Modification of vaccination strategies is necessary to improve the immune response to SARS‐CoV‐2 vaccination in kidney transplant recipients (KTRs). This multicenter observational study analyzed the ...effects of the third SARS‐CoV‐2 vaccination in previously seronegative KTRs with the focus on temporary mycophenolate mofetil (MMF) dose reduction within propensity matched KTRs. 56 out of 174 (32%) previously seronegative KTRs became seropositive after the third vaccination with only three KTRs developing neutralizing antibodies against the omicron variant. Multivariate logistic regression revealed that initial antibody levels, graft function, time after transplantation and MMF trough levels had an influence on seroconversion (P < .05). After controlling for confounders, the effect of MMF dose reduction before the third vaccination was calculated using propensity score matching. KTRs with a dose reduction of ≥33% showed a significant decrease in MMF trough levels to 1.8 (1.2–2.5) μg/ml and were more likely to seroconvert than matched controls (P = .02). Therefore, a MMF dose reduction of 33% or more before vaccination is a promising approach to improve success of SARS‐CoV‐2 vaccination in KTRs.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract
This joint consensus paper of the German Roentgen Society and the German Cardiac Society provides physical and electrophysiological background information and specific recommendations for ...the procedural management of patients with cardiac pacemakers (PM) and implantable cardioverter defibrillators (ICD) undergoing magnetic resonance (MR) imaging. The paper outlines the responsibilities of radiologists and cardiologists regarding patient education, indications, and monitoring with modification of MR sequences and PM/ICD reprogramming strategies being discussed in particular. The aim is to optimize patient safety and to improve legal clarity in order to facilitate the access of SM/ICD patients to MR imaging.
Key Points:
Conventional PM and ICD systems are no longer an absolute but rather a relative contraindication for performing an MR examination. Procedural management includes the assessment of the individual risk/benefit ratio, comprehensive patient informed consent about specific risks and “off label” use, extensive PM/ICD-related and MR-related safety precautions to reduce these risks to the greatest extent possible, as well as adequate monitoring techniques.
MR conditional pacemaker and ICD systems have been tested and approved for MR examination under specific conditions (“in-label” use). Precise understanding of and compliance with the terms of use for the specific pacemaker system are essential for patient safety.
The risk for an ICD patient during MR examinations is to be considered significantly higher compared to PM patients due to the higher vulnerability of the structurally damaged myocardium and the higher risk of irreversible damage to conventional ICD systems. The indication for a MR examination of an ICD patient should therefore be determined on a stricter basis and the expected risk/benefit ratio should be critically reviewed.
This complex subject requires close collaboration between radiology and cardiology.
Citation Format
Sommer T, Bauer W, Fischbach K et al. MR Imaging in Patients with Cardiac Pacemakers and Implantable Cardioverter Defibrillators. Fortschr Röntgenstr 2017; 189: 204 – 217
Zusammenfassung
In diesem gemeinsamen Konsensuspapier der Deutschen Röntgengesellschaft und der Deutschen Gesellschaft für Kardiologie werden der MR-physikalische und elektrophysiologische Hintergrund sowie das prozedurale Management für MR-Untersuchungen von Patienten mit Herzschrittmachern und implantierbaren Kardioverter-Defibrillatoren dargestellt. Es werden detaillierte Handlungsanweisungen bezüglich Indikationsstellung, den spezifischen Untersuchungsbedingungen mit Umprogrammierung des SM/ICD-Systems, Modifikation der MR-Sequenzen und Monitoring gegeben sowie die Verantwortlichkeiten und Aufklärungsnotwendigkeiten zwischen Radiologie und Kardiologie definiert. Ziel ist es, ein Maximum an Patientensicherheit zu gewährleisten sowie Rechtssicherheit für die beteiligten Ärzte herzustellen, um insgesamt den Zugang von Patienten mit aktiven kardialen Implantaten zu notwendigen MR-Untersuchungen zu verbessern.
