Layer-specific and whole wall global longitudinal strain predict major adverse cardiovascular events in patients with stable angina pectoris

The International Journal of Cardiovascular Imaging - Global longitudinal strain (GLS) has proven to be a powerful prognostic marker in various patient populations, but the prognostic value of...     

Qualitätsentwicklung im Gesundheitswesen: Sind wir schon so weit,wie wir wollten?

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz -     

Nanotherapy: New Approach for Impeding Hepatic Cancer Microenvironment via Targeting Multiple Molecular Pathways

Objective: Hepatocellular carcinoma (HCC) microenvironment has been recognized as a key contributor for cancer progression, metastasis, and drug resistance. The crosstalk between tumor cells, the vascular endothelial growth factor (VEGF), and the chemokine (C-C motif) ligand 2 (CCL2) signaling networks mediates immunoinhibitory impact and facilitates tumor angiogenesis. The current investigation aimed at exploring the potent anti-cancer activity of the newly designed nano-based anti-cancer therapy comprising anti-VEGF drug, avastin (AV), and CCR2 antagonist (CR) to counteract HCC and tracking its mode of action in vivo. Methods: The prepared AV, CR, and AVCR nanoprototypes were characterized by nanoscale characterization techniques in our previous work. Here, they are applied for unearthing their anti-cancer properties / mechanisms in hepatic cancer-induced rats via analyzing protein levels and genetic expression of the elements incorporated in the angiogenesis, apoptosis, and metastasis signalling pathways. Results: The present results revealed a significant down-regulation in the angiogenesis, survival and metastasis indices along with up-regulation in the pro-apoptotic mediators upon treatment of hepatic cancer-bearing rats with the novel synthesized nanomaterials when compared with the untreated counterparts. We showed across HCC model that anti-VEGF in combination with CCR2 antagonism therapy leads to sensitization and enhanced tumor response over anti-VEGF or CCR2 antagonism monotherapy, particularly in its nanoscale formulation. Conclusion: The present approach provides new mechanistic insights into the powerful anti-hepatic cancer advantage of the novel nanoprototypes which is correlated with modulating critical signal transduction pathways implicated in tumor microenviroment such as angiogenesis, apoptosis and metastasis. This research work presents a substantial foundation for future studies focused on prohibiting cancer progression and recovery by targeting tumor microenviroment.     

Glycaemic control for patients with severe acute brain injury: Protocol for a systematic review

Background

Hyperglycaemia is common in patients with acute brain injury admitted to an intensive care unit (ICU). Many studies have found associations between development of hyperglycaemia and increased mortality in hospitalised patients. However, the optimal target for blood glucose control is unknown. We want to conduct a systematic review with meta-analysis and trial sequential analysis to explore the beneficial and harmful effects of restrictive versus liberal glucose control on patient outcomes in adults with severe acute brain injury.

Methods

We will systematically search medical databases including CENTRAL, Embase, MEDLINE and trial registries. We will search the following websites for ongoing or unpublished trials: http://www.controlled-trials.com/ , http://www.clinicaltrials.gov/ , www.eudraCT.com , http://centerwatch.com/ , The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded and CINAHL. Two authors will independently review and select trials and extract data. We will include randomised trials comparing levels of glucose control in our analyses and observational studies will be included to address potential harms. The primary outcomes are defined as all-cause mortality, functional outcome and health-related quality of life. Secondary outcomes include serious adverse events including hypoglycaemia, length of ICU stay and duration of mechanical ventilation, and explorative outcomes including intracranial pressure and infection. Trial Sequential Analysis will be used to investigate the risk of type I error due to repetitive testing and to further explore imprecision. Quality of trials will be evaluated using the Cochrane Risk of Bias tool, and quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Discussion

The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice.     

Development of an automated production process of [64Cu][Cu (ATSM)] for positron emission tomography imaging and theranostic applications

Cyclotron-produced copper-64 radioisotope tracers offer the possibility to perform both diagnostic investigation by positron emission tomography (PET) and radiotherapy by a theranostic approach with bifunctional chelators. The versatile chemical properties of copper add to the importance of this isotope in medicinal investigation. [⁶⁴Cu][Cu (ATSM)] has shown to be a viable candidate for imaging of tumor hypoxia; a critical tumor microenvironment characteristic that typically signifies tumor progression and resistance to chemo-radiotherapy. Various production and radiosynthesis methods of [⁶⁴Cu][Cu (ATSM)] exist in labs, but usually involved non-standardized equipment with varying production qualities and may not be easily implemented in wider hospital settings. [⁶⁴Cu][Cu (ATSM)] was synthesized on a modified GE TRACERlab FXN automated synthesis module. End-of-synthesis (EOS) molar activity of [⁶⁴Cu][Cu (ATSM)] was 2.2–5.5 Ci/μmol (HPLC), 2.2–2.6 Ci/μmol (ATSM-titration), and 3.0–4.4 Ci/μmol (ICP-MS). Radiochemical purity was determined to be >99% based on radio-HPLC. The final product maintained radiochemical purity after 20 h. We demonstrated a simple and feasible process development and quality control protocols for automated cyclotron production and synthesis of [⁶⁴Cu][Cu (ATSM)] based on commercially distributed standardized synthesis modules suitable for PET imaging and theranostic studies.     

Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma

Background

Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.

Methods

Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.

Results

Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.

Conclusions

Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS.     

Bioimpedance as a measure of fluids in patients with septic shock. A prospective observational study

Background

Septic shock is often treated with aggressive fluid resuscitation leading to profound fluid overload. The assessment of fluid status relies on suboptimal measures making treatment difficult. Bioelectrical impedance analysis is an alternative but the validity is unclear. The aim of this study was to determine the validity of bioelectrical impedance analysis for fluid measures in patients with septic shock.

Methods

Single-center, prospective observational cohort study. We included adult ICU patients with septic shock. We evaluated the agreement between measures on the left and right side of the patient and measures 1 h apart by two bioelectrical impedance devices. Results are presented as Bland Altman plots with 95% Limits of Agreements (LoA) and as correlations between bioelectrical impedance analysis results and clinical markers of fluids.

Results

Forty-nine patients were included. The agreement between measures on the left and the right side of the patient and after 1 h was overall without bias, but with wide LoA's. Fluid overload 1 h apart showed the most narrow 95% LoA (−2.4–2.9 L). The same wide limits of agreements were observed when comparing devices. For example, total body water with 95% LoA of −14.8 –16.7 L. Correlations between bioelectrical impedance analysis and clinical measures were low but statistically significant.

Conclusions

In patients with septic shock bioelectrical impedance analysis had no systematic errors or bias, but wide limits of agreement, indicating that the devices have a large and uncorrectable random error. Fluid status by bioelectrical impedance analysis is not sufficiently accurate to guide treatment in this group of patients.