Viscoelastometry for detecting oral anticoagulants.

BACKGROUND: Determination of anticoagulant therapy is of pronounced interest in emergency situations. However, routine tests do not provide sufficient insight. This study was performed to investigate the impact of anticoagulants on the results of viscoelastometric assays using the ClotPro device. METHODS: This prospective, observational study was conducted in patients receiving dabigatran, factor Xa (FXa)-inhibitors, phenprocoumon, low molecular weight heparin (LMWH) or unfractionated heparin (UFH) (local ethics committee approval number: 17-525-4). Healthy volunteers served as controls. Viscoelastometric assays were performed, including the extrinsic test (EX-test), intrinsic test (IN-test) Russel's viper venom test (RVV-test), ecarin test (ECA-test), and the tissue plasminogen activator test (TPA-test). RESULTS: 70 patients and 10 healthy volunteers were recruited. Clotting time in the EX-test (CTEX-test) was significantly prolonged versus controls by dabigatran, FXa inhibitors and phenprocoumon. CTIN-test was prolonged by dabigatran, FXa inhibitors and UFH. Dabigatran, FXa inhibitors and UFH significantly prolonged CTRVV-test in comparison with controls (median 200, 207 and 289 vs 63 s, respectively; all p < 0.0005). Only dabigatran elicited a significant increase in CTECA-test compared to controls (median 307 vs 73 s; p < 0.0001). CTECA-test correlated strongly with dabigatran plasma concentration (measured by anti-IIa activity; r = 0.9970; p < 0.0001) and provided 100% sensitivity and 100% specificity for detecting dabigatran. Plasma concentrations (anti-XA activity) of FXa inhibitors correlated with CTRVV-test (r = 0.7998; p < 0.0001), and CTRVV-test provided 83% sensitivity and 64% specificity for detecting FXa inhibitors. CONCLUSIONS: In emergency situations, ClotPro viscoelastometric assessment of whole-blood samples may help towards determining the presence and type of anticoagulant class that a patient is taking. TRIAL REGISTRATION: German clinical trials database ID: DRKS00015302 .

In-vitro analysis of the microbicidal activity of 6 contact lens care solutions.

BACKGROUND: Contact lens-related infections are often associated with inadequate contact lens hygiene, and therefore, contact lens care products should be able to sufficiently minimise the amount of pathogens that are responsible for these infections. In 2001, the EN ISO 14729 was introduced to ensure adequate disinfection efficacy of contact lens care solutions, but this norm has recently been criticised. METHODS: In this study, six frequently used contact lens care solutions were retested according to the Stand Alone Test of the EN ISO 14729 (2001). The Stand Alone Test is a quantitative suspension test. In addition, the products were tested in a modified setting adding an organic load. The load was a mixture of human blood serum, lysozyme, and mucine, which resembles tear fluid. RESULTS: The criteria of the Stand Alone Test recommended in EN ISO 14729 were only met by Aosept Plus. This 3% hydrogen-peroxide-based contact lens care solution attained a reduction factor of > 5 log units for bacteria and > 4 for fungi in all cases. Two further contact lens care solutions, Blue Vision and Optifree Replenish, met the criteria of a reduction factor of > 3 log units for bacteria and > 1 log unit for fungi, but only in the presence of artificial tear fluid. The three remaining products did not exhibit adequate disinfecting efficacy, at least against one of the tested microorganisms. CONCLUSIONS: Through the observation that the artificial tear fluid used in this study influences the disinfecting efficacy of contact lens care solutions, especially that of multi-purpose solutions, in a different way than does albumin, mucine, or even the organic load suggested in EN ISO 14729, it becomes obvious that the test conditions in the EN ISO 14729 should be revised in order to create more realistic conditions, e.g., by using a more realistic artificial tear fluid. Furthermore, we suggest adapting the EN ISO 14729 to the European test hierarchy for chemical disinfectants and antiseptics, which consists of three test phases and also requests meeting stricter criteria in order to pass the test. Unless the test conditions guarantee a sufficient reduction of potential pathogens, the risk of contact lens-related microbial keratitis and other infections will remain for the users.

Overestimation of low-dose radiation in intensity-modulated radiotherapy with sliding-window technique.

