Is Mode Switching Beneficial? A Randomized Study in Patients With Paroxysmal Atrial Tachyarrhythmias

AbstractObjectives. We sought 1) to compare three pacing modalities—DDDR with mode switching (DM), DDDR with conventional upper rate behavior (DR) and VVIR (VR)—in patients with a history of atrial tachyarrhythmias, and 2) to assess the efficacy of six mode-switching algorithms.Background. A history of atrial tachyarrhythmias has been a relative contraindication to dual-chamber pacing. Several mode-switching algorithms have recently been developed to prevent rapid tracking of atrial tachyarrhythmias.Methods. Forty-eight patients (mean age 64 years, 58% male) with a history of atrial tachyarrhythmias and heart block had a DM pacemaker implanted. Pacemakers were programmed to DM, DR and VR modes for 4 weeks each in a randomized crossover design. All subjects used a patient-activated electrocardiographic (ECG) recorder throughout the study and additionally underwent ambulatory ECG monitoring and a treadmill exercise test in each mode. They completed three symptom questionnaires at the end of each pacing period. At the end of the study, patients chose their preferred pacing period.Results. DM was significantly better than VR mode objectively (exercise time DM 8.1 min, VR 7.0 min, p < 0.01) and subjectively (perceived well-being DM 69, VR 51, p < 0.001; functional class DM 2.2, VR 2.5, p < 0.05; subjective symptom score DM 21.2, VR 26.8, p = 0.01). Patient-perceived well-being was significantly better with DM than with DR mode (DM 69, DR 60, p = 0.02). DM mode was the preferred pacing period (DM 51%, DR 14%, VR 14%). Early termination of pacing because of adverse symptoms was requested by 33% of patients during VR, 19% during DR but only 3% during DM mode. A higher proportion of patients with a fast mode-switching device preferred DM mode (fast 55%, slow 49%), whereas no patients with a fast mode-switching device chose VR as the preferred mode (fast 0%, slow 19%). In the subgroup of patients who had had atrioventricular node ablation, DM was also preferred to VR mode (DM 53%, VR 27%). Overall, there were only two cases of inappropriate mode switching and one case of inappropriate tracking of an atrial tachyarrhythmia.Conclusions. DM is the pacing mode of choice of patients with paroxysmal atrial tachyarrhythmias. With optimal programming, inappropriate mode switching and tracking of atrial tachyarrthmias was very uncommon

Front-line Bevacizumab in combination with Oxaliplatin, Leucovorin and 5-Fluorouracil (FOLFOX) in patients with metastatic colorectal cancer: a multicenter phase II study

<p>Abstract</p> <p>Purpose</p> <p>To evaluate the efficacy and the toxicity of front line FOLFOX4 combined with bevacizumab in patients with metastatsic CRC (mCRC).</p> <p>Patients and Methods</p> <p>Chemotherapy-naïve patients with mCRC, received bevacizumab (5 mg/kg every 2 weeks d₁), oxaliplatin (85 mg/m²on d₁), leucovorin (200 mg/m²) on days 1 and 2 and 5-Fluorouracil (400 mg/m²as i.v. bolus and 600 mg/m²as 22 h i.v. continuous infusion on days 1 and 2) every 2 weeks.</p> <p>Results</p> <p>Fifty three patients (46 with a PS 0–1) were enrolled. Complete and partial response was achieved in eight (15.1%) and 28 (52.8%) patients, respectively (ORR: 67.9%; 95% C.I.: 53.8%–92%); 11 (20.7%) patients had stable disease and six (11.3%) progressive disease. With a median follow up period of 13.5 months, time to tumor progression was 11 months while the median survival has not yet been reached; the probability of 1-, 2- and 3- year survival was 79.8%, 63.8% and 58.3%, respectively; Two patients relapsed during the follow up period. Eight (15%) patients underwent metastasectomy with R0 resections. Grade 3–4 neutropenia occurred in 15.1% of patients and one (1.9%) of them presented febrile neutropenia. Non-hematologic toxicity included grade 3 diarrhea (7.6%) and grade 2 and 3 neurotoxicity in 16.9 and 15.1% of patients, respectively. One (1.9%) patient presented pulmonary embolism and one (1.9%) cardiac ischaemia. There was one (1.9%) sudden death after the first cycle.</p> <p>Conclusion</p> <p>The combination of FOLFOX4/bevacizumab appears to be highly effective, well tolerated and merits further evaluation in patients with mCRC.</p

An individual patient-data meta-analysis of metronomic oral vinorelbine in metastatic non-small cell lung cancer

MOV is an active and well-tolerated chemotherapy in metastatic NSCLC and is a manageable therapy in frail patients

A randomized phase III study of the docetaxel/carboplatin combination versus docetaxel single-agent as second line treatment for patients with advanced/metastatic Non-Small Cell Lung Cancer

<p>Abstract</p> <p>Background</p> <p>To compare the activity and toxicity of docetaxel/carboplatin (DC) doublet vs single agent docetaxel (D) as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>Patients pre-treated with front-line platinum-free regimens, were randomized to receive either docetaxel/carboplatin (DC), (docetaxel 50 mg/m²; carboplatin AUC4; both drugs administered on days 1 and 15) or docetaxel single-agent (D), (docetaxel 50 mg/m²on days 1 and 15).</p> <p>Results</p> <p>Response rate was similar between the two arms (DC vs D: 10.4% vs 7.7%; p = 0.764). After a median follow-up time of 28.0 months for DC arm and 34.5 months for D arm, progression free survival (PFS) was significantly higher in the DC arm (DC vs D:3.33 months vs 2.60 months; p-value = 0.012), while no significant difference was observed in terms of overall survival (OS) (DC vs D: 10.3 months vs 7.70 months; p-value = 0.550). Chemotherapy was well-tolerated and grade III/IV toxicities were relatively infrequent. No toxic deaths were observed.</p> <p>Conclusions</p> <p>This study has not achieved its primary objective of significant OS prolongation with docetaxel/carboplatin combination over single-agent docetaxel in patients who had not received front-line docetaxel; however, the docetaxel/carboplatin combination was associated with a significant clinical benefit in terms of PFS.</p

Early farmers from across Europe directly descended from Neolithic Aegeans

Farming and sedentism first appeared in southwestern Asia during the early Holocene and later spread to neighboring regions, including Europe, along multiple dispersal routes. Conspicuous uncertainties remain about the relative roles of migration, cultural diffusion, and admixture with local foragers in the early Neolithization of Europe. Here we present paleogenomic data for five Neolithic individuals from northern Greece and northwestern Turkey spanning the time and region of the earliest spread of farming into Europe. We use a novel approach to recalibrate raw reads and call genotypes from ancient DNA and observe striking genetic similarity both among Aegean early farmers and with those from across Europe. Our study demonstrates a direct genetic link between Mediterranean and Central European early farmers and those of Greece and Anatolia, extending the European Neolithic migratory chain all the way back to southwestern Asia

Προοπτική μελέτη της δράσης αντινεοπλασματικών φαρμάκων στο Τ-λεμφοκυτταρικό σύστημα

Patients with cancer develop significant deduct of the immune system, which is worsened by the use of antineoplastic agents, since they are active against all regenerated tissues. That often results in severe infections, neutropenic (neutrophils <500/mm³) or non-neutropenic, which can be shared by common microbes or opportunistic infections, usually developed in patients with disorders of cellular immunity. In our study the administration of Docetaxel caused no statistically significant reduction in the absolute number of neutrophils (p=0.065), while the first administration found significant depletion of lymphocytes and CD3+, CD4+, CD8+, CD56+ subpopulations and also, after the second administration, and CD20+. Lymphopenia was partially reversible after discontinuation of the drug (CD3+ and CD4+ returned after 1-3 months, but did not apply the same for CD8+, CD20+, CD56+). There was also increased incidence of non-neutropenic infections in patients who received Docetaxel accompanied by a significant reduction in CD3+, CD4+, CD8+ lymphocytes. In multivariate analysis was established that treatment with Docetaxel represents an independent prognosticative factor of non-neutropenic infections. The mechanism of lymphopenia by Docetaxel is not clarified; however, it seems that has direct effects on lymphocytes (cytotoxicity) at exit from the mitosis, resulting in the increased incidence of non-neutropenic infections. During treatment with Docetaxel, it requires close monitoring of patients for early diagnosis of infections.Οι ασθενείς με καρκίνο παρουσιάζουν σημαντικού βαθμού έκπτωση του ανοσοποιητικού τους συστήματος, η οποία επιτείνεται με τη χρήση αντινεοπλασματικών παραγόντων, αφού αυτοί είναι δραστικοί έναντι όλων των αναγεννώμενων ιστών με αποτέλεσμα συχνά βαριές λοιμώξεις, ουδετεροπενικές (ουδετερόφιλα <500/mm³) η μη ουδετεροπενικές, που μπορεί να είναι από κοινά μικρόβια ή ευκαιριακές λοιμώξεις που αναπτύσσονται συνήθως σε ασθενείς με διαταραχές της κυτταρικής ανοσίας. Στη μελέτη μας η χορήγηση Docetaxel δεν προκάλεσε στατιστικά σημαντική ελάττωση του απόλυτου αριθμού ουδετερόφιλων (p=0.065), ενώ αντιθέτως από την πρώτη χορήγηση διαπιστώθηκε σημαντική ελάττωση των λεμφοκυττάρων και των CD3+, CD4+, CD8+, CD56+ υποπληθυσμών και επί πλέον μετά τη δεύτερη χορήγηση και των CD20+. Η λεμφοπενία ήταν μερικά αναστρέψιμη μετά την διακοπή του φαρμάκου (τα CD3+ και CD4+ επανέρχονταν μετά από 1-3 μήνες, δεν ίσχυε όμως το ίδιο για τα CD8+, CD20+, CD56+). Παρατηρήθηκε επίσης, αυξημένη επίπτωση μη ουδετεροπενικών λοιμώξεων σε ασθενείς που έλαβαν Docetaxel που συνοδευόταν από σημαντική μείωση των CD3+, CD4+, CD8+ λεμφοκυττάρων. Στην πολυπαραγοντική ανάλυση διαπιστώθηκε ότι η θεραπεία με Docetaxel αποτελεί ανεξάρτητο προβλεπτικό παράγοντα εκδήλωσης μη ουδετεροπενικών λοιμώξεων. Ο μηχανισμός της λεμφοπενίας από Docetaxel δεν είναι διευκρινισμένος, φαίνεται όμως πως έχει απευθείας επίδραση στα λεμφοκύτταρα (κυτταροτοξικότητα) κατά τη φάση εξόδου από τη μίτωση, με συνέπεια την αυξημένη επίπτωση μη ουδετεροπενικών λοιμώξεων. Κατά τη θεραπεία με Docetaxel απαιτείται στενή παρακολούθηση των ασθενών για την έγκαιρη διάγνωση των λοιμώξεων

Η διαμόρφωση του πολιτισμικού τοπίου της νήσου Νάξου από το 1204 έως και την ίδρυση του ελληνικού κράτους

In the first two chapters of the thesis, a brief survey is done regarding the political andecclesiastical history of the island of Naxos from the antiquity up to the establishment of theGreek State, emphasizing on the late medieval and early modern period and on the eventsassociated with the latin presence there. The reference to the historical context was deemednecessary, since for the data interpretation of the cultural phenomenon that are analyzedbelow, not only the knowledge of the historical background was deemed necessary too, inwhich the configuration of the cultural phenomenon is included but also the production ofthe test material remains that are being examined here in.Then aspects of the cultural history of the island are being examined, in light of the historicalevents that defined among other the character of the cultural landscape. The paper discussesand attempts to interpret and illuminate the causes that led to the creation of the rare andunique phenomena in Greece, as a result of cultural osmosis between the indigenous GreekOrthodox of Naxos and the Western outlanders and their descendants. Fields which form theobjects of this study here, are the cultural interactions between the monumental art of theOrthodox and Catholics, the existence of temples of the western worship western "doubleworship", the construction of fortifications works and forts Western-style buildings, includingthe castellated mansions, the heraldry existence, and other phenomena related to the Westernpresence there and the coexistence and cohabitation of the two sides (Chapters C, D, E, F, G).It is also said and written by the sources that illuminate aspects of the historical reality,referring again to the cultural osmosis between Greek Orthodox and Western. The variousWesterners mostly travelers and visitors of the Roman Catholic Apostolic Church, who visitedthe island from the 14th to the 19th century, give us their own image with respect to the goalsof the present study (Chapter H). And the detailed study concerning the lowpracticedocuments of the Velasti Collection, that is located in the Local File of Naxos, the presentstudy aims to contribute in the the creation of a more complete picture regarding the culturallandscape of the island, acting as a complement to the study of the material remains, withoutbecoming a more extensive all over study of the published and unpublished naxian lowpractice documents, since it would exceed the objectives of this thesis (chapter I). Theuniqueness of this study lies in the fact that it does not approach the historical reality in termsthat are related to the "classical" historical science, but it does move on the field of culturalhistory, largely using different methodological tools, utilizing among other testimonies thatprovide us the material remainsΣτα πρώτα δύο κεφάλαια της εργασίας γίνεται μία αναδρομή στην πολιτική καιεκκλησιαστική ιστορία της νήσου Νάξου από την αρχαιότητα έως και την ίδρυση τουΕλληνικού Κράτους, με έμφαση στην ύστερη μεσαιωνική και νεώτερη περίοδο και σταγεγονότα που συσχετίζονται με την εκεί λατινική παρουσία. Η αναφορά στο ιστορικό αυτόπλαίσιο κρίθηκε απαραίτητη, δεδομένου ότι για την ερμηνεία στοιχείων του πολιτισμικούφαινομένου που αναλύονται παρακάτω, απαραίτητη θεωρείται και η γνώση τόσο τουιστορικού περιγράμματος μέσα στο οποίο εντάσσεται η διαμόρφωση του πολιτισμικούφαινομένου όσο και η παραγωγή των εξεταζομένων εδώ υλικών καταλοίπων.Εν συνεχεία εξετάζονται πτυχές της πολιτισμικής ιστορίας του νησιού, υπό το πρίσμακαι των ιστορικών γεγονότων που καθόρισαν μεταξύ άλλων τη φυσιογνωμία του πολιτισμικούτου τοπίου. Η εργασία λοιπόν πραγματεύεται και επιχειρεί να ερμηνεύσει και να φωτίσει τααίτια που οδήγησαν στη δημιουργία φαινομένων σπανίων ή και μοναδικών για τον ελλαδικόχώρο, απόρροια της πολιτισμικής ωσμώσεως μεταξύ των γηγενών Ελλήνων Ορθοδόξων τηςΝάξου και των Δυτικών επήλυδων και των απογόνων τους. Πεδία τα οποία αποτελούν εδώαντικείμενα μελέτης είναι οι πολιτισμικές αλληλεπιδράσεις στη μνημειακή τέχνη τωνΟρθοδόξων και των Καθολικών, η ύπαρξη ναών δυτικής λατρείας και ναών «διπλήςλατρείας», η κατασκευή οχυρωματικών έργων και οχυρών κτισμάτων δυτικού τύπου,συμπεριλαμβανομένων και των πυργοειδών επαύλεων, η ύπαρξη οικοσήμων, καθώς και άλλαφαινόμενα που άπτονται της εκεί δυτικής παρουσίας και της συνύπαρξης και συμβίωσης τωνδύο πλευρών (Κεφάλαια Γ΄, Δ΄, Ε΄, Στ΄, Ζ΄).Γίνεται επίσης λόγος και σε γραπτές πηγές που φωτίζουν πτυχές της ιστορικήςπραγματικότητας, αναφορικά και πάλι με την πολιτισμική ώσμωση μεταξύ ΕλλήνωνΟρθοδόξων και Δυτικών. Οι διάφοροι Δυτικοί κυρίως περιηγητές και αποστολικοί επισκέπτες______________________________________________________________________ΕΚΤ | www.didaktorika.gr | 5της Ρωμαιοκαθολικής Εκκλησίας, που επισκέφθηκαν το νησί από τον 14ο έως και τον 19οαιώνα, μας δίνουν τη δική τους εικόνα αναφορικά με τα ζητούμενα της παρούσας εργασίας(Κεφάλαιο Η΄). Η δε περιπτωσιολογική μελέτη δικαιοπρακτικών εγγράφων της ΣυλλογήςΒελάστη, που βρίσκεται στο Τοπικό Αρχείο Νάξου, σκοπό έχει να συμβάλει στη δημιουργίαμίας πληρέστερης εικόνας αναφορικά με το πολιτισμικό τοπίο του νησιού, λειτουργώνταςσυμπληρωματικά ως προς τη μελέτη των υλικών καταλοίπων, χωρίς να γίνεται μίαεκτενέστερη μελέτη στο σύνολο του δημοσιευμένου και αδημοσίευτου υλικού των ναξιακώνδικαιοπρακτικών εγγράφων, δεδομένου ότι αυτό θα υπερέβαινε τους στόχους της παρούσαςδιατριβής (Κεφάλαιο Θ΄). Η ιδιαιτερότητα της παρούσας εργασίας έγκειται στο γεγονός ότιδεν προσεγγίζει την ιστορική πραγματικότητα με όρους που άπτονται της «κλασσικής»ιστορικής επιστήμης, αλλά κινείται στον χώρο της Ιστορίας του Πολιτισμού, χρησιμοποιώνταςδιαφορετικά εν πολλοίς μεθοδολογικά εργαλεία, αξιοποιώντας μεταξύ άλλων τις μαρτυρίεςπου μας παρέχουν τα υλικά κατάλοιπ

Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer

Myeloid-derived suppressor cells (MDSCs) constitute a vast population of immature myeloid cells implicated in various conditions. Most notably, their role in cancer is of great complexity. They exert immunosuppressive functions like hampering cancer immunity mediated by T lymphocytes and natural killer cells, while simultaneously they can recruit T regulatory cells to further promote immunosuppression, thus shielding tumor cells against the immune defenses. In addition, they were shown to support tumor invasion and metastasis by inducing vascularization. Yet again, in order to exert their angiogenic activities, they do have at their disposal a variety of occasionally overlapping mechanisms, mainly driven by VEGF/JAK/STAT signaling. In this concept, they have risen to be a rather attractive target for therapies, including depletion or maturation, so as to overcome cancer immunity and suppress angiogenic activity. Even though, many studies have been conducted to better understand these cells, there is much to be done yet. This article hopes to shed some light on the paradoxal complexity of these cells, while elucidating some of the key features of MDSCs in relation to immunosuppression and, most importantly, to the vascularization processes, along with current therapeutic options in cancer, in relation to MDSC depletion