Winterthur, Switzerland
Winterthur, Switzerland

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Curatolo M.,University of Washington | Muller M.,University of Bern | Ashraf A.,University of Bern | Neziri A.Y.,Cantonal Hospital of Winterthur | And 3 more authors.
Pain | Year: 2015

Hypersensitivity of pain pathways is considered a relevant determinant of symptoms in chronic pain patients, but data on its prevalence are very limited. To our knowledge, no data on the prevalence of spinal nociceptive hypersensitivity are available. We studied the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity in 961 consecutive patients with various chronic pain conditions. Pain threshold and nociceptive withdrawal reflex threshold to electrical stimulation were used to assess pain hypersensitivity and spinal nociceptive hypersensitivity, respectively. Using 10th percentile cutoff of previously determined reference values, the prevalence of pain hypersensitivity and spinal nociceptive hypersensitivity (95% confidence interval) was 71.2 (68.3-74.0) and 80.0 (77.0-82.6), respectively. As a secondary aim, we analyzed demographic, psychosocial, and clinical characteristics as factors potentially associated with pain hypersensitivity and spinal nociceptive hypersensitivity using logistic regression models. Both hypersensitivity parameters were unaffected by most factors analyzed. Depression, catastrophizing, pain-related sleep interference, and average pain intensity were significantly associated with hypersensitivity. However, none of them was significant for both unadjusted and adjusted analyses. Furthermore, the odds ratios were very low, indicating modest quantitative impact. To our knowledge, this is the largest prevalence study on central hypersensitivity and the first one on the prevalence of spinal nociceptive hypersensitivity in chronic pain patients. The results revealed an impressively high prevalence, supporting a high clinical relevance of this phenomenon. Electrical pain thresholds and nociceptive withdrawal reflex explore aspects of pain processing that are mostly independent of sociodemographic, psychological, and clinical pain-related characteristics. © 2015 International Association for the Study of Pain.


PubMed | Red Cross, University of Zürich, University of Ulm, Cantonal Hospital of Winterthur and 2 more.
Type: | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2016

Although pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor, like other common cancers, it displays a wide range of biology. However, at present, there are no reliable tests to predict patients cancer-specific outcomes and guide personalized treatment decisions. In this study, we aim to identify such biomarkers in resectable PDAC by studying single nucleotide polymorphisms (SNPs) in the CD44 gene, which drives the progression of pancreatic cancer.348 PDAC patients from three independent cohorts (Switzerland, Germany, The Cancer Genome Atlas (TCGA)) who underwent pancreatic resection are included in the study. Information on the haplotype structure of the CD44 gene is obtained using 1000 Genomes Project data and the genotypes of the respective tagging SNPs are determined. Cox proportional hazards models are utilized to analyze the impact of SNP genotype on patients survival.We identify a SNP in the CD44 gene (SNPrs187115) that independently associates with allelic differences in prognosis in all study cohorts. Specifically, in 121 Swiss patients, we observe an up-to 2.38-fold (p=0.020) difference in tumor-related death between the genotypes of SNPrs187115. We validate those results in both the German (hazard ratio (HR)=2.32, p=0.044, 101 patients) and the TCGA cohort (HR=2.36, p=0.044, 126 patients).CD44 SNPrs187115 can serve as a novel biomarker readily available at the time of PDAC diagnosis that identifies patients at risk for faster tumor progression and guide personalized treatment decisions. It has the potential to significantly expand the pool of patients that would benefit from tumor resection.


Mekker A.,University of Zürich | Tchang V.S.,University of Zürich | Haeberli L.,University of Zürich | Oxenius A.,ETH Zurich | And 3 more authors.
PLoS Pathogens | Year: 2012

Immune senescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterised by impaired protective immunity and decreased efficacy of vaccines. Recent clinical, epidemiological and immunological studies suggest that Cytomegalovirus (CMV) infection may be associated with accelerated immune senescence, possibly by restricting the naïve T cell repertoire. However, direct evidence whether and how CMV-infection is implicated in immune senescence is still lacking. In this study, we have investigated whether latent mouse CMV (MCMV) infection with or without thymectomy (Tx) alters antiviral immunity of young and aged mice. After infection with lymphocytic choriomeningitis virus (LCMV) or Vaccinia virus, specific antiviral T cell responses were significantly reduced in old, old MCMV-infected and/or Tx mice compared to young mice. Importantly, control of LCMV replication was more profoundly impaired in aged MCMV-infected mice compared to age-matched MCMV-naïve or young mice. In addition, latent MCMV infection was associated with slightly reduced vaccination efficacy in old Tx mice. In contrast to the prevailing hypothesis of a CMV-mediated restriction of the naïve T cell repertoire, we found similar naïve T cell numbers in MCMV-infected and non-infected mice, whereas ageing and Tx clearly reduced the naïve T cell pool. Instead, MCMV-infection expanded the total CD8+ T cell pool by a massive accumulation of effector memory T cells. Based on these results, we propose a new model of increased competition between CMV-specific memory T cells and any 'de novo' immune response in aged individuals. In summary, our results directly demonstrate in a mouse model that latent CMV-infection impairs immunity in old age and propagates immune senescence. © 2012 Mekker et al.


