48 results on '"Jan Lim"'
Search Results
2. Nucleotide Composition of Ultra-Conserved Elements Shows Excess of GpC and Depletion of GG and CC Dinucleotides
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Larisa Fedorova, Oleh A. Mulyar, Jan Lim, and Alexei Fedorov
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Genome ,Base Sequence ,Nucleotides ,Genetics ,computational biology ,polymorphism ,genetic variation ,evolution ,DNA structure ,bioinformatics ,genomics ,Humans ,Animals ,DNA ,Chickens ,Genetics (clinical) - Abstract
The public UCNEbase database, comprising 4273 human ultra-conserved noncoding elements (UCNEs), was thoroughly investigated with the aim to find any nucleotide signals or motifs that have made these DNA sequences practically unchanged over three hundred million years of evolution. Each UCNE comprises over 200 nucleotides and has at least 95% identity between humans and chickens. A total of 31,046 SNPs were found within the UCNE database. We demonstrated that every human has over 300 mutations within 4273 UCNEs. No association of UCNEs with non-coding RNAs, nor preference of a particular meiotic recombination rate within them were found. No sequence motifs associated with UCNEs nor their flanking regions have been found. However, we demonstrated that UCNEs have strong nucleotide and dinucleotide sequence abnormalities compared to genome averages. Specifically, UCNEs are depleted for CC and GG dinucleotides, while GC dinucleotides are in excess of 28%. Importantly, GC dinucleotides have extraordinarily strong stacking free-energy inside the DNA helix and unique resistance to dissociation. Based on the adjacent nucleotide stacking abnormalities within UCNEs, we conjecture that peculiarities in dinucleotide distribution within UCNEs may create unique 3D conformation and specificity to bind proteins. We also discuss the strange dynamics of multiple SNPs inside UCNEs and reasons why these sequences are extraordinarily conserved.
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- 2022
3. Mitotane Targets Lipid Droplets to Induce Lipolysis in Adrenocortical Carcinoma
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Kate M Warde, Yi Jan Lim, Eduardo Ribes Martinez, Felix Beuschlein, Paula O’Shea, Constanze Hantel, Michael Conall Dennedy, University of Zurich, and Dennedy, Michael Conall
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Endocrinology ,Cholesterol ,Antineoplastic Agents, Hormonal ,Cell Line, Tumor ,Lipolysis ,Adrenocortical Carcinoma ,10265 Clinic for Endocrinology and Diabetology ,Humans ,610 Medicine & health ,Lipid Droplets ,Mitotane ,Adrenal Cortex Neoplasms ,1310 Endocrinology - Abstract
Introduction Adrenocortical carcinoma (ACC) is a rare aggressive cancer with low overall survival. Adjuvant mitotane improves survival but is limited by poor response rates and resistance. Mitotane’s efficacy is attributed to the accumulation of toxic free cholesterol, predominantly through cholesterol storage inhibition. However, targeting this pathway has proven unsuccessful. We hypothesize that mitotane-induced free-cholesterol accumulation is also mediated through enhanced breakdown of lipid droplets. Methodology ATCC-H295R (mitotane-sensitive) and MUC-1 (mitotane-resistant) ACC cells were evaluated for lipid content using specific BODIPY dyes. Protein expression was evaluated by immunoblotting and flow cytometry. Cell viability was measured by quantifying propidium iodide-positive cells following mitotane treatment and pharmacological inhibitors of lipolysis. Results H295R and MUC-1 cells demonstrated similar neutral lipid droplet numbers at baseline. However, evaluation of lipid machinery demonstrated distinct profiles in each model. Analysis of intracellular lipid droplet content showed H295R cells preferentially store cholesteryl esters, whereas MUC-1 cells store triacylglycerol. Decreased lipid droplets were associated with increased lipolysis in H295R and in MUC-1 at toxic mitotane concentrations. Pharmacological inhibition of lipolysis attenuated mitotane-induced toxicity in both models. Conclusion We highlight that lipid droplet breakdown and activation of lipolysis represent a putative additional mechanism for mitotane-induced cytotoxicity in ACC. Further understanding of cholesterol and lipids in ACC offers potential novel therapeutic exploitation, especially in mitotane-resistant disease.
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- 2022
4. T1-relaxation times along the corticospinal tract as a diagnostic marker in patients with amyotrophic lateral sclerosis
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Fiona Dierksen, Johanna S. Geibel, Janika Albrecht, Sabine Hofer, Peter Dechent, Amelie C. Hesse, Jens Frahm, Mathias Bähr, Jan C. Koch, Jan Liman, and Ilko L. Maier
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T1-mapping ,T1 relaxometry ,T1-relaxation time ,amyotrophic lateral sclerosis ,real-time MRI ,corticospinal tract ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background and purposeIn the differential diagnostic workup of amyotrophic lateral sclerosis (ALS), magnetic resonance imaging (MRI) is primarily used to rule out significant differential diagnoses. So far, whole-brain T1-mapping has not been assessed as a diagnostic tool in this patient population.MethodsWe investigated the diagnostic potential of a novel T1-mapping method based on real-time MRI with 0.5 mm in-plane resolution and 4s acquisition time per slice. The study included patients aged 18 to 90 years who met the revised El Escorial criteria for at least possible ALS. T1-relaxation times were measured along the corticospinal tract in predefined regions of interest.ResultsTwenty-nine ALS-patients and 43 control group patients (CG) were included in the study. Median ALS Functional Rating Scale revised (ALSFRS-R) was 37 (IQR, 35–44) points and the mean duration from symptom onset to MRI was 21 ± 17 (SD) months. ALS patients showed significantly higher T1-relaxation times in all ROIs compared to CG with mean differences in the hand knob of 50 ms (p < 0.001), corona radiata 24 ms (p = 0.034), internal capsule 27 ms (p = 0.002) and midbrain peduncles 48 ms (p < 0.001). There was a consistent negative correlation between the ALSFRS-R and T1-relaxation times in all ROIs.ConclusionsT1-relaxation times along the corticospinal tract are significantly elevated in ALS patients compared to CG and associated with lower ALSFRS-R. These results imply the analysis of T1-relaxation times as a promising diagnostic tool that can distinguish ALS patients from the control group. Ongoing longitudinal studies may provide deeper insights into disease progression and the effects of therapeutic interventions.
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- 2025
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5. Rehabilitation interventions in Rett syndrome: a scoping review
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Jan Lim, Dayna Greenspoon, Anne Hunt, and Laura McAdam
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030506 rehabilitation ,medicine.medical_specialty ,medicine.medical_treatment ,Gross motor skill ,Psychological intervention ,MEDLINE ,CINAHL ,PsycINFO ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Quality of life (healthcare) ,Developmental Neuroscience ,Rett Syndrome ,medicine ,Humans ,Rehabilitation ,Recovery of Function ,Treatment Outcome ,Communication Intervention ,Pediatrics, Perinatology and Child Health ,Quality of Life ,Neurology (clinical) ,0305 other medical science ,Psychology ,030217 neurology & neurosurgery - Abstract
Aim To summarize existing interventions and their outcomes in Rett syndrome (RTT) rehabilitation and identify gaps in the literature. Method Five databases (Ovid MEDLINE, Ovid Embase Classic, Ovid PsycINFO, EBSCO CINAHL Plus, and ProQuest ERIC) were systematically searched up to 23rd July 2018 for studies describing rehabilitation interventions. Data on study participants, design, and outcomes were extracted. Results Sixty-two articles were included in the final review. Evidence consistently demonstrated that females with RTT can improve their gross motor, fine motor, and communicative skills with rehabilitation. All 11 interventions targeting gross motor function, namely ambulation, achieved functional improvements. Twenty of 24 articles describing fine motor rehabilitation studies succeeded in decreasing stereotypies, improving functional hand use, and/or reducing self-injurious behaviors. Twenty-one of 22 studies describing communication interventions succeeded in training choice-making, communicative language, or socialization behavior. Other key findings include the positive interplay between physical and communicative rehabilitation outcomes, and the ability of females with RTT to improve their cognitive abilities during intervention. Interpretation Rehabilitation can impact the daily lives of females with RTT and their caregivers in clinically meaningful ways.
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- 2020
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6. Analysis of Common SNPs across Continents Reveals Major Genomic Differences between Human Populations
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Larisa Fedorova, Andrey Khrunin, Gennady Khvorykh, Jan Lim, Nicholas Thornton, Oleh A. Mulyar, Svetlana Limborska, and Alexei Fedorov
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Africa ,Genetics ,Humans ,Genomics ,computational biology ,genomics ,polymorphism ,single nucleotide ,genetic variation ,Selection, Genetic ,Polymorphism, Single Nucleotide ,Genetics (clinical) ,Alleles - Abstract
Common alleles tend to be more ancient than rare alleles. These common SNPs appeared thousands of years ago and reflect intricate human evolution including various adaptations, admixtures, and migration events. Eighty-four thousand abundant region-specific alleles (ARSAs) that are common in one continent but absent in the rest of the world have been characterized by processing 3100 genomes from 230 populations. Also computed were 17,446 polymorphic sites with regional absence of common alleles (RACAs), which are widespread globally but absent in one region. A majority of these region-specific SNPs were found in Africa. America has the second greatest number of ARSAs (3348) and is even ahead of Europe (1911). Surprisingly, East Asia has the highest number of RACAs (10,524) and the lowest number of ARSAs (362). ARSAs and RACAs have distinct compositions of ancestral versus derived alleles in different geographical regions, reflecting their unique evolution. Genes associated with ARSA and RACA SNPs were identified and their functions were analyzed. The core 100 genes shared by multiple populations and associated with region-specific natural selection were examined. The largest part of them (42%) are related to the nervous system. ARSA and RACA SNPs are important for both association and human evolution studies.
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- 2022
7. Telehealth Technology Application in Enhancing Continuous Positive Airway Pressure Adherence in Obstructive Sleep Apnea Patients: A Review of Current Evidence
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Benjamin Ka Seng Thong, Grace Xin Yun Loh, Jia Jan Lim, Christina Jia Liang Lee, Shu Ning Ting, Hong Peng Li, and Qing Yun Li
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General Medicine - Abstract
Obstructive sleep apnea (OSA) is a common type of sleep-disordered breathing associated with multiple comorbidities. Continuous positive airway pressure (CPAP) is the first choice for moderate-severe OSA but poor compliance brings a great challenge to its effectiveness. Telehealth interventions ease the follow-up process and allow healthcare facilities to provide consistent care. Fifth-generation wireless transmission technology has also greatly rationalized the wide use of telemedicine. Herein, we review the efficacy of the telehealth system in enhancing CPAP adherence. We recommend applying telemonitoring in clinical practice and advocate the development of a biopsychosocial telemedicine model with the integration of several interventions. Big databases and promising artificial intelligent technologies make clinical decision support systems and predictive models based on these databases possible.