PURPOSE: To analyze different control-system limitations on the measured dose distributions in low-dose regions of simplified intensity fields with an electronic portal imaging device to ascertain the optimal settings for the control-system limitations in the planning system. MATERIAL AND METHODS: The authors created one field with an "optimal fluence" of intensity 1.0 (full dose) and one field with intensity 0.0 (no dose) in the central part of the field. The influence of different dose rates (DRs) and maximum leaf speeds (LS) on the calculated and measured dose and dose profiles were analyzed. RESULTS: Good agreement between calculated and measured dose in the case of a field of intensity 1.0 was found. For the field with intensity 0.0, the measured dose was 20-60% lower than the dose calculated by the "actual fluence". The results were found dependent on the DR and LS. CONCLUSION: The overestimation in regions of optimal intensity 0.0 by the planning system cannot be resolved by the user. Taking the measured dose in the region of desired intensity 1.0 and other technical limitations (like beam hold interrupts or spikes in the cross and longitudinal profiles) into consideration, the application of an LS of 2.5 cm/s and a DR of 500 MU/min is recommended in order to minimize radiation dose applied to organs at risk, which are located in regions of low intensity, like, for example, the spinal cord.

In vivo dosimetry in the urethra using alanine/ESR during (192)Ir HDR brachytherapy of prostate cancer--a phantom study.

A phantom study for dosimetry in the urethra using alanine/ESR during (192)Ir HDR brachytherapy of prostate cancer is presented. The measurement method of the secondary standard of the Physikalisch-Technische Bundesanstalt had to be slightly modified in order to be able to measure inside a Foley catheter. The absorbed dose to water response of the alanine dosimetry system to (192)Ir was determined with a reproducibility of 1.8% relative to (60)Co. The resulting uncertainty for measurements inside the urethra was estimated to be 3.6%, excluding the uncertainty of the dose rate constant Lambda. The applied dose calculated by a treatment planning system is compared to the measured dose for a small series of (192)Ir HDR irradiations in a gel phantom. The differences between the measured and applied dose are well within the limits of uncertainty. Therefore, the method is considered to be suitable for measurements in vivo.

In vitro study to assess the efficacy of CDK4/6 inhibitor Palbociclib (PD-0332991) for treating canine mammary tumours.

Therapy of canine mammary tumours (CMTs) with classical antitumour drugs is problematic, so better therapeutic options are needed. Palbociclib (PD-0332991) is an innovative and effective anticancer drug for the treatment of breast cancer in women. Palbociclib is an inhibitor of cyclin-dependent kinase 4 (CDK4) and CDK6, which are key regulators of the cell cycle machinery and thus cell proliferation. In the present in vitro study, we investigated whether Palbociclib also represents a candidate drug to combat CMT. For this purpose, the effect of Palbociclib was analysed in P114 and CF41 cells, two CMT cell lines with an endogenous CDK4/6 co-expression. Incubation of P114 and CF41 cells with Palbociclib resulted in a dose- and time-dependent loss of phosphorylated retinoblastoma protein (pRb), a classical CDK4/6 substrate within the cell cycle machinery. Moreover, treatment of CMT cells with Palbociclib-induced cell cycle arrest affected cell viability, prevented colony formation and impaired cell migration activity. Palbociclib also inhibited the growth of P114 and CF41 cell spheroids. Immunohistochemical analysis of canine patient samples revealed a consistent expression of CDK6 in different canine mammary carcinoma types, but an individual and tumour-specific expression pattern of phosphorylated pRb independent of the tumour grade. Together, our findings let us suggest that Palbociclib has antitumour effects on CMT cells and that canine patients may represent potential candidates for treatment with this CDK4/6 inhibitor.

In vivo alanine/electron spin resonance (ESR) dosimetry in radiotherapy of prostate cancer: a feasibility study.

PURPOSE: We have developed a device to evaluate the potential of alanine/electron spin resonance (ESR) dosimetry for quality assurance in 3D conformal radiotherapy for prostate cancer. It consists of a rectal balloon carrying eight alanine dosimeter probes and two metal markers to document the exact position of the balloon. We measured the effects of an air-filled rectal balloon on the dose at the rectal wall and compared these results with the applied dose distribution of the treatment planning system. MATERIALS AND METHODS: During 10 fractions with 2.0 Gy per fraction, the accumulated doses were measured in 3 patients. The results of the ESR measurements were compared to the applied doses. RESULTS: It was possible to insert the device without clinical complications and without additional rectal discomfort for the patients. The measurements of the dose accumulated at the anterior and the posterior rectal wall agreed with the applied dose within a mean deviation of 1.5% (overestimation of the dose) and 3.5% (underestimation of the dose), respectively. However, clinically significant differences between applied and measured rectal doses were seen in a patient with a hip prosthesis. In this case, the dose at the anterior rectal wall was overestimated by the TPS by about 11% and the dose at the posterior rectal wall was underestimated by approximately 7%. CONCLUSION: The method presented in this study is useful for quality control of irradiations in vivo.

