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  • 1
    In: The Thoracic and Cardiovascular Surgeon, 2019, Vol.67(04)
    In: The Thoracic and Cardiovascular Surgeon, 2017, Vol.67(04), pp.236-242
    Description: BACKGROUND The latest generation of balloon-expandable valve, the Edwards Sapien 3 valve (S3V), was designed to reduce paravalvular regurgitation (PVR). We retrospectively compared S3V with Edwards Sapien XT valve (SXTV) with regard to postprocedural transvalvular pressure gradients (PGs). METHODS Analysis of 152 patients receiving SXTV and 125 patients receiving S3V between February 2009 and April 2015 was performed. Transvalvular PGs and the incidence and extent of aortic regurgitation (AR) were compared postprocedurally by echocardiography for each valve size. RESULTS Postprocedurally, mean PGs for the 23 mm valves were 10.9 ± 5.3 versus 13.9 ± 5.1 (p = 0.017), whereas maximum PGs were 19.9 ± 8.3 versus 26.1 ± 10.4 mm Hg (p = 0.005) in SXTV and S3V patients, respectively. For the 26 mm valves, gradients were also significantly higher in S3V patients (mean PG: 11.6 ± 4.9 vs. 9.2 ± 4.2 [p = 0.004]; maximum PG: 23.0 ± 10.1 vs. 17.2 ± 7.4 mm Hg [p 〈 0.001]). Analysis revealed no significant differences in postprocedural transvalvular PGs for 29 mm valves (mean PG of 9.3 ± 3.9 and 11.2 ± 4.3 mm Hg [p = ns] and maximum PG of 17.5 ± 7.2 vs. 20.9 ± 6.8 mm Hg [p = ns]) between SXTV and S3V groups, respectively. With respect to PVR, the incidence of AR was significantly lower in S3V group (p = 0.001). CONCLUSION S3V shows lower incidence of PVR; however, it is associated with significantly higher postprocedural transvalvular PGs for 23 and 26 mm valve sizes. These data might contribute to the scientific discussion, especially with respect to prosthesis selection in individual patients with small annular dimension.
    Keywords: Aorta/aortic ; Echocardiography ; Heart ; Valve ; Transapical ; Percutaneous
    ISSN: 0171-6425
    E-ISSN: 1439-1902
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  • 2
    In: PLoS ONE, 2017, Vol.12(8)
    Description: Objectives To quantitatively and qualitatively assess abdominal arterial and venous phase contrast-enhanced spectral detector computed tomography (SDCT) virtual mono-energetic (MonoE) datasets in comparison to conventional CT reconstructions provided by the same system. Materials and methods Conventional and MonoE images at 40–120 kilo-electron volt (keV) levels with a 10 keV increment as well as 160 and 200 keV were reconstructed in abdominal SDCT datasets of 55 patients. Attenuation, image noise, and contrast- / signal-to-noise ratios (CNR, SNR) of vessels and solid organs were compared between MonoE and conventional reconstructions. Two readers assessed contrast conditions, detail visualization, overall image quality and subjective image noise with both, fixed and adjustable window settings. Results Attenuation, CNR and SNR of vessels and solid organs showed a stepwise increase from high to low keV reconstructions in both contrast phases while image noise stayed stable at low keV MonoE reconstruction levels. Highest levels were found at 40 keV MonoE reconstruction (p〈0.001), respectively. Solid abdominal organs showed a stepwise decrease from low to high energy levels in regard to attenuation, CNR and SNR with significantly higher values at 40 and 50 keV, compared to conventional images. The 70 keV MonoE was comparable to conventional poly-energetic reconstruction (p≥0.99). Subjective analysis displayed best image quality for the 70 keV MonoE reconstruction level in both phases at fixed standard window presets and at 40 keV if window settings could be adjusted. Conclusion SDCT derived low keV MonoE showed markedly increased CNR and SNR values due to constantly low image noise values over the whole energy spectrum from 40 to 200 keV.