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- 2022
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8. 'Odstřel se nekoná.' (Ne)úřední vyjednávání jako hybná síla v pozadí rekonstrukce kulturní památky v Československu po roce 1948
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Jan Limberský
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czechoslovakia ,renovation ,rescue ,negotiation ,stratégy ,monument ,culture ,communism ,staré hrady ,History of Central Europe ,DAW1001-1051 - Abstract
This paper examines official negotiation methods behind the renovation and simultaneous use of the Staré Hrady castle between 1949 and 1993, as an example of the rescue of a cultural monument in communist Czechoslovakia. It is concerned with the mechanisms of actor-institutional communication at regional level at work within the broader circumstances prevailing in then Czechoslovakia, arguing that this negotiation was in fact the driving force behind the successful reconstruction of this castle after many years of expert-led volunteer work.
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- 2024
9. Genetic and genomic resources to study natural variation in Brassica rapa
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Richard M. Amasino, Timothy Woody, C. Robertson McClung, Shuxing Shen, Ping Lou, Kathleen Greenham, Jan Lim, Yakun Zheng, Nathan Levendoski, Patrick P. Edger, Scott T. Woody, Marivi Colle, Robert VanBuren, Ryan C. Sartor, Calvin So, Brian Stoveken, and Jianjun Zhao
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education.field_of_study ,Genetic diversity ,Ecology ,Advanced‐Intercross Recombinant Inbred Lines ,Population ,Brassica rapa ,Quantitative Trait Loci ,food and beverages ,Plant Science ,Biotic stress ,Biology ,Quantitative trait locus ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Genome ,seed coat color ,Evolutionary biology ,natural variation ,Gene pool ,Domestication ,education ,Ecology, Evolution, Behavior and Systematics ,Reference genome ,Original Research - Abstract
The globally important crop Brassica rapa, a close relative of Arabidopsis, is an excellent system for modeling our current knowledge of plant growth on a morphologically diverse crop. The long history of B. rapa domestication across Asia and Europe provides a unique collection of locally adapted varieties that span large climatic regions with various abiotic and biotic stress tolerance traits. This diverse gene pool provides a rich source of targets with the potential for manipulation towards the enhancement of productivity of crops both within and outside the Brassicaceae. To expand the genetic resources available to study natural variation in B. rapa, we constructed an Advanced Intercross Recombinant Inbred (AI-RIL) population using B. rapa subsp. trilocularis (Yellow Sarson) R500 and the B. rapa subsp. parachinensis (Cai Xin) variety L58. Our current understanding of genomic structure variation across crops suggests that a single reference genome is insufficient for capturing the genetic diversity within a species. To complement this AI-RIL population and current and future B. rapa genomic resources, we generated a de novo genome assembly of the B. rapa subsp. trilocularis (Yellow Sarson) variety R500, the maternal parent of the AI-RIL population. The genetic map for the R500 x L58 population generated using this de novo genome was used to map QTL for seed coat color and revealed the improved mapping resolution afforded by this new assembly.
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- 2020
10. Liver X receptor inhibition potentiates mitotane-induced adrenotoxicity in ACC
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Erik Schoenmakers, Constanze Hantel, Yi Jan Lim, Michael Conall Dennedy, Krishna Chatterjee, Eduardo Ribes Martinez, Paula M O'Shea, Kate Warde, Sarah J Lawless, Maeve Leonard, Mark Gurnell, University of Zurich, and Dennedy, Michael Conall
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0301 basic medicine ,Cancer Research ,Endocrinology, Diabetes and Metabolism ,10265 Clinic for Endocrinology and Diabetology ,Apoptosis ,610 Medicine & health ,Pharmacology ,Transfection ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,medicine ,Adrenocortical Carcinoma ,Adrenocortical carcinoma ,Humans ,Mitotane ,1306 Cancer Research ,Liver X receptor ,Liver X Receptors ,biology ,Chemistry ,Cholesterol ,Liver X receptor alpha ,Middle Aged ,medicine.disease ,1310 Endocrinology ,2712 Endocrinology, Diabetes and Metabolism ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,ABCA1 ,biology.protein ,Female ,2730 Oncology ,Cholesterol storage ,Intracellular ,medicine.drug - Abstract
Adrenocortical carcinoma (ACC) is a rare aggressive malignancy with a poor outcome largely due to limited treatment options. Here, we propose a novel therapeutic approach through modulating intracellular free cholesterol via the liver X receptor alpha (LXRα) in combination with current first-line pharmacotherapy, mitotane. H295R and MUC-1 ACC cell lines were pretreated with LXRα inhibitors in combination with mitotane. In H295R, mitotane (20, 40 and 50 µM) induced dose-dependent cell death; however, in MUC-1, this only occurred at a supratherapeutic concentration (200 µM). LXRα inhibition potentiated mitotane-induced cytotoxicity in both cell lines. This was confirmed through use of the CompuSyn model which showed moderate pharmacological synergism and was indicative of apoptotic cell death via an increase in annexinV and cleaved-caspase 3 expression. Inhibition of LXRα was confirmed through downregulation of cholesterol efflux pumps ABCA1 and ABCG1; however, combination treatment with mitotane attenuated this effect. Intracellular free-cholesterol levels were associated with increased cytotoxicity in H295R (r2 = 0.5210) and MUC-1 (r2 = 0.9299) cells. While both cell lines exhibited similar levels of free cholesterol at baseline, H295R were cholesterol ester rich, whereas MUC-1 were cholesterol ester poor. We highlight the importance of LXRα mediated cholesterol metabolism in the management of ACC, drawing attention to its role in the therapeutics of mitotane sensitive tumours. We also demonstrate significant differences in cholesterol storage between mitotane sensitive and resistant disease.
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- 2020
11. Investigating the role of cholesterol and lipid trafficking in mitotane resistance in adrenocortical carcinoma
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Warde, Kate, primary, Yi, Jan Lim, additional, Beuschlein, Felix, additional, Constanze, Hantel, additional, and Conall, Dennedy Michael, additional
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- 2021
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12. Investigating the Role of Cholesterol and Lipid Trafficking in Mitotane Resistance in Adrenocortical Carcinoma
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Dennedy Michael Conall, Kate Warde, Hantel Constanze, Felix Beuschlein, and Jan Lim Yi
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Cholesterol ,business.industry ,Endocrinology, Diabetes and Metabolism ,Lipid trafficking ,Adrenal - Basic and Translational Aspects ,medicine.disease ,chemistry.chemical_compound ,chemistry ,Cancer research ,medicine ,Adrenocortical carcinoma ,Mitotane ,Adrenal ,business ,AcademicSubjects/MED00250 ,medicine.drug - Abstract
Introduction: Adrenocortical Carcinoma (ACC) is a rare aggressive cancer which carries a poor prognosis. Adjuvant mitotane improves survival but is limited by poor response rates and resistance following tumour recurrence. Mitotane’s efficacy has been attributed to intracellular accumulation of toxic free cholesterol (FC) predominantly through inhibition of cholesterol storage through SOAT1. Yet SOAT1 specific inhibitors demonstrate inferior efficacy to mitotane in inducing ACC cell death. We hypothesize that mitotane’s efficacy to induce toxic FC accumulation in ACC cells is also mediated through enhanced breakdown of stored cholesterol within intracellular lipid droplets (LDs). Methodology: ATCC-H295R (mitotane sensitive) and MUC-1 (mitotane resistant) ACC cells were evaluated for neutral lipid content using BODIPY493/503 under baseline and cholesterol loaded conditions using Amnis ImageStream, additionally cells were treated with mitotane (H295R - 20, 40, 50µM; MUC1 - 50, 100, 200µM) for 6hr. Analysis of LDs using CE-BODIPY and FA-BODIPY identified cholesterol ester (CE) and triacylglycerol (TAG)-containing LDs, respectively. Lipid droplet-associated proteins (LDAPs) Perilipin (PLIN) 1–4 and hormone sensitive lipase (HSL) were evaluated using western blotting and PCR. Lipid uptake receptors; SRB1, LDLR, LRP1 and CD36 were measured by flow cytometry. Results: Mitotane treatment, within therapeutic range, decreased staining for LDs significantly in H295R. This was also reflected by decreased expression of LDAPs, PLIN1 and PLIN3. The decrease in H295R LDs was associated with increased activation of HSL (pHSL and LIPE). However, this effect was only evident in MUC-1 at supratherapeutic mitotane (200µM). H295R and MUC-1 demonstrated similar overall LD numbers at baseline and under cholesterol supplementation. Expression of PLIN3 was high in both cell lines, while PLIN1, PLIN2 and PLIN4 demonstrated distinct LD profiles in each. Investigation of LD content showed that H295R preferentially store CEs while MUC-1 store only TAG, irrespective of cholesterol-loading. Mitotane treatment significantly reduces both CE and TAG LDs in H295R and MUC-1. Expression of lipid uptake receptors also demonstrated significant variability between cell lines including SRB1 and LRP1. Conclusion: We highlight that lipolysis through LD breakdown and activation of HSL represents a putative additional mechanism for mitotane induced FC cytotoxicity in ACC. We also demonstrate significant differences in cholesterol handling and LDAPs between mitotane sensitive and mitotane resistant models, in particular, the absence of CE LDs in MUC-1. We therefore propose a mechanism of resistance to mitotane through absent CE storage. Further understanding of cholesterol and lipid handling in ACC offers novel therapeutic exploitation, especially in the setting of mitotane resistant disease.
