Downsizing Treatment with Tyrosine Kinase Inhibitors in Patients with Advanced Gastrointestinal Stromal Tumors Improved Resectability

Background  

Gastrointestinal stromal tumors (GISTs) express the receptor tyrosine kinase KIT. Most GISTs have mutations in the KIT or PDGFRA gene, causing activation of tyrosine kinase. Imatinib, a tyrosine kinase inhibitor (TKI), is the first-line palliative treatment for advanced GISTs. Sunitinib was introduced for patients with mutations not responsive to imatinib. The aim was to compare the survival of patients with high-risk resected GISTs treated with TKI prior to surgery with historical controls and to determine if organ-preserving surgery was facilitated.     

Serotonin 1B receptor density mapping of the human brainstem using positron emission tomography and autoradiography

The serotonin 1B (5-HT_1B) receptor has lately received considerable interest in relation to psychiatric and neurological diseases, partly due to findings based on quantification using Positron Emission Tomography (PET). Although the brainstem is an important structure in this regard, PET radioligand binding quantification in brainstem areas often shows poor reliability. This study aims to improve PET quantification of 5-HT_1B receptor binding in the brainstem.Volumes of interest (VOIs) were selected based on a 3D [³H]AZ10419369 Autoradiography brainstem model, which visualized 5-HT_1B receptor distribution in high resolution. Two previously developed VOI delineation methods were tested and compared to a conventional manual method. For a method based on template data, a [¹¹C]AZ10419369 PET template was created by averaging parametric binding potential (BP_ND) images of 52 healthy subjects. VOIs were generated based on a predefined volume and BP_ND thresholding and subsequently applied to test-retest [¹¹C]AZ10419369 parametric BP_ND images of 8 healthy subjects. For a method based on individual subject data, VOIs were generated directly on each individual parametric image.Both methods showed improved reliability compared to a conventional manual VOI. The VOIs created with [¹¹C]AZ10419369 template data can be automatically applied to future PET studies measuring 5-HT_1B receptor binding in the brainstem.     

The RUSH2A Study: Dark-Adapted Visual Fields in Patients With Retinal Degeneration Associated With Biallelic Variants in the USH2A Gene

PurposeTo measure visual fields using two-color dark-adapted chromatic perimetry in a subset of participants in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A), a study of USH2A-mediated syndromic (USH2) and autosomal recessive nonsyndromic retinitis pigmentosa, determine percentage retaining rod function, and explore relationships between dark-adapted visual fields (DAVF) and rod function from ERG and full-field stimulus thresholds (FST).MethodsFull-field rod mean sensitivity, number of rod loci, maximum sensitivity, DAVF full-field hill of vision (DAVF V_TOT), and 30° hill of vision (DAVF V₃₀) were measured in one eye for DAVF ancillary study participants (n = 49). Loci where cyan relative to red sensitivity was more than 5 dB on dark-adapted chromatic perimetry were considered rod mediated. Correlation coefficients between the DAVF measures and standard clinical measures were estimated, as were kappa statistics (κ) for agreement between DAVF and other measures of rod function.ResultsOf 49 participants tested with DAVF, 38 (78%) had evidence of rod function, whereas 15 (31%) had measurable rod ERGs. DAVF maximum sensitivity was highly correlated with FST white thresholds (r = −0.80; P < .001). Although not statistically significant, the number of rod loci and DAVF V_TOT were lower in eyes with longer disease duration by 0.82 (95% confidence interval, −1.76, 0.12) loci/year and 0.59 (95% confidence interval, −1.82, 0.64) dB-steradians/year, respectively.ConclusionsRod-mediated function on FST and DAVF is present in many patients with symptomatic USH2A-related retinal degeneration, including some without measurable rod ERGs. RUSH2A longitudinal data will determine how these measures change with disease progression and whether they are useful for longitudinal studies in inherited retinal degenerations.     

