Aneuploidy and elevated CEA indicate an increased risk for metachronous metastasis in colorectal cancer

Purpose

Presently, no markers exist to predict metachronous metastasis at the time a primary colorectal cancer is diagnosed. While aneuploidy indicates poor survival prognosis and elevated carcinoembryonic antigen (CEA) levels the presence of recurrent disease, the predictive value of both markers regarding imminent metachronous metastases is unclear.

Methods

Sixty patients with distant recurrence throughout a 5-year follow-up (TM+) were randomly chosen and 60 patients without metastasis matched to this cohort (TM?). In addition, an enlarged collective (n?=?217; n _TM+?=?85, n _TM-?=?132) with median follow-up of 79.2 months was assessed by logistic regression regarding metachronous metastases. Univariate and stepwise regression analyses included clinicopathological characteristics, preoperative CEA levels and aneuploidy assessed by DNA image cytometry.

Results

The matched-pair collective showed aneuploidy in 71.1 % (TM?) and 85.0 % (TM+; p?=?0.076), and elevated CEA in 24.5 % (TM?) and 52.2 % [TM+; odds ratio (OR), 3.414; p?=?0.007]. The enlarged collective presented aneuploidy in 71.2 % (TM?) and 83.5 % (TM+; OR 2.050, p?=?0.038), and elevated CEA in 28.6 % (TM?) and 48.9 % (TM+; OR 2.391, p?=?0.020). Elevated CEA and aneuploidy did not show any association (p?=?0.919). In contrast, logistic regression analyses demonstrated that besides increased T category (OR 1.745, p?=?0.019), both elevated CEA level (OR 2.633, p?=?0.015) and aneuploidy (OR 1.929, p?=?0.058) were independent predictive markers for metachronous metastasis.

Conclusions

Our data show that aneuploidy and elevated CEA levels besides increased T category could serve for individual risk assessment to predict metachronous metastases. The fact that still aneuploidy missed the significance level by a small margin emphasizes the need for larger validation studies.     

Temperature-memory polymer actuators

Reading out the temperature-memory of polymers, which is their ability to remember the temperature where they were deformed recently, is thus far unavoidably linked to erasing this memory effect. Here temperature-memory polymer actuators (TMPAs) based on cross-linked copolymer networks exhibiting a broad melting temperature range (ΔT_m) are presented, which are capable of a long-term temperature-memory enabling more than 250 cyclic thermally controlled actuations with almost constant performance. The characteristic actuation temperatures T_acts of TMPAs can be adjusted by a purely physical process, guiding a directed crystallization in a temperature range of up to 40 °C by variation of the parameter T_sep in a nearly linear correlation. The temperature T_sep divides ΔT_m into an upper T_m range (T > T_sep) forming a reshapeable actuation geometry that determines the skeleton and a lower T_m range (T < T_sep) that enables the temperature-controlled bidirectional actuation by crystallization-induced elongation and melting-induced contraction. The macroscopic bidirectional shape changes in TMPAs could be correlated with changes in the nanostructure of the crystallizable domains as a result of in situ X-ray investigations. Potential applications of TMPAs include heat engines with adjustable rotation rate and active building facades with self-regulating sun protectors.     

Improved PET Imaging of Tumors in Mice Using a Novel 18 F-Folate Conjugate with an Albumin-Binding Entity

Purpose

The folate receptor (FR) is a promising target for nuclear imaging due to its overexpression in many different cancer types. A drawback of using folate radioconjugates is the high accumulation of radioactivity in the kidneys. Therefore, the aim of this study was to develop a ¹⁸?F-labeled folate conjugate with an albumin-binding entity to enhance the blood circulation time and hence improve the tumor-to-kidney ratio.

Procedures

The novel ¹⁸?F-folate was prepared by conjugation of a ¹⁸?F-labeled glucose azide to an alkyne-functionalized folate precursor containing an albumin-binding entity via Cu(I)-catalyzed 1,3-dipolar cycloaddition. The radioconjugate was tested in vitro on FR-positive KB tumor cells and by biodistribution and positron emission tomography (PET) imaging studies using KB tumor-bearing mice.

Results

The radiosynthesis of the albumin-binding [¹⁸?F]fluorodeoxyglucose–folate ([¹⁸?F]3) resulted in a radiochemical yield of 1–2 % decay corrected (d.c.) and a radiochemical purity of ≥95 %. The specific activity of [¹⁸?F]3 ranged from 20 to 50 GBq/μmol. In vitro experiments revealed FR-specific binding of [¹⁸?F]3 to KB tumor cells. In vivo we found an increasing uptake of [¹⁸?F]3 into tumor xenografts over time reaching a value of ～?15 % injected dose (ID)/g at 4 h post-injection (p.i.). Uptake in the kidneys (～?13 % ID/g; 1 h p.i.) was approximately fourfold reduced compared to previously published ¹⁸?F-labeled folic acid derivatives. An excellent visualization of tumor xenografts with an unprecedentedly high tumor-to-kidney ratio (～?1) was obtained by PET imaging.

Conclusions

[¹⁸?F]3 showed a favorable accumulation in tumor xenografts compared to the same folate conjugate without albumin-binding properties. Moreover, the increased tumor-to-kidney ratios improved the PET imaging quality significantly, in spite of a somewhat higher background radioactivity which was a consequence of the slower blood clearance of [¹⁸?F]3.     