    Keywords: Research Article ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Research And Analysis Methods ; Biology And Life Sciences ; Medicine And Health Sciences ; Research And Analysis Methods ; Biology And Life Sciences ; Medicine And Health Sciences ; Research And Analysis Methods ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences
    E-ISSN: 1932-6203
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  • 3
    Language: English
    In: Magnetic Resonance Materials in Physics, Biology and Medicine, 2018, Vol.31(3), pp.367-374
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s10334-017-0658-4 Byline: Florian Siedek (1), Thorsten Persigehl (1), Roman-Ulrich Mueller (2), Volker Burst (2), Thomas Benzing (2), David Maintz (1), Stefan Haneder (1) Keywords: Temporary remote ischemic preconditioning; Acute kidney injury; BOLD MRI; Kidney; Healthy volunteers Abstract: Objective Acute kidney injury (AKI) is an important risk factor for a number of adverse outcomes including end-stage renal disease and cardiovascular morbidity and mortality. Whilst many clinical situations that can induce AKI are known--e.g. drug toxicity, contrast agent exposure or ischemia during surgery--targeted preventive or therapeutic measures are still lacking. As to renoprotective strategies, remote ischemic preconditioning (RIPC) is one of the most promising novel approaches and has been examined by a number of clinical trials. The aim of this study was to use blood oxygenation level-dependent (BOLD) MRI as a surrogate parameter to assess the effect of RIPC in healthy volunteers. Materials and methods In this IRB-approved, prospective study, 40 healthy volunteers were stratified with 20 undergoing an RIPC procedure (i.e. RIPC group) with a transient ischemia of the right arm, and 20 undergoing a sham procedure. Before and after the procedure, both kidneys of all participants were scanned using a 12-echo mGRE sequence for functional BOLD imaging at 3T. For each volunteer, 180 ROIs were placed in the cortex and the medulla of the kidneys. Ultimately, R2* values, which have an inverse correlation with the oxygenation level of tissue, were averaged for the RIPC and control groups. Results Following intervention, mean R2* values significantly decreased in the RIPC group in both the cortex (18.6 [+ or -] 2.3 vs. 17.5 [+ or -] 1.7 Hz p = 0.0047) and medulla (34 [+ or -] 5.2 vs. 32.2 [+ or -] 4.2 Hz p = 0.0001). However, no significant differences were observed in the control group. Conclusion RIPC can be non-invasively assessed in healthy volunteers using BOLD MRI at 3T, demonstrating a higher oxygen content in kidney tissue. This study presents a first-in-man trial establishing a quantifiable readout of RIPC and its effects on kidney physiology. BOLD measurements may advance clinical trials in further evaluating RIPC for future clinical care. Author Affiliation: (1) 0000 0000 8852 305X, grid.411097.a, Institute of Diagnostic and Interventional Radiology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany (2) 0000 0000 8852 305X, grid.411097.a, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany Article History: Registration Date: 10/10/2017 Received Date: 10/06/2017 Accepted Date: 02/10/2017 Online Date: 23/10/2017
    Keywords: Temporary remote ischemic preconditioning ; Acute kidney injury ; BOLD MRI ; Kidney ; Healthy volunteers
    ISSN: 0968-5243
    E-ISSN: 1352-8661
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  • 4
    Language: English
    In: Magnetic Resonance Imaging, November 2018, Vol.53, pp.52-62
    Description: This study aims to assess the feasibility of 4D flow MRI measurements in complex vascular territories; namely, the celiac artery (CA) and superior mesenteric artery (SMA). In this prospective study, 22 healthy volunteers and 10 patients were scanned at 3 T. Blood flow parameters were compared between healthy volunteers and patients with stenosis of the CA and/or SMA as a function of stenosis grade characterized by prior contrast-enhanced computed tomography (CE-CT). The 4D flow MRI acquisition covered the CA, SMA and adjusting parts of the abdominal aorta (AO). Measurements of velocity- (peak velocity [PV], average velocity [AV]) and volume-related parameters (peak flow [PF], stroke volume [SV]) were conducted. Further, stenosis grade and wall shear stress in the CA, SMA and AO were evaluated. In patients, prior evaluation by CE-CT revealed 11 low- and 5 mid-grade stenoses of the CA and/or SMA. PV and AV were significantly higher in patients than in healthy volunteers [PV: p 〈 0.0001; AV: p = 0.03, p 〈 0.001]. PF and SV did not differ significantly between healthy volunteers and patients; however, a trend towards lower PF and SV could be detected in patients with mid-grade stenoses. Comparison of 4D flow MRI with CE-CT revealed a strong positive correlation in estimated degree of stenosis (CA: r = 0.86, SMA: r = 0.98). Patients with mid-grade stenoses had a significantly higher average WSS magnitude (AWM) than healthy volunteers (p = 0.02). This feasibility study suggests that 4D flow MRI is a viable technique for the evaluation of complex flow characteristics in small vessels such as the CA and SMA. 4D flow MRI approves comparable to the morphologic assessment of complex vascular territories using CE-CT but, in addition, offers the functional evaluation of flow parameters that goes beyond the morphology.
