Background and Purpose:
To identify factors associated with prior stroke at presentation in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO).
Methods:
We studied cross-sectional ...data from the International PFO Consortium Study (NCT00859885). Patients with first-ever stroke and those with prior stroke at baseline were analyzed for an association with PFO-related (right-to-left shunt at rest, atrial septal aneurysm, deep venous thrombosis, pulmonary embolism, and Valsalva maneuver) and PFO-unrelated factors (age, gender, BMI, hypertension, diabetes mellitus, hypercholesterolemia, smoking, migraine, coronary artery disease, aortic plaque). A multivariable analysis was used to adjust effect estimation for confounding, e.g., owing to the age-dependent definition of study groups in this cross-sectional study design.
Results:
We identified 635 patients with first-ever and 53 patients with prior stroke. Age, BMI, hypertension, diabetes mellitus, hypercholesterolemia, coronary artery disease, and right-to-left shunt (RLS) at rest were significantly associated with prior stroke. Using a pre-specified multivariable logistic regression model, age (Odds Ratio 1.06), BMI (OR 1.06), hypercholesterolemia (OR 1.90) and RLS at rest (OR 1.88) were strongly associated with prior stroke.Based on these factors, we developed a nomogram to illustrate the strength of the relation of individual factors to prior stroke.
Conclusion:
In patients with CS and PFO, the likelihood of prior stroke is associated with both, PFO-related and PFO-unrelated factors.
Abstract only Background and purpose: Recurrent ischemic stroke in patients with CS and PFO has been proposed as a marker of increased risk for paradoxical embolism. It is unclear, whether the excess ...risk is driven by specific features of the PFO (right-to-left shunt (RLS) size, RLS at rest, associated atrial septum aneurysm (ASA)) or the presence of vascular risk factors (vRF). We compare the prevalence of vRF, TEE features, and baseline medications in PFO patients with first-ever versus multiple CS. Methods: From September 2008 to March 2013, the International PFO Consortium enrolled 993 patients with ischemic stroke or transient ischemic attack (TIA) and newly diagnosed PFO. In this analysis of baseline data, we included 386 patients with first-ever CS and no radiological evidence of prior cerebral ischemia (first-ever CS group, mean age, 52y) as well as 71 patients with recurrent CS and multiple ischemic lesions on CT and/or MRI (multiple CS group, mean age, 59y). Patients with TIA as index event, those with first-ever CS but additional “silent” ischemic lesions on imaging as well as those with recurrent CS without radiological findings of prior cerebral ischemia were excluded. We used nonparametric tests for independent samples and the Bonferroni correction for multiple comparisons. Results: Age > 55y (63% vs. 44%, P=0.001), hypertension (52% vs. 30%, P=0.001), hyperlipidemia (64% vs. 44%, P=0.003), and coronary artery disease (15% vs. 3%, P=0.001) were significantly more frequent in the multiple CS than in the first-ever CS group. The frequencies of male gender, current smoking, diabetes, migraine with or without aura, associated ASA, RLS size, and RLS at rest did not differ between groups. At baseline, patients with multiple CS were more likely to be on antiplatelets (50% vs. 18%), antihypertensive (51% vs. 22%) or lipid lowering drugs (44% vs. 10%, P=0.001 for each comparison) than patients with first-ever CS. The frequency of anticoagulant treatment did not differ between groups. Conclusions: In patients with CS, vRF but not specific PFO features were associated with recurrent cerebral ischemic events. The ongoing prospective part of the International PFO Consortium will likely shed light upon the role of vRF control for secondary stroke prevention in patients with PFO.
Laparoscopic/robotic radical hysterectomy has been historically considered oncologically equivalent to open radical hysterectomy for patients with early cervical cancer. However, a recent prospective ...randomized trial (Laparoscopic Approach to Cervical Cancer, LACC) has demonstrated significant inferiority of the minimally invasive approach. The aim of this study is to evaluate the oncologic outcomes of combined laparoscopic-vaginal radical hysterectomy.
Between August 1994 and December 2018, patients with invasive cervical cancer were treated using minimally-invasive surgery at the Universities of Jena, Charité Berlin (Campus CCM and CBF) and Cologne and Asklepios Clinic Hamburg. 389 patients with inclusion criteria identical to the LACC trial were identified. In contrast to the laparoscopic/robotic technique used in the LACC trial, all patients in our cohort underwent a combined transvaginal-laparoscopic approach without the use of any uterine manipulator.
A total of 1952 consecutive patients with cervical cancer were included in the analysis. Initial International Federation of Gynecology and Obstetrics (FIGO) stage was IA1 lymphovascular space invasion (LVSI+), IA2 and IB1/IIA1 in 32 (8%), 43 (11%), and 314 (81%) patients, respectively, and histology was squamous cell in 263 (68%), adenocarcinoma in 117 (30%), and adenosquamous in 9 (2%) patients. Lymphovascular invasion was confirmed in 106 (27%) patients. The median number of lymph nodes was 24 (range 2-86). Lymph nodes were tumor-free in 379 (97%) patients. Following radical hysterectomy, 71 (18%) patients underwent adjuvant chemoradiation or radiation. After a median follow-up of 99 (range 1-288) months, the 3-, 4.5-, and 10-year disease-free survival rates were 96.8%, 95.8%, and 93.1 %, and the 3-, 4.5-, and 10-year overall survival rates were 98.5%, 97.8%, and 95.8%, respectively. Recurrence location was loco-regional in 50% of cases with recurrence (n=10). Interestingly, 9/20 recurrences occurred more than 39 months after surgery.