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- 2021
13. Doppler flow morphology characteristics of epiaortic arteries in aortic valve pathologies: a retrospective study on a cohort of patients with ischemic stroke
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Stefanie Meyer, Lara Wilde, Frieder Wolf, Jan Liman, Mathias Bähr, and Ilko L. Maier
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Doppler sonography ,Stroke ,Aortic valve regurgitation ,Aortic valve stenosis ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Abstract Background and aims Neurovascular ultrasound (nvUS) of the epiaortic arteries is an integral part of the etiologic workup in patients with ischemic stroke. Aortic valve disease shares similar vascular risk profiles and therefore not only presents a common comorbidity, but also an etiologic entity. The aim of this study is to investigate the predictive value of specific Doppler curve flow characteristics in epiaortic arteries and the presence of aortic valve disease. Methods Retrospective, single-center analysis of ischemic stroke patients, both receiving full nvUS of the extracranial common- (CCA), internal- (ICA) and external carotid artery (ECA) and echocardiography (TTE/TEE) during their inpatient stay. A rater blinded for the TTE/TEE results investigated Doppler flow curves for the following characteristics: ‘pulsus tardus et parvus’ for aortic valve stenosis (AS) and ‘bisferious pulse’, ‘diastolic reversal’, ‘zero diastole’ and ‘no dicrotic notch’ for aortic valve regurgitation (AR). Predictive value of these Doppler flow characteristics was investigated using multivariate logistic regression models. Results Of 1320 patients with complete examination of Doppler flow curves and TTE/TEE, 75 (5.7%) showed an AS and 482 (36.5%) showed an AR. Sixty-one (4.6%) patients at least showed a moderate-to-severe AS and 100 (7.6%) at least showed a moderate-to-severe AR. After adjustment for age, coronary artery disease, arterial hypertension, diabetes mellitus, smoking, peripheral arterial disease, renal failure and atrial fibrillation, the following flow pattern predicted aortic valve disease: ‘pulsus tardus et parvus’ in the CCA and ICA was highly predictive for a moderate-to-severe AS (OR 1158.5, 95% CI 364.2–3684.8, p
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- 2023
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14. Population-based validation of a policy change to use long-term androgen deprivation therapy for cT3–4 prostate cancer: Impact of the EORTC22863 and RTOG 85-31 and 92-02 trials
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Justin Jay, Jeremy Hamm, Matthew Paquette, Mira Keyes, Scott Tyldesley, Jan Lim, Winkle Kwan, M. Liu, Eric Tran, and Tom Pickles
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Male ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,Cohort Studies ,Androgen deprivation therapy ,Prostate cancer ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Stage (cooking) ,education ,Aged ,Retrospective Studies ,Aged, 80 and over ,Gynecology ,education.field_of_study ,business.industry ,Prostatic Neoplasms ,Androgen Antagonists ,Hematology ,Middle Aged ,medicine.disease ,Comorbidity ,Cancer registry ,Radiation therapy ,Cohort ,Neoplasm Grading ,business - Abstract
After publication of EORTC-22863 trial, prolonged androgen deprivation therapy (ADT) combined with radiation therapy (RT) became standard policy for high-risk prostate cancer patients in British Columbia (BC) in 1997. We evaluated whether population-based survival improved after this policy change.Two cohorts comprising all patients with T3-T4 prostate cancer treated with curative-intent RT in BC were reviewed. The Early cohort (n=730) was all patients treated between 1993 and 1995, and the Late cohort (n=584) was all patients treated between 1999 and 2001. The BC Cancer Registry, which collects data on survival, was linked to RT and pharmacy databases. Duration of ADT, age, stage, grade, presenting PSA, and Charlson comorbidity index (CCI; none=0, minor=1, major=2+), were abstracted from charts.Usage of ≥6 months and ≥18 months of neoadjuvant and adjuvant ADT increased from 14% and 1% to 97% and 59% (p0.0001). Baseline characteristics were similar, except for lower Gleason score (G2-6: 45% vs. 20%, G7: 35% vs. 48%, G8-10: 19% vs. 32%; p0.0001), higher T-stage (T4: 9% vs. 5%, p=0.004) and higher comorbidity (CCI 0: 62% vs. 71%, CCI 1: 26% vs. 20%, CCI 2+: 11% vs. 9%, p=0.002) in the Early cohort. Disease-specific survival adjusted for competing risks from other causes mortality was improved (90% vs. 86%, p=0.042). On multivariate analysis, the Late cohort was independently associated with improved 8-year overall survival (76% vs. 64%, p=0.0002).This population-based study demonstrated improved overall survival following a policy change to use of prolonged ADT with curative RT for patients with T3-T4 prostate cancer.
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- 2013
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15. Neoadjuvant hormone therapy and external-beam radiation for localized high-risk prostate cancer: The importance of PSA nadir before radiation
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Brenna Eldridge, Eric Berthelet, Gary Steinhoff, P. Blood, Darcy Bishop, Jan Lim, G. Bruce Piercy, Charles Ludgate, and Howard Pai
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Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Urology ,urologic and male genital diseases ,Disease-Free Survival ,Prostate cancer ,Prostate ,Internal medicine ,Confidence Intervals ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Stage (cooking) ,Neoadjuvant therapy ,Aged ,Retrospective Studies ,Aged, 80 and over ,Analysis of Variance ,Radiation ,business.industry ,Prostatic Neoplasms ,Androgen Antagonists ,Middle Aged ,Prostate-Specific Antigen ,medicine.disease ,Neoadjuvant Therapy ,Radiation therapy ,Prostate-specific antigen ,Treatment Outcome ,medicine.anatomical_structure ,T-stage ,Hormone therapy ,business - Abstract
To examine the impact of various patient, disease, and treatment characteristics on outcome in patients treated with neoadjuvant hormone therapy (NAHT) and external-beam radiation therapy (EBRT) for clinically localized, high-risk prostate adenocarcinoma (initial prostate-specific antigen [PSA] level20, Gleason score 8-10 or Stageor = T3).A retrospective chart review was conducted on 407 patients treated between 1991 and 2001 with NAHT and EBRT for high-risk prostate cancer. The effect of tumor (PSA level, Gleason score, and T stage) and treatment (NAHT duration, total-hormone duration, preradiation PSA) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival, and overall survival were examined.Median follow-up time was 78 months (range: 5-140 months). Actuarial bDFS at 5 years was 52% (95% confidence interval [CI], 46% to 57%) for the entire group. On multivariate analysis, initial PSA level (p = 0.004), Gleason score (p = 0.005), and preradiation PSA level (p0.001) were predictive of bDFS, whereas age, T stage, duration of NAHT, and duration of total hormone therapy were not predictive of outcomes. Gleason score and preradiation PSA level were also predictive of prostate cancer-specific survival rates.Improved bDFS in patients with high-risk prostate cancer was associated with lower initial PSA level, lower Gleason score, and lower preradiation PSA level. The duration of NAHT did not have an impact on outcomes, but the preradiation PSA was an important predictor of bDFS in high-risk patients.
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- 2005
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16. Report of a multicenter Canadian phase III randomized trial of 3 months vs. 8 months neoadjuvant androgen deprivation before standard-dose radiotherapy for clinically localized prostate cancer
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Shawn Malone, Jan Lim, Gina Lockwood, Libne Eapen, Susan J. Robertson, G. Perry, Julie Bowen, Charles Ludgate, and Juanita Crook
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Male ,Cancer Research ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,medicine.medical_treatment ,Urology ,Statistics, Nonparametric ,Prostate cancer ,Prostate ,Statistical significance ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Survival rate ,Neoadjuvant therapy ,Aged ,Aged, 80 and over ,Radiation ,business.industry ,Goserelin ,Prostatic Neoplasms ,Androgen Antagonists ,Middle Aged ,Prostate-Specific Antigen ,medicine.disease ,Flutamide ,Neoadjuvant Therapy ,Surgery ,Survival Rate ,Radiation therapy ,medicine.anatomical_structure ,Oncology ,Hormonal therapy ,business ,medicine.drug - Abstract
To evaluate the effect of 3 months vs. 8 months of neoadjuvant hormonal therapy before conventional dose radiotherapy (RT) on disease-free survival using prostate-specific antigen PSA and biopsies as end points for clinically localized prostate cancer.Between February 1995 and June 2001, 378 men were randomized to either 3 or 8 months of flutamide and goserelin before conventional-dose RT (66 Gy) at four participating centers. The median patient age was 72 years (range, 50-84 years). The stage distribution was 17% T1c, 35% T2a, 34% T2b-T2c, 13% T3-T4. The Gleason score (GS) wasor =6 in 51%, 7 in 38%, and 8-10 in 11%. The median baseline PSA level was 9.7 ng/mL (range, 1.3-189 ng/mL). Of the 378 men, 26% were low risk (Stage T1c-T2a, GSor =6, PSA10 ng/mL), 43% were intermediate risk (Stage T2b or GS 7 or PSA 10-20 ng/mL), and 31% were high risk (Stage T3 or GS 8-10 or PSA20 ng/mL). The two arms were balanced in terms of age, GS, T stage, risk group, and presenting PSA level. The median follow-up was 44 months (range, 10-84 months), and 361 patients were available for evaluation.The 8-month arm achieved a lower PSA level before starting RT (0.37 vs. 0.74 ng/mL, por =0.001) and had a greater downsizing of the prostate (mean volume 26.6 cm(3) vs. 30.5 cm(3), por =0.001). However, the actuarial freedom from failure rate (biochemical by American Society for Therapeutic Radiology and Oncology definition, local or distant) for the 3-month vs. 8-month arms at 3 years was 66% vs. 68% and by 5 years was 61% vs. 62%, respectively (p = 0.36). No statistically significant difference was noted in the types of failure between the two arms (crude final status): biochemical, 22.2% vs. 22.3%; local, 10.2% vs. 6.5%; and distant, 3.4% vs. 4.4% (p = 0.61). Two-year post-RT biopsies were done in 57% (n = 205). Negative biopsies were obtained in 68% of the 3-month and 77% of the 8-month patients; 18% and 14% had indeterminate biopsies and 14% and 9% were positive for residual cancer (p = 0.34) in the two arms, respectively. The median PSA level for nonfailing patients was 0.50 ng/mL in both the 3-months and 8-month arms. A suggestion of improvement was found in the 8-month arm for disease-free survival at 5 years for high-risk patients (39% vs. 52%) but did not achieve statistical significance.A longer period of neoadjuvant hormonal therapy before standard-dose RT does not appear to confer a benefit in terms of disease-free survival or to alter failure patterns. Failure was delayed in the 8-month arm, but this advantage was lost by 5 years of follow-up. A suggestion of benefit was noted with a longer period of hormonal therapy for high-risk patients.
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- 2004
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17. Do age and comorbidity impact treatment allocation and outcomes in limited stage small-cell lung cancer? a community-based population analysis
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Jan Lim, J Ludbrook, Mary Lesperance, Adam Webber, Pauline T. Truong, Howard Joe, Mary V. MacNeil, and Heidi Martins
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Male ,Cancer Research ,Lung Neoplasms ,Comorbidity ,Cohort Studies ,Radiotherapy, High-Energy ,Risk Factors ,Antineoplastic Combined Chemotherapy Protocols ,Proton Therapy ,Life Tables ,Carcinoma, Small Cell ,Etoposide ,education.field_of_study ,Radiation ,Palliative Care ,Age Factors ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Treatment Outcome ,Oncology ,Vincristine ,Female ,Cohort study ,medicine.medical_specialty ,Population ,Small-cell carcinoma ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Lung cancer ,education ,Cyclophosphamide ,Survival analysis ,Aged ,Retrospective Studies ,British Columbia ,Performance status ,business.industry ,Patient Selection ,medicine.disease ,Survival Analysis ,Surgery ,Doxorubicin ,Cisplatin ,Cranial Irradiation ,business ,Chemoradiotherapy - Abstract
The effects of age and comorbidity on treatment and outcomes for patients with limited stage small-cell lung cancer (L-SCLC) are unclear. This study analyzes relapse and survival in a community-based population with L-SCLC according to age and comorbidity.A retrospective review was performed on 174 patients with L-SCLC referred to the British Columbia Cancer Agency, Vancouver Island Centre, between January 1991 and December 1999. Patient and treatment characteristics, disease response, relapse, and survival were compared among three age cohorts:65 years (n = 55, 32%), 65-74 years (n = 76, 44%), andor =75 years (n = 43, 25%); and according to Charlson comorbidity scores 0, 1, andor =2. Multivariate analysis was performed to identify independent prognostic factors associated with treatment response and survival.Patient factors that significantly differed with age were functional status classified by Eastern Cooperative Oncology Group performance status and number of comorbidities. Increasing age was significantly associated with fewer diagnostic scans. Combined modality chemoradiotherapy (CRT) was given in 86%, 66%, and 40% of patients ages65, 65-74, andor =75 years, respectively, (p0.0001). Thoracic irradiation use was comparable among the age cohorts (p0.05), but chemotherapy use varied significantly with less intensive regimens, fewer cycles, and lower total doses with advancing age (p0.05). Prophylactic cranial irradiation (PCI) was used in 41 patients, only 3 of whom were age70 years. Overall response rates to primary treatment significantly decreased with advancing age: 91%, 79%, and 74% in patients ages65, 65-74, andor =75 years, respectively (p = 0.014). Treatment toxicity and relapse patterns were similar across the age cohorts. Overall 2-year survival rates were significantly lower with advancing age: 37%, 22%, and 19% (p = 0.003), with corresponding median survivals of 17, 12, and 7 months among patients ages65, 65-74, andor =75 years, respectively. On multivariate analysis, age and Charlson comorbidity scores were not significantly associated with treatment response and survival. Independent prognostic factors favorably associated with survival were good performance status, normal lactate dehydrogenase, absence of pleural effusion, andor =four cycles of chemotherapy.Increasing age was associated with decreased performance status and increased comorbidity. Older patients with L-SCLC were less likely to be treated with CRT, intensive chemotherapy, and PCI. Treatment response and survival rates were lower with advancing age, but this may be attributed to poor performance status and suboptimal treatment rather than age.
