Are Hospital Admissions (Costs) and Mortality Rate Impacted by Guideline-driven Treatment of Heart Failure?: A Comparison between Participants in the "CorBene" CMP and Standard-care Patients on the Basis of Propensity Score Matching.

Heart failure (HF) is one of the most common diagnoses on admission to hospital in Germany, and one which incurs high costs. Integrated care in case management programs (CMPs) aims to improve treatment quality in the sense of guideline-driven treatment, while reducing hospital admissions, hospital costs, and mortality. A total of 1,844 patient data records from 11 German statutory health insurance companies enrolled in the CMP (intervention group [IG]) were compared with 1,844 standard-care patients (control group) using propensity score matching.

The value of AI-based analysis of fractional flow reserve of volume computed tomographically detected coronary artery stenosis with regard to their hemodynamic relevance.

Purpose: The aim of our work was to demonstrate the importance of artificial intelligence-based analysis of fractional flow reserves of computed tomographically detected coronary artery stenosis with regard to their hemodynamic relevance in patients with unclear chest pain and suspected stable coronary heart disease with a low to medium pre-test probability.

Material And Methods: The collective of our retrospective analysis includes 63 patients in whom coronary artery stenosis was detected by volume computed tomographic examination in "one beat, whole heart" mode in the period from March to October 2022. In these patients, the fractional flow reserve was also determined by computed tomography, which was modulated by the use of artificial intelligence.

CCL2 chemokine inhibition primes the tumor vasculature for improved nanomedicine delivery and efficacy.

Blood vessel functionality is crucial for efficient tumor-targeted drug delivery. Heterogeneous distribution and perfusion of angiogenic blood vessels contribute to suboptimal accumulation of (nano-) therapeutics in tumors and metastases. To attenuate pathological angiogenesis, an L-RNA aptamer inhibiting the CC motif chemokine ligand 2 (CCL2) was administered to mice bearing orthotopic 4T1 triple-negative breast cancer tumors.

ITIH5-Derived Polypeptides Covering the VIT Domain Suppress the Growth of Human Cancer Cells In Vitro.

Oncogenic drivers such as mutated are the preferred targets in modern drug development. However, restoring the lost function of tumor suppressor proteins could also be a valid approach to combatting cancer. ITIH5 has been revealed as a potent metastasis suppressor in both breast and pancreatic cancer.

Incidental Finding Prevalences in 3-Tesla Brain and Spine MRI of Military Pilot Applicants.

Incidental findings in brain and spine MRI are common. In aerospace medicine, pilot selection may be affected by improved sensitivity of modern MRI devices. We investigated the occurrence of medically unfit rates caused by incidental findings in military pilot applicants using a 3-Tesla scanner as compared to the outcomes of a lower field strength 1-Tesla device based on similar screening protocols.

A collagen-binding protein enables molecular imaging of kidney fibrosis in vivo.

Pathological deposition of collagen is a hallmark of kidney fibrosis. To illustrate this process we employed multimodal optical imaging to visualize and quantify collagen deposition in murine models of kidney fibrosis (ischemia-reperfusion or unilateral ureteral obstruction) using the collagen-binding adhesion protein CNA35. For in vivo imaging, we used hybrid computed tomography-fluorescence molecular tomography and CNA35 labeled with the near-infrared fluorophore Cy7.

Elastin imaging enables noninvasive staging and treatment monitoring of kidney fibrosis.

Fibrosis is the common endpoint and currently the best predictor of progression of chronic kidney diseases (CKDs). Despite several drawbacks, biopsies remain the only available means to specifically assess the extent of renal fibrosis. Here, we show that molecular imaging of the extracellular matrix protein elastin allows for noninvasive staging and longitudinal monitoring of renal fibrosis.

Fibrosis imaging: Current concepts and future directions.

Fibrosis plays an important role in many different pathologies. It results from tissue injury, chronic inflammation, autoimmune reactions and genetic alterations, and it is characterized by the excessive deposition of extracellular matrix components. Biopsies are routinely employed for fibrosis diagnosis, but they suffer from several drawbacks, including their invasive nature, sampling variability and limited spatial information.

