Kooperativer Bibliotheksverbund

In: World Journal of Surgical Oncology, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2017-12)

Type of Medium: Online Resource

ISSN: 1477-7819

URL: Article

DOI: 10.1186/s12957-017-1121-8

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

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In: Journal of Communication Disorders, Elsevier BV, Vol. 93 ( 2021-09), p. 106135-

Type of Medium: Online Resource

ISSN: 0021-9924

URL: Article

DOI: 10.1016/j.jcomdis.2021.106135

Language: English

Publisher: Elsevier BV

Publication Date: 2021

detail.hit.zdb_id: 2012755-8

SSG: 5,2

SSG: 7,11

In: Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 15, No. 688 ( 2023-03-22)

Abstract: Musculoskeletal tissue engineering approaches require a reliable source of precursor cells. Hochmann et al . report that despite having some transcriptional similarities, the inherent differentiation potential of different stromal cell types is constrained by their enhancer landscapes. In contrast to stromal cells derived from white adipose tissue or umbilical cord, only bone marrow–derived cells had an epigenetic signature permitting their differentiation into functional hypertrophic cartilage discs capable of ameliorating a critical-size bone defect model after transplantation into mice. These findings have ramifications for the development of regenerative cell–based musculoskeletal therapies. —CAC

Type of Medium: Online Resource

ISSN: 1946-6234 , 1946-6242

URL: Article

DOI: 10.1126/scitranslmed.abm7477

Language: English

Publisher: American Association for the Advancement of Science (AAAS)

Publication Date: 2023

In: Trials, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2021-12)

Abstract: Tonsillectomy is one of the most frequently performed surgeries in children and young adults worldwide. For decades, tonsillectomy was the surgical treatment of choice for recurrent acute tonsillitis. Tonsillotomy was used in some countries as an alternative to tonsillectomy only for the treatment of obstructive sleep apnea in young children. In recent years, an increase of tonsillotomy also to treat recurrent acute tonsillitis can be observed. Therefore, the German Institute for Quality and Efficiency in Health Care (IQWiG) was commissioned by the Federal Joint Committee (G-BA) to investigate whether tonsillotomy offers advantages compared to tonsillectomy. The meta-analysis of the IQWiG including studies until 2016 revealed that the long-term benefits and harms of tonsillotomy compared to tonsillectomy are unclear. Consequently, the G-BA performed a European call for a clinical trial. A consortium of the German Professional Association of ENT-surgeons (BVHNO), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), and the Jena University Hospital were finally selected to perform the TOTO study. Methods TOTO is a multicenter, 1:1 two-arm, randomized non-blinded non-inferiority trial. Four hundred fifty-four patients ≥ 3 years of age will be randomly allocated to undergo either tonsillotomy or tonsillectomy as surgical treatment of recurrent acute tonsillitis. All participants will be followed up for a total of 24 months. The primary outcome is the number of sore throat days experienced over the 24-month follow-up. Discussion TOTO is designed to evaluate the effectiveness and efficiency of tonsillectomy versus tonsillectomy for the management of patients with recurrent acute tonsillitis. Tonsil disease and surgery have a major impact on preschool and school children as well as on economically active young adults, with individual and societal costs through loss of school visits, earnings, and productivity. If tonsillotomy is at least as effective as tonsillectomy but with reduced morbidity, this would reduce costs to the healthcare system and society. Trial registration German Clinical Trials Register DRKS00020823 . Registered on 04 September 2020.

Type of Medium: Online Resource

ISSN: 1745-6215

URL: Article

DOI: 10.1186/s13063-021-05434-y

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2040523-6

In: Trials, Springer Science and Business Media LLC, Vol. 24, No. 1 ( 2023-05-11)