Palladium(II) Complexes with N‐Heteroaromatic Bidentate Hydrazone Ligands: The Effect of the Chelate Ring Size and Lipophilicity on in vitro Cytotoxic Activity

Novel Pd(II) complex with N‐heteroaromatic Schiff base ligand, derived from 8‐quinolinecarboxaldehyde (q8a) and ethyl hydrazinoacetate (haOEt), was synthesized and characterized by analytical and spectroscopy methods. The structure of novel complex, as well as structures of its quinoline and pyridine analogues, was optimized by density functional theory calculations, and theoretical data show good agreement with experimental results. A cytotoxic action of the complexes was evaluated on cultures of human promyelocytic leukemia (HL‐60), human glioma (U251), rat glioma (C6), and mouse fibrosarcoma (L929) cell lines. Among investigated compounds, only complexes with quinoline‐based ligands reduce the cell numbers in a dose‐dependent manner in investigated cell lines. The observed cytotoxic effect of two isomeric quinoline‐based complexes is predominantly mediated through the induction of apoptotic cell death in HL‐60 cell line. The cytotoxicity of most efficient novel Pd(II) complex is comparable to the activity of cisplatin, in all cell lines investigated.     

PAMAM G4 dendrimers lower high glucose but do not improve reduced survival in diabetic rats

For nearly a decade poly(amidoamine) (PAMAM) dendrimers G4 were claimed unnegligible cytotoxic agents. Here we monitored whether in vivo cytotoxic effect of PAMAM G4 (0.5 micromol kg(-1) day(-1)) may be compromised by its ameliorating effect on severe hyperglycaemia in chronic streptozotocin-diabetic Wistar rats. PAMAM G4 significantly reduced the 60-day overall survival in long-term experimental diabetes: treated animals were 6.7 times more likely to die than control animals (p<0.025). PAMAM G4 significantly reduced numerous biochemical parameters in blood, including glucose, glycated haemoglobin or protein oxidation, cholesterol and triglycerides, but apparently unchanged plasma insulin peptide C. Terminal blood glucose in PAMAM-treated animals was significantly higher in survivors, pointing to the possible preventive role of glycation in reducing of PAMAM G4 cytotoxicity. Our results provide the first in vivo evidence that PAMAM G4 is able to lower plasma glucose and suppress long-term markers of diabetic hyperglycaemia. Nevertheless, this beneficial influence cannot override PAMAM G4 cytotoxic effects in the increased mortality of streptozotocin-diabetic rats.     

Kinetics of lactose fermentation in milk with kombucha starter

The aim of this research was to investigate the effect of new, non-conventional starter culture on the kinetics of the lactose transformation during milk fermentation by kombucha, at pH 5.8; 5.4; 5.1; 4.8; and 4.6, at two different temperatures 37 °C and 42 °C. Milk fermentation at 42 °C lasted significantly shorter (about 5 h, 30 min) compared to the fermentation at 37 °C. Changes of lactose concentration at the both temperatures are consisting of two retaining stages and very steep decline in–between. The analysis of the rate curves showed that the reaction rate passes through the maximum after 9 h, 30 min at 37 °C and after 4 h at 42 °C. The sigmoidal saturation curve indicates a complex kinetics of lactose fermentation by kombucha starter.     

Cancer patients' perceptions of quality‐of‐care attributes—Associations with age,perceived health status,gender and education

Aims and objectives

The aim of this study was to explore the associations between patients' gender, education, health status in relation to assessments of patient‐centred quality and individuality in care and trust in nurses for those <65 (working age) and ≥65 years (older people).

Background

Patients' assessments of the quality of care they receive are essential for the development of the provision of patient care and services. Previous studies have revealed age of the patient is associated with their assessment of care quality attributes.

Design

The study employed a cross‐sectional, multicultural comparative survey design.

Methods

The data were collected using questionnaires among hospitalised cancer patients (N = 876, n = 599, 68%) in four European countries: Greece, Cyprus, Sweden and Finland. The data were divided into two subgroups based on age (cut point 65 years) and were analysed statistically.

Results

Cancer patients' age, gender and level of education were not related to their assessments of care quality attributes: person‐centred care quality, individuality in care and trust in nurses. Subgroup analysis of the older adults and those of working age showed clear associations with patients' assessments of quality‐of‐care attributes and perceived health status. The lower the perceived health status, the lower the assessment of care quality attributes.

Discussion

The results suggest that the cancer itself is the strongest determinant of the care delivered, rather than any patient characteristics, such as age, education or gender. Perceived health status, in association with cancer patient assessments of care quality attributes, may be useful in the development of patient‐centred, individualised care strategies alongside a stronger focus on people instead of cancer‐care‐related processes and duties.

Conclusions

Health status was the only factor associated with cancer patients' assessments of care quality attributes. Cancer itself may be the strongest determinant of the care quality perceptions, rather than any patient characteristics.

Relevance to clinical practice

The findings of this study have implications for cancer care professionals in terms of patient assessment and care planning. The measures may be useful in assessing quality of cancer nursing care.