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- 2003
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18. What is the added value of CT-angiography in patients with transient ischemic attack?
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Ilko L. Maier, Gerrit U. Herpertz, Mathias Bähr, Marios-Nikos Psychogios, and Jan Liman
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Transient ischemic attack (TIA) is an important predictor for a pending stroke. Guidelines recommend a workup for TIA-patients similar to that of stroke patients, including an assessment of the extra- and intracranial arteries for vascular pathologies with direct therapeutic implications via computed tomography angiography (CTA). Aim of our study was a systematic analysis of TIA-patients receiving early CTA-imaging and to evaluate the predictive value of TIA-scores and clinical characteristics for ipsilateral vascular pathologies and the need of an invasive treatment. Methods We analysed clinical and imaging data from TIA patients being admitted to a tertiary university hospital between September 2015 and March 2018. Following subgroups were identified: 1) no- or low-grade vascular pathology 2) ipsilateral high-risk vascular pathology and 3) high-risk findings that needed invasive, surgical or interventional treatment. We investigated established TIA-scores (ABCD2-, the ABCD3- and the SPI-II score) and various clinical characteristics as predictive factors for ipsilateral vascular pathologies and the need for invasive treatment. Results Of 812 patients, 531 (65.4%) underwent initial CTA in the emergency department. In 121 (22.8%) patients, ipsilateral vascular pathologies were identified, of which 36 (6.7%) needed invasive treatment. The ABCD2-, ABCD3- and SPI-II-scores were not predictive for ipsilateral vascular pathologies or the need for invasive treatment. We identified male sex (OR 1.579, 95%CI 1.049–2.377, p = 0.029), a short duration of symptoms (OR 0.692, 95% CI 0.542–0.884, p = 0.003), arterial hypertension (OR 1.718, 95%CI 0.951–3.104, p = 0.073) and coronary heart disease (OR 1.916, 95%CI 1.184–3.101, p = 0.008) as predictors for ipsilateral vascular pathologies. As predictors for the need of invasive treatment, a short duration of symptoms (OR 0.565, 95%CI 0.378–0.846, p = 0.006), arterial hypertension (OR 2.612, 95%OR 0.895–7.621, p = 0.079) and hyperlipidaemia (OR 5.681, 95%CI 0.766–42.117, p = 0.089) as well as the absence of atrial fibrillation (OR 0.274, OR 0.082–0.917, p = 0.036) were identified. Conclusion More than every fifth TIA-patient had relevant vascular findings revealed by acute CTA. TIA-scores were not predictive for these findings. Patients with a short duration of symptoms and a vascular risk profile including coronary heart disease, arterial hypertension and hyperlipidaemia most likely might benefit from early CTA to streamline further diagnostics and therapy.
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- 2022
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19. Long-Term Follow-up of Enhanced Holter-Electrocardiography Monitoring in Acute Ischemic Stroke
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Rolf Wachter, Mark Weber-Krüger, Gerhard F. Hamann, Pawel Kermer, Jan Liman, Meinhard Mende, Joachim Seegers, Katrin Wasser, Sonja Gröschel, Timo Uphaus, Holger Poppert, Martin Köhrmann, Markus Zabel, Ulrich Laufs, Peter U. Heuschmann, David Conen, and Klaus Gröschel
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stroke ,atrial fibrillation ,electrocardiographic monitoring ,randomized controlled trial ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background and Purpose Prolonged electrocardiography (ECG)-monitoring in stroke patients improves the detection of paroxysmal atrial fibrillation (pAF). However, most randomized studies only had short follow-up. We aimed to provide 3-year follow-up data for AF detection and stroke recurrence risk. Methods We randomized 402 patients aged ≥60 years with acute ischemic strokes without AF to either enhanced and prolonged monitoring (EPM; 3×10-day Holter-ECG-monitoring) or standard-of-care (≥24 hours ECG-monitoring). The endpoint of the current analysis was AF within 36 months analyzed by intention to treat. Long-term follow-up was performed for 36 months. Results Two hundred and seventy-four patients (80%) participated in the extended follow-up (median duration of follow-up was 36 months [interquartile range, 12 to 36]). During the first 6 months, more AF was documented in the EPM arm compared to the control arm (13.5% vs. 5.1%; 95% confidence interval, 2.9% to 14.4%; P=0.004). During months 6 to 36, AF was less detected in the EPM intervention arm than in the control arm (2.0% vs. 7.3%; 95% confidence interval, 0.7% to 9.9%; P=0.028). Overall, the detection rate of AF within 36 months was numerically higher within the EPM group (15.0% vs. 11.1%, P=0.30). Numerically less patients in the EPM arm had recurrent ischemic strokes (5.5% vs. 9.1%, P=0.18), transient ischemic attacks (3.0% vs. 4.5%, P=0.44) or died (4.5% vs. 6.6%, P=0.37). Conclusions Enhanced and prolonged ECG monitoring increased AF detection during the first six months, but there was significantly more clinical AF during months 6 to 36 observed in the usual-care arm. This suggests that EPM leads to an earlier detection of clinically relevant AF.
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- 2022
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20. Importance of First Pass Reperfusion in Endovascular Stroke Care ‐ Insights From Thrombectomy and Aneurysm Registry (STAR)
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Ilko L. Maier, Eyad Almallouhi, Marios‐Nikos Psychogios, Jan Liman, Sami Al Kasab, Ali Alawieh, Reda Chalhoub, Stacey Wolfe, Adam Arthur, Amir Shaban, Travis Dumont, Peter Kan, Joon‐Tae Kim, Reade De Leacy, Joshua Osbun, Ansaar Rai, Pascal Jabbour, Brian M. Howard, Min Park, Robert M. Starke, Roberto Crosa, Justin Mascitelli, Michael R. Levitt, Adam Polifka, Walter Casagrande, Shinichi Yoshimura, Charles Matouk, Richard W. Williamson, Benjamin Gory, Maxim Mokin, Isabel Fragata, Daniele G. Romano, Shakeel Chowdry, Mark Moss, Alejandro M. Spiotta, and Daniel Behme
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acute ischemic stroke ,clinical outcomes ,first‐pass effect ,influencing factors ,mechanical thrombectomy ,multiple‐pass effect ,Neurology. Diseases of the nervous system ,RC346-429 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Mechanical thrombectomy has become the first‐line treatment strategy for patients with large‐vessel occlusion strokes. Often >1 thrombectomy maneuver is necessary to achieve reperfusion. A first‐pass (FP) effect with improved functional outcomes after mechanical thrombectomy has been described. Aim of the present study is to investigate the FP effect in a large, international, multicenter stroke database. Methods Patients who underwent mechanical thrombectomy for large‐vessel occlusion stroke in the anterior cerebral circulation between January 2014 and January 2021 and achieved complete reperfusion were identified from the STAR (Stroke Thrombectomy and Aneurysm Registry). We compared functional outcomes of patients with FP (defined as modified treatment in cerebral ischemia score 3 after a single thrombectomy maneuver) versus multiple‐pass complete reperfusion (defined as modified treatment in cerebral ischemia 3 after ≥1 thrombectomy maneuver). Results A total of 1481 patients with anterior circulation large‐vessel occlusion stroke and successful recanalization were included in the analysis. FP complete recanalization was achieved in 778 patients versus 703 patients with multiple‐pass complete reperfusion. Patients with FP complete recanalization had higher Alberta Stroke Programme Early CT [Computed Tomography] Score at baseline (9 [7–10] versus 8 [7–10]; P=0.002), were less likely to be men (47% versus 51%; P=0.078) and to have intracranial internal carotid artery occlusions (14% versus 27%), as well as more likely to have M1/M2 occlusions (86% versus 73%; P
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- 2022
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21. A phase II trial of a soy beverage for subjects without clinical disease with rising prostate-specific antigen after radical radiation for prostate cancer
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Graeme Duncan, Winkle Kwan, Cheri Van Patten, Jan Lim, and Mitchell Liu
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Male ,Cancer Research ,medicine.medical_specialty ,Side effect ,Medicine (miscellaneous) ,Gastroenterology ,Prostate cancer ,Prostate ,Internal medicine ,medicine ,Doubling time ,Humans ,Testosterone ,Treatment Failure ,Aged ,Aged, 80 and over ,Nutrition and Dietetics ,business.industry ,Cancer ,Prostatic Neoplasms ,Middle Aged ,Prostate-Specific Antigen ,medicine.disease ,Isoflavones ,Surgery ,Soy Milk ,Prostate-specific antigen ,Kinetics ,medicine.anatomical_structure ,Oncology ,Tolerability ,Cohort ,business - Abstract
Our objective was to evaluate the tolerability and effect of a daily soy beverage in prostate cancer patients with biochemical failure after radiotherapy. Patients with rising prostate-specific antigen (PSA) after radical radiation for prostate cancer were instructed to consume 500 ml of soy beverage daily for 6 mo. Tolerability of the soy beverage and compliance were assessed. PSA doubling times before and after the consumption of soy were compared. Thirty-four subjects were enrolled; 5 withdrew before 1 mo of soy for reasons unrelated to soy consumption. All remaining 29 subjects were included in the analysis. Mean consumption of the assigned soy beverage was 93%. Mild gastrointestinal upset (38%) not affecting soy consumption was the commonest side effect. PSA showed a declining trend in 4 patients (13.8%), and there was a > 100% prolongation of PSA doubling time in 8 patients (27.6%). However, PSA doubling time also showed a 50% or more shortening in 5 patients (17.2%). In our cohort of North American subjects, 6 mo of a daily soy beverage was well tolerated and was associated with a declining trend or more than 2 times prolongation of PSA doubling time in 41% of subjects. Confirmatory studies are warranted.
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- 2010
22. Does neoadjuvant hormone therapy improve outcome in prostate cancer patients receiving radiotherapy after radical prostatectomy?
