Publications by authors named "Andreas Jacobs"

Article Synopsis
  • Research highlights the significant role of immune processes in the development of Alzheimer's disease, which is the leading cause of dementia.
  • Various studies indicate that both innate and adaptive immune responses contribute to the disease's pathology and are influenced by genetics and lifestyle factors.
  • New therapeutic approaches targeting neuroinflammation are being explored in clinical settings, offering potential treatment options for Alzheimer's patients.
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History And Admission Findings:  A 76-year old man was admitted with a globus sensation and weight loss for further investigations to our geriatric ward. A gastroscopic evaluation executed before had been unremarkable.

Investigations:  Physical examination was unremarkable, including a neurological examination.

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Background: The Comprehensive Geriatric Assessment (CGA) records geriatric syndromes in a standardized manner, allowing individualized treatment tailored to the patient's needs and resources. Its use has shown a beneficial effect on the functional outcome and survival of geriatric patients. A recently published German S1 guideline for level 2 CGA provides recommendations for the use of a broad variety of different assessment instruments for each geriatric syndrome.

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Article Synopsis
  • - Autoimmune limbic encephalitis (ALE) is characterized by new seizures, memory issues, and changes in behavior and cognition, primarily affecting the mesial temporal lobe.
  • - CD8 T cells are important in cases without detectable autoantibodies, but identifying these patients is challenging, highlighting the need for better imaging techniques.
  • - The use of [F]DPA-714-PET-MRI to visualize microglia activation in the hippocampus and amygdala shows promise for assessing innate immunity in patients with CD8 T cell-mediated ALE, and findings were supported by results in a mouse model.
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Background: To evaluate medication-related risks in older patients with cancer and their association with severe toxicity during antineoplastic therapy.

Methods: This is a secondary analysis of two prospective, single-center observational studies which included patients ≥ 70 years with cancer. The patients' medication lists were investigated regarding possible risks: polymedication (defined as the use of ≥ 5 drugs), potentially inappropriate medication (PIM), and relevant potential drug-drug interactions (rPDDI).

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Objectives: In view of the increased attention to reverse shoulder arthroplasty (rTSA) as a treatment for complex proximal humeral fractures in the elderly, the present study analyzes in-hospital complications and the postoperative management of rTSA versus open reduction and internal fixation (ORIF).

Methods: We retrospectively reviewed patients hospitalized from 2016 to 2018 for proximal humeral fractures (ICD-9 codes: S42.21), III- and IV-part, who underwent an ORIF with locking plates, rTSA or nonoperative treatment.

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Objective: The aim of this study was the verification of the Subdural Hematoma in the Elderly (SHE) score proposed by Alford et al. as a mortality predictor in patients older than 65 years with nontraumatic/minor trauma acute subdural hematoma (aSDH). Additionally, we evaluated further predictors associated with poor outcome.

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Glioblastoma is the most common primary brain tumor, highly aggressive by being proliferative, neovascularized and invasive, heavily infiltrated by immunosuppressive glioma-associated myeloid cells (GAMs), including glioma-associated microglia/macrophages (GAMM) and myeloid-derived suppressor cells (MDSCs). Quantifying GAMs by molecular imaging could support patient selection for GAMs-targeting immunotherapy, drug target engagement and further assessment of clinical response. Magnetic resonance imaging (MRI) and amino acid positron emission tomography (PET) are clinically established imaging methods informing on tumor size, localization and secondary phenomena but remain quite limited in defining tumor heterogeneity, a key feature of glioma resistance mechanisms.

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Introduction: One of the most important geriatric syndromes is dizziness in conjunction with gait disorder and consequent falls. There are various differential diagnoses for dizziness, one of them is benign paroxysmal positional vertigo (BPPV).

Objectives: A targeted diagnostic work-up and treatment of BPPV can prevent subsequent falls and a decline in the patients' quality of life, prolonged hospitalization with unnecessary examinations and medication.

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History And Clinical Findings:  In the following case report, we describe a patient with acute renal failure due to an urinary congestion level II-III under BCG-(Bacillus Calmette-Guérin)-therapy because of bladder cancer. Cystoscopy revealed the diagnosis of BCG-induced intramural narrowing of distal ureters bilaterally.

Therapy And Further Development:  After receiving a double-J-catheter the renal function returned to normal.

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Glioma-associated microglia and macrophages (GAMMs) are key players in creating an immunosuppressive microenvironment. They can be efficiently targeted by inhibiting the colony-stimulating factor 1 receptor (CSF-1R). We applied noninvasive PET/CT and PET/MRI using F-fluoroethyltyrosine (F-FET) (amino acid metabolism) and -diethyl-2-[4-(2-F-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-]pyrimidine-3-acetamide (F-DPA-714) (translocator protein) to understand the role of GAMMs in glioma initiation, monitor in vivo therapy-induced GAMM depletion, and observe GAMM repopulation after drug withdrawal.

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Studies on colony-stimulating factor 1 receptor (CSF-1R) inhibition-induced microglia depletion indicated that inhibitor withdrawal allowed the renewal of the microglia compartment via repopulation and resolved the inflammatory imbalance. Therefore, we investigated for the first time (to our knowledge) the effects of microglia repopulation on inflammation and functional outcomes in an ischemic mouse model using translocator protein (TSPO)-PET/CT and MR imaging, ex vivo characterization, and behavioral tests. Eight C57BL/6 mice per group underwent a 30-min transient occlusion of the middle cerebral artery.