Kernaussagen:
Konventionelle SM- und ICD-Systeme sind nicht mehr als eine absolute, sondern als eine relative Kontraindikation für die Durchführung einer MR-Untersuchung anzusehen. Entscheidend bei Indikationsstellung und Untersuchungsdurchführung sind die Abschätzung des individuellen Nutzen-Risiko-Verhältnisses, eine umfassende Aufklärung über „off-label use“ und spezifische Risiken, dedizierte SM-/ICD-bezogene und MR-bezogene Sicherheitsmaßnahmen zur weitestgehenden Reduzierung dieser Risiken sowie adäquate Monitortechniken während der MR-Untersuchung.
Bedingt MR-sichere („MR conditional“) SM- und ICD-Systeme sind für eine MR-Untersuchung unter spezifischen Rahmenbedingungen getestet und zugelassen. Entscheidend für die Patientensicherheit sind hier die genaue Kenntnis und die Einhaltung der für das jeweilige SM/ICD-System spezifischen Nutzungsbedingungen.
Das Risiko eines ICD-Patienten während einer MR-Untersuchung ist aufgrund der höheren elektrophysiologischen Vulnerabilität des per se strukturell geschädigten Myokards sowie des höheren Risikos irreversibler Funktionsstörungen konventioneller ICD-Systeme im Vergleich zu SM-Patienten als deutlich höher einzuschätzen. Die Indikationsstellung zu einer MR-Untersuchung eines ICD-Patienten sollte somit strenger erfolgen und kritisch hinterfragt werden, ob der zu erwartende Nutzen der MR-Untersuchung in einem adäquaten Verhältnis zum Risiko steht.
Die komplexe Thematik erfordert eine enge und abgestimmte Kooperation zwischen Radiologie und Kardiologie.
Zitierweise
Sommer T, Bauer W, Fischbach K et al. MR Imaging in Patients with Cardiac Pacemakers and Implantable Cardioverter Defibrillators. Fortschr Röntgenstr 2017; 189: 204 – 218
Oncogene addiction provides ideal targets for successful immunotherapy. MLXIP (MAX like protein X interacting protein, also known as MondoA) is a metabolic stress sensor and a proglycolytic ...transcription factor potentially involved in metabolic addiction features of leukemia, the Warburg effect and anoikis. MLXIP dimerizes with MLX within the MYC interactome and promotes longevity in C. elegans (Johnson et al. 2014). The MYC interactome comprises the MYC/MAX/MAD/MLX/MLXIPtranscriptionfactornetwork: Its key players MYC, MAD and MLXIP differentially mediate proliferation, differentiation or metabolism by heterodimerization with MAX or MLX: While MAX is available for partnering with MYC vs. MAD, MLX may partner with MAD or MLXIP alternatively. In contrast to the perception of MLXIP as a tumor suppressor gene in some solid tumors such as breast and colon cancer (O’Shea and Ayer, 2013), we have extended our previous notion of up regulation of MLXIP in B cell acute lymphoblastic leukemia(ALL, Burdach & Richter 2007, Haferlach et al. 2010) by demonstrating that MLXIP is highly overexpressed and induces stemness, proliferation and B cell receptor signaling pathway signatures in common ALL (cALL, Wernicke et al. 2012). Here we report on the role of MLXIP in malignancy of cALL in vivo. Given the non accessibility of transcription factors by chimeric antigen receptor transgenic T cells (CARs) and the superiority of allorestricted T cells in T cell receptor (TCR) based immunotherapy of leukemia (Burdach & Kolb 2013), we also tested the targetability of MLXIP by allorestricted peptide specific T cells to ultimately generate MLXIP specific allorestricted TCR transgenic T cells (ATRs, instead of CARs).
