Health-economic evaluation of orthogeriatric co-management for patients with pelvic or vertebral fragility fractures.

Background: Orthogeriatric co-management (OGCM) addresses the special needs of geriatric fracture patients. Most of the research on OGCM focused on hip fractures while results concerning other severe fractures are rare. We conducted a health-economic evaluation of OGCM for pelvic and vertebral fractures.

Health-economic evaluation of orthogeriatric co-management for patients with forearm or humerus fractures: an analysis of insurance claims data from Germany.

Orthogeriatric co-management (OGCM) describes a collaboration of orthopedic surgeons and geriatricians for the treatment of fragility fractures in geriatric patients. While its cost-effectiveness for hip fractures has been widely investigated, research focusing on fractures of the upper extremities is lacking. Thus, we conducted a health economic evaluation of treatment in OGCM hospitals for forearm and humerus fractures.

P-Terminated InP (001) Surfaces: Surface Band Bending and Reactivity to Water.

Stable InP (001) surfaces are characterized by fully occupied and empty surface states close to the bulk valence and conduction band edges, respectively. The present photoemission data show, however, a surface Fermi level pinning only slightly below the midgap energy which gives rise to an appreciable surface band bending. By means of density functional theory calculations, it is shown that this apparent discrepancy is due to surface defects that form at finite temperature.

Discovery of Novel Allosteric EGFR L858R Inhibitors for the Treatment of Non-Small-Cell Lung Cancer as a Single Agent or in Combination with Osimertinib.

Addressing resistance to third-generation EGFR TKIs such as osimertinib via the EGFR mutation remains a highly unmet need in EGFR-driven non-small-cell lung cancer (NSCLC). Herein, we present the discovery of the allosteric EGFR inhibitor , a novel fourth-generation inhibitor to overcome EGFR-mediated resistance in patients harboring the activating EGFR mutation. exhibits an improved potency compared to previous allosteric EGFR inhibitors.

Association of two geriatric treatment systems on care home admission and mortality in patients with hip fracture.

Background: In Germany, geriatricians deliver acute geriatric care during an acute hospital stay and subacute rehabilitation after transfer to a rehabilitation clinic. However, the proportion of patients who receive acute geriatric care (AGC) or are transferred to subacute rehabilitation (TSR) differs considerably between hospitals. The aim of this study was to analyse the association between the two geriatric treatment systems and care home admission or mortality in patients following hip fracture.

Increased Geriatric Treatment Frequency Improves Mobility and Secondary Fracture Prevention in Older Adult Hip Fracture Patients-An Observational Cohort Study of 23,828 Patients from the Registry for Geriatric Trauma (ATR-DGU).

Interdisciplinary orthogeriatric care of older adult hip fracture patients is of growing importance due to an ageing population, yet there is ongoing disagreement about the most effective model of care. This study aimed to compare different forms of orthogeriatric treatment, with focus on their impact on postoperative mobilization, mobility and secondary fracture prevention. In this observational cohort study, patients aged 70 years and older with a proximal femur fracture requiring surgery, were included from 1 January 2016 to 31 December 2019.

Preclinical Characterization of a Next-Generation Brain Permeable, Paradox Breaker BRAF Inhibitor.

Purpose: Disease progression in BRAF V600E/K positive melanomas to approved BRAF/MEK inhibitor therapies is associated with the development of resistance mediated by RAF dimer inducing mechanisms. Moreover, progressing disease after BRAFi/MEKi frequently involves brain metastasis. Here we present the development of a novel BRAF inhibitor (Compound Ia) designed to address the limitations of available BRAFi/MEKi.

BET Inhibition Enhances TNF-Mediated Antitumor Immunity.

Targeting chromatin binding proteins and modifying enzymes can concomitantly affect tumor cell proliferation and survival, as well as enhance antitumor immunity and augment cancer immunotherapies. By screening a small-molecule library of epigenetics-based therapeutics, BET (bromo- and extra-terminal domain) inhibitors (BETi) were identified as agents that sensitize tumor cells to the antitumor activity of CD8 T cells. BETi modulated tumor cells to be sensitized to the cytotoxic effects of the proinflammatory cytokine TNF.

Effect of the COVID-19 Pandemic in German Trauma Centres and Geriatric Trauma Centres DGU.

Background: The COVID 19 pandemic is a major challenge to all social systems, particularly the healthcare system. Within an international study, German Trauma Centres DGU and Geriatric Trauma Centres DGU have been questioned about their situation.

Method: The questionnaire was translated from English into German and sent to all contacts.

Relicts from Glacial Times: The Ground Beetle Eschscholtz, 1823 (Coleoptera: Carabidae) in the Austrian Alps.

The last ice age considerably influenced distribution patterns of extant species of plants and animals, with some of them now inhabiting disjunct areas in the subarctic/arctic and alpine regions. This arctic-alpine distribution is characteristic for many cold-adapted species with a limited dispersal ability and can be found in many invertebrate taxa, including ground beetles. The ground beetle Eschscholtz, 1823 of the subgenus was previously known to have a holarctic-circumpolar distribution, in Europe reaching its southern borders in Wales and southern Scandinavia.

Implementation of an integrated care programme to avoid fragility fractures of the hip in older adults in 18 Bavarian hospitals - study protocol for the cluster-randomised controlled fracture liaison service FLS-CARE.