    Keywords: 4d Flow Mri ; Celiac Artery ; Superior Mesenteric Artery ; Vessel Stenosis ; Blood Flow Characteristics ; Medicine
    ISSN: 0730-725X
    E-ISSN: 1873-5894
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  • 5
    Language: English
    In: Cell, 02 July 2015, Vol.162(1), pp.146-159
    Description: is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat -mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell-cycle checkpoint-abrogating Chk1- and MK2 inhibitors, specifically in - and -driven cells. Mechanistically, we show that -mutant cancer displays intrinsic genotoxic stress, leading to tonic Chk1- and MK2 activity. We demonstrate that simultaneous Chk1- and MK2 inhibition leads to mitotic catastrophe in -mutant cells. This actionable synergistic interaction is validated using xenograft models, as well as distinct - or -driven autochthonous murine cancer models. Lastly, we show that combined checkpoint inhibition induces apoptotic cell death in - or -mutant tumor cells directly isolated from patients. These results strongly recommend simultaneous Chk1- and MK2 inhibition as a therapeutic strategy for the treatment of - or -driven cancers. PreCISE, a new platform that reliably captures synergic drug interactions from large-scale cell-line-based screens, shows that simultaneous inhibition of the cell-cycle checkpoint kinases Chk1 and MK2 effectively eradicates KRAS-mutant cancer cells directly isolated from patients and in distinct Kras-driven murine tumor models.
    Keywords: Biology
    ISSN: 0092-8674
    E-ISSN: 1097-4172
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  • 6
    Language: English
    In: Cell, 27 August 2015, Vol.162(5), pp.1169-1169
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2015.08.017 Byline: Felix Dietlein, Bastian Kalb, Mladen Jokic, Elisa M. Noll, Alexander Strong, Lars Tharun, Luka Ozretic, Helen Kunstlinger, Kato Kambartel, Winfried J. Randerath, Christian Jungst, Anna Schmitt, Alessandro Torgovnick, Andre Richters, Daniel Rauh, Florian Siedek, Thorsten Persigehl, Cornelia Mauch, Jirina Bartkova, Allan Bradley, Martin R. Sprick, Andreas Trumpp, Roland Rad, Dieter Saur, Jiri Bartek, Jurgen Wolf, Reinhard Buttner, Roman K. Thomas, H. Christian Reinhardt
    Keywords: Biology
    ISSN: 0092-8674
    E-ISSN: 1097-4172
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  • 7
    Language: English
    In: Acta Radiologica, December 2018, Vol.59(12), pp.1458-1465
    Description: Background A novel, multi-energy, dual-layer spectral detector computed tomography (SDCT) is commercially available now with the vendor’s claim that it yields the same or better quality of polychromatic, conventional CT images like modern single-energy CT scanners without any radiation dose penalty. Purpose To intra-individually compare the quality of conventional polychromatic CT images acquired with a dual-layer spectral detector (SDCT) and the latest generation 128-row single-energy-detector (CT128) from the same manufacturer. Material and Methods Fifty patients underwent portal-venous phase, thoracic-abdominal CT scans with the SDCT and prior CT128 imaging. The SDCT scanning protocol was adapted to yield a similar estimated dose length product (DLP) as the CT128. Patient dose optimization by automatic tube current modulation and CT image reconstruction with a state-of-the-art iterative algorithm were identical on both scanners. CT image contrast-to-noise ratio (CNR) was compared between the SDCT and CT128 in different anatomic structures. Image quality and noise were assessed independently by two readers with 5-point-Likert-scales. Volume CT dose index (CTDIvol), and DLP were recorded and normalized to 68 cm acquisition length (DLP68). Results The SDCT yielded higher mean CNR values of 30.0% ± 2.0% (26.4–32.5%) in all anatomic structures (P 〈 0.001) and excellent scores for qualitative parameters surpassing the CT128 (all P 〈 0.0001) with substantial inter-rater agreement (κ ≥ 0.801). Despite adapted scan protocols the SDCT yielded lower values for CTDIvol (–10.1 ± 12.8%), DLP (−13.1 ± 13.9%), and DLP68 (–15.3 ± 16.9%) than the CT128 (all P 〈 0.0001). Conclusion The SDCT scanner yielded better CT image quality compared to the CT128 and lower radiation dose parameters.