Abstract: Graft rejection and chronic CNI toxicity remain obstacles to organ transplant success. Current formulations of tacrolimus, such as Prograf® and Advagraf™, exhibit limitations in terms of pharmacokinetics and tolerability, related in part to suboptimal bioavailability. As dosing non-compliance can result in graft rejection, the once daily formulation of tacrolimus, Advagraf™, was developed (vs 2x/day Prograf®). Benefits of Advagraf™ are counterbalanced by delayed achievement of therapeutic trough levels and need for up to 50% higher doses to maintain Prograf®-equivalent troughs. Envarsus® is also a prolonged-release once-daily tacrolimus formulation, developed using MeltDose™ drug-delivery technology to increase drug bioavailability; improved bioavailability results in low patient drug absorption variability and less pronounced peak-to-trough fluctuations. In phase III de novo kidney transplant studies, Envarsus® proved non-inferior to twice-daily tacrolimus; however, no phase IV studies show superiority of Envarsus® vs Advagraf™ in de novo liver transplant (LTx) recipients. Methods The EnGraft compares bioavailability and tests superiority of Envarsus® (test arm) versus Advagraf™ (comparator arm) in de novo LTx recipients. A total of 268 patients from 15 German transplant centres will be randomised 1:1 within 14 days post-LTx. The primary endpoint is dose-normalised trough level (C/D ratio) measured 12 weeks after randomisation. Secondary endpoints include the number of dose adjustments, time to reach first defined trough level and incidence of graft rejections. Additionally, clinical and laboratory parameters will be assessed over a 3-year period. Discussion C/D ratio is an estimate for tacrolimus bioavailability. Improving bioavailability and increasing C/D ratio using Envarsus could reduce renal dysfunction and other tacrolimus-related toxicities; previous trials have shown that a higher C/D ratio (i.e. slower tacrolimus metabolism) is not only associated with improved renal function but also linked to reduced neurotoxic side effects. A higher C/D ratio could improve clinical outcomes for LTx recipients; EnGraft has begun, with one third of patients recruited by January 2022. Trial registration This trial has been registered (4 May 2020) in the EU Clinical Trials Register, EudraCT-Nummer: 2020–000796-20. Additionally, this trial has been registered (22 January 2021) at ClinicalTrials.gov: NCT04720326. The trial received a favourable opinion from the concerned lead ethics committee at the University of Regensburg, under the reference 20–1842-112.

Type of Medium: Online Resource

ISSN: 1745-6215

URL: Article

DOI: 10.1186/s13063-023-07344-7

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2040523-6

In: Haematologica, Ferrata Storti Foundation (Haematologica), Vol. 103, No. 5 ( 2018-05), p. 799-809

Type of Medium: Online Resource

ISSN: 0390-6078 , 1592-8721

URL: Article

DOI: 10.3324/haematol.2017.179895

Language: English

Publisher: Ferrata Storti Foundation (Haematologica)

Publication Date: 2018

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detail.hit.zdb_id: 2030158-3

detail.hit.zdb_id: 2805244-4

In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 307, No. 9 ( 2014-11-01), p. F1041-F1051

Abstract: Renal tubular handling of urate is realized by a network of uptake and efflux transporters, including members of drug transporter families such as solute carrier proteins and ATP-binding cassette transporters. Solute carrier family 2, member 9 (SLC2A9), is one key factor of this so called “urate transportosome.” The aim of the present study was to understand the transcriptional regulation of SLC2A9 and to test whether identified factors might contribute to a coordinated transcriptional regulation of the transporters involved in urate handling. In silico analysis and cell-based reporter gene assays identified a hepatocyte nuclear factor (HNF)4α-binding site in the promoter of SLC2A9 isoform 1, whose activity was enhanced by transient HNF4α overexpression, whereas mutation of the binding site diminished activation. HNF4α overexpression induced endogenous SLC2A9 expression in vitro. The in vivo role of HNF4α in the modulation of renal SLC2A9 gene expression was supported by findings of quantitative real-time RT-PCR analyses and chromatin immunoprecipitation assays. Indeed, mRNA expression of SLC2A9 and HNF4α in human kidney samples was significantly correlated. We also showed that in renal clear cell carcinoma, downregulation of HNF4α mRNA and protein expression was associated with a significant decline in expression of the transporter. Taken together, our data suggest that nuclear receptor family member HNF4α contributes to the transcriptional regulation of SLC2A9 isoform 1. Since HNF4α has previously been assumed to be a modulator of several urate transporters, our findings support the notion that there could be a transcriptional network providing synchronized regulation of the functional network of the urate transportosome.

