6 results on '"Seeber, S."'
Search Results
2. Analysis of systemic serum vancomycin levels following intraarticular application in primary total joint arthroplasty.
- Author
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R S, P S, Gh S, S B, M E, and Ja B
- Subjects
- Humans, Male, Female, Aged, Prospective Studies, Middle Aged, Pilot Projects, Injections, Intra-Articular, Aged, 80 and over, Vancomycin administration & dosage, Vancomycin blood, Vancomycin pharmacokinetics, Arthroplasty, Replacement, Knee, Arthroplasty, Replacement, Hip, Prosthesis-Related Infections prevention & control, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents blood, Anti-Bacterial Agents pharmacokinetics
- Abstract
Introduction: Periprosthetic joint infection (PJI) is a serious complication following primary total joint arthroplasty (TJA). PJI accounts for 15-25% of revision surgeries, therefore it is associated with PJI is associated with substantial patient morbidity and mortality as well as increased healthcare expenditures due to complex treatment strategies. Recently, intraoperative local application of vancomycin powder is increasingly being used in primary total hip and knee arthroplasty (THA, TKA) as an additive strategy for PJI prevention. Whereas local vancomycin concentrations have already been investigated in prior studies, evidence on systemic vancomycin levels and potential adverse drug reactions (ADR) is limited. Purpose of this study was to investigate systemic vancomycin levels following intraarticular application in primary TJA., Materials and Methods: This pilot study is a prospective analysis of patients undergoing primary THA and TKA between April and July 2023. One gram of vancomycin powder was applied to the prosthesis prior to wound closure. Serum vancomycin levels were measured at two standardised time points, 24 and 48 h postoperatively., Results: In total, 103 patients were included, and the patient collective was further stratified by surgical procedure into a THA subgroup (n = 52) and a TKA subgroup (n = 51). Mean serum vancomycin levels showed a significant group difference at both time points (24 h: p < 0.001; 48 h: p = 0.044) with higher serum vancomycin concentrations in the THA cohort. Mean serum vancomycin levels in THA patients were 1.25 μg/ml (range 0.00-7.00 μg/ml) after 24 h and 0.34 μg/ml (range 0.00-4.80 μg/ml) 48 h postoperatively. In TKA, no systemic vancomycin levels were detected. Vancomycin concentrations did not reach therapeutic levels in any patient. No ADR was detected in the whole study collective., Conclusion: Following intraarticular administration of vancomycin powder, no systemic vancomycin levels within the therapeutic range were detected, thus it may serve as a safe and cost-effective adjunct to strategies for prevention of PJI., Competing Interests: Declarations. Conflict of interests: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: The observational study was approved by the local ethics committee at the University of Oldenburg (#2023–173) and was conducted in accordance with the principles of the Declaration of Helsinki of 1964 and its later amendments. Informed consent was obtained prior inclusion to the study., (© 2024. The Author(s).)
- Published
- 2024
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3. Promoting coping competence for psychological stressors in nursing training: a controlled pedagogical intervention.
- Author
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Warwas J, Krebs P, Vorpahl W, Weyland U, Wilczek L, Seeber S, and Wittmann E
- Abstract
Background: Multiple stressors as well as health-and quality-impairing effects of strain in the nursing profession require the systematic acquisition of competence in dealing with these demands, starting at the stage of initial vocational training. This study investigates whether an instructional design, which merges didactic principles of nursing education with concepts and training measures from stress psychology, promotes the acquisition of stress coping competence more effectively than regular teaching on the relevant curricular field at nursing schools., Methods: The quasi-experimental study design, based on the Solomon four-group plan, included 332 trainees in Germany. The assessment of stress coping competence at the beginning and at the end of the intervention provided a video-stimulated situational judgment test covering nursing-specific stressful situations. All were validated by field experts. Complementing group comparisons, regression analyses examined intervention effects at the individual level while controlling for other predictors of learning success., Results: The highest solution rates for the two basic dimensions of stress coping competence, i.e., (1) situation assessment and (2) strategy selection and justification , occurred in the treatment classes without a pretest. At the individual level, treatment effects were confirmed for the first dimension. Students with a migration background showed lower competence gains than other students., Conclusion: The instructional design and the competence test provide valuable foundations for promoting and for diagnosing coping skills. Nevertheless, subsequent studies should examine adaptive support for different learner groups. Furthermore, additional observational phases should focus on the deliberate practice of acquired coping strategies in the practical training settings of nursing education., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Warwas, Krebs, Vorpahl, Weyland, Wilczek, Seeber and Wittmann.)