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Radioligand theranostics (RT) in oncology use cancer-type specific biomarkers and molecular imaging (MI), including positron emission tomography (PET), single-photon emission computed tomography (SPECT) and planar scintigraphy, for patient diagnosis, therapy, and personalized management. While the definition of theranostics was initially restricted to a single compound allowing visualization and therapy simultaneously, the concept has been widened with the development of theranostic pairs and the combination of nuclear medicine with different types of cancer therapies. Here, we review the clinical applications of different theranostic radiopharmaceuticals in managing different tumor types (differentiated thyroid, neuroendocrine prostate, and breast cancer) that support the combination of innovative oncological therapies such as gene and cell-based therapies with RT.

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Immunomodulatory therapies have fueled interest in targeting microglial cells as part of the innate immune response after infection or injury. In this context, the colony-stimulating factor 1 (CSF-1) and its receptor (CSF-1R) have gained attention in various neurological conditions to deplete and reprogram the microglia/macrophages compartment. Published data in physiological conditions support the use of small-molecule inhibitors to study microglia/macrophages dynamics under inflammatory conditions and as a therapeutic strategy in pathologies where those cells support disease progression.

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Purpose: Multimodal molecular imaging allows a direct coregistration of different images, facilitating analysis of the spatial relation of various imaging parameters. Here, we further explored the relation of proliferation, as measured by [F]FLT PET, and water diffusion, as an indicator of cellular density and cell death, as measured by diffusion-weighted (DW) MRI, in preclinical tumor models. We expected these parameters to be negatively related, as highly proliferative tissue should have a higher density of cells, hampering free water diffusion.

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Object: In the light of an aging population and ongoing advances in cancer control, the optimal management in geriatric patients with brain metastases (BM) poses an increasing challenge, especially due to the scarce data available. We therefore analyzed our institutional data with regard to factors influencing overall survival (OS) in geriatric patients with BM.

Methods: Between 2013 and 2018, patients aged ≥ 65 years with surgically treated BM were included in this retrospective analysis.

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Neurosurgical resection represents an important therapeutic pillar in patients with brain metastasis (BM). Such extended treatment modalities require preoperative assessment of patients' physical status to estimate individual treatment success. The aim of the present study was to analyze the predictive value of frailty and sarcopenia as assessment tools for physiological integrity in patients with non-small cell lung cancer (NSCLC) who had undergone surgery for BM.

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Microglia-induced neuroinflammation after stroke contributes to the exacerbation of postischemic damage but also supports neurorestorative events. Longitudinal molecular imaging of microglia-targeted therapies will support the assessment of target engagement, therapy efficacy, and deciphering of the mode of action. We investigated the effects of chronic colony-stimulating factor 1 receptor (CSF-1R) inhibitor-mediated microglia depletion on translocator protein (TSPO)-dependent neuroinflammation and cerebrovascular parameters using PET/MRI.

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Article Synopsis
  • Glioblastoma (GBM) is a very aggressive brain tumor with low survival rates, and current treatments like Temozolomide (TMZ) show limited effectiveness.
  • This study tested the cancer drug Metformin (MET) alongside TMZ, finding that MET boosts TMZ's efficiency by altering cell survival pathways and promoting cell death in both TMZ-sensitive and resistant GBM cell lines in mouse models.
  • PET imaging revealed that MET plus TMZ can improve survival outcomes in mice and reduce tumor recurrence, with specific radiotracers indicating treatment response and survival but varying in their predictive capabilities.
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Immune cells have been implicated in influencing stroke outcomes depending on their temporal dynamics, number, and spatial distribution after ischemia. Depending on their activation status, immune cells can have detrimental and beneficial properties on tissue outcome after stroke, highlighting the need to modulate inflammation towards beneficial and restorative immune responses. Novel dietary therapies may promote modulation of pro- and anti-inflammatory immune cell functions.

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Gliomas are highly dynamic and heterogeneous tumours of the central nervous system (CNS). They constitute the most common neoplasm of the CNS and the second most common cause of death from intracranial disease after stroke. The advances in detailing the genetic profile of paediatric and adult gliomas along with the progress in MRI and PET multimodal molecular imaging technologies have greatly improved prognostic stratification of patients with glioma and informed on treatment decisions.

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Article Synopsis
  • - The study focuses on gliomas, highlighting how their complex nature and the role of infiltrating myeloid cells contribute to tumor growth and resistance to treatments like temozolomide (TMZ).
  • - Researchers utilized advanced PET/MRI imaging techniques, specifically [F]FET and [F]DPA-714, to analyze the effects of TMZ on tumor characteristics and immune cell activity in a mouse model.
  • - Results showed that TMZ significantly decreased tumor size and [F]FET uptake but increased [F]DPA-714 uptake in specific tumor areas, indicating changes in the inflammatory tumor microenvironment and suggesting the potential of these imaging techniques in tracking treatment response.
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Indication for surgical treatment in patients with intracranial meningioma must include both clinical aspects and an individual risk-benefit stratification, especially in geriatric patients. Prolonged mechanical ventilation (PMV) has not been investigated for its potential effects in patients with meningioma. We therefore analyzed the impact of PMV on mortality in geriatric patients who had undergone meningioma resection.

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