer. These results underscore the effect of mosaic MSH2 deficiency, leading to variable cancer risks, and could form the basis of an optimised protocol for the recognition and targeted prevention of cancer in EPCAM deletion carriers. Funding: Sacha Swarttouw-Hijmans Foundation, Dutch Cancer Society, Deutsche Krebshilfe (German Cancer Aid), Hong Kong Cancer Fund, Hungarian Research Grant OTKA, Norwegian EEA Financial Mechanism (Hungarian National Institute of Oncology), and US National Cancer Institute. © 2011 Elsevier Ltd.


Rey V.,University of Lausanne | Du Pasquier R.,University of Lausanne | Muehl A.,Service de Neurologie | Peter O.,Institute Central des Hopitaux Valaisans | Michel P.,University of Lausanne
Revue Neurologique | Year: 2010

The most frequent clinical manifestation of borreliosis in Switzerland is erythema migrans, with about 2500 patients each year. Neurological manifestations are rare, mostly hyperalgesic radiculitis (Bannwarth syndrome), aseptic meningitis or cranial nerve involvement. We report the first Swiss patient with meningovasculitis due to neuroborreliosis, with recurrent multiple ischemic strokes in multiple vascular territories. The treatment with ceftriaxone stopped the progression, but the patient is still suffering from severe invalidating cognitive disorders. We also comment on the pathophysiology and review the literature of other clinical cases. © 2010 Elsevier Masson SAS. All rights reserved.


Fernandez P.,Kantonsspital Aarau | Solenthaler M.,University of Bern | Spertini O.,University of Lausanne | Quarroz S.,University of Lausanne | And 9 more authors.
PLoS ONE | Year: 2012

Background: The diagnosis of malignant hematologic diseases has become increasingly complex during the last decade. It is based on the interpretation of results from different laboratory analyses, which range from microscopy to gene expression profiling. Recently, a method for the analysis of RNA phenotypes has been developed, the nCounter technology (Nanostring® Technologies), which allows for simultaneous quantification of hundreds of RNA molecules in biological samples. We evaluated this technique in a Swiss multi-center study on eighty-six samples from acute leukemia patients. Methods: mRNA and protein profiles were established for normal peripheral blood and bone marrow samples. Signal intensities of the various tested antigens with surface expression were similar to those found in previously performed Affymetrix microarray analyses. Acute leukemia samples were analyzed for a set of twenty-two validated antigens and the Pearson Correlation Coefficient for nCounter and flow cytometry results was calculated. Results: Highly significant values between 0.40 and 0.97 were found for the twenty-two antigens tested. A second correlation analysis performed on a per sample basis resulted in concordant results between flow cytometry and nCounter in 44-100% of the antigens tested (mean = 76%), depending on the number of blasts present in a sample, the homogeneity of the blast population, and the type of leukemia (AML or ALL). Conclusions: The nCounter technology allows for fast and easy depiction of a mRNA profile from hematologic samples. This technology has the potential to become a valuable tool for the diagnosis of acute leukemias, in addition to multi-color flow cytometry. © 2012 Fernandez et al.


Benoit E.,Institute Central des Hopitaux Valaisans | Eckert P.,Hospital of Sion Center | Theytaz C.,Hospital of Sion Center | Joris-Frasseren M.,Hospital of Sion Center | And 2 more authors.
Acta Anaesthesiologica Scandinavica | Year: 2012

Background Multiple interventions were made to optimize the medication process in our intensive care unit (ICU). 1 Transcriptions from the medical order form to the administration plan were eliminated by merging both into a single document; 2 the new form was built in a logical sequence and was highly structured to promote completeness and standardization of information; 3 frequently used drug names, approved units, and fixed routes were pre-printed; 4 physicians and nurses were trained with regard to the correct use of the new form. This study was aimed at evaluating the impact of these interventions on clinically significant types of medication errors. Methods Eight types of medication errors were measured by a prospective chart review before and after the interventions in the ICU of a public tertiary care hospital. We used an interrupted time-series design to control the secular trends. Results Over 85 days, 9298 lines of drug prescription and/or administration to 294 patients, corresponding to 754 patient-days were collected and analysed for the three series before and three series following the intervention. Global error rate decreased from 4.95 to 2.14% (-56.8%, P<0.001). Conclusions The safety of the medication process in our ICU was improved by simple and inexpensive interventions. In addition to the optimization of the prescription writing process, the documentation of intravenous preparation, and the scheduling of administration, the elimination of the transcription in combination with the training of users contributed to reducing errors and carried an interesting potential to increase safety. © 2012 The Authors.