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- 2024
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4. Deciphering molecular and cellular ex vivo responses to bispecific antibodies PD1-TIM3 and PD1-LAG3 in human tumors.
- Author
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Natoli M, Hatje K, Gulati P, Junker F, Herzig P, Jiang Z, Davydov II, Germann M, Trüb M, Marbach D, Zwick A, Weber P, Seeber S, Wiese M, Lardinois D, Heinzelmann-Schwarz V, Rosenberg R, Tietze L, Mertz KD, Umaña P, Klein C, Codarri-Deak L, Kao H, and Zippelius A
- Subjects
- Humans, CD8-Positive T-Lymphocytes, Hepatitis A Virus Cellular Receptor 2, Programmed Cell Death 1 Receptor, Lymphocyte Activation Gene 3 Protein, Antibodies, Bispecific, Neoplasms metabolism
- Abstract
Background: Next-generation cancer immunotherapies are designed to broaden the therapeutic repertoire by targeting new immune checkpoints including lymphocyte-activation gene 3 (LAG-3) and T cell immunoglobulin and mucin-domain containing-3 (TIM-3). Yet, the molecular and cellular mechanisms by which either receptor functions to mediate its inhibitory effects are still poorly understood. Similarly, little is known on the differential effects of dual, compared with single, checkpoint inhibition., Methods: We here performed in-depth characterization, including multicolor flow cytometry, single cell RNA sequencing and multiplex supernatant analysis, using tumor single cell suspensions from patients with cancer treated ex vivo with novel bispecific antibodies targeting programmed cell death protein 1 (PD-1) and TIM-3 (PD1-TIM3), PD-1 and LAG-3 (PD1-LAG3), or with anti-PD-1., Results: We identified patient samples which were responsive to PD1-TIM3, PD1-LAG3 or anti-PD-1 using an in vitro approach, validated by the analysis of 659 soluble proteins and enrichment for an anti-PD-1 responder signature. We found increased abundance of an activated (HLA-DR
+ CD25+ GranzymeB+ ) CD8+ T cell subset and of proliferating CD8+ T cells, in response to bispecific antibody or anti-PD-1 treatment. Bispecific antibodies, but not anti-PD-1, significantly increased the abundance of a proliferating natural killer cell subset, which exhibited enrichment for a tissue-residency signature. Key phenotypic and transcriptional changes occurred in a PD-1+ CXCL13+ CD4+ T cell subset, in response to all treatments, including increased interleukin-17 secretion and signaling toward plasma cells. Interestingly, LAG-3 protein upregulation was detected as a unique pharmacodynamic effect mediated by PD1-LAG3, but not by PD1-TIM3 or anti-PD-1., Conclusions: Our in vitro system reliably assessed responses to bispecific antibodies co-targeting PD-1 together with LAG-3 or TIM-3 using patients' tumor infiltrating immune cells and revealed transcriptional and phenotypic imprinting by bispecific antibody formats currently tested in early clinical trials., Competing Interests: Competing interests: KH, PG, IID, FJ, DM, AZw, PW, SS, PU, CK, LC-D and HK are current or former employees of F. Hoffmann-La Roche and declare patent applications and stock ownership with Roche. AZ received consulting/advisor fees from Bristol-Myers Squibb, Merck Sharp & Dohme, Hoffmann-La Roche, NBE Therapeutics, Secarna, ACM Pharma and Hookipa and maintains further non-commercial research agreements with Secarna, Hookipa, Roche and Beyondsprings. All other authors declare they have no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2022
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5. PD-1-cis IL-2R agonism yields better effectors from stem-like CD8 + T cells.