ITIH5 mediates epigenetic reprogramming of breast cancer cells.

Background: Extracellular matrix (ECM) is known to maintain epithelial integrity. In carcinogenesis ECM degradation triggers metastasis by controlling migration and differentiation including cancer stem cell (CSC) characteristics. The ECM-modulator inter- α-trypsin inhibitor heavy chain family member five (ITIH5) was recently identified as tumor suppressor potentially involved in impairing breast cancer progression but molecular mechanisms underlying its function are still elusive.

Contrast-enhanced CT imaging in patients with chronic kidney disease.

Renal microvascular rarefaction characterizes chronic kidney disease (CKD). In murine models of CKD, micro-CT imaging reflected capillary rarefaction using quantification of renal relative blood volume (rBV). In addition, micro-CT imaging revealed morphological alterations of the intrarenal vasculature including reduced vascular branching and lumen diameter.

The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance.

Receptor-interacting protein kinase 3 (RIPK3) mediates necroptosis, a form of programmed cell death that promotes inflammation in various pathological conditions, suggesting that it might be a privileged pharmacological target. However, its function in glucose homeostasis and obesity has been unknown. Here we show that RIPK3 is over expressed in the white adipose tissue (WAT) of obese mice fed with a choline-deficient high-fat diet.

Imalytics Preclinical: Interactive Analysis of Biomedical Volume Data.

A software tool is presented for interactive segmentation of volumetric medical data sets. To allow interactive processing of large data sets, segmentation operations, and rendering are GPU-accelerated. Special adjustments are provided to overcome GPU-imposed constraints such as limited memory and host-device bandwidth.

In situ validation of VEGFR-2 and α v ß 3 integrin as targets for breast lesion characterization.

Vascular endothelial growth factor receptor 2 (VEGFR-2) and α v ß 3 integrin are the most frequently addressed targets in molecular imaging of tumor angiogenesis. In preclinical studies, molecular imaging of angiogenesis has shown potential to detect and differentiate benign and malignant lesions of the breast. Thus, in this retrospective clinical study employing patient tissues, the diagnostic value of VEGFR-2, α v ß 3 integrin and vascular area fraction for the diagnosis and differentiation of breast neoplasia was evaluated.

Histidine-rich glycoprotein promotes macrophage activation and inflammation in chronic liver disease.

Unlabelled: Pathogen- and injury-related danger signals as well as cytokines released by immune cells influence the functional differentiation of macrophages in chronic inflammation. Recently, the liver-derived plasma protein, histidine-rich glycoprotein (HRG), was demonstrated, in mouse tumor models, to mediate the transition of alternatively activated (M2) to proinflammatory (M1) macrophages, which limit tumor growth and metastasis. We hypothesized that liver-derived HRG is a critical endogenous modulator of hepatic macrophage functionality and investigated its implications for liver inflammation and fibrosis by comparing C57BL/6N wild-type (WT) and Hrg(-/-) mice.

Role of platelet-derived growth factor-CC in capillary rarefaction in renal fibrosis.

We have identified platelet-derived growth factor (PDGF)-CC as a potent profibrotic mediator in kidney fibrosis and pro-angiogenic mediator in glomeruli. Because renal fibrosis is associated with progressive capillary rarefaction, we asked whether PDGF-CC neutralization in fibrosis might have detrimental anti-angiogenic effects leading to aggravated peritubular capillary loss. We analyzed capillary rarefaction in mice with and without PDGF-CC neutralization (using genetically deficient mice and neutralizing antibodies), in three different models of renal interstitial fibrosis, unilateral ureteral obstruction, unilateral ischemia-reperfusion, Col4a3-deficient (Alport) mice, and healthy animals.

Quantitative Micro-Computed Tomography Imaging of Vascular Dysfunction in Progressive Kidney Diseases.