Our human/murine xenotransplantation model with immunodeficient RAG2-/-gc-/- mice was used (Richter et al. 2009). NALM6 and 697 cALL lines were retrovirally transduced with MLXIP short hairpin RNA (shRNA). Upon successful MLXIP knock down (kd), kd and control lines were injected into the mice; CD10+ blasts in blood, spleen and marrow were assessed. MLXIP specific T cells were generated by priming of donor HLAA0201 negative (A2-) T-cells with A2+ dendritic cells bearing MLXIP peptides, multimer-based sorting and subcloning of A2-CD8+ T-cells. For priming of T cells, five MLXIP peptides were chosen by SYMPEITHI, BIMAS and NetCTL1.2. analyses. Peptide 428 stabilized best A2 expression on TAP-deficient T2 cells. Specificity and functionality of T cell clones were tested by ELISpot interferon g (IFg) and granzyme B assays with six MLXIP+ leukemia lines (A2+, A2-). Off target effects of MLXIP specific T-cell clones were assessed by IFg reactivity against the MLXIP expressing A2+ NALM6 cell line vs. A2+ and A2- EBV immortalized lymphoblastoid cell lines from six donors. Peptide homology was assessed with BLAST algorithms in SWISSPROT.
We found MLXIP to be overexpressed in both ALL and AML, while it was low in solid tumors including breast and colon cancer. MLXIP kd in the cALL cell line NALM-6 reduced the transcript by 80%. Importantly, in vivo MLXIP maintained 90-99% of CD10+ leukemic blasts in blood, marrow and spleen. Spleen size and weight normalized by MLXIP kd: While signs of leukemia engraftment were observed in all mice, the differences of CD10+ blasts in blood, marrow and spleens in the control vs. the MLXIP kd group were highly significant (p=0.008). The decrease of leukemic splenomegaly after MLXIP kd was impressive. Median spleen weight was 0.22g vs. 0.08g in the control vs. the kd group (Figure 1: The upper spleen displays the leukemic infiltration in control mice. The two lower spleens are from mice injected with MLXIP kd NALM6 cells).
MLXIP peptide 428 specific T cell clones successfully recognized and killed A2 positive MLXIP expressing NALM6 and 697 cALL lines. In contrast, MLXIP specific T cell clones did not release IFg and granzyme B under stimulation with A2- REH, RS4;11 cALL lines. We identified the nucleotide sequence of alpha and beta variable chains of MLXIP specific A2 restricted TCR to finally obtain MLXIP specific ATRs. Peptide dependent and independent off target alloreactivity was very low compared to reactivity against NALM-6 cALL.
In conclusion, these findings demonstrate that MLXIP maintains leukemic burden and malignancy of cALL in vivo. Moreover, we identified MLXIP as a promising target for immunotherapy of cALL and potentially other MLXIP expressing leukemias, including AML.
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Haferlach:MLL: Equity Ownership. Burdach:PDLI: Equity Ownership.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Here, we provide the first bone histological examination of an ontogenetic series of the basal ichthyosaur
Mixosaurus encompassing postnatal to large adult specimens. Growth marks are present in ...sampled humeri, a femur, a fibula, as well as in other skeletal elements (gastral ribs). Ontogenetic changes are traceable throughout stylo- and zeugopodial development, but interior remodelling and resorption deleted part of the internal growth record in the primary cortex.
Mixosaurus humeri started as flat structures consisting of a core of endochondral woven bone and residual calcified cartilage, whereas growth continued by deposition of periosteal fibrolamellar and parallel-fibred bone. Unlike the fast-growing post-Triassic ichthyosaurs that lack growth marks, microstructural and life history data are now becoming available for a basal ichthyosaur. The high growth rate of
Mixosaurus may indicate that higher metabolic rates characterised small, non-thunniform ichthyosaurs, as had been suggested already for post-Triassic, cruising forms.
