Smits P.C.,Maasstad Ziekenhuis |
Hofma S.,Medisch Centrum Leeuwarden |
Togni M.,HOpital Cantonal de Fribourg |
Vazquez N.,Hospitalario Juan Canalejo |
And 10 more authors.
The Lancet | Year: 2013
Background Drug-eluting stents with durable biocompatible or biodegradable polymers have been developed to address the risk of thrombosis associated with first-generation drug-eluting stents. We aimed to compare the safety and efficacy of a biodegradable polymer-coated biolimus-eluting stent with a thin-strut everolimus-eluting stent coated with a durable biocompatible polymer. Methods This open-label, prospective, randomised, controlled, non-inferiority trial was undertaken at 12 sites across Europe. We used limited exclusion criteria (age p>18 years, life expectancy p>5 years, reference vessel diameter 2•0-4•0 mm) to enrol patients eligible for percutaneous coronary intervention. Patients were randomly allocated (2:1) by computer-generated random numbers to receive either a biodegradable polymer biolimus-eluting stent (Nobori, Terumo, Tokyo, Japan) or a durable fluoropolymer-based everolimus-eluting stent (Xience V or Prime, Abbott Vascular, Santa Clara, CA, USA, or Promus, Boston Scientific, Natick, MA, USA). The primary endpoint was a composite of safety (cardiac death and non-fatal myocardial infarction) and efficacy (clinically indicated target vessel revascularisation) at 12 months, analysed by intention to treat. Patients received dual antiplatelet therapy for 12 months after discharge. The trial is registered with ClinicalTrials.gov, number NCT01233453. Findings From Jan 12, 2009, to Feb 7, 2011, we enrolled 2707 patients (4025 lesions), 1795 of whom were assigned to receive the biolimus-eluting stent (2638 lesions) and 912 to an everolimus-eluting stent (1387 lesions). 2688 (99•3%) patients completed 12 months' follow-up. Significantly more patients in the biolimus-eluting stent group received a non-assigned stent than did those in the everolimus-eluting stent group (105 [5•9%] vs 19 [2•1%]; p<0•0001). The primary endpoint occurred in 93 (5•2%) patients in the biolimus-eluting stent group and 44 (4•8%) patients in the everolimus-eluting stent group at 12 months (relative risk 1•07 [95% CI 0•75-1•52]; p non-inferiorityp<0•0001). Analysis per protocol did not change the outcome of this trial (pnon-inferiorityp<0•0001). Interpretation Biodegradable polymer biolimus-eluting stents are as safe and efficacious as the current standard of a thin-strut everolimus-eluting stent with a durable biocompatible polymer. We need to follow-up patients for longer to show whether the biolimus-eluting stent reduces the risk of stent thrombosis after 1 year when compared with the everolimus-eluting stent. Funding Terumo Europe (Leuven, Belgium) and the Research Foundation of the Cardiology Department, Maasstad Hospital (Rotterdam, Netherlands).
Schroder F.H.,Erasmus University Rotterdam |
Hugosson J.,Sahlgrenska University Hospital |
Carlsson S.,Sahlgrenska University Hospital |
Tammela T.,University of Tampere |
And 5 more authors.
European Urology | Year: 2012
Background: Metastatic disease is a major morbidity of prostate cancer (PCa). Its prevention is an important goal. Objective: To assess the effect of screening for PCa on the incidence of metastatic disease in a randomized trial. Design, setting, and participants: Data were available for 76 813 men aged 55-69 yr coming from four centers of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The presence of metastatic disease was evaluated by imaging or by prostate-specific antigen (PSA) values >100 ng/ml at diagnosis and during follow-up. Intervention: Regular screening based on serum PSA measurements was offered to 36 270 men randomized to the screening arm, while no screening was provided to the 40 543 men in the control arm. Outcome measurements and statistical analysis: The Nelson-Aalen technique and Poisson regression were used to calculate cumulative incidence and rate ratios of M+ disease. Results and limitations: After a median follow-up of 12 yr, 666 men with M+ PCa were detected, 256 in the screening arm and 410 in the control arm, resulting in cumulative incidence of 0.67% and 0.86% per 1000 men, respectively (p < 0.001). This finding translated into a relative reduction of 30% (hazard ratio [HR]: 0.70; 95% confidence interval [CI], 0.60-0.82; p = 0.001) in the intention-to-screen analysis and a 42% (p = 0.0001) reduction for men who were actually screened. An absolute risk reduction of metastatic disease of 3.1 per 1000 men randomized (0.31%) was found. A large discrepancy was seen when comparing the rates of M+ detected at diagnosis and all M+ cases that emerged during the total follow-up period, a 50% reduction (HR: 0.50; 95% CI, 0.41-0.62) versus the 30% reduction. The main limitation is incomplete explanation of the lack of an effect of screening during follow-up. Conclusions: PSA screening significantly reduces the risk of developing metastatic PCa. However, despite earlier diagnosis with screening, certain men still progress and develop metastases. The ERSPC trial is registered under number ISRCTN49127736. © 2012 European Association of Urology.