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Codarri Deak L, Nicolini V, Hashimoto M, Karagianni M, Schwalie PC, Lauener L, Varypataki EM, Richard M, Bommer E, Sam J, Joller S, Perro M, Cremasco F, Kunz L, Yanguez E, Hüsser T, Schlenker R, Mariani M, Tosevski V, Herter S, Bacac M, Waldhauer I, Colombetti S, Gueripel X, Wullschleger S, Tichet M, Hanahan D, Kissick HT, Leclair S, Freimoser-Grundschober A, Seeber S, Teichgräber V, Ahmed R, Klein C, and Umaña P
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- Antibodies, Blocking immunology, Antibodies, Blocking pharmacology, Antibodies, Blocking therapeutic use, B7-H1 Antigen antagonists & inhibitors, B7-H1 Antigen immunology, Infections drug therapy, Infections immunology, Interleukin-2 immunology, Interleukin-2 pharmacology, Interleukin-2 therapeutic use, Interleukin-2 Receptor alpha Subunit agonists, Neoplasms drug therapy, Neoplasms immunology, CD8-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes immunology, Programmed Cell Death 1 Receptor antagonists & inhibitors, Receptors, Interleukin-2 agonists
- Abstract
Expansion and differentiation of antigen-experienced PD-1
+ TCF-1+ stem-like CD8+ T cells into effector cells is critical for the success of immunotherapies based on PD-1 blockade1-4 . Hashimoto et al. have shown that, in chronic infections, administration of the cytokine interleukin (IL)-2 triggers an alternative differentiation path of stem-like T cells towards a distinct population of 'better effector' CD8+ T cells similar to those generated in an acute infection5 . IL-2 binding to the IL-2 receptor α-chain (CD25) was essential in triggering this alternative differentiation path and expanding better effectors with distinct transcriptional and epigenetic profiles. However, constitutive expression of CD25 on regulatory T cells and some endothelial cells also contributes to unwanted systemic effects from IL-2 therapy. Therefore, engineered IL-2 receptor β- and γ-chain (IL-2Rβγ)-biased agonists are currently being developed6-10 . Here we show that IL-2Rβγ-biased agonists are unable to preferentially expand better effector T cells in cancer models and describe PD1-IL2v, a new immunocytokine that overcomes the need for CD25 binding by docking in cis to PD-1. Cis binding of PD1-IL2v to PD-1 and IL-2Rβγ on the same cell recovers the ability to differentiate stem-like CD8+ T cells into better effectors in the absence of CD25 binding in both chronic infection and cancer models and provides superior efficacy. By contrast, PD-1- or PD-L1-blocking antibodies alone, or their combination with clinically relevant doses of non-PD-1-targeted IL2v, cannot expand this unique subset of better effector T cells and instead lead to the accumulation of terminally differentiated, exhausted T cells. These findings provide the basis for the development of a new generation of PD-1 cis-targeted IL-2R agonists with enhanced therapeutic potential for the treatment of cancer and chronic infections., (© 2022. The Author(s).)- Published
- 2022
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6. An abdominal phantom with anthropomorphic organ motion and multimodal imaging contrast for MR-guided radiotherapy.
- Author
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Weidner A, Stengl C, Dinkel F, Dorsch S, Murillo C, Seeber S, Gnirs R, Runz A, Echner G, Karger CP, and Jäkel O
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- Abdomen diagnostic imaging, Humans, Magnetic Resonance Imaging methods, Male, Motion, Multimodal Imaging, Phantoms, Imaging, Sepharose, Organ Motion, Radiotherapy, Image-Guided
- Abstract
Purpose . Improvements in image-guided radiotherapy (IGRT) enable accurate and precise treatment of moving tumors in the abdomen while simultaneously sparing healthy tissue. However, the lack of validation tools for newly developed MR-guided radiotherapy hybrid devices such as the MR-Linac is an open issue. This study presents a custom developed abdominal phantom with respiratory organ motion and multimodal imaging contrast to perform end-to-end tests for IGRT treatment planning scenarios. Methods . The abdominal phantom contains deformable and anatomically shaped liver and kidney models made of Ni-DTPA and KCl-doped agarose mixtures that can be reproducibly positioned within the phantom. Organ models are wrapped in foil to avoid ion exchange with the surrounding agarose and to provide stable T1 and T2 relaxation times as well as HU numbers. Breathing motion is realized by a diaphragm connected to an actuator that is hydraulically controlled via a programmable logic controller. With this system, artificial and patient-specific breathing patterns can be carried out. In 1.5 T magnetic resonance imaging (MRI), diaphragm, liver and kidney motion was measured and compared to the breathing motion of a healthy male volunteer for different breathing amplitudes including shallow, normal and deep breathing. Results . The constructed abdominal phantom demonstrated organ-equivalent intensity values in CT as well as in MRI. T1-weighted (T1w) and T2-weighted (T2w) relaxation times for 1.5 T and CT numbers were 552.9 ms, 48.2 ms and 48.8 HU (liver) as well as 950.42 ms, 79 ms and 28.2 HU (kidney), respectively. These values were stable for more than six months. Extracted breathing motion from a healthy volunteer revealed a liver to diaphragm motion ratio (LDMR) of 64.4% and a kidney to diaphragm motion ratio (KDMR) of 30.7%. Well-comparable values were obtained for the phantom (LDMR: 65.5%, KDMR: 27.5%). Conclusions . The abdominal phantom demonstrated anthropomorphic T1 and T2 relaxation times as well as HU numbers and physiological motion pattern in MRI and CT. This allows for wide use in the validation of IGRT including MRgRT., (© 2022 Institute of Physics and Engineering in Medicine.)
- Published
- 2022
- Full Text
- View/download PDF
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