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Howard Huaihan, Pai, Brenna, Eldridge, Darcy, Bishop, Abraham, Alexander, Mary, Lesperance, Paul, Blood, Jan, Lim, and Charles, Ludgate
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Male ,Prostatectomy ,Salvage Therapy ,Prostatic Neoplasms ,Androgen Antagonists ,Radiotherapy Dosage ,Adenocarcinoma ,Middle Aged ,Prostate-Specific Antigen ,Neoadjuvant Therapy ,Treatment Outcome ,Humans ,Radiotherapy, Adjuvant ,Aged - Abstract
To assess outcome and predictive factors in men with prostate cancer who receive post radical prostatectomy (RP) radiotherapy (RT) either in the adjuvant or salvage setting, with or without neoadjuvant androgen deprivation therapy (NADT).A retrospective analysis was performed on 175 patients with clinically localized prostate cancer treated with RP who subsequently received RT (dose range 50 Gy-68 Gy). Twenty-two patients received adjuvant RT (ART), 57 received NADT + ART, 15 received salvage RT (SRT), and 81 received NADT + SRT. Outcome was assessed by biochemical disease free survival (BDFS), prostate cancer specific survival and overall survival (OS).Although BDFS favored patients who received NADT with 5 year rates of 67%, 80%, 27% and 62% for the ART, NADT + ART, SRT, and NADT + SRT groups respectively; this was not a significant predictor on multivariable analysis. Significant independent predictive factors of improved BDFS were pre-RT PSAor = 0.2 ng/ml, low Gleason score and positive surgical margins. Age and Gleason score were independent predictors of OS.Pre-RT PSA is an important predictor of outcome. NADT appears to benefit patients who presented with a pre-RT PSA0.2 ng/ml, particularly for patients receiving SRT. NADT can be considered for patients receiving RT after RP who present with a high pre-RT PSA but may not be necessary for patients without. Results of ongoing randomized studies such as RADICALS will also help clarify the role of hormone therapy in conjunction with RT.
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- 2009
23. Clinical Ethics Consultation in Neurology – a case series
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Benjamin Ilse, Bernd Alt-Epping, Albrecht Günther, Jan Liman, and Alfred Simon
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Clinical decision-making ,Clinical ethics consultation (CEC) ,Neurology ,Individual patient will ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background The concept of clinical ethics consultation (CECs) was implemented to provide support in ethical controversies in clinical settings and are offered in at least every second hospital in Germany. Neurological disorders often require complex decision-making. The aims of this study were to determine which situations lead to CEC in neurology and to investigate the influence of the individual patient’s wishes on the recommendation. Methods Standardised CEC protocols in the years 2011 to 2017 at the University Hospitals of Goettingen and Jena were retrospectively surveyed. The contents were categorised along existing protocol templates of CEC scenarios and subsequently paraphrased and reduced to significant meanings. Results 27 CEC scenarios which were facilitated by various professional disciplines were reviewed. Stroke was the most frequent underlying condition. Nearly all patients were not able to consent. Mostly, the relatives acted as representatives or health advocates. In 67 % of cases, a sense of conflict triggered a CEC; in 33 % a sense of uncertainty was the reason for the CEC request. In 21 CEC scenarios, a recommendation was reached in consensus with all parties involved. In 59 % of cases, a decision was made to continue medical therapy. In seven cases, the patient’s wishes led to a limitation of therapy, while in just two cases this decision was made primarily relying on the patient’s best interest. In only 13 % of cases, a valid advance directive led to respective therapeutic consequences. Conclusions CEC is feasible for consensus-finding not only in conflicts, but also in situations of therapeutic uncertainty in neurology. There is a special importance of the patient’s wishes in decision-making in neurology. However, only in a few cases were advance directives precise and specific enough to have sufficient and decisive weight in therapeutic decision-making.
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- 2021
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24. Comparing the diagnostic value of Echocardiography In Stroke (CEIS) – results of a prospective observatory cohort study
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Marlena Schnieder, Mohammed Chebbok, Michael Didié, Frieder Wolf, Mostafa Badr, Ibrahim Allam, Mathias Bähr, Gerd Hasenfuß, Jan Liman, and Marco Robin Schroeter
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Stroke ,Echocardiography ,Patent foramen ovale ,Cardio-embolic stroke ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Echocardiography is one of the main diagnostic tools for the diagnostic workup of stroke and is already well integrated into the clinical workup. However, the value of transthoracic vs. transesophageal echocardiography (TTE/TEE) in stroke patients is still a matter of debate. Aim of this study was to characterize relevant findings of TTE and TEE in the management of stroke patients and to correlate them with subsequent clinical decisions and therapies. Methods We evaluated n = 107 patients admitted with an ischemic stroke or transient ischemic attack to our stroke unit of our university medical center. They underwent TTE and TEE examination by different blinded investigators. Results Major cardiac risk factors were found in 8 of 98 (8.2%) patients and minor cardiac risk factors for stroke were found in 108 cases. We found a change in therapeutic regime after TTE or TEE in 22 (22.5%) cases, in 5 (5%) cases TEE leads to the change of therapeutic regime, in 4 (4%) TTE and in 13 cases (13.3%) TTE and TEE lead to the same change in therapeutic regime. The major therapy change was the indication to close a patent foramen ovale (PFO) in 9 (9.2%) patients with TTE and in 10 (10.2%) patients with TEE (p = 1.000). Conclusion Major finding with clinical impact on therapy change is the detection of PFO. But for the detection of PFO, TTE is non inferior to TEE, implicating that TTE serves as a good screening tool for detection of PFO, especially in young age patients. Trial registration The trial was registered and approved prior to inclusion by our local ethics committee (1/3/17).
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- 2021
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25. Hemoglobin levels do not predict biochemical outcome for localized prostate cancer treated with neoadjuvant androgen-suppression therapy and external-beam radiotherapy
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Scott Tyldesley, Graeme Duncan, Charmaine Kim-Sing, Winkle Kwan, Charles Ludgate, Howard Pai, Chuck Paltiel, Tom Pickles, Jan Lim, Mitchell Liu, Alex Agranovich, and Eric Berthelet
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Male ,Cancer Research ,medicine.medical_specialty ,Side effect ,Anemia ,medicine.medical_treatment ,Urology ,Androgen suppression ,Prostate cancer ,Prostate ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,External beam radiotherapy ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Analysis of Variance ,Radiation ,business.industry ,Prostatic Neoplasms ,Androgen Antagonists ,Hemoglobin A ,Radiotherapy Dosage ,Middle Aged ,Prostate-Specific Antigen ,medicine.disease ,Neoadjuvant Therapy ,Surgery ,Radiation therapy ,Prostate-specific antigen ,medicine.anatomical_structure ,Oncology ,business - Abstract
Purpose: To investigate whether hemoglobin (Hb) levels affect outcome in men with localized prostate adenocarcinoma (LPA) treated with neoadjuvant androgen-suppression therapy (NAST) and external-beam radiotherapy (EBRT). Methods and Materials: A total of 563 men with LPA treated with NAST (median: 5.3 months) and EBRT who had Hb levels during treatment were retrospectively reviewed. Patient, tumor, and treatment variables, including the following Hb variables, were subjected to univariate and multivariable analyses to identify factors that predict biochemical control (bNED) and overall survival (OS): pre-EBRT Hb, Hb nadir during EBRT, and change in Hb from pre-EBRT to nadir during EBRT. Results: Median PSA follow-up was 4.25 years. Forty-nine percent of men were anemic during EBRT, with a median Hb of 13.4 g/dL, and 68% experienced a decline in Hb from pre-EBRT to during EBRT of median 0.6 g/dL. Five-year Nadir + 2 bNED and OS rates were similar for anemic and nonanemic patients during EBRT. High percent-positive biopsies, PSA and Gleason score, and use of AA monotherapy predicted worse bNED. High stage and age predicted worse OS. Hb variables were not predictive of bNED or OS. Conclusions: Anemia is a common side effect of NAST and is usually mild. Hb levels, however, do not predict biochemical control or survival.
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- 2005
26. Bridging therapy is associated with improved cognitive function after large vessel occlusion stroke – an analysis of the German Stroke Registry
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Philipp Ettelt, Ilko L. Maier, Marlena Schnieder, Mathias Bähr, Daniel Behme, Marios-Nikos Psychogios, Jan Liman, and on behalf of the GSR-ET Collaborators
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Ischemic stroke ,LVOS ,Intravenous thrombolysis ,Mechanical thrombectomy ,Cognitive function ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background The targeted use of endovascular therapy (EVT), with or without intravenous thrombolysis (IVT) in acute large cerebral vessel occlusion stroke (LVOS) has been proven to be superior compared to IVT alone. Despite favorable functional outcome, many patients complain about cognitive decline after EVT. If IVT in addition to EVT has positive effects on cognitive function is unclear. Methods We analyzed data from the German Stroke Registry (GSR, an open, multicenter and prospective observational study) and compared cognitive function 90 days after index ischemic stroke using MoCA in patients with independent (mRS ≤ 2 pts) and excellent (mRS = 0 pts) functional outcome receiving combined EVT and IVT (EVT + IVT) vs. EVT alone (EVT-IVT). Results Of the 2636 GSR patients, we included 166 patients with mRS ≤ 2 at 90 days in our analysis. Of these, 103 patients (62%) received EVT + IVT, 63 patients (38%) were treated with EVT alone. There was no difference in reperfusion status between groups (mTICI ≥ 2b in both groups at 95%, p = 0.65). Median MoCA score in the EVT + IVT group was 20 pts. (18–25 IQR) vs. 18 pts. (16–21 IQR) in the EVT-IVT group (p = 0.014). There were more patients with cognitive impairment (defined as MoCA
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- 2020
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27. Predictive Factors for the Need of Tracheostomy in Patients With Large Vessel Occlusion Stroke Being Treated With Mechanical Thrombectomy
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Ilko L. Maier, Katarina Schramm, Mathias Bähr, Daniel Behme, Marios-Nikos Psychogios, and Jan Liman
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ischemic stroke ,mechanical thrombectomy (MT) ,large vessel occlusion (LVO) ,intensive care medicine (ICM) ,tracheostomy (TS) ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Patients with large vessel occlusion stroke (LVOS) eligible for mechanical thrombectomy (MT) are at risk for stroke- and non-stroke-related complications resulting in the need for tracheostomy (TS). Risk factors for TS have not yet been systematically investigated in this subgroup of stroke patients.Methods: Prospectively derived data from patients with LVOS and MT being treated in a large, academic neurological ICU (neuro-ICU) between 2014 and 2019 were analyzed in this single-center study. Predictive value of peri- and post-interventional factors, stroke imaging, and pre-stroke medical history were investigated for their potential to predict tracheostomy during ICU stay using logistic regression models.Results: From 635 LVOS-patients treated with MT, 40 (6.3%) underwent tracheostomy during their neuro-ICU stay. Patients receiving tracheostomy were younger [71 (62–75) vs. 77 (66–83), p < 0.001], had a higher National Institute of Health Stroke Scale (NIHSS) at baseline [18 (15–20) vs. 15 (10–19), p = 0.009] as well as higher rates of hospital acquired pneumonia (HAP) [39 (97.5%) vs. 224 (37.6%), p < 0.001], failed extubation [15 (37.5%) vs. 19 (3.2%), p < 0.001], sepsis [11 (27.5%) vs. 16 (2.7%), p < 0.001], symptomatic intracerebral hemorrhage [5 (12.5%) vs. 22 (3.9%), p = 0.026] and decompressive hemicraniectomy (DH) [19 (51.4%) vs. 21 (3.8%), p < 0.001]. In multivariate logistic regression analysis, HAP (OR 21.26 (CI 2.76–163.56), p = 0.003], Sepsis [OR 5.39 (1.71–16.91), p = 0.004], failed extubation [OR 8.41 (3.09–22.93), p < 0.001] and DH [OR 9.94 (3.92–25.21), p < 0.001] remained as strongest predictors for TS. Patients with longer periods from admission to TS had longer ICU length of stay (r = 0.384, p = 0.03). There was no association between the time from admission to TS and clinical outcome (NIHSS at discharge: r = 0.125, p = 0.461; mRS at 90 days: r = −0.179, p = 0.403).Conclusions: Patients with LVOS undergoing MT are at high risk to require TS if extubation after the intervention fails, DH is needed, and severe infectious complications occur in the acute phase after ischemic stroke. These factors are likely to be useful for the indication and timing of TS to reduce overall sedation and shorten ICU length of stay.