    Keywords: Computed Tomography ; CT ; Abdomen ; Thorax ; Adults ; Radiation Safety ; Medicine
    ISSN: 0284-1851
    E-ISSN: 1600-0455
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  • 8
    Language: English
    In: European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, June 2016, Vol.25(6), pp.1683-9
    Description: The technique of pedicle screw stabilization is finding increasing popularity for use in the cervical spine. Implementing anterior transpedicular screws (ATPS) in cervical spine offers theoretical advantages compared to posterior stabilization. The goal of the current study was the development of a new setting for navigated insertion of ATPS, combining the advantage of reduced invasiveness of an anterior approach with the technical advantages of navigation. 20 screws were implanted in levels C3 to C6 of four cervical spine models (SAWBONES(®) Cervical Vertebrae with Anterior Ligament) with the use of 3D fluoroscopy navigation system [Arcadis Orbic 3D, Siemens and VectorVision fluoro 3D trauma software (BrainLAB)]. The accuracy of inserted screws was analyzed according to postoperative CT scans and following the modified Gertzbein and Robbins classification. 20 anterior pedicle screws were placed in four human cervical spine models. Of these, eight screws were placed in C3, two screws in C4, six screws in C5, and four screws in C6. 16 of 20 screws (80 %) reached a grade 1 level of accuracy according to the modified Gertzbein and Robbins Classification. Three screws (15 %) were grade 2, and one screw (5 %) was grade 3. Grade 4 and 5 positions were not evident. Summing grades 1 and 2 together as "good" positions, 95 % of the screws achieved this level. Only a single screw did not fulfill these criteria. The setting introduced in this study for navigated insertion of ATPS into cervical spine bone models is well implemented and shows excellent results, with an accuracy of 95 % (Gertzbein and Robbins grade 2 or better). Thus, this preliminary study represents a prelude to larger studies with larger case numbers on human specimens.