Background: The economic and public health burden of fragility fractures of the hip in Germany is high. The likelihood of requiring long-term care and the risk of suffering from a secondary fracture increases substantially after sustaining an initial fracture. Neither appropriate confirmatory diagnostics of the suspected underlying osteoporosis nor therapy, which are well-recognised approaches to reduce the burden of fragility fractures, are routinely initiated in the German healthcare system.

[120-day follow-up after proximal femoral fractures-first results from the Geriatric Trauma Registry DGU®].

Background: Geriatric trauma centers which are certified to the status of a Geriatic Trauma Center DGU® based on the criteria catalogue as outlined by the German Trauma Society (DGU), are required to participate in the Geriatric Trauma Register (ATR-DGU) for quality management and outcome analyses. The evaluation is pseudoanonymous and includes data on all treated hip fracture patients over 70 years old. This has been in regular use since 2016.

[Online survey for assessment of geriatric early rehabilitation complex treatment in geriatric trauma centers of the DGU by the medical services of the health funds].

Background: Orthogeriatric co-management of proximal femoral fractures has been proven to effectively reduce mortality rates. This involves extending resources in hospitals treating these patients as well as dealing with the possibility of prolonged periods of hospitalization. The increase in costs of orthogeriatric co-management are best illustrated by the implementation of geriatric early rehabilitation complex treatment.

Translation and evaluation of a pre-clinical 5-protein response prediction signature in a breast cancer phase Ib clinical trial.

Human protein biomarker discovery relies heavily on pre-clinical models, in particular established cell lines and patient-derived xenografts, but confirmation studies in primary tissue are essential to demonstrate clinical relevance. We describe in this study the process that was followed to clinically translate a 5-protein response signature predictive for the activity of an anti-HER3 monoclonal antibody (lumretuzumab) originally measured in fresh frozen xenograft tissue. We detail the development, qualification, and validation of the multiplexed targeted mass spectrometry assay used to assess the signature performance in formalin-fixed, paraffin-embedded human clinical samples collected in a phase Ib trial designed to evaluate lumretuzumab in patients with metastatic breast cancer.

[Geriatric Trauma Center DGU®: Evaluation of clinical and economic parameters : A pilot study in a german university hospital].

Background: Previous studies on orthogeriatric models of care suggest that there is substantial variability in how geriatric care is integrated in the patient management and the necessary intensity of geriatric involvement is questionable.

Objective: The aim of the current prospective cohort study was the clinical and economic evaluation of fragility fracture treatment pathways before and after the implementation of a geriatric trauma center in conformity with the guidelines of the German Trauma Society (DGU).

Methods: A comparison of three different treatment models (6 months each) was performed: A: Standard treatment in Orthopaedic Trauma; B: Special care pathways with improvement of the quality management system and implementation of standard operating procedures; C: Interdisciplinary treatment with care pathways and collaboration with geriatricians (ward round model).

[Results of the pilot phase of the Age Trauma Registry DGU®].

Background: Since 2014, hospitals with ortho-geriatric fracture centres could be certified as AltersTraumaZentrum DGU® in Germany. To measure the quality of treatment in these centres, a geriatric trauma registry (AltersTraumaRegister DGU®) was established.

Objectives: The aim of this work was to report the results of the pilot phase of the AltersTraumaRegister DGU® from the year 2015.

Targeting Tumor Cells with Anti-CD44 Antibody Triggers Macrophage-Mediated Immune Modulatory Effects in a Cancer Xenograft Model.

CD44, a transmembrane receptor reported to be involved in various cellular functions, is overexpressed in several cancer types and supposed to be involved in the initiation, progression and prognosis of these cancers. Since the sequence of events following the blockage of the CD44-HA interaction has not yet been studied in detail, we profiled xenograft tumors by RNA Sequencing to elucidate the mode of action of the anti-CD44 antibody RG7356. Analysis of tumor and host gene-expression profiles led us to the hypothesis that treatment with RG7356 antibody leads to an activation of the immune system.

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models.

Background: Venetoclax, a small molecule BH3 mimetic which inhibits the anti-apoptotic protein Bcl-2, and idasanutlin, a selective MDM2 antagonist, have both shown activity as single-agent treatments in pre-clinical and clinical studies in acute myeloid leukemia (AML). In this study, we deliver the rationale and molecular basis for the combination of idasanutlin and venetoclax for treatment of p53 wild-type AML.

Methods: The effect of idasanutlin and venetoclax combination on cell viability, apoptosis, and cell cycle progression was investigated in vitro using established AML cell lines.

RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis.

Dysregulated cellular apoptosis and resistance to cell death are hallmarks of neoplastic initiation and disease progression. Therefore, the development of agents that overcome apoptosis dysregulation in tumor cells is an attractive therapeutic approach. Activation of the extrinsic apoptotic pathway is strongly dependent on death receptor (DR) hyperclustering on the cell surface.

Antitumour activity of the glycoengineered type II anti-CD20 antibody obinutuzumab (GA101) in combination with the MDM2-selective antagonist idasanutlin (RG7388).

Objectives: To investigate whether the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) combined with the selective MDM2 antagonist idasanutlin (RG7388) offers superior efficacy to monotherapy in treating B-lymphoid malignancies in preclinical models.

Methods: The combined effect of obinutuzumab or rituximab plus idasanutlin on direct cell death/apoptosis induction and antibody-dependent cellular cytotoxicity (ADCC) was evaluated using p53 wild-type Z-138 and DoHH-2 lymphoma cells. Furthermore, whole blood B-cell depletion was analysed, and tumour growth inhibition was evaluated in subcutaneous xenograft models.