Campe G.V.,Medical University of Graz |
Moschopulos M.,Kantonsspital Aarau |
Hefti M.,Neurochirurgisches Zentrum
Acta Neurochirurgica | Year: 2012
Background Frameless stereotactic biopsies are replacing frame-based stereotaxy as a diagnostic approach to brain lesions. In order to avoid a sampling bias or negative histology, multiple specimens are often taken. This in turn increases the risk of hemorrhagic complications. Objective We present the use of 5-aminolevulinic acid (5- ALA)-induced protoporphyrin IX fluorescence in frameless stereotaxy to improve the procedure duration and yield, and thereby reduce the risk of complications. Methods Patients with suspected high-grade brain tumors are given 5-ALA 4 h prior to stereotactic biopsy. The biopsy needle is guided to the target using frameless stereotaxy based either on preoperative images or combined with intraoperative MRI sequences. The specimen is illuminated with blue light to look for fluorescence. In case of a positive fluorescence within the tissue sample, no frozen sections are obtained, and no further specimens are taken. Results The samples of 13 patients revealed a positive fluorescence and were histologically confirmed as malignant or high-grade brain neoplasms. four cases were fluorescence-negative, requiring frozen section confirmation and/or multiple samples. In theses cases histology was either nonspecific gliotic changes or low-grade tumors. There were no complications related to the additional use of 5-ALA. Conclusion 5-ALA fluorescence in stereotactic biopsies can increase the safety and accuracy of these procedures by reducing sampling errors and eliminating the need for multiple samples and/or frozen section verification, creating a more accurate, faster and safer procedure for cases of suspected malignant or high-grade brain tumors situated in deep or eloquent areas. © Springer-Verlag 2012.
Sarlos D.,Kantonsspital Aarau |
Aigmueller T.,Medical University of Graz |
Magg H.,Kantonsspital Aarau |
Schaer G.,Kantonsspital Aarau
American Journal of Obstetrics and Gynecology | Year: 2015
Laparoscopic sacrocolpopexy is a well-established technique to treat apical vaginal prolapse. De novo micturition disorders, pelvic pain, and defecation disorders have been reported and may be due to intraoperative compromise of the superior hypogastric plexus. The video demonstrates our technique for nerve-sparing laparoscopic sacrocolpopexy. The patient is a 62-year-old woman with symptomatic stage III posthysterectomy vaginal vault prolapse. Key steps of the procedure are opening the peritoneum at the level of the promontory, identification of the fibers of the superior hypogastric plexus, deep anterior and posterior dissection with attachment of the mesh to the vagina, displacement of the nerve fibers to the left side during suturing of the mesh to the longitudinal ligament, and complete peritonealization. This technique of the identification and protection of relevant nerve structures appears to be reproducible and can be considered by surgeons who perform laparoscopic sacrocolpopexy. © 2015 Elsevier Inc. All rights reserved.
Schwappach D.L.B.,Swiss Patient Safety Foundation |
Schwappach D.L.B.,University of Bern |
Wernli M.,Kantonsspital Aarau
Annals of Oncology | Year: 2011
Background: Medical errors are a serious threat to chemotherapy patients. Patients can make contributions to safety but little is known about the acceptability of error-preventing behaviors and its predictors. Patients and methods: A cross-sectional survey study among chemotherapy patients treated at the oncology/hematology unit of a regional hospital was conducted. Patients were presented vignettes of errors and unsafe acts and responded to measures of attitudes, behavioral control, norms, barriers, and anticipated reaction. Results: A total of 479 patients completed the survey (52% response rate). Patients reported a high level of anticipated activity but intentions to engage for safety varied considerably between the hypothetical scenarios (range: 57%-96%, χ2 P < 0.001). Health, knowledge and staff time pressure were perceived as most important barriers. Instrumental [odds ratio (OR) = 1.3, P = 0.046] and experiential attitudes (OR = 1.4, P < 0.001), expectations attributed to clinical staff (OR = 1.2, P = 0.024) and behavioral control (OR = 1.8, P < 0.001) were predictors for patients' behaviors. Conclusions: Patients are affirmative toward engaging for safety but perceive considerable barriers. Intentions to engage in error prevention vary by clinical context and are strongly influenced by attitudes, normative and control beliefs. To successfully involve patients in medical error, prevention clinicians need to address their patients' beliefs and reduce barriers through education. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Giannarini G.,University of Bern |
Birkhauser F.D.,University of Bern |