Validation of a new method based on ultrasound velocity dilution to measure cardiac output in paediatric patients

Purpose

To validate a novel method of ultrasound dilution (COstatus^®; Transonic Systems, Ithaca, NY) for measuring cardiac output in paediatric patients after biventricular repair of congenital heart disease.

Methods

Children undergoing biventricular repair of congenital heart disease were prospectively identified. Patients with significant intracardiac shunts were excluded. Postoperative cardiac output was measured by ultrasound dilution (COud) and concurrently calculated by the Fick equation (COrms) using measured oxygen consumption by respiratory mass spectrometry.

Results

Thirty-five patients were studied generating 66 individual data sets. Subjects had a median (interquartile range) age of 147 days (11, 216), weight of 4.98 kg (3.78, 6.90) and body surface area of 0.28 m² (0.22, 0.34). Of the patients, 66 % had peripheral arterial catheters and 34 % had femoral cannulation; peripheral arterial lines accounted for 6/8 of unsuccessful studies due to inability to generate sufficient flow. The site of the central venous cannula did not impact the feasibility of completing the study. A mean bias of 0.00 L/min [2 standard deviation (SD) ± 0.76 L/min] between COud and COrms was found with a percentage error of 97 %. When comparing cardiac index, bias increased to 0.13 L/min/m² (2SD ± 2.16 L/min/m²).

Conclusions

Cardiac output by ultrasound dilution showed low bias with wide limits of agreement when compared to measurement derived by the Fick equation. Although measurements through central and peripheral arterial lines were completed with minimal difficulties in the majority of patients, the application of COstatus^® in neonates with low body surface area may be limited.     

Mesenchymal stem cells are sensitive to treatment with kinase inhibitors and ionizing radiation

Introduction

Mesenchymal stem cells (MSCs) can regenerate damaged tissues and may therefore be of importance for normal tissue repair after cancer treatment. Small molecule receptor kinase inhibitors (RKIs) have recently been introduced into cancer treatment. However, the influence of these drugs—particularly in combination with radiotherapy—on the survival of MSCs is largely unknown.

Methods

The sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells to small molecule kinase inhibitors of the vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and transforming growth factor β (TGFβ) receptors, as well to inhibitors of c-Kit, was examined in combination with ionizing radiation (IR); cell survival and proliferation were assessed. Expression patterns of different kinase receptors and ligands were investigated using gene arrays.

Results

MSCs were highly sensitive to the tyrosine kinase inhibitors SU14816 (imatinib) and SU11657 (sunitinib), but showed only moderate sensitivity to the selective TGFβ receptor 1 inhibitor LY2109761. Primary adult human fibroblasts were comparably resistant to all three inhibitors. The addition of IR had an additive or supra-additive effect in the MSCs, but this was not the case for differentiated fibroblasts. Proliferation was markedly reduced in MSCs following kinase inhibition, both with and without IR. Gene expression analysis revealed high levels of the PDGF α and β receptors, and lower levels of the TGFβ receptor 2 and Abl kinase. IR did not alter the expression of kinase receptors or their respective ligands in either MSCs or adult fibroblasts.

Conclusion

These data show that MSCs are highly sensitive to RKIs and combination treatments incorporating IR. Expression analyses suggest that high levels of PDGF receptors may contribute to this effect.     

Attitudes of mental health professionals and lay-people towards involuntary admission and treatment in England and Germany--a questionnaire analysis.

OBJECTIVES: To identify attitudes about involuntary admission and treatment in mental health professionals and lay-people and to compare results between England and Germany. METHOD: Three scenarios of potentially detainable patients were presented to identify attitudes. A questionnaire asked about attitudes towards involuntary admission as well as treatment. A questionnaire analysis was then performed. RESULTS: There were similar attitudes towards involuntary admission and treatment between lay-people and mental health professionals with the exception of professionals not actively involved in the detention process. The different legal frameworks between Germany and England did not influence attitudes much. Support for involuntary admission and treatment broadly increased with age. CONCLUSIONS: Psychiatrists and other mental health workers are in tune with society with regards to attitudes towards involuntary admission. People involved with mentally ill patients but not in the detention process have negative attitudes towards involuntary admission.     

Auswirkungen des Lockdowns während der ersten COVID-19-Welle auf 34 kinder- und jugendärztliche Praxen im Saarland

Monatsschrift Kinderheilkunde - Das Saarland war in der ersten Welle der COVID-19-Pandemie eines der am stärksten betroffenen Bundesländer. Niedergelassene Kinder- und Jugendärzte...     

Changes in hepatic risk factors, metabolic variables, body composition, and physical fitness in obese children after a one-year weight loss program

Obesity can cause insulin resistance and cardiovascular and liver disease. The aim of this study was to analyze changes in laboratory values, body composition, and physical fitness before and after a one-year weight loss program with nutritional education, psychological care, and physical exercise. Twenty-two obese children (16 boys, 6 girls; median age 11.9 [range 7-15] years; BMI SDS +2.4 [1.6-3.1]) participated in the program. Outcome measures included liver enzymes, insulin resistance (HOMA), lipids, body composition, physical strength and endurance. All children had an inverse HOMA/body composition correlation; Group 1 (reduced BMI SDS after one year) had lower triglycerides, liver enzymes and improved body composition and fitness (p < 0.05). Group 2 (unchanged or increased BMI SDS) had worse body composition and increased endurance and strength of trunk extension (p < 0.05). Weight loss reduced risk factors for liver disease and improved insulin sensitivity. Body composition proved useful as a non-invasive indicator for insulin sensitivity.