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- 2021
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28. Intracranial mechanical thrombectomy of large vessel occlusions in the posterior circulation using SAVE
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Volker Maus, Hanna Styczen, Jan Liman, Ilko Maier, Alex Brehm, Ioannis Tsogkas, and Marios-Nikos Psychogios
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Acute ischemic stroke ,Posterior circulation stroke ,Mechanical thrombectomy ,SAVE ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Mechanical thrombectomy (MT) using stent retriever assisted vacuum-locked extraction (SAVE) is a promising method for anterior circulation strokes. We present our experience with SAVE for large vessel occlusions (LVO) of the posterior circulation. Methods We retrospectively analyzed 66 consecutive MT patients suffering from LVO of the posterior circulation. Primary endpoints were first-pass and overall complete/near complete reperfusion, defined as a modified thrombolysis in cerebral infarction (mTICI) score of 2c and 3. Secondary endpoints contained number of passes, time interval from groin puncture to reperfusion and rate of postinterventional symptomatic intracranial hemorrhage (sICH). Results Median age was 75 years (interquartile range (IQR) 54–81 years). Baseline median National Institutes of Health stroke scale (NIHSS) was 13 (IQR 8–21). Fifty-five (83%) patients had LVO of the basilar artery and 11 (17%) of the posterior cerebral artery. Eighteen (27%) patients were treated with SAVE and 21 (32%) with aspiration only. First pass mTICI2c or 3 and overall mTICI2c or 3 were documented in 11/18 (61%) and 14/18 (78%) with SAVE and in 4/21 (19%) and 13/21 (33%) with aspiration only. Median attempt was 1 (IQR 1–2) with SAVE and 2 (IQR 1–4) with aspiration (p = 0.0249). Median groin to reperfusion time did not differ significantly between groups. The rate of sICH was 5% without any complications in the SAVE cohort. Conclusion Mechanical thrombectomy of posterior large vessel occlusions with SAVE is feasible, safe, and effective with high rates of near-complete and complete reperfusion.
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- 2019
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29. EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry
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Charles B L M Majoie, Patrik Michel, Marcel Arnold, Jan Gralla, Urs Fischer, Jan F Scheitz, Didier Leys, Peter Arthur Ringleb, Daniel Strbian, David J Seiffge, George Ntaios, Andreas Kastrup, Ronen R Leker, José E Cohen, Nicolas Bricout, Alex Brehm, Hilde Henon, Zsolt Kulcsar, Turgut Tatlisumak, Alexandros Rentzos, Katarina Jood, Nicolas Martinez-Majander, Alessandro Pezzini, Ashraf Eskandari, Jan Liman, Katharina Feil, Lars Kellert, Markus Möhlenbruch, Georg Bohner, Marios Psychogios, Mauro Magoni, Annika Nordanstig, Andrea Zini, Henrik Gensicke, Sanne M Zinkstok, Sami Curtze, Christian Hametner, Visnja Padjen, Susanne Wegener, Georg Kägi, Christian H Nolte, Jan-Erik Karlsson, Camilla Karlsson, Christopher Traenka, Hebun Erdur, Johannes Weber, Stefan Engelter, Gerli Sibolt, Philippe Lyrer, Merih I Baharoglu, Hakan Sarikaya, Dejana R Jovanovic, Andreas Luft, Kimmo Lappalainen, John Gomori, Ivan Vukasinovic, Vladimir Cvetic, Eftychia Kapsalaki, and Paul J J Nederkoorn
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Medicine - Abstract
Purpose The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.Participants All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Findings to date Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.Future plans This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
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- 2021
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30. Inhouse Bridging Thrombolysis Is Associated With Improved Functional Outcome in Patients With Large Vessel Occlusion Stroke: Findings From the German Stroke Registry
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Ilko L. Maier, Andreas Leha, Mostafa Badr, Ibrahim Allam, Mathias Bähr, Ala Jamous, Amelie Hesse, Marios-Nikos Psychogios, Daniel Behme, and Jan Liman
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ischemic stroke ,LVOS ,bridging ,endovascular treatment ,rtPA ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Endovascular treatment (EVT) for large vessel occlusion stroke (LVOS) is highly effective. To date, it remains controversial if intravenous thrombolysis (IVT) prior to EVT is superior compared with EVT alone. The aim of our study was to specifically address the question, whether bridging IVT directly prior to EVT has additional positive effects on reperfusion times, successful reperfusion, and functional outcomes compared with EVT alone.Methods: Patients with LVOS in the anterior circulation eligible for EVT with and without prior IVT and direct admission to endovascular centers (mothership) were included in this multicentric, retrospective study. Patient data was derived from the German Stroke Registry (an open, multicenter, and prospective observational study). Outcome parameters included groin-to-reperfusion time, successful reperfusion [defined as a Thrombolysis in Cerebral Infarction (TICI) scale 2b-3], change in National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and mortality at 90 days.Results: Of the 881 included mothership patients with anterior circulation LVOS, 486 (55.2%) received bridging therapy with i.v.-rtPA prior to EVT, and 395 (44.8%) received EVT alone. Adjusted, multivariate linear mixed effect models revealed no difference in groin-to-reperfusion time between the groups (48 ± 36 vs. 49 ± 34 min; p = 0.299). Rates of successful reperfusion (TICI ≥ 2b) were higher in patients with bridging IVT (fixed effects estimate 0.410, 95% CI, 0.070; 0.750, p = 0.018). There was a trend toward a higher improvement in the NIHSS during hospitalization [ΔNIHSS: bridging-IVT group 8 (IQR, 9.8) vs. 4 (IQR 11) points in the EVT alone group; fixed effects estimate 1.370, 95% CI, −0.490; 3.240, p = 0.149]. mRS at 90 days follow-up was lower in the bridging IVT group [3 (IQR, 4) vs. 4 (IQR, 4); fixed effects estimate −0.350, 95% CI, −0.680; −0.010, p = 0.041]. There was a non-significantly lower 90 day mortality in the bridging IVT group compared with the EVT alone group (22.4% vs. 33.6%; fixed effects estimate 0.980, 95% CI −0.610; 2.580, p = 0.351). Rates of any intracerebral hemorrhage did not differ between both groups (4.1% vs. 3.8%, p = 0.864).Conclusions: This study provides evidence that bridging IVT might improve rates of successful reperfusion and long-term functional outcome in mothership patients with anterior circulation LVOS eligible for EVT.
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- 2021
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31. P-64 The timeliness of diagnosis, staging and treatment in patients with limited stage small cell lung cancer (L-SCLC): A population-based analysis
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Pauline T. Truong, Mary Lesperance, Eric Berthelet, Jan Lim, Mary V. MacNeil, and Jane Ludbrook
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Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Limited stage small cell lung cancer ,In patient ,Population based ,business - Published
- 2003
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32. Enlarged Area of Mesencephalic Iron Deposits in Adults Who Stutter
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Jan Liman, Alexander Wolff von Gudenberg, Mathias Baehr, Walter Paulus, Nicole E. Neef, and Martin Sommer
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stuttering ,mesencephalic iron ,transcranial ultrasound ,dopamine ,finger tapping ,walking ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
PurposeChildhood onset speech fluency disorder (stuttering) is possibly related to dopaminergic dysfunction. Mesencephalic hyperechogenicity (ME) detected by transcranial ultrasound (TCS) might be seen as an indirect marker of dopaminergic dysfunction. We here determined whether adults who stutter since childhood (AWS) show ME.MethodsWe performed TCS in ten AWS and ten matched adults who never stuttered. We also assessed motor performance in finger tapping and in the 25 Foot Walking test.ResultsCompared to controls, AWS showed enlarged ME on either side. Finger tapping was slower in AWS. Walking cadence, i.e., the ratio of number of steps by time, tended to be higher in AWS than in control participants.DiscussionThe results demonstrate a motor deficit in AWS linked to dopaminergic dysfunction and extending beyond speech. Since iron deposits evolve in childhood and shrink thereafter, ME might serve as an easily quantifiable biomarker helping to predict the risk of persistency in children who stutter.
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- 2021
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33. Preliminary report of a multi center canadian phase III randomized trial of 3 months vs 8 months neoadjuvant androgen ablation prior to standard dose radiotherapy for clinically localized prostate cancer
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Juanita Crook, J. Bowen, Libni Eapen, Shawn Malone, Jan Lim, Charles Ludgate, Gina Lockwood, Susan J. Robertson, and G. Perry
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Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,medicine.drug_class ,business.industry ,medicine.medical_treatment ,Urology ,Androgen ,Ablation ,medicine.disease ,law.invention ,Radiation therapy ,Prostate cancer ,Randomized controlled trial ,Preliminary report ,law ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,business - Published
- 2002
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34. T1 Mapping Quantifies Spinal Cord Compression in Patients With Various Degrees of Cervical Spinal Canal Stenosis
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Ilko L. Maier, Sabine Hofer, Eva Eggert, Katharina Schregel, Marios-Nikos Psychogios, Jens Frahm, Mathias Bähr, and Jan Liman
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cervical spinal canal stenosis ,cervical spondylotic myelopathy ,spinal cord compression ,MRI ,T1 mapping ,T1 relaxometry ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Age-related degeneration of the cervical spinal column is the most common cause of spinal cord lesions. T1 mapping has been shown to indicate the grade and site of spinal cord compression in low grade spinal canal stenosis (SCS). Aim of our study was to further investigate the diagnostic potential of a novel T1 mapping method at 0.75 mm resolution and 4 s acquisition time in 31 patients with various grades of degenerative cervical SCS. T1 mapping was performed in axial sections of the stenosis as well as above and below. Included subjects received standard T2-weighted MRI of the cervical spine (including SCS-grading 0-III), electrophysiological, and clinical examination. We found that patients with cervical SCS showed a significant difference in T1 relaxation times within the stenosis (727 ± 66 ms, mean ± standard deviation) in comparison to non-stenotic segments above (854 ± 104 ms, p < 0.001) and below (893 ± 137 ms, p < 0.001). There was no difference in mean T1 in non-stenotic segments in patients (p = 0.232) or between segments in controls (p = 0.272). Mean difference of the T1 relaxation times was significantly higher in grade III stenosis (234 ± 45) vs. in grade II stenosis (176 ± 45, p = 0.037) vs. in grade I stenosis (90 ± 87 ms, p = 0.010). A higher difference in T1 relaxation time was associated with a central efferent conduction deficit. In conclusion, T1 mapping may be useful as a tool for SCS quantification in all grades of SCS, including high-grade stenosis with myelopathy signal in conventional T2-weighted imaging.