Recker F.,Kantonsspital Aarau |
Thalmann G.N.,University of Bern |
Studer U.E.,University of Bern
European Urology | Year: 2014
Background Various reasons exist for so-called bacillus Calmette-Guérin (BCG) failure in patients with non-muscle-invasive urothelial bladder carcinoma (NMIBC). Objective To explore whether urothelial carcinoma of the upper urinary tract (UUT) and/or prostatic urethra may be a cause for BCG failure. Design, setting, and participants Retrospective analysis of 110 patients with high-risk NMIBC repeatedly treated with intravesical BCG, diagnosed with disease recurrence, and followed for a median time of 9.1 yr. Intervention Two or more intravesical BCG induction courses without maintenance. Outcome measurements and statistical analysis Primary outcome was pattern of disease recurrence (BCG failure) within the urinary tract categorised into UUT and/or urethral carcinoma (with or without intravesical recurrence), and intravesical recurrence alone. Secondary outcome was survival. Predictors of UUT and/or urethral carcinoma and the effect of pattern of disease recurrence on cancer-specific survival were assessed with multivariable Cox regression analysis adjusting for multiple clinical and tumour characteristics. Results and limitations Of the 110 patients, 57 (52%) had UUT and/or urethral carcinoma (with or without intravesical recurrence), and 53 (48%) had intravesical recurrence alone. In patients with UUT and/or urethral carcinoma, bladder carcinoma in situ (Tis) before the first and second BCG course was present in 42 of 57 (74%) and 47 of 57 (82%) patients, respectively. On multivariable analysis, bladder Tis before the first and/or second BCG course was the only independent predictor of UUT and/or urethral carcinoma. Of the 110 patients, 69 (63%) were alive at last follow-up visit, 18 (16%) had died due to metastatic urothelial carcinoma, and 23 (21%) had died of other causes. Pattern of disease recurrence within the urinary tract was not an independent predictor of cancer-specific survival. Main study limitations were retrospective design and limited power for survival analysis. Conclusions In our patients with high-risk NMIBC failing after two or more courses of intravesical BCG, UUT and/or urethral carcinoma was detected in >50% of the cases during follow-up. The vast majority of these patients had bladder Tis before the first and/or second BCG course. In patients experiencing the so-called BCG failure, a diagnostic work-up of UUT and prostatic urethra should always be performed to exclude urothelial carcinoma before additional intravesical therapy or even a radical cystectomy is considered. © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Maslehaty H.,University of Kiel |
Cordovi S.,Kantonsspital Aarau |
Hefti M.,University of Kiel
Journal of Neuro-Oncology | Year: 2011
To demonstrate clinical characteristics of symptomatic spinal metastases of intracranial glioblastoma multiforme (GBM) and different spreading mechanisms relating to astrocytic cell differentiation, we present an extraordinary case of a 47-year-old patient with rapid progressive paraplegia due to coincident intramedullary and leptomeningeal dissemination of a supratentorial GBM. Serial biopsies of the intracranial, leptomeningeal, and intramedullary GBM lesions of our patient were analyzed for glial fibrillary acidic protein (GFAP). Furthermore, we present 19 additional cases of intracranial GBM with symptomatic spinal seeding, identified through literature review. GFAP expression was high in intracranial and intramedullary tumors, but low in leptomeningeal dissemination of our patient. Mean patient age was 45 years. Mean interval between identification of spinal metastases and death was 4.5 months. Mean overall survival was 18.6 months. Location of symptomatic spinal metastases was more frequently leptomeningeal (14 cases) than intramedullary (7 cases). The case presented herein supports the hypothesis of higher incidence of low GFAP expression in GBM cells in leptomeningeal manifestations after primary intracranial GBM. Because of the proposed tendency for early leptomeningeal spread from primary tumors with low astrocytic differentiation (low GFAP expression), patients with these tumors should be followed more closely to identify leptomeningeal tumor progression early on. Early identification of leptomeningeal spread could enable these patients to benefit from radiation therapy before they develop severe neurological deficits, which might translate into longer acceptable quality of life for these mostly young patients. This is an important finding, but further prospective studies are needed to verify our observations. © 2010 Springer Science+Business Media, LLC.
Sur Chowdhury C.,University of Basel |
Giaglis S.,University of Basel |
Walker U.A.,University of Basel |
Buser A.,University of Basel |
And 2 more authors.