An easy irradiation technique (partial half-beam) to reduce renal dose in radiotherapy of cervical cancer including paraaortic lymph nodes.

PURPOSE: : For radiation treatment of patients with cervical cancer and a high risk for paraaortic lymph node involvement, an easy three-dimensional (3-D) conformal irradiation technique (partial half-beam [PHB]) for protection of organs at risk, especially of renal tissue, was developed. PATIENTS AND METHODS: : In five consecutive female patients a computed tomography scan was performed. Dose-volume histograms of the renal tissue and other organs at risk were analyzed for PHB, three other 3-D conformal techniques, and an intensitymodulated radiotherapy (IMRT) technique. RESULTS: : The PHB technique reduced the renal volume and volumes of other organs at risk exposed to radiation doses when comparing all patients to the other 3-D conformal techniques. With use of the IMRT technique more renal tissue volume received very low radiation doses (

In vivo dosimetry with alanine/electron spin resonance dosimetry to evaluate the urethra dose during high-dose-rate brachytherapy.

PURPOSE: To determine the dose of the urethra during Ir-192 high-dose-rate brachytherapy in 15 patients, a new detector form developed for in vivo measurements was used as described by Anton et al. 2009. METHODS AND MATERIALS: The detector consists of alanine powder with paraffin as binder which was filled in a shrinkable tube for measurements. The alanine strand so produced was inserted in the foley catheter during high-dose-rate brachytherapy of the prostate. The measured dose was compared with the dose calculated by the treatment planning system SWIFT for 15 patients. After 8 patients, a marker was introduced for better positioning of the alanine strand using transrectal ultrasound images. RESULTS: The measurements of the dose of the urethra agreed very well with the dose calculated by SWIFT within the estimated standard uncertainty of the method for 8 patients with a mean absolute deviation of 0.08 Gy. However, for the other 7 patients, a mean absolute deviation between delivered and measured dose of -5.13 Gy was seen. For these patients, the active volume of the alanine dosimeter could not properly be reconstructed on the ultrasound images. CONCLUSION: The method presented in this study is useful for quality control of irradiations in vivo. To reconstruct the active volume on the corresponding ultrasound images, the correct application of the alanine strand in the urethra is very important. This procedure needs a well-trained physician.

Feasibility study of entrance and exit dose measurements at the contra lateral breast with alanine/electron spin resonance dosimetry in volumetric modulated radiotherapy of breast cancer.

The Physikalisch-Technische Bundesanstalt has established a secondary standard measurement system for the dose to water, D W, based on alanine/ESR (Anton et al 2013 Phys. Med. Biol. 58 3259-82). The aim of this study was to test the established measurement system for the out-of-field measurements of inpatients with breast cancer. A set of five alanine pellets were affixed to the skin of each patient at the contra lateral breast beginning at the sternum and extending over the mammilla to the distal surface. During 28 fractions with 2.2 Gy per fraction, the accumulated dose was measured in four patients. A cone beam computer tomography (CBCT) scan was generated for setup purposes before every treatment. The reference CT dataset was registered rigidly and deformably to the CBCT dataset for 28 fractions. To take the actual alanine pellet position into account, the dose distribution was calculated for every fraction using the Acuros XB algorithm. The results of the ESR measurements were compared to the calculated doses. The maximum dose measured at the sternum was 19.9 Gy ± 0.4 Gy, decreasing to 6.8 Gy ± 0.2 Gy at the mammilla and 4.5 Gy ± 0.1 Gy at the distal surface of the contra lateral breast. The absolute differences between the calculated and measured doses ranged from -1.9 Gy to 0.9 Gy. No systematic error could be seen. It was possible to achieve a combined standard uncertainty of 1.63% for D W = 5 Gy for the measured dose. The alanine/ESR method is feasible for in vivo measurements.

Making the right software choice for clinically used equipment in radiation oncology.

The customer of a new system for clinical use in radiation oncology must consider many options in order to find the optimal combination of software tools. Many commercial systems are available and each system has a large number of technical features. However an appraisal of the technical capabilities, especially the options for clinical implementations, is hardly assessable at first view.The intention of this article was to generate an assessment of the necessary functionalities for high precision radiotherapy and their integration in ROKIS (Radiation oncology clinic information system) for future customers, especially with regard to clinical applicability. Therefore we analysed the clinically required software functionalities and divided them into three categories: minimal, enhanced and optimal requirements for high conformal radiation treatment.