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- 2020
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35. CARASIL with coronary artery disease and distinct cerebral microhemorrhage: A case report and literature review
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Sebastian J Müller, Eya Khadhraoui, Ibrahim Allam, Loukas Argyriou, Ute Hehr, Jan Liman, Gerd Hasenfuß, Mathias Bähr, Christian H Riedel, and Jan C Koch
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL, Maeda syndrome) is an extremely rare autosomal-recessive genetic disorder with a serious arteriopathy causing subcortical infarcts and leukoencephalopathy. In less than 20 cases, a genetic mutation was proven. Patients suffer from alopecia, disc herniations, and spondylosis. Between the age of 30 and 40, the patients typically develop severe cerebral infarcts. Clinical symptoms, genetic study, magnetic resonance imaging (MRI), and coronary angiography of a patient with proven CARASIL are presented. The patient showed the typical phenotype with cerebral small-vessel disease, cerebral infarcts, spondylosis, and abnormal hair loss. Additionally, distinct cerebral microhemorrhage and a severe coronary artery disease (CAD) were found, which have not been reported before for CARASIL. Mutation screening revealed the presence of a homozygous c.1022G > T substitution in the HTRA1 gene. Evidence from other publications supports a pathogenetic link between the HTRA1 mutation and CAD as a new feature of CARASIL. This is the first report about CARASIL with a concomitant severe CAD. Thus, in patients with CARASIL, other vessel diseases should also be considered.
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- 2020
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36. Outcome Prediction Using Perfusion Parameters and Collateral Scores of Multi-Phase and Single-Phase CT Angiography in Acute Stroke: Need for One, Two, Three, or Thirty Scans?
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Katharina Schregel, Ioannis Tsogkas, Carolin Peter, Antonia Zapf, Daniel Behme, Marlena Schnieder, Ilko L. Maier, Jan Liman, Michael Knauth, and Marios-Nikos Psychogios
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acute stroke ,collateral circulation ,perfusion ,computed tomography angiography ,treatment outcome ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background and Purpose Collateral status is an important factor determining outcome in acute ischemic stroke (AIS). Hence, different collateral scoring systems have been introduced. We applied different scoring systems on single- and multi-phase computed tomography (CT) angiography (spCTA and mpCTA) and compared them to CT perfusion (CTP) parameters to identify the best method for collateral evaluation in patients with AIS. Methods A total of 102 patients with AIS due to large vessel occlusion in the anterior circulation who underwent multimodal CT imaging and who were treated endovascularly were included. Collateral status was assessed on spCTA and mpCTA using four different scoring systems and compared to CTP parameters. Logistic regression was performed for predicting favorable outcome. Results All collateral scores correlated well with each other and with CTP parameters. Comparison of collateral scores stratified by extent of perfusion deficit showed relevant differences between groups (P
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- 2018
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37. Transcranial doppler sonography is not a valid diagnostic tool for detection of basilar artery stenosis or in-stent restenosis: a retrospective diagnostic study
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Woori Koh, Kai Kallenberg, André Karch, Tobias Frank, Michael Knauth, Mathias Bähr, and Jan Liman
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Doppler sonography ,Duplex sonography ,Basilar artery stenosis ,In stent restenosis ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background There are contradictory reports concerning the validity of transcranial sonography (TCD and TCCS) for examinations of the basilar artery. Here we investigated sensitivity and specificity of transcranial sonography for the detection of basilar artery stenosis and in-stent-restenosis compared to cerebral angiography. Methods We analyzed data of 104 examinations of the basilar artery. The association between sonographic peak systolic velocity (PSV) and degree of stenosis obtained by cerebral angiography was evaluated applying Spearman’s correlation coefficient. Receiver Operating Characteristics (ROC) curves and areas under the curve (AUC) were calculated for the detection of a ≥50% stenosis defined by angiography. Optimal cut-off was derived using the Youden-index. Results A weak but statistically significant correlation between PSV and the degree of stenosis was found (n=104, rho=0.35, p
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- 2017
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38. Quantification of spinal cord compression using T1 mapping in patients with cervical spinal canal stenosis – Preliminary experience
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Ilko L. Maier, Sabine Hofer, Arun A. Joseph, K. Dietmar Merboldt, Eva Eggert, Daniel Behme, Katharina Schregel, Christian von der Brelie, Veit Rohde, Jan Koch, Marios-Nikos Psychogios, Jens Frahm, Jan Liman, and Mathias Bähr
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Degenerative changes of the cervical spinal column are the most common cause of spinal cord lesions in the elderly. Conventional clinical, electrophysiological and radiological diagnostics of spinal cord compression are often inconsistent. Materials and methods: The feasibility and diagnostic potential of a novel T1 mapping method at 0.5 mm resolution and 4 s acquisition time was evaluated in 14 patients with degenerative cervical spinal canal stenosis (SCS) and 6 healthy controls. T1 mapping was performed in axial sections of the stenosis as well as above and below. All subjects received standard T2-weighted MRI of the cervical spine (including SCS-grading 0-III), electrophysiological and clinical examinations. Results: Patients revealed significantly decreased T1 relaxation times of the compressed spinal cord within the SCS (912 ± 53 ms, mean ± standard deviation) in comparison to unaffected segments above (1027 ± 39 ms, p
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- 2019
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39. The cardiac diagnostic work-up in stroke patients-A subanalysis of the Find-AFRANDOMISED trial.
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Katrin Wasser, Mark Weber-Krüger, Falko Jürries, Jan Liman, Gerhard F Hamann, Pawel Kermer, Timo Uphaus, Evgeny Protsenko, Joachim Seegers, Meinhard Mende, Klaus Gröschel, and Rolf Wachter
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Medicine ,Science - Abstract
BackgroundThe cardiac diagnostic workup of stroke patients, especially the value of echocardiography and enhanced and prolonged Holter-ECG monitoring, is still a matter of debate. We aimed to analyse the impact of pathologies detected by echocardiography and ECG monitoring on therapeutic decisions and prognosis.MethodsFind-AFRANDOMISED was a prospective multicenter study which randomised 398 acute ischemic stroke patients ≥ 60 years to enhanced and prolonged Holter-ECG monitoring or usual stroke unit care. This substudy compared therapeutic consequences of echocardiography and routine Holter-ECG or enhanced and prolonged Holter-ECG monitoring, respectively, and prognosis of patients with or without pathologic findings in echocardiography or Holter-ECG monitoring.Results50.3% received enhanced and prolonged Holter-ECG monitoring and 49.7% routine ECG monitoring. 82.9% underwent transthoracic echocardiography (TTE), 38.9% transesophageal echocardiography (TEE) and 25.6% both procedures. 14/89 TEE pathologies and 1/90 TTE pathology led to a change in therapy, resulting in a number needed to change decision (NNCD) of 12 and 330 (p < 0.001), respectively. In comparison, enhanced and prolonged Holter-ECG monitoring found atrial fibrillation (AF) in 27 of 200 patients, and routine ECG monitoring in twelve of 198 patients, leading to therapeutic changes in all patients (NNCD 8 and 17, respectively, p < 0.001).ConclusionsMost changes in therapeutic decisions were triggered by enhanced and prolonged Holter-ECG monitoring, which should therefore play a more prominent role in future guidelines. Echocardiography identifies a patient group at high cardiovascular risk, but rarely result in therapeutic changes. Whether this patient group requires further cardiovascular workup remains unknown. This should be further investigated by interdisciplinary neurocardiologic teams and in appropriate future trials.Trial registrationClinicalTrials.gov NCT01855035.
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- 2019
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40. Validation of the extended thrombolysis in cerebral infarction score in a real world cohort.
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Daniel Behme, Ioannis Tsogkas, Ruben Colla, Roland G Gera, Katharina Schregel, Amélie C Hesse, Ilko L Maier, Jan Liman, David S Liebeskind, and Marios-Nikos Psychogios
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Medicine ,Science - Abstract
BackgroundA thrombolysis in cerebral infarction (TICI) score of 2b is defined as a good recanalization result although the reperfusion may only cover 50% of the affected territory. An additional mTICI2c category was introduced to further differentiate between mTICI scores. Despite the new mTICI2c category, mTICI2b still covers a range of 50-90% reperfusion which might be too imprecise to predict neurological improvement after therapy.AimTo compare the 7-point "expanded TICI" (eTICI) scale with the traditional mTICI in regard to predict functional independence at 90 days.MethodsRetrospective review of 225 patients with large artery occlusion. Angiograms were graded by 2 readers according the 7-point eTICI score (0% = eTICI0; reduced clot = eTICI1; 1-49% = eTICI2a, 50-66% = eTICI2b50; 67-89% = eTICI2b67, 90-99% = eTICI2c and complete reperfusion = eTICI3) and the conventional mTICI score. The ability of e- and mTICI to predict favorable outcome at 90days was compared.ResultsGiven the ROC analysis eTICI was the better predictor of favorable outcome (p-value 0.047). Additionally, eTICI scores 2b50, 2b67 and 2c (former mTICI2b) were significantly superior at predicting the probability of a favorable outcome at 90 days after endovascular therapy with a p-value of 0.033 (probabilities of 17% for mTICI2b50, 24% for mTICI2b67 and 54% for mTICI2c vs. 36% for mTICI2b).ConclusionsThe 7-point eTICI allows for a more accurate outcome prediction compared to the mTICI score because it refines the broad range of former mTICI2b results.