Nous rapportons ici la première étude ostéohistologique d’une série ontogénétique quasi-complète (spécimens postnataux à adultes) de l’ichthyosaure basal
Mixosaurus. Des stries de croissance sont visibles sur les humérus échantillonnés, ainsi que sur un fémur, un péroné et d’autres éléments du squelette (côtes gastriques). On peut suivre les changements ontogénétiques au cours du développement des stylo- et zeugopodes, mais le remodelage interne et la résorption ont en partie effacé l’enregistrement de la croissance interne dans le cortex primaire. Les humérus de
Mixosaurus sont initialement des structures plates consistant en un noyau d’os endochondral en « sucre mouillé » et de cartilage calcifié rémanent. La croissance continue par dépôt d’os périostique fibrolamellaire et à fibres parallèles. Contrairement aux ichthyosaures post-triasiques à croissance rapide, qui ne présentent pas de stries de croissance, des données microstructurelles et d’histoire de vie sont maintenant disponibles pour un taxon basal du groupe. Le haut taux de croissance de
Mixosaurus pourrait indiquer que les petits ichthyosaures non thunniformes étaient caractérisés par des taux métaboliques élevés, comme cela fut déjà suggéré pour les formes migrantes post-triasiques.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present a simulation and data-processing framework that incorporates full 3-D configuration, simulation, and reconstruction functionalities for hybrid synthetic aperture THz systems, which combine ...mechanically scanned real imaging projection (1-D) and synthetic imaging reconstruction (2-D). The simulation is based on a ray-casting approach including models for reflections at rough surfaces and angular antenna sensitivity. A near real-time GPU reconstruction is introduced to process large amounts of data in parallel. Techniques for fast fusion of reconstructed data from several acquisition directions are presented. They serve as basis to visualize a fully consistent 3-D object. The modular framework allows a fast, easy, and efficient evaluation and prediction of system properties including scattering behavior for these types of scanner setups.
Microchannel reactors and heat exchangers have been developed by application of a novel laser welding technique, which generates durable sealing of the reactors for operating temperatures up to 1000 ...°C. A microreactor for exhaust gas cleaning purposes has been operated for 35 000 h in a laboratory environment. Results from the operation of a diesel oxidative steam reformer in combination with a hot gas driven evaporator are presented.
Microreactors for high temperature applications have been developed applying laser welding as sealing technique. One of these reactors was operated for 35 000 h for exhaust gas cleaning purposes. A diesel steam reformer was operated at temperatures as high as 1000 °C approaching the maximum operating temperature of stainless steel without damage of welding seams.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The gold mineralization of the Hutti Mine is hosted by nine parallel, N–S trending, steeply dipping, 2–10 m wide shear zones, that transect Archaean amphibolites. The shear zones were formed after ...peak metamorphism during retrograde ductile D
2 shearing in the lower amphibolite facies. They were reactivated in the lower to mid greenschist facies by brittle–ductile D
3 shearing and intense quartz veining. The development of a S
2–S
3 crenulation cleavage facilitates the discrimination between the two deformation events and contemporaneous alteration and gold mineralization. Ductile D
2 shearing is associated with a pervasively developed distal chlorite–sericite alteration assemblage in the outer parts of the shear zones and the proximal biotite–plagioclase alteration in the center of the shear zones. D
3 is characterized by development of the inner chlorite-K-feldspar alteration, which forms a centimeter-scale alteration halo surrounding the laminated quartz veins and replaces earlier biotite along S
3. The average size of the laminated vein systems is 30–50 m along strike as well as down-dip and 2–6 m in width.
Mass balance calculations suggest strong metasomatic changes for the proximal biotite–plagioclase alteration yielding mass and volume increase of ca. 16% and 12%, respectively. The calculated mass and volume changes of the distal chlorite–sericite alteration (ca. 11%, ca. 8%) are lower. The decrease in
δ
18O values of the whole rock from around 7.5‰ for the host rocks to 6–7‰ for the distal chlorite–sericite and the proximal biotite–plagioclase alteration and around 5‰ for the inner chlorite-K-feldspar alteration suggests hydrothermal alteration during two-stage deformation and fluid flow.
The ductile D
2 deformation in the lower amphibolite facies has provided grain scale porosities by microfracturing. The pervasive, steady-state fluid flow resulted in a disseminated style of gold–sulfide mineralization and a penetrative alteration of the host rocks. Alternating ductile and brittle D
3 deformation during lower to mid greenschist facies conditions followed the fault-valve process. Ductile creep in the shear zones resulted in a low permeability environment leading to fluid pressure build-up. Strongly episodic fluid advection and mass transfer was controlled by repeated seismic fracturing during the formation of laminated quartz(-gold) veins. The limitation of quartz veins to the extent of earlier shear zones indicate the importance of pre-existing anisotropies for fault-valve action and economic gold mineralization.
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