The combined laparoscopic-vaginal technique for radical hysterectomy with avoidance of spillage and manipulation of tumor cells provides excellent oncologic outcome for patients with early cervical cancer. Our retrospective data suggest that laparoscopic-vaginal surgery may be oncologically safe and should be validated in further randomized trials.
Abstract
Purpose:
The optimal application of maintenance PARP inhibitor therapy for ovarian cancer requires accessible, robust, and rapid testing of homologous recombination deficiency (HRD). ...However, in many countries, access to HRD testing is problematic and the failure rate is high. We developed an academic HRD test to support treatment decision-making.
Experimental Design:
Genomic Instability Scar (GIScar) was developed through targeted sequencing of a 127-gene panel to determine HRD status. GIScar was trained from a noninterventional study with 250 prospectively collected ovarian tumor samples. GIScar was validated on 469 DNA tumor samples from the PAOLA-1 trial evaluating maintenance olaparib for newly diagnosed ovarian cancer, and its predictive value was compared with Myriad Genetics MyChoice (MGMC).
Results:
GIScar showed significant correlation with MGMC HRD classification (kappa statistics: 0.780). From PAOLA-1 samples, more HRD-positive tumors were identified by GIScar (258) than MGMC (242), with a lower proportion of inconclusive results (1% vs. 9%, respectively). The HRs for progression-free survival (PFS) with olaparib versus placebo were 0.45 95% confidence interval (CI), 0.33–0.62 in GIScar-identified HRD-positive BRCA-mutated tumors, 0.50 (95% CI, 0.31–0.80) in HRD-positive BRCA-wild-type tumors, and 1.02 (95% CI, 0.74–1.40) in HRD-negative tumors. Tumors identified as HRD positive by GIScar but HRD negative by MGMC had better PFS with olaparib (HR, 0.23; 95% CI, 0.07–0.72).
Conclusions:
GIScar is a valuable diagnostic tool, reliably detecting HRD and predicting sensitivity to olaparib for ovarian cancer. GIScar showed high analytic concordance with MGMC test and fewer inconclusive results. GIScar is easily implemented into diagnostic laboratories with a rapid turnaround.
UNICORE 6 — Recent and Future Advancements Streit, Achim; Bala, Piotr; Beck-Ratzka, Alexander ...
Annales des télécommunications,
12/2010, Letnik:
65, Številka:
11-12
Journal Article
Recenzirano
Odprti dostop
UNICORE is a European Grid Technology with more than 10 years of history. Originating from the Supercomputing domain, the latest version UNICORE 6 has turned into a general-purpose Grid technology ...that follows established standards and offers a rich set of features to its users. The paper starts with an architectural insight into UNICORE 6, highlighting the workflow features, standards and the different clients. Next, the current state of advancement is presented by describing recent developments. The paper closes with an outlook on future planned developments.
Especially within grid infrastructures driven by high-performance computing (HPC), collaborative online visualization and steering (COVS) has become an important technique to dynamically steer the ...parameters of a parallel simulation or to just share the outcome of simulations via visualizations with geographically dispersed collaborators. In earlier work, we have presented a COVS framework reference implementation based on the UNICORE grid middleware used within DEISA. This paper lists current limitations of the COVS framework design and implementation related to missing fine-grained authorization capabilities that are required during collaborative COVS sessions. Such capabilities use end-user information about roles, project membership, or participation in a dedicated virtual organization (VO). We outline solutions and present a design and implementation of our architecture extension that uses attribute authorities such as the recently developed virtual organization membership service (VOMS) based on the security assertion markup language (SAML).
Today's large-scale scientific research often relies on the collaborative use of a Grid or c-Science infrastructure (e.g. DEISA, EGEE, TeraGrid, OSG) with computational, storage, or other types of ...physical resources. One of the goals of these emerging infrastructures is to support the work of scientists with advanced problem-solving tools. Many e-Science applications within these infrastructures aim at simulations of a scientific problem on powerful parallel computing resources. Typically, a researcher first performs a simulation for some fixed amount of time and then analyses results in a separate post-processing step, for instance, by viewing results in visualizations. In earlier work we have described early prototypes of a Collaborative Online Visualization and Steering (COVS) Framework in Grids that performs both -simulation and visualization -at the same time (online) to increase the efficiency of e-Scientists. This paper evaluates the evolved mature reference implementation of the COVS framework design that is ready for production usage within Web service-based Grid and e-Science infrastructures.
The UNICORE grid system provides a seamless, secure and intuitive access to distributed grid resources. In recent years, UNICORE 5 is used as a well-tested grid middleware system in production grids ...(e.g. DEISA, D-Grid) and at many supercomputer centers world-wide. Beyond this production usage, UNICORE serves as a solid basis in many European and International research projects and business scenarios from T-Systems, Philips Research, Intel, Fujitsu and others. To foster ongoing developments in multiple projects, UNICORE is open source under BSD license at SourceForge. More recently, the new Web services-based UNICORE 6 has become available that is based on open standards such as the Web services addressing (WS-A) and the Web services resource framework (WS-RF) and thus conforms to the open grid services architecture (OGSA) of the open grid forum (OGF). In this paper we present the evolution from production UNICORE 5 to the open standards-based UNICORE 6 and its various Web services-based interfaces. It describes the interface integration of emerging open standards such as OGSA-BES and OGSA-RUS and thus provides an overview of UNICORE 6.
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