Robert T.,Hopital de Sion | Duc C.,Institute Central des Hopitaux Valaisans | Ruiz D.S.M.,Hopital de Sion | Morard M.,Hopital de Sion
Neurologia i Neurochirurgia Polska | Year: 2014

Solitary fibrous tumours (SFTs) are rare WHO grade I mesenchymal neoplasms that were first described in the visceral pleura. A wide variety of locations of SFT have been reported but only twelve cases of intramedullary solitary fibrous tumour. We report a case of thoracic spinal cord SFT. A 49-year-old woman presented with clinical signs of dorsal myelopathy. Magnetic resonance imaging revealed an intradural mass at level T9-T10 which showed imaging features consistent both for an intra- and an extramedullary location of a solid tumour. Imaging findings were confirmed during surgery which was successful in resecting the extramedullary component. The intramedullary component could only be partially resected. Solitary fibrous tumour is a rare pathological entity in the central nervous system. The course of intramedullary SFT is unknown and careful long-term follow-up is recommended. © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.


The pandemic was declared over in October 2010. In this article we review some publications that describe the specificity of the 2009 A(N1N1) virus or suggest new approaches to design more efficacious and better accepted vaccines. Antibiotics resistance continue to increase with the emergence of enterobacteria resistant to almost all available agents. Use of old drugs like fosfomycin is reconsidered. 2010 has also brought progress in the diagnosis of infectious diseases.


Croxatto A.,University of Lausanne | Rieille N.,Institute Central des HOpitaux Valaisans | Kernif T.,Institute Pasteur | Bitam I.,Institute Pasteur | And 3 more authors.
Ticks and Tick-borne Diseases | Year: 2014

The Chlamydiales order includes the Chlamydiaceae, Parachlamydiaceae, Waddliaceae, Simkaniaceae, Criblamydiaceae, Rhabdochlamydiaceae, Clavichlamydiaceae, and Piscichlamydiaceae families. Members of the Chlamydiales order are obligate intracellular bacteria that replicate within eukaryotic cells of different origins including humans, animals, and amoebae. Many of these bacteria are pathogens or emerging pathogens of both humans and animals, but their true diversity is largely underestimated, and their ecology remains to be investigated. Considering their potential threat on human health, it is important to expand our knowledge on the diversity of Chlamydiae, but also to define the host range colonized by these bacteria. Thus, using a new pan-Chlamydiales PCR, we analyzed the prevalence of Chlamydiales DNA in ticks and fleas, which are important vectors of several viral and bacterial infectious diseases. To conduct this study, 1340 Ixodes ricinus ticks prepared in 192 pools were collected in Switzerland and 55 other ticks belonging to different tick species and 97 fleas belonging to different flea species were harvested in Algeria. In Switzerland, the prevalence of Chlamydiales DNA in the 192 pools was equal to 28.1% (54/192) which represents an estimated prevalence in the 1340 individual ticks of between 4.0% and 28.4%. The pan-Chlamydiales qPCR was positive for 45% (25/55) of tick samples collected in Algeria. The sequencing of the positive qPCR amplicons revealed a high diversity of Chlamydiales species. Most of them belonged to the Rhabdochlamydiaceae and Parachlamydiaceae families. Thus, ticks may carry Chlamydiales and should thus be considered as possible vectors for Chlamydiales propagation to both humans and animals. © 2014 Elsevier GmbH.