Arthritis Research and Therapy | Year: 2014
Introduction: Neutrophil extracellular traps (NETs) have recently been implicated in a number of autoimmune conditions, including rheumatoid arthritis (RA). We examined the underlying signaling pathways triggering enhanced NETosis in RA and ascertained whether the products of NETosis had diagnostic implications or usefulness.Methods: Neutrophils were isolated from RA patients with active disease and from controls. Spontaneous NET formation from RA and control neutrophils was assessed in vitro with microscopy and enzyme-linked immunosorbent assay (ELISA) for NETosis-derived products. The analysis of the signal-transduction cascade included reactive oxygen species (ROS) production, myeloperoxidase (MPO), neutrophil elastase (NE), peptidyl arginine deiminase 4 (PAD4), and citrullinated histone 3 (citH3). NET formation was studied in response to serum and synovial fluid and immunoglobulin G (IgG) depleted and reconstituted serum. Serum was analyzed for NETosis-derived products, for which receiver operator characteristic (ROC) curves were calculated.Results: Neutrophils from RA cases exhibited increased spontaneous NET formation in vitro, associated with elevated ROS production, enhanced NE and MPO expression, nuclear translocation of PAD4, PAD4-mediated citrullination of H3, and altered nuclear morphology. NET formation in both anti-citrullinated peptide antibody (ACPA)-positive and -negative RA was abolished by IgG depletion, but restored only with ACPA-positive IgG. NETosis-derived products in RA serum demonstrated diagnostic potential, the ROC area under the curve for cell-free nucleosomes being >97%, with a sensitivity of 91% and a specificity of 92%. No significant difference was observed between ACPA-positive and -negative cases.Conclusions: Signaling elements associated with the extrusion of NETs are significantly enhanced to promote NETosis in RA compared with healthy controls. NETosis depended on the presence of ACPA in ACPA-positive RA serum. The quantitation of NETosis-derived products, such as cell-free nucleosomes in serum, may be a useful complementary tool to discriminate between healthy controls and RA cases. © 2014 Sur Chowdhury et al.; licensee BioMed Central Ltd.
Hahn S.,University of Basel |
Giaglis S.,University of Basel |
Chowdury C.S.,University of Basel |
Hosli I.,University of Basel |
Hasler P.,Kantonsspital Aarau
Seminars in Immunopathology | Year: 2013
The ability of neutrophils and other leucocyte members of the innate immune system to expel their DNA into the extracellular environment in a controlled manner in order to trap and kill pathogenic microorganisms lead to a paradigm shift in our understanding of host microbe interactions. Surprisingly, the neutrophil extracellular trap (NET) cast by neutrophils is very wide and extends to the entrapment of viruses as well as multicellular eukaryotic parasites. Not unexpectedly, it has emerged that pathogenic microorganisms can employ a wide array of strategies to avoid ensnarement, including expression of DNAse enzymes that destroy the lattice backbone of NETs. Alternatively, they may use molecular mimicry to avoid detection or trigger events leading to the expression of immune modulatory cytokines such as IL-10, which dampen the NETotic response of neutrophils. In addition, the host microenvironment may contribute to the innate immune response by the production of lectin-like molecules that bind to bacteria and promote their entrapment on NETs. An example of this is the production of surfactant protein D by the lung epithelium. In addition, pregnancy provides a different challenge, as the mother needs to mount an effective response against pathogens, without harming her unborn child. An examination of these decoy and host response mechanisms may open the path for new therapies to treat pathologies mediated by overt NETosis. © 2013 The Author(s).
Sarlos D.,Kantonsspital Aarau |
Kots L.A.,Kantonsspital Aarau
Current Opinion in Obstetrics and Gynecology | Year: 2011
PURPOSE OF REVIEW: To illustrate the current stand on robotic versus conventional laparoscopic hysterectomy regarding operating times, clinical outcome and costs. RECENT FINDINGS: Only six studies were reviewed, as there are only few recent studies comparing robotic with laparoscopic hysterectomy and most are retrospective. Apart from one multicentre study with over 36000 patients, 350 institutions and numerous surgeons, most studies were performed with few cases by one or two surgeons at one or two hospitals. Operating times for robotic hysterectomies generally were longer, ranging from 89.9 to 267min. Surgery time for conventional laparoscopic hysterectomies was between 83 and 206min. In all studies, clinical outcomes such as blood loss, complications or hospital stay of both the robotic and the conventional laparoscopic procedure were similar. Only two studies compared costs and both came up with very similar findings. Cost for a robot-assisted hysterectomy is approximately 2600 USD higher than that for conventional laparoscopic hysterectomy not including investment and amortization. SUMMARY: Robotic and conventional laparoscopic hysterectomy are essentially equivalent regarding surgical and clinical outcome. Operating times are slightly higher and costs are significantly higher for the robotic procedure. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.