    Keywords: Accuracy of Screw Insertion ; Anterior Transpedicular Screws ; Navigated Screw Insertion ; Spine Surgery ; Pedicle Screws ; Cervical Vertebrae -- Surgery ; Fluoroscopy -- Methods ; Imaging, Three-Dimensional -- Methods ; Surgery, Computer-Assisted -- Methods
    ISSN: 09406719
    E-ISSN: 1432-0932
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  • 9
    Language: English
    In: Abdominal Radiology, 2019, Vol.44(4), pp.1481-1492
    Description: Byline: Florian Siedek (1), Stefan Haneder (1), Jonas Dorner (1), John N. Morelli (2), Seung-Hun Chon (3), David Maintz (1), Christian Houbois (1) Keywords: Renal cortex volumetry; Modified ellipsoid volume; Split renal function; Kidney; Living kidney donation Abstract: Purpose This study aims to determine whether contrast-enhanced (CE)-magnetic resonance imaging (MRI) is comparable to CE-computed tomography (CT) for estimation of split renal function (SRF). For this purpose, two different kidney volumetry methods, the renal cortex volumetry (RCV) and modified ellipsoid volume (MELV), are compared for both acquisition types (CT vs. MRI) with regard to accuracy and reliability, subsequently referred to as RCV.sub.CT/RCV.sub.MRI and MELV.sub.CT/MELV.sub.MRI. Methods This retrospective study included 29 patients (18 men and 11 women mean age 62.8[+ or -]12.4 years) who underwent CE-MRI and CE-CT of the abdomen within a period of 3 months. Two independent readers (R1/R2) performed RCV and MELV in all datasets with corresponding semiautomated software tools. RCV was performed with datasets in the arterial phase and MELV in the venous phase. Statistics were calculated using one-way ANOVA, two-tailed Student's t test, PearsonA[acute accent]s correlation, and Bland--Altman plots with pa[currency]0.05 being considered statistically significant. Results In all datasets, SRF was almost identical for both volumetry methods with a mean difference of 〈1%. Bland--Altman analysis comparing RCV in CT and MRI showed very good agreement for R1/R2. Interreader agreement was strong for RCV.sub.CT and good for RCV.sub.MRI (r=0.89 r=0.69). MELV.sub.CT/MRI interreader agreement was only moderate (r=0.54 r=0.50) with a high range of values. Intrareader agreement was excellent for all measurements, except MELV.sub.MRI which showed a high mean bias and range of values (RCV.sub.CT: r=0.93, RCV.sub.MRI: r=0.98, MELV.sub.CT: r=0.89, MELV.sub.MRI: r=0.54). Conclusion Renal volumetric estimates of SRF are almost as accurate and reliable with CE-MRI as with CE-CT using RCV method. In distinction, the calculation of SRF using MELV was inferior to RCV with respect to accuracy and reliability. Thus, RCV method is recommended to estimate SRF, primarily using CT datasets. However, RCV with MRI datasets for kidney volumetry allows for comparable accuracy and reliability while sparing patients and healthy donors of unnecessary radiation exposure. Author Affiliation: (1) 0000 0000 8852 305X, grid.411097.a, Institute of Diagnostic and Interventional Radiology, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany (2) St. John's Medical Center, 1923 South Utica Ave, Tulsa, OK, 74104, USA (3) 0000 0000 8852 305X, grid.411097.a, General, Visceral, and Cancer Surgery, University Hospital Cologne, Cologne, Germany Article History: Registration Date: 27/11/2018 Online Date: 01/12/2018
    Keywords: Renal cortex volumetry ; Modified ellipsoid volume ; Split renal function ; Kidney ; Living kidney donation
    ISSN: 2366-004X
    E-ISSN: 2366-0058
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  • 10
    Language: English
    In: Cell Reports, 23 October 2018, Vol.25(4), pp.1027-1039.e6
    Description: , which encodes p21, functions as a major route for p53-mediated cell-cycle arrest. However, the consequence of gene dosage on tumor suppression has not been systematically investigated. Here, we employed BAC transgenesis to generate a mouse, which harbors an additional allele within its natural genomic context. We show that these mice display enhanced cell-cycle arrest and reduced apoptosis in response to genotoxic stress. Furthermore, using a chemically induced skin cancer model and an autochthonous -driven lung adenocarcinoma model, we show that mice display a cancer protection phenotype that is indistinguishable from that observed in animals. Moreover, we demonstrate that and cooperate in mediating cancer resistance, using a chemically induced fibrosarcoma model. Overall, our allele enabled us to assess the contribution of to -mediated tumor suppression. Torgovnick et al. create a mouse model, carrying a third copy of (p21), which shows enhanced cell-cycle arrest capacity and protection against DNA damage-induced apoptosis. The animals display delayed epithelial regeneration and a robust cancer resistance phenotype, highlighting the importance of p21 in p53-dependent tumor suppression.
    Keywords: Cdkn1a ; P21 ; P53 ; Mouse Model ; Cancer ; Tumor Suppressor ; Cell Cycle Arrest ; Apoptosis ; Cancer Protection ; Biology
    ISSN: 2211-1247
    E-ISSN: 2211-1247
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