Type of Medium: Online Resource

ISSN: 1931-857X , 1522-1466

URL: Article

DOI: 10.1152/ajprenal.00640.2013

Language: English

Publisher: American Physiological Society

Publication Date: 2014

detail.hit.zdb_id: 1477287-5

In: Stem Cells, Oxford University Press (OUP), Vol. 27, No. 6 ( 2009-06-01), p. 1288-1297

Abstract: Progenitor cells such as mesenchymal stem cells (MSCs) have elicited great hopes for therapeutic augmentation of physiological regeneration processes, e.g., for bone fracture healing. However, regeneration potential decreases with age, which raises questions about the efficiency of autologous approaches in elderly patients. To elucidate the mechanisms and cellular consequences of aging, the functional and proteomic changes in MSCs derived from young and old Sprague–Dawley rats were studied concurrently. We demonstrate not only that MSC concentration in bone marrow declines with age but also that their function is altered, especially their migratory capacity and susceptibility toward senescence. High-resolution two-dimensional electrophoresis of the MSC proteome, under conditions of in vitro self-renewal as well as osteogenic stimulation, identified several age-dependent proteins, including members of the calponin protein family as well as galectin-3. Functional annotation clustering revealed that age-affected molecular functions are associated with cytoskeleton organization and antioxidant defense. These proteome screening results are supported by lower actin turnover and diminished antioxidant power in aged MSCs, respectively. Thus, we postulate two main reasons for the compromised cellular function of aged MSCs: (a) declined responsiveness to biological and mechanical signals due to a less dynamic actin cytoskeleton and (b) increased oxidative stress exposure favoring macromolecular damage and senescence. These results, along with the observed similar differentiation potentials, imply that MSC-based therapeutic approaches for the elderly should focus on attracting the cells to the site of injury and oxidative stress protection, rather than merely stimulating differentiation. Disclosure of potential conflicts of interest is found at the end of this article.