Progressive kidney diseases and renal fibrosis are associated with endothelial injury and capillary rarefaction. However, our understanding of these processes has been hampered by the lack of tools enabling the quantitative and noninvasive monitoring of vessel functionality. Here, we used micro-computed tomography (µCT) for anatomical and functional imaging of vascular alterations in three murine models with distinct mechanisms of progressive kidney injury: ischemia-reperfusion (I/R, days 1-56), unilateral ureteral obstruction (UUO, days 1-10), and Alport mice (6-8 weeks old).

Role of chemokine pathways in hepatobiliary cancer.

Persistent hepatic inflammation resulting from hepatitis B or C virus infections (HBV or HCV, respectively), obesity-associated non-alcoholic steatohepatitis (NASH) or alcohol abuse is a hallmark feature of chronic liver diseases and appears to be an essential prerequisite of hepatocarcinogenesis. The inflammatory processes in the liver are regulated by various chemokines, which orchestrate the interaction between parenchymal liver cells, Kupffer cells (resident macrophages), hepatic stellate cells (HSC), endothelial cells, and infiltrating immune cells. In consequence, these cellular interactions result in the re-modeling of the hepatic microenvironment toward a pro-inflammatory, pro-fibrotic, pro-angiogenic and thus pre-neoplastic milieu.

Complete Regression of Xenograft Tumors upon Targeted Delivery of Paclitaxel via Π-Π Stacking Stabilized Polymeric Micelles.

Treatment of cancer patients with taxane-based chemotherapeutics, such as paclitaxel (PTX), is complicated by their narrow therapeutic index. Polymeric micelles are attractive nanocarriers for tumor-targeted delivery of PTX, as they can be tailored to encapsulate large amounts of hydrophobic drugs and achiv prolonged circulation kinetics. As a result, PTX deposition in tumors is increased, while drug exposure to healthy tissues is reduced.

Theranostic USPIO-Loaded Microbubbles for Mediating and Monitoring Blood-Brain Barrier Permeation.

Efficient and safe drug delivery across the blood-brain barrier (BBB) remains to be one of the major challenges of biomedical and (nano-) pharmaceutical research. Here, we show that poly(butyl cyanoacrylate)-based microbubbles (MB), carrying ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles within their shell, can be used to mediate and monitor BBB permeation. Upon exposure to transcranial ultrasound pulses, USPIO-MB are destroyed, resulting in acoustic forces inducing vessel permeability.

Algorithmically generated rodent hepatic vascular trees in arbitrary detail.

Physiologically realistic geometric models of the vasculature in the liver are indispensable for modelling hepatic blood flow, the main connection between the liver and the organism. Current in vivo imaging techniques do not provide sufficiently detailed vascular trees for many simulation applications, so it is necessary to use algorithmic refinement methods. The method of Constrained Constructive Optimization (CCO) (Schreiner et al.

The Theranostic Path to Personalized Nanomedicine.

Advances in nanotechnology and chemical engineering have led to the development of many different drug delivery systems. These 1-100(0) nm-sized carrier materials aim to increase drug concentrations at the pathological site, while avoiding their accumulation in healthy non-target tissues, thereby improving the balance between the efficacy and the toxicity of systemic (chemo-) therapeutic interventions. An important advantage of such nanocarrier materials is the ease of incorporating both diagnostic and therapeutic entities within a single formulation, enabling them to be used for theranostic purposes.

Optical tomography of MMP activity allows a sensitive noninvasive characterization of the invasiveness and angiogenesis of SCC xenografts.

For improved tumor staging and therapy control, imaging biomarkers are of great interest allowing a noninvasive characterization of invasiveness. In squamous epithelial skin and cervix lesions, transition to invasive stages is associated with enhanced matrix metalloproteinase (MMP) activity, increased angiogenesis, and worsened prognosis. Thus, we investigated MMP activity as imaging biomarker of invasiveness and the potential of optical tomography in characterizing the angiogenic and invasive behavior of skin squamous cell carcinoma (SCC) xenografts.

Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging.

The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomography-fluorescence molecular tomography (CT-FMT), the tumor accumulation of a ~10 nm-sized near-infrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice.