The effect of low molecular weight heparins on biochemical markers of angiogenesis and the coagulation mechinsm, in patients with colon cancer undergoing therapeutic surgery

BACKGROUND: The vascular endothelial growth factor (VEGF-A) is a potent regulator of angiogenesis and most likely has a prognostic value in patients with colon cancer. In these patients, low molecular weight heparins (LMWH), are indicated for the perioperative thromoboprophylaxis.AIM OF THE STUDY: The main goal of the study was to evaluate the impact of the usage of different doses (3.500 IU vs. 4.500 IU) and/or different time periods (10 vs. 30 days) of a specific LMWH (tinzaparin), for perioperative thromboprophylaxis, upon the perioperative levels of serum VEGF, in colon cancer patients who underwent planned to have curative tumor resection (R0). MATERIALS & METHODS: 76 consecutive colon cancer patients were initially randomized and the results of 59, who conducted the four study groups, were finally analyzed. In groups I and II, the patients received 3.500 IU of tinzaparin once per day for 10 and 30 days accordingly. In groups III and IV, the patients received 4.500 IU of tinzaparin once per day for the same time-periods. Blood samples for the evaluation of serum VEGF levels and the activities of protein C, Antithrombin III (ATIII) and coagulation factor VIII (FVIII) were obtained at the following days: pre-op, 10th and 30th post-op day. Genetic analysis for thrombophilic gene mutations were performed by PCR. Statistical analysis of the results was done using repeated measurements in mixed desing ANOVA (SPSS v21, Inc. Chicago, Ill).RESULTS: With regard to the main study groups (group I to IV), all patients showed a constant increase in VEGF-A levels at the 10th post-op day, compared to the pre-op day. This increase was statistically significant in groups I, II and IV (p=0.008, p=0.017, p=0.000 accordingly). Patients of groups I and II (short duration thromboprophylaxis) showed increased serum VEGF-A levels at 30th post-op day, compared to that of patients with extended duration thromboprophylaxis (groups II and IV - p=0.000). This result was mainly due to the effect of group IV in which the serum VEGF levels at the 30th post-op day were comparable to the pre-op levels. Additionally, the higher dose of tinzaparin administered for the extended period, was the most effective in regulating the coagulation cascade. This regulation was achieved through a better regulation of fluctuation of the activity levels of proteins C, ATIII, FVIII.CONCLUSIONS: In colon cancer patients the perioperative thromboprophylaxis with LMWH 4.500 IU for 30 days results in regulation of the variations of serum VEGF levels during the post operative period. At the 30th post-op day these levels are similar to that preoperatively. Simultaneously this thromboprophylaxis scheme regulates more effectively the coagulation cascade proteins.ΕΙΣΑΓΩΓΗ: Ο αυξητικός παράγοντας του ενδοθηλίου (VEGF-A) είναι ένας ισχυρός ρυθμιστής της αγγειογένεσης και επιπλέον πιθανά έχει προγνωστική αξία σε ασθενείς με καρκίνο του παχέος εντέρου. Στους ασθενείς αυτούς, οι μικρού μοριακού βάρους ηπαρίνες (LMWH), ενδείκνυνται για την περιεγχειρητική θρομβοπροφύλαξη.ΣΚΟΠΟΣ ΤΗΣ ΜΕΛΕΤΗΣ: Στόχος της μελέτης ήταν η εκτίμηση της επίδρασης διαφορετικών δόσεων και διαφορετικής χρονικής διάρκειας χορήγησης της τινζαπαρίνης, στα περιεγχειρητικά επίπεδα του VEGF-Α, σε ασθενείς με καρκίνο του παχέος εντέρου που υποβλήθηκαν σε θεραπευτική εκτομή (R0). ΥΛΙΚΟ & ΜΕΘΟΔΟΙ: Στη μελέτη τυχαιοποιήθηκαν 76 ασθενείς, από τους οποίους τελικά, τα αποτελέσματα αναλύθηκαν σε 59, που αποτέλεσαν τον πληθυσμό των 4 ομάδων μελέτης. Στις ομάδες I και II, οι ασθενείς έλαβαν περιεγχειρητική θρομβοπροφύλαξη με τινζαπαρίνη, 3.500 IU, μια φορά την ημέρα, για 10 και 30 ημέρες, αντίστοιχα. Στις ομάδες III και IV, οι ασθενείς έλαβαν 4.500 IU τινζαπαρίνης, για αντίστοιχες χρονικές περιόδους. Αιμοληψίες, για εκτίμηση των επιπέδων VEGF και ενεργότητας της πρωτεΐνης C, αντιθρομβίνης III (ATIII) και του παράγοντα VIII, ελήφθησαν στις κάτωθι ημέρες: προεγχειρητικά (pre-op), τη 10η μετεγχειρητική ημέρα (10th post-op day) και την 30η μετεγχειρητική ημέρα (30th post-op day). Γενετική ανάλυση για γονιδιακές μεταλλάξεις σχετιζόμενες με θρομβοφιλία έγιναν με PCR. Η στατιστική ανάλυση των αποτελεσμάτων, έγινε με επαναλαμβανόμενες μετρήσεις μικτού σχεδιασμού ANOVA (SPSS v21, Inc, Chicago, Ill).ΑΠΟΤΕΛΕΣΜΑΤΑ: Oι ασθενείς όλων των ομάδων έδειξαν αύξηση των επιπέδων VEGF την 10th post-op day, σε σχέση με την pre-op day. Η αύξηση αυτή ήταν στατιστικά σημαντική στις ομάδες I, II και IV (p=0.008, p=0.017 και p=0.000, αντίστοιχα). Οι ασθενείς των ομάδων I και IIΙ (βραχεία διάρκεια θρομβοπροφύλαξης) είχαν, κατά την 30th post-op day, υψηλότερα επίπεδα VEGF, σε σχέση με τα αντίστοιχα των ασθενών με μακράς διάρκειας θρομβοπροφύλαξη, δηλαδή των ομάδων II και IV (p=0.000). Το αποτέλεσμα αυτό οφείλονταν κυρίως στα επίπεδα της ομάδας IV, οι ασθενείς της οποίας ήταν οι μόνοι των οποίων τα επίπεδα VEGF κατά την 30η post-op day, δεν διέφεραν από αυτά της pre-op day. Επιπλέον, η υψηλή δόση τινζαπαρίνης, για μακρά διάρκεια χορήγησης, έχει ως αποτέλεσμα συνολικά την αποτελεσματικότερη ρύθμιση του συστήματος πήξης, μέσω ρύθμισης της διακύμανσης των επιπέδων ενεργότητας των πρωτεϊνών ATIII, C και του παράγοντα VIII.ΣΥΜΠΕΡΑΣΜΑΤΑ: Η περιεγχειρητική θρομβοπροφύλαξη των ασθενών με καρκίνο του παχέος εντέρου, με δόση LMWH 4.500 IU για 30 ημέρες, έχει ως αποτέλεσμα την ομαλοποίηση των διακυμάνσεων των επιπέδων του VEGF, κατά τη μετεγχειρητική περίοδο, έτσι ώστε αυτά την 30th post-op day να μη διαφέρουν από τα αντίστοιχα της pre-op day και ταυτόχρονα την αποτελεσματικότερη ρύθμιση παραγόντων του μηχανισμού πήξη

An Approach to Model the Willingness to Use of E-Scooter Sharing Services in Different Urban Road Environments

E-scooter sharing services been grown exponentially within the last five years. They are based on the flexibility of accessing dense urban areas without specialized infrastructure. In modern cities, there are diverse road environments that impact the comfort, and therefore the attractiveness, of micro-mobility services. This study aims to investigate the willingness to use e-scooter sharing services, while considering the road environment. To formulate area-specific pricing policies, a stated preferences experiment with 243 respondents, who can be considered as potential users, is conducted in Athens, Greece and a binary logistic regression model with random beta parameters is developed. The analysis of the model marginal effects indicates that the integration of bonus points into micro-mobility services, combined with the option of transferring these points to parking services, can compensate a non-friendly road environment, thus increasing the service demand. The existence of roads with good pavement conditions and wide sidewalks significantly increased the willingness of respondents to use e-scooter sharing services. Unexpectedly, pedestrianized zones in a buffer area of 2 km radius from the trip origin reinforce the attractiveness of shared e-scooters, while the contribution of bike lanes and traffic calming streets (or shared space) were proven to be insignificant

The evolving role of PARP inhibitors in advanced ovarian cancer

The field of ovarian cancer has been revolutionized with the use of poly (ADP-ribose) polymerase (PARP) inhibitors, which present greater inhibition effect in epithelial subtype due to high rates of homologous recombination deficiency. PARP inhibition exploits this cancer pitfall by disrupting DNA repair, leading to genomic instability and apoptosis. Three PARP inhibitors (olaparib, niraparib, and rucaparib) are now approved for use in women with epithelial ovarian cancer, while others are under development. Among women with BRCA1/2 mutations, maintenance PARP therapy has led to a nearly fourfold prolongation of PFS, while those without BRCA1/2 mutations experience an approximately twofold increase in PFS. Differences in trial design, patient selection and primary analysis population affect the conclusions on PARP inhibitors. Limited OS data have been published and there is also limited experience regarding long-term safety. With regard to toxicity profile, there are no differences in serious adverse events between the experimental and control groups. However, combining adverse event data from maintenance phases, a trend towards more events in the experimental group, compared with controls, has been shown. The mechanisms of PARP-inhibitor resistance include restoration of HR through reversion mutations in HR genes, leading to resumed HR function. Other mechanisms that sustain sufficient DNA repair are discussed as well. PARP inhibitors play a pivotal role in the management of ovarian cancer, affecting the future treatment choices. Defining exactly which patients will benefit from them is a challenge and the need for HRD testing to define ‘BRCA-ness’ will add additional costs to treatment

Mathematical modelling of spatio-temporal glioma evolution

Summarization: Gliomas are the mos tcommon types of brain cancer,well known for their aggressive proliferation and the invasive behavior leading to a high mortality rate. Several mathematical models have been developed for identifying the interactions between glioma cells and tissue microenvironment, which play an important role in the mechanism of the tumor formation and progression.Presented on: Theoretical Biology and Medical Modellin

A glycolysis-based In silico model for the solid tumor growth

Summarization: Cancer-tumor growth is a complex process depending on several biological factors, such as the chemical microenvironment of the tumor, the cellular metabolic profile, and its proliferation rate. Several mathematical models have been developed for identifying the interactions between tumor cells and tissue microenvironment, since they play an important role in tumor formation and progression. Toward this direction we propose a new continuum model of avascular glioma-tumor growth, which incorporates a new factor, namely, the glycolytic potential of cancer cells, to express the interactions of three different tumor-cell populations (proliferative, hypoxic, and necrotic) with their tissue microenvironment. The glycolytic potential engages three vital nutrients, i.e., oxygen, glucose, and lactate, which provide cells with the necessary energy for their survival and proliferation. Extensive simulations are performed for different evolution times and various proliferation rates, in order to investigate how the tumor growth is affected. According to medical experts, the experimental observations indicate that the model predicts quite satisfactorily the overall tumor growth as well as the expansion of each region separately. Following extensive evaluation, the proposed model may provide an essential tool for patient-specific tumor simulation and reliable prediction of glioma spatiotemporal expansion.Presented on: IEEE Journal of Biomedical and Health Informatic

Describing Micro-Mobility First/Last-Mile Routing Behavior in Urban Road Networks through a Novel Modeling Approach

E-scooters aspire to provide flexibility to their users while covering the first/last mile of a multimodal trip. Yet, their dual travel behavior, i.e., utilizing both vehicles’ roadways and pedestrians’ sidewalks, creates new challenges to transport modelers. This study aims to model e-scooter riding behavior in comparison to traditional urban transport modes, namely car and walking. The new modeling approach is based on perceived safety that is influenced by the road environment and affects routing behavior. An ordinal logistic model of perceived safety is applied to classify road links in a 7-point Likert scale. The parametric utility function combines only three basic parameters: time, cost, and perceived safety. First/last mile routing choices are modeled in a test road network developed in Athens, Greece, utilizing the shortest-path algorithm. The proposed modeling approach proved to be useful, as the road environment of an urban area is heterogenous in terms of safety perceptions. Indeed, the model outputs show that the flexibility of e-scooters is limited in practice by their low-perceived safety. To avoid unsafe road environments where motorized traffic dominates, e-scooter riders tend to detour. This decision-making process tool can identify road network discontinuities. Nevertheless, their significance regarding routing behavior should be further discussed

Describing Micro-Mobility First/Last-Mile Routing Behavior in Urban Road Networks through a Novel Modeling Approach

E-scooters aspire to provide flexibility to their users while covering the first/last mile of a multimodal trip. Yet, their dual travel behavior, i.e., utilizing both vehicles’ roadways and pedestrians’ sidewalks, creates new challenges to transport modelers. This study aims to model e-scooter riding behavior in comparison to traditional urban transport modes, namely car and walking. The new modeling approach is based on perceived safety that is influenced by the road environment and affects routing behavior. An ordinal logistic model of perceived safety is applied to classify road links in a 7-point Likert scale. The parametric utility function combines only three basic parameters: time, cost, and perceived safety. First/last mile routing choices are modeled in a test road network developed in Athens, Greece, utilizing the shortest-path algorithm. The proposed modeling approach proved to be useful, as the road environment of an urban area is heterogenous in terms of safety perceptions. Indeed, the model outputs show that the flexibility of e-scooters is limited in practice by their low-perceived safety. To avoid unsafe road environments where motorized traffic dominates, e-scooter riders tend to detour. This decision-making process tool can identify road network discontinuities. Nevertheless, their significance regarding routing behavior should be further discussed

Treatment with Umbilical Cord Blood Platelet Lysate Gel Improves Healing of Diabetic Foot Ulcer

Background: This study was conducted to examine the hypothesis that umbilical cord blood platelet lysate (UCB-PL) gel has a significant impact on the healing rate of DFU. Μethods: In this open-labeled, randomized controlled trial, 110 patients were randomized to treatment with UCB-PL gel (UCB-PL group, n = 52) every three days for one month or dressing with normal saline (control group, n = 58). All participants were followed up for 20 weeks post treatment. Ulcer surface area was assessed with the imitoMeasure application at two, four, and six weeks, and two, four and six months. This study’s main outcome was the reduction in ulcer size over the six-month study period. Results: The mean ulcer area at baseline was 4.1 cm2 in the UCB-PL group and 1.7 cm2 in the control group. At six months post treatment, patients on the UCB-PL treatment displayed a significant reduction in ulcer size compared to baseline 0.12 (0–8.16) in contrast to a more modest change in the control group 1.05 (0–24.7). The ulcer area was decreased at the end of the study in 40 patients (97.6%) in the UCB-PL group and 27 (73%) in the control group (Fisher’s p = 0.002). Conclusions: The application of UCB-PL gel in DFU resulted in a significant reduction in ulcer size compared to regular saline dressing