Type of Medium: Online Resource

ISSN: 1066-5099 , 1549-4918

URL: Article

DOI: 10.1002/stem.49

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2009

detail.hit.zdb_id: 2030643-X

detail.hit.zdb_id: 1143556-2

detail.hit.zdb_id: 605570-9

SSG: 12

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 5031-5031

Abstract: Introduction: Commonly accepted standardized sets of outcomes to be measured in clinical trials are still limited. In accordance, outcome measures vary widely between clinical trials even within defined hematological malignancy (HM) entities. Definition of a core outcome set (COS), which represents a standardized agreed set of outcomes that should be measured and reported in all trials for the respective disease of interest may improve this situation. Furthermore, respective COS should address the need of all stakeholders, i.e. not only the views of physicians and industry running the trials, but also the interests of patients and regulators. To perform a task like this, HARMONY - Healthcare Alliance for Resourceful Medicine Offensive against Neoplasms in Hematology - a private-public partnership established in January 2017, including 53 partners and 43 associated partners in 18 different European countries and also 6 patient organizations, poses an optimal platform to define COS for HMs. Methods: To define COS for 5 selected HMs, it was decided to use the Delphi survey method provided by COMET initiative. Since HARMONY has members of several important stakeholder groups (clinicians, industry, health authorities and patient groups) it was decided to include all stakeholders to participate in the Delphi surveys. A pilot study was implemented for the COS for acute myeloid leukemia (AML) based on which additional Delphi surveys were developed for myelodysplastic syndrome (MDS), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and chronic lymphocytic leukemia (CLL). As starting point preliminary outcome lists were generated based on published reports and available guidelines. Surveys were performed with representatives from each stakeholder group to agree within a pre-defined and iterative process on a COS for each HM. Conditions and criteria were defined in study protocols. Each outcome was rated into 3 categories (1-3 "not important", 4-6 "important but not critical" and 7-9 "critical"). A "consensus-in criterion" was defined if 70 % or more respondents scored the outcome as critically important (7-9) and 15% or fewer rated the outcome as limited important (1-3). To make sure that the patients' voice was heard within the consensus process, a special "patient-important criterion" had been implemented during data analysis. Outcomes ranked with a median of 7 or higher in the patient group were highlighted, showing these are really important for patients. According to a bottom-up-approach, an overarching COS was then created based on the individual survey results. Results: For the Delphi surveys a total of 365 individuals participated including 126 clinicians (35%), 46 EFPIA members (13%), 177 patients/patient advocates (48%) and 16 regulators (4%). While there was a large overlap of outcomes among HMs, there were also many disease specific outcomes such as leukemia-free survival (LFS) for AML, very good partial response (VGPR) for MM to name only few. In addition, there were sometimes major differences in the assessment of individual stakeholders within an outcome, e.g. between clinicians and patients. Finally, the general COS applicable to all HMs included core outcomes that met the consensus-in criterion for all HMs. Conclusion: Using Delphi surveys to define specific COS for HMs revealed meaningful results. Based on the bottom-up-approach not only disease specific HM COS could be defined, but also an overarching COS applicable to all HMs. This overarching COS will subsequently not only allow to compare results more easily within a distinct HM subgroup but also results across different HMs. To our knowledge, this is the first multidisciplinary approach to define COS across four different stakeholder groups. These COS should now be a starting point to further refine COS and to apply them within future clinical trials, thereby reducing inconsistencies and bias in outcome-reporting. Results of COS based clinical trials will simplify the development of novel clinical recommendations, which will improve future patient management and clinical patient care in the real-world setting. Figure 1 Figure 1. Disclosures Lang: Roche: Honoraria. Ossenkoppele: Jazz: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Abbvie, AGIOS, BMS/Celgene Astellas,AMGEN, Gilead,Servier,JAZZ,Servier Novartis: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Servier: Consultancy, Honoraria. Döhner: Gilead: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Jazz: Consultancy, Honoraria, Research Funding; Helsinn: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Berlin-Chemie: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Ulm University Hospital: Current Employment; Astellas: Consultancy, Honoraria, Research Funding; Astex: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Pfizer: Research Funding; Oxford Biomedicals: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; GEMoaB: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Salles: Genmab: Consultancy; Incyte: Consultancy; Velosbio: Consultancy; Genentech/Roche: Consultancy; Loxo: Consultancy; Miltneiy: Consultancy; Debiopharm: Consultancy; Allogene: Consultancy; Rapt: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Morphosys: Consultancy, Honoraria; Kite/Gilead: Consultancy; Ipsen: Consultancy; Takeda: Consultancy; Regeneron: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; BMS/Celgene: Consultancy; Beigene: Consultancy; Abbvie: Consultancy, Honoraria; Bayer: Honoraria. Dreyling: Abbvie: Research Funding; Roche: Consultancy, Research Funding, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Genmab: Consultancy; Gilead/Kite: Consultancy, Research Funding, Speakers Bureau; Astra Zeneca: Consultancy, Speakers Bureau; BeiGene: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau; Bayer HealthCare Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau. Sonneveld: Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; SkylineDx: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene/BMS: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. San-Miguel: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Merck Sharpe & Dohme, Novartis, Regeneron, Roche, Sanofi, SecuraBio, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Boccadoro: Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol-Myers Squibb, and AbbVie: Honoraria; Janssen and GSK: Membership on an entity's Board of Directors or advisory committees; Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol-Myers Squibb, and Mundipharma: Research Funding. Fenaux: Celgene/BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria. Santini: Gilead: Membership on an entity's Board of Directors or advisory committees; Astex: Membership on an entity's Board of Directors or advisory committees; Geron: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Menarini: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ghia: Acerta/AstraZeneca: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; ArQule/MSD: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Sunesis: Research Funding; Celgene/Juno/BMS: Consultancy, Honoraria; Gilead: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Guillevic: BMS: Current Employment. Calado: Novartis: Current Employment. Sanz: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Helsinn Healthcare: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Other: Travel, accommodations, and expenses; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses, Research Funding. Hernández-Rivas: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Barbus: Abbvie: Current Employment. Schulze-Rath: Bayer: Current Employment. Bullinger: Menarini: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceutical: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hexal: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Research Funding; Bristol-Myers Squibb / Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria; Amgen: Honoraria; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-145002

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 5285-5287

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-157549

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7