Guber I.,Cantonal Hospital of Lucerne | Guber I.,Cantonal Hospital of Winterthur | Guber J.,Cantonal Hospital of Lucerne | Kaufmann C.,Cantonal Hospital of Lucerne | And 2 more authors.
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2013

Purpose: To evaluate visual recovery and intraocular straylight in keratoconus patients 3 months and 1 year after corneal crosslinking (CXL) Patients and Methods: Thirty-three eyes of 28 consecutive patients with mild to moderate keratoconus were included. The following were assessed at baseline, 3 months and 1 year after CXL: corrected distance visual acuity (CDVA), intraocular straylight, spherical equivalent (SE), keratometry (Kmax and K min (Diopters D and axis), the regularity index and pachymetry. Changes from baseline were calculated using mixed linear regression models. Results: The CDVA remained unchanged 3 months after CXL (-0.003 (95 % CI: -0.038 to 0.044); p = 0.880) and improved after 1 year (-0.042 (95 % CI: -0.078 to -0.007; p = 0.021)). The mean straylight value increased significantly by 0.27 (95 % CI: 0.18 to 0.35; p < 0.001) 3 months after CX and normalized to preoperative values after 1 year (0.06 (95 % CI: -0.03 to 0.14; p = 0.215)). SE improved from the mean preoperative value of -2.61 D (95 % CI: -3.83 to -1.39) by 1.95 (95 % CI: 1.03 to 2.86; p < 0.001) at 3 months and remained stable at the 1-year follow-up visit (2.17 (95 % CI: 1.21 to 3.12; p < 0.001)). Parameters of of keratometry changed only minimally. The regularity index remained almost unchanged at 3 months (2.45 (95 % CI: -4.97 to 9.88; p = 0.503)) and decreased by 6.97 (95 % CI: -14.08 to 0.14; p = 0.054). Pachymetry decreased by 44.0 μm (95 % CI: 56.1 to 31.9; p < 0.001) at 3 months and almost returned to preoperative values at 12 months (-11.3 μm (95 % CI: -27.9 to 5.3; p = 0.175)). Conclusions: In accordance with the decrease in CDVA and patients' complaints of disability due to glare, intraocular straylight increased 3 months after surgery. One year after CXL, there was an increase in CDVA due to an improved SE and regularity index, and intraocular straylight had normalized. © 2012 Springer-Verlag.


Guber J.,University of London | Josifova T.,University of Basel | Henrich P.B.,University of Basel | Guber I.,Cantonal Hospital of Winterthur
Open Ophthalmology Journal | Year: 2014

Purpose: To identify OCT-based anatomical features and clinical characteristics for poor central retinal thickness (CRT) response to ranibizumab in neovascular age-related macular degeneration (AMD). Patients and Methods: Investigating our electronic patient records (Eyeswide), patients with neovascular AMD treated with intravitreal injections of 0.5mg/0.05ml ranibizumab were identified and their notes reviewed. Data collected included gender, age, initial best-corrected visual acuity (BCVA), prior photodynamic therapy, lesion type (classic versus occult), type of macular edema (intraretinal fluid, subretinal fluid, pigment epithelium detachment) and the total number of previous ranibizumab injections. Results: A total of 210 eyes of 182 patients with neovascular AMD were identified. Mean follow-up time was 1.34 years (SD ± 0.77). Central retinal thickness reduction in women was significantly inferior to that in men (p=0.05). Patients with cystoid type macular edema had significantly greater reduction in CRT compared to patients with subretinal fluid (p<0.001) or pigment epithelium detachment (p<0.001). The percentage drop of CRT was no longer statistically significant after the sixth injection. Age, initial BCVA, prior photodynamic therapy and lesion type had no statistically effect on CRT response. Conclusion: Risk factors for poor central retinal thickness response to ranibizumab include female gender and patients with predominant subretinal fluid or pigment epithelium detachment. Furthermore, the anatomical response decreased after the sixth injection of ranibizumab. © Guber et al.; Licensee Bentham Open.


PubMed | Cantonal Hospital of Winterthur, University of Basel and University of London
Type: | Journal: The open ophthalmology journal | Year: 2014

To identify OCT-based anatomical features and clinical characteristics for poor central retinal thickness (CRT) response to ranibizumab in neovascular age-related macular degeneration (AMD).Investigating our electronic patient records (Eyeswide), patients with neovascular AMD treated with intravitreal injections of 0.5mg/0.05ml ranibizumab were identified and their notes reviewed. Data collected included gender, age, initial best-corrected visual acuity (BCVA), prior photodynamic therapy, lesion type (classic versus occult), type of macular edema (intraretinal fluid, subretinal fluid, pigment epithelium detachment) and the total number of previous ranibizumab injections.A total of 210 eyes of 182 patients with neovascular AMD were identified. Mean follow-up time was 1.34 years (SD 0.77). Central retinal thickness reduction in women was significantly inferior to that in men (p=0.05). Patients with cystoid type macular edema had significantly greater reduction in CRT compared to patients with subretinal fluid (p<0.001) or pigment epithelium detachment (p<0.001). The percentage drop of CRT was no longer statistically significant after the sixth injection. Age, initial BCVA, prior photodynamic therapy and lesion type had no statistically effect on CRT response.Risk factors for poor central retinal thickness response to ranibizumab include female gender and patients with predominant subretinal fluid or pigment epithelium detachment. Furthermore, the anatomical response decreased after the sixth injection of ranibizumab.