Jaton K.,University of Lausanne | Peter O.,Institute Central des Hopitaux Valaisans | Raoult D.,Aix - Marseille University | Tissot J.-D.,Sanguine | Greub G.,University of Lausanne
New Microbes and New Infections | Year: 2013

Q fever is a worldwide zoonotic infectious disease due to Coxiella burnetii. The clinical presentation may be acute (pneumonia and/or hepatitis) or chronic (most commonly endocarditis). Diagnosis mainly relies on serology and PCR. We therefore developed a quantitative real-time PCR. We first tested blindly its performance on various clinical samples and then, when thoroughly validated, we applied it during a 7-year period for the diagnosis of both acute and persistent C. burnetii infection. Analytical sensitivity (< 10 copies/PCR) was excellent. When tested blindly on 183 samples, the specificity of the PCR was 100% (142/142) and the sensitivity was 71% (29/41). The sensitivity was 88% (7/8) on valvular samples, 69% (20/29) on blood samples and 50% (2/4) on urine samples. This new quantitative PCR was then successfully applied for the diagnosis of acute Q fever and endovascular infection due to C. burnetii, allowing the diagnosis of Q fever in six patients over a 7-year period. During a local small cluster of cases, the PCR was also applied to blood from 1355 blood donors; all were negative confirming the high specificity of this test. In conclusion, we developed a highly specific method with excellent sensitivity, which may be used on sera for the diagnosis of acute Q fever and on various samples such as sera, valvular samples, aortic specimens, bone and liver, for the diagnosis of persistent C. burnetii infection. © 2013 European Society of Clinical Microbiology and Infectious Diseases.


Volluz S.D.,Center Hospitalier du Center du Valais | Abbet P.,Center Hospitalier du Center du Valais | Troillet N.,Institute Central des Hopitaux Valaisans
Revue Medicale Suisse | Year: 2010

Defining the optimal duration of antibiotic treatments is crucial to reduce toxicity and the emergence of resistance. Community acquired pneumonia can be treated in 5 days when the clinical response is rapidly favorable, as determined by simple clinical criterias. Acute cystitis can be treated by a 5-day course of nitrofurantoïne, or 3 days of trimethoprimsulfaméthoxazole, saving the use of quinolones for complicated urinary tract infections or when the upper urinary tract is involved. Antibiotics are rarely needed for the treatment of sinusitis. When indicated, a 5-day course should suffice. There is no consensus for the duration of antibiotic treatment in skin infections. The benefit of inflammation biomarkers to diminish the duration of antibiotics has not yet been established for common infections.


Bouzourene H.,University of Lausanne | Hutter P.,Institute Central des Hopitaux valaisans | Losi L.,University of Modena and Reggio Emilia | Martin P.,University of Lausanne | Benhattar J.,University of Lausanne
Familial Cancer | Year: 2010

Lynch syndrome is one of the most common hereditary colorectal cancer (CRC) syndrome and is caused by germline mutations of MLH1, MSH2 and more rarely MSH6, PMS2, MLH3 genes. Whereas the absence of MSH2 protein is predictive of Lynch syndrome, it is not the case for the absence of MLH1 protein. The purpose of this study was to develop a sensitive and cost effective algorithm to select Lynch syndrome cases among patients with MLH1 immunohistochemical silencing. Eleven sporadic CRC and 16 Lynch syndrome cases with MLH1 protein abnormalities were selected. The BRAF c.1799T>A mutation (p.Val600Glu) was analyzed by direct sequencing after PCR amplification of exon 15. Methylation of MLH1 promoter was determined by Methylation-Sensitive Single- Strand Conformation Analysis. In patients with Lynch syndrome, there was no BRAF mutation and only one case showed MLH1 methylation (6%). In sporadic CRC, all cases were MLH1 methylated (100%) and 8 out of 11 cases carried the above BRAF mutation (73%) whereas only 3 cases were BRAF wild type (27%). We propose the following algorithm: (1) no further molecular analysis should be performed for CRC exhibiting MLH1 methylation and BRAF mutation, and these cases should be considered as sporadic CRC;(2) CRC with unmethylated MLH1 and negative for BRAF mutation should be considered as Lynch syndrome;and (3) only a small fraction of CRC with MLH1 promoter methylation but negative for BRAF mutation should be true Lynch syndrome patients. These potentially Lynch syndrome patients should be offered genetic counselling before searching for MLH1 gene mutations. ©Springer Science+Business Media B.V. 2009.

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