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- 2019
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41. Heart Failure Is Not Associated with a Poor Outcome after Mechanical Thrombectomy in Large Vessel Occlusion of Cerebral Arteries
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Marlena Schnieder, Anneki von Glasenapp, Amelie Hesse, Marios N. Psychogios, Mathias Bähr, Gerd Hasenfuß, Marco R. Schroeter, and Jan Liman
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
The impact of heart failure on outcome in stroke patients is not fully understood. There is evidence for an increased mortality and morbidity, but it remains uncertain whether thrombectomy in patients with large vessel occlusion (LVO) in the anterior circulation is less effective in patients with heart failure compared to patients without. Retrospectively, we analyzed echocardiographic data of all patients in our stroke database, who underwent mechanical thrombectomy (n=668) for the presence of heart failure. Furthermore, we collected baseline characteristics and neurological and neuroradiological parameters. In the analysis, 373 of the 668 patients of our stroke database underwent echocardiography. Of these 373 patients, 90 patients (24%) suffered from heart failure with reduced left ventricular ejection fraction measured by echocardiography according to the current guidelines. After adjustment for age, the Alberta stroke program early CT score (ASPECTS), and time from symptom onset to recanalization, the analysis revealed that thrombectomy in patients with heart failure and LVO is not associated with less favorable outcome measured by the modified Rankin Scale after 90 days (3 (0-6) vs. 3 (1-5); p=0.380). Moreover, we could not find a significant difference in mortality compared to patients without heart failure (11.0% vs. 7.4%; p=0.313).
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- 2019
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42. Influence of beta-blocker therapy on the risk of infections and death in patients at high risk for stroke induced immunodepression.
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Ilko L Maier, Johannes C Becker, Johanna Rosemarie Leyhe, Marlena Schnieder, Daniel Behme, Marios-Nikos Psychogios, and Jan Liman
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Medicine ,Science - Abstract
Stroke-induced immunodepression is a well characterized complication of acute ischemic stroke. In experimental studies beta-blocker therapy reversed stroke-induced immunodepression, reduced infection rates and mortality. Recent, heterogeneous studies in stroke patients could not provide evidence of a protective effect of beta-blocker therapy. Aim of this study is to investigate the potential preventive effect of beta-blockers in subgroups of patients at high risk for stroke-induced immunodepression.Data from a prospectively derived registry of major stroke patients receiving endovascular therapy between 2011-2017 in a tertiary stroke center (University Medical Center Göttingen. Germany) was used. The effect of beta-blocker therapy on pneumonia, urinary tract infection, sepsis and mortality was assessed using multivariate logistic regression analysis.Three hundred six patients with a mean age of 72 ± 13 years and a median NIHSS of 16 (IQR 10.75-20) were included. 158 patients (51.6%) had pre-stroke- and continued beta-blocker therapy. Beta-blocker therapy did not reduce the incidence of pneumonia (OR 0.78, 95% CI 0.31-1.92, p = 0.584), urinary tract infections (OR 1.51, 0.88-2.60, p = 0.135), sepsis (OR 0.57, 0.18-1.80, p = 0.334) or mortality (OR 0.59, 0.16-2.17, p = 0.429). Strokes involving the insula and anterio-medial cortex increased the risk for pneumonia (OR 4.55, 2.41-8.56, p
- Published
- 2018
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43. Early computed tomography-based scores to predict decompressive hemicraniectomy after endovascular therapy in acute ischemic stroke.
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Ilko L Maier, Daniel Behme, Marlena Schnieder, Ioannis Tsogkas, Katharina Schregel, Mathias Bähr, Michael Knauth, Jan Liman, and Marios-Nikos Psychogios
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Medicine ,Science - Abstract
BACKGROUND:Identification of patients requiring decompressive hemicraniectomy (DH) after endovascular therapy (EVT) is crucial as clinical signs are not reliable and early DH has been shown to improve clinical outcome. The aim of our study was to identify imaging-based scores to predict the risk for space occupying ischemic stroke and DH. METHODS:Prospectively derived data from patients with acute large artery occlusion within the anterior circulation and EVT was analyzed in this monocentric study. Predictive value of non-contrast cranial computed tomography (ncCT) and cerebral blood volume (CBV) Alberta Stroke Program Early CT score (ASPECTS) were investigated for DH using logistic regression models and Receiver Operating Characteristic Curve analysis. RESULTS:From 218 patients with EVT, DH was performed in 20 patients (9.2%). Baseline- (7 vs. 9; p = 0.009) and follow-up ncCT ASPECTS (1 vs. 7, p
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- 2017
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44. Association between Embolic Stroke Patterns, ESUS Etiology, and New Diagnosis of Atrial Fibrillation: A Secondary Data Analysis of the Find-AF Trial
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Ilko L. Maier, Katharina Schregel, André Karch, Mark Weber-Krueger, Rafael T. Mikolajczyk, Raoul Stahrenberg, Klaus Gröschel, Mathias Bähr, Michael Knauth, Marios-Nikos Psychogios, Rolf Wachter, and Jan Liman
- Subjects
Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background. Atrial fibrillation (AF) is an important cause of embolic stroke of undetermined source (ESUS). Imaging-patterns like multiple infarcts, simultaneous involvement of different circulations, infarcts of different ages, and isolated cortical infarcts are likely to indicate cardioembolic stroke. The aim of our study was to evaluate the association between embolic stroke patterns, ESUS, and the new diagnosis of AF. Methods. Stroke etiology and imaging characteristics from patients included in the Find-AF study were obtained. Embolic stroke patterns in CT- or MR-imaging were correlated with the diagnosis of ESUS as well as the short- (on baseline ECG and during 7-day Holter) and long-term (12-month follow-up) diagnosis of AF. Results. From 281 patients included in the Find-AF study, 127 (45.2%) patients with ischemic lesions detected in CT or MRI were included. 26 (20.5%) of these patients had ESUS. At least one embolic stroke pattern was detected in 67 (52.7%) patients. Embolic stroke patterns were not associated with ESUS (OR 1.57, 0.65–3.79, p=0.317), the short-term (OR 0.64, 0.26–1.58, p=0.327) or long-term diagnosis of AF (OR 0.72, 0.31–1.68, p=0.448). Conclusions. This secondary data analysis of the Find-AF study could not provide evidence for an association between embolic stroke patterns, ESUS, and the new diagnosis of AF.
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- 2017
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45. Modulation of Huntingtin Toxicity by BAG1 is Dependent on an Intact BAG Domain
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Mathias Bähr, Pawel Kermer, Sebastian Deeg, Christoph P. Dohm, Kamila Sroka, and Jan Liman
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BAG1 ,Huntington’s disease ,Chaperone system ,Siah1 ,Organic chemistry ,QD241-441 - Abstract
Huntington´s disease, one of the so-called poly-glutamine diseases, is a dominantly inherited movement disorder characterized by formation of cytosolic and nuclear inclusion bodies and progressive neurodegeneration. Recently, we have shown that Bcl-2-associated athanogene-1 (BAG1), a multifunctional co-chaperone, modulates toxicity, aggregation, degradation and subcellular distribution in vitro and in vivo of the disease-specific mutant huntingtin protein. Aiming at future small molecule-based therapeutical approaches, we further analysed structural demands for these effects employing the C-terminal deletion mutant BAGDC. We show that disruption of the BAG domain known to eliminate intracellular heat shock protein 70 (Hsp70) binding and activation also precludes binding of Siah-1 thereby leaving nuclear huntingtin translocation unaffected. At the same time BAGDC fails to induce increased proteasomal huntingtin turnover and does not inhibit intracellular huntingtin aggregation, a pre-requisite necessary for prevention of huntingtin toxicity.
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- 2010
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46. Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration
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Jan Liman, Jochen H. Weishaupt, Mathias Bähr, and Gunnar P.H. Dietz
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Cdk5 ,Tat-technique ,neurodegenerative diseases ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Cdk5 is essential for neuronal differentiation processes in the brain. Activation of Cdk5 requires the association with the mostly neuron-specific p35 or p39. Overactivation of CDK5 by cleavage of p35 into p25 is thought to be involved in neurodegenerative processes. Here, we have tested an approach to inhibit pathological Cdk5 activation with a Tat-linked dominant-negative fragment of p25. It reduced cell death induced by staurosporine and showed a tendency to alleviate manganese-induced cell death, while it did not protect against 6-OHDA toxicity. Our results suggest that the Tat technique is a suitable tool to inhibit dysregulated CDK5.
- Published
- 2010
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47. Effects of Workflow Optimization in Endovascularly Treated Stroke Patients - A Pre-Post Effectiveness Study.
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Katharina Schregel, Daniel Behme, Ioannis Tsogkas, Michael Knauth, Ilko Maier, André Karch, Rafael Mikolajczyk, José Hinz, Jan Liman, and Marios-Nikos Psychogios
- Subjects
Medicine ,Science - Abstract
Endovascular treatment of acute ischemic stroke has become standard of care for patients with large artery occlusion. Early restoration of blood flow is crucial for a good clinical outcome. We introduced an interdisciplinary standard operating procedure (SOP) between neuroradiologists, neurologists and anesthesiologists in order to streamline patient management. This study analyzes the effect of optimized workflow on periprocedural timings and its potential influence on clinical outcome. Data were extracted from a prospectively maintained university hospital stroke database. The standard operating procedure was established in February 2014. Of the 368 acute stroke patients undergoing endovascular treatment between 2008 and 2015, 278 patients were treated prior to and 90 after process optimization. Outcome measures were periprocedural time intervals and residual functional impairment. After implementation of the SOP, time from symptom onset to reperfusion was significantly reduced (median 264 min prior and 211 min after SOP-introduction (IQR 228-32 min and 161-278 min, respectively); P
- Published
- 2016
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48. Effect of beta-blocker therapy on the risk of infections and death after acute stroke--a historical cohort study.
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Ilko L Maier, André Karch, Rafael Mikolajczyk, Mathias Bähr, and Jan Liman
- Subjects
Medicine ,Science - Abstract
BACKGROUND:Infections are a frequent cause for prolonged hospitalization and increased mortality after stroke. Recent studies revealed a stroke-induced depression of the peripheral immune system associated with an increased susceptibility for infections. In a mice model for stroke, this immunosuppressive effect was reversible after beta-blocker administration. The aim of our study was to investigate the effect of beta-blocker therapy on the risk of infections and death after stroke in humans. METHODS:625 consecutive patients with ischemic or hemorrhagic stroke, admitted to a university hospital stroke unit, were included in this historical cohort study. The effect of beta-blocker therapy on post-stroke pneumonia, urinary tract infections and death was investigated using multivariable Poisson and Cox regression models. RESULTS:553 (88.3%) patients were admitted with ischemic stroke, the remaining 72 (11.7%) had a hemorrhagic stroke. Median baseline NIHSS was 8 (IQR 5-16) points. 301 (48.2%) patients received beta-blocker therapy. There was no difference in the risk of post-stroke pneumonia between patients with and without beta-blocker therapy (Rate Ratio = 1.00, 95%CI 0.77-1.30, p = 0.995). Patients with beta-blocker therapy showed a decreased risk for urinary tract infections (RR = 0.65, 95%CI 0.43-0.98, p = 0.040). 7-days mortality did not differ between groups (Hazard Ratio = 1.36, 95%CI 0.65-2.77, p = 0.425), while patients with beta-blocker therapy showed a higher 30-days mortality (HR = 1.93, 95%CI 1.20-3.10, p = 0.006). CONCLUSIONS:Beta-blocker therapy did not reduce the risk for post-stroke pneumonia, but significantly reduced the risk for urinary tract infections. Different immune mechanisms underlying both diseases might explain these findings that need to be confirmed in future studies.
- Published
- 2015
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