Pfortmueller C.A.,University of Bern | Kunz M.,Cantonal Hospital of Winterthur | Lindner G.,University of Bern | Zisakis A.,University of Bern | And 2 more authors.
The Scientific World Journal | Year: 2014

Principals. Throughout the world, falls are a major public health problem and a socioeconomic burden. Nevertheless there is little knowledge about how the injury types may be related to the aetiology and setting of the fall, especially in the elderly. We have therefore analysed all patients presenting with a fall to our Emergency Department (ED) over the past five years. Methods. Our retrospective data analysis comprised adult patients admitted to our Emergency Department between January 1, 2006, and December 31, 2010, in relation to a fall. Results. Of a total of 6357 patients 78% (n = 4957) patients were younger than 75 years. The main setting for falls was patients home (n = 2239, 35.3%). In contrast to the younger patients, the older population was predominantly female (56.3% versus 38.6%; P < 0.0001). Older patients were more likely to fall at home and suffer from medical conditions (all P < 0.0001). Injuries to the head (P < 0.0001) and to the lower extremity (P < 0.019) occurred predominantly in the older population. Age was the sole predictor for recurrent falls (OR 1.2, P < 0.0001). Conclusion. Falls at home are the main class of falls for all age groups, particularly in the elderly. Fall prevention strategies must therefore target activities of daily living. Even though falls related to sports mostly take place in the younger cohort, a significant percentage of elderly patients present with falls related to sporting activity. Falls due to medical conditions were most likely to result in mild traumatic brain injury. © 2014 Carmen A. Pfortmueller et al.


Crivelli-Ochsner S.,Cantonal Hospital of Winterthur | Bode-Lesniewska B.,University of Zürich | Nussbaumer-Ochsner Y.,Cantonal Hospital of Muensterlingen | Fuchs B.,University of Zürich
Rare Tumors | Year: 2013

Giant cell angioblastoma is a very rare, locally destructive vascular tumor of intermediate malignancy without metastatic potential. There are only a few cases reported in the literature exclusively in the soft tissue of children. For the first time, we report on an adult patient with a giant cell angioblastoma in the popliteal fossa. The therapy included tumor resection with favorable clinical, oncological and functional outcome. Due to its locally destructive nature, surgery remains the mainstay of treatment. Histologically, giant cell angioblastoma is comprised of nodular aggregates of histiocytoid cells arranged around bland angiomatous spaces. Because of insufficient available data in regard to the definition of the entity, diagnostic criteria and its biological potential, it is not included in the new World Health Organization classification of tumors of soft tissue and bone. The differential diagnosis includes plexiform fibrohistiocytic tumor, myofibroma and giant cell fibroblas-toma. © S. Crivelli-Ochsner et al., 2013.


Tchang V.S.Y.,University of Basel | Tchang V.S.Y.,University of Zürich | Mekker A.,University of Zürich | Siegmund K.,University of Basel | And 3 more authors.
Molecular Immunology | Year: 2013

Coronin 1-deficient mice can control LCMV infection.•Coronin 1-deficient mice mount a normal CD8+ T cells response upon viral infection.•Coronin 1-deficient mice are susceptible to VSV infection.•Coronin 1-deficiency is associated with compromised CD4+ T cell response upon viral infection. Coronin 1 is a member of the evolutionary conserved WD repeat protein family and is highly expressed in hematopoietic cells. Coronin 1 is essential for Ca2+ mobilization upon T cell receptor (TCR) stimulation providing a pro-survival signal for naïve peripheral T cells. Both in mouse and in human, coronin 1 deficiency is associated with severe T cell lymphopenia. In this work, we have analyzed antiviral T cell-mediated immunity in the presence and absence of coronin 1 in vivo after infection with lymphocytic choriomenigitis virus (LCMV) and vesicular stomatitis virus (VSV) in mice. Despite low peripheral T cell numbers we found that LCMV-specific CD8+ T cell responses were normal in the absence of coronin 1 and kinetics of LCMV-clearance were similar compared to wild type mice. In contrast, CD4+ T cell responses were profoundly decreased after LCMV- and VSV-infection. We propose that coronin 1 plays a differential role in CD8+ versus CD4+ T cell responses and activation. © 2013 Elsevier Ltd.


Sasse T.,University of Zürich | Moehrlen U.,University of Zürich | Meuli M.,University of Zürich | Vuille-dit-Bille R.N.,Cantonal Hospital of Winterthur
Cochrane Database of Systematic Reviews | Year: 2016

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess and summarize the evidence of the prevalence of CPPV (1) and of the incidence of MCIH (2) in children with unilateral inguinal hernia, and therefore to propose or to reject hernia exploration and/or surgical management of the contralateral side. © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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