COVID-19 vaccinations: summary guidance for Cancer patients in 28Languages: breaking barriers to Cancer patient Information

Background: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations. Methods: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. Results: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. Conclusion: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.info:eu-repo/semantics/publishedVersio

The role of cell surface cluster of the differentiation (CD) molecules in cancer development and the role of the canonical NF-κB signaling in CD regulation

Carcinogenesis is a multistep process, which at a cellular level involves the accumulation of genetic mutations in conjunction with epigenetic modifications, resulting in dominant alterations in gene expression and cellular physiology. Consequently, these changes lead to uncontrolled cell division and evasion of apoptosis. The development and progression of cancer, however, is a much more complex process involving also cells and other factors present in the tumor microenvironment, including the host's immune system. Among the cluster of differentiation cell surface molecules that are involved in carcinogenesis are tetraspanins. Tetraspanins are transmembrane proteins that span the cell membrane with 4 α-helices and regulate multiple biological processes through their ability to cluster and organize specific receptors and signaling proteins into micro-regions/-domains on the cell surface. These proteins combine with each other, as well as with a series of other transmembrane and cytoplasmic proteins to form membrane microdomains (tetraspanin enriched microdomains - TEMs). These protein complexes are also referred to in the literature as tetraspanin webs. By definition, a key feature of tetraspanins is to organize specific receptors and signaling proteins into membrane microdomains on the cell surface. Tetraspanins have received particular recognition, as their distinct mechanism of action allows them to have multiple and diverse functions within a single cell and/or between different cell types. Tetraspanins are involved normally in fundamental cellular processes such as cell proliferation, differentiation and migration. In the immune system, tetraspanins interact with prominent leukocyte receptors leading to their activation and the downstream signal transduction pathways. Among the biological processes tetraspanins are involved in, there is evidence that they are implicated in carcinogenesis, acting as tumor of metastasis suppressors or promoters, as well as regulating the immune response in the tumor microenvironment. However, due to the pleiotropic functions of tetraspanins, the precise molecular mechanisms contributing to carcinogenesis but also in the immune response are not fully understood. The tetraspanin family includes the surface molecules CD81 and CD82. CD82 tetraspanin is thought to act as a tumor suppressor, while CD81 tetraspanin has been thought to be a tumor promoter, however, given their pleiotropic functions, their role in colon cancer remains unknown. With the present proposal we aim to investigate the role of tetraspanins CD81 and CD82 in the development and progression of colon cancer. In the current study we examined, in patients with colon cancer by using immunohistochemistry, the expression of the tetraspanins CD81 and CD82 and the expression of the markers PD1 and PDL1 in tumor cells as well as in tumor infiltrating lymphocytes. We also examined the infiltration of the tumor microenvironment by CD3(+) and CD8(+) lymphocytes. For that purpose, fixed patient tissues in the form of tissue-microarrays (TMAs) were used. The patients' immunohistochemical data were correlated with their clinical and laboratory findings. We also estimated the overall survival and progression-free survival of the colon cancer patients according to their pathologic, clinical and laboratory characteristics. Our aim was to evaluate the role of each of these molecules/markers in colon cancer, acting either as suppressors or promoters of carcinogenesis, as well as to determine their prognostic and/or predictive value. Furthermore, we studied the role of tetraspanin CD81 in the progression (growth, tumor cell motility and tumorigenicity) of colon cancer in vitro, investigated possible mechanisms of action and examined whether the normal NF-κB signaling pathway is involved in the regulation of its expression CD81 in colon cancer cells. For this reason, we modified the expression of CD81 in DLD1, HCT116, CACO2 colon cancer cells. Using retroviral vectors, we were able to downregulate the expression of CD81 in DLD1, HCT116, CACO2 cells (using shRNA against CD81), and also upregulate CD81 expression in HCT116, CACO2 cells (using a retroviral vector carrying a of the CD81 gene).Results:•We observed that patients with a performance status (PS) 0, had a lower expression of CD81 by immunohistochemistry on cancer cells compares to patients with PS 1 or 2.•Patients with mismatch-repair (MMR) proficient tumors had a higher CD81 expression by immunohistochemistry on cancer cells than MMR-deficient patients •Non-metastatic patients were found to have a higher percentage of CD81(+)-lymphocytes infiltrating their tumors than metastatic patients.• We observed a negative correlation between the expression by immunohistochemistry of CD81 on tumor cells and tumor infiltrating CD3(+) and CD8(+) lymphocytes. •We found that CD82 expression on cancer cells by immunohistochemistry was less prominent in higher disease stages according to TNM staging, with metastatic patients displaying much lower levels of CD82 expression compared to non-metastatic patients. •We observed that patients with R1 or R2 resection had reduced expression of CD82 in tumor tissues compared to patients who had R0 resection. •Patients with elevated values of the tumor markers CEA and CA 19-9 displayed reduced CD82 expression on tumor cells by immunohistochemistry. •We observed that left-sided primary tumors displayed higher CD82 expression on cancer cells by immunohistochemistry, compared to right-sided primary tumors. •Metastatic patients, patients with a poor general health status (PS1 or 2) and patients with elevated CEA and CA 19-9 values, displayed a reduced percentage of CD82(+) tumor infiltrating lymphocytes. •The percentage of PD1(+) tumor cells was higher in non-metastatic patients compared to metastatic patients. •A higher percentage of PD1(+) tumor cells and PD1(+) lymphocytes was observed in patients with low CEA and CA 19-9 tumor marker values. •We observed a positive correlation between the expression of CD81 and CD82 on tumor cells and the expression of PD1 on tumor cells. •We observed a positive correlation between PD1(+)-lymphocytes and CD81(+)-lymphocytes, CD82(+)-lymphocytes, CD3(+)-lymphocytes, CD8(+)-lymphocytes. •The percentage of CD3(+) and CD8(+) tumor infiltrating lymphocytes was higher in non-metastatic patients compared to metastatic. •The percentage of CD3(+) and CD8(+) tumor infiltrating lymphocytes was higher in patients with a good performance status (PS0 vs PS1&2).•Infiltration by CD8(+)-lymphocytes was lower in patients with high CEA and Ca 19-9 values. •Infiltration by CD8(+) lymphocytes was higher in MMR-deficient patients. •Patients with a higher percentage of infiltrating CD81(+) lymphocytes demonstrated better overall survival (OS) and progression-free survival (PFS). •We observed that increased expression by immunohistochemistry of tetraspanin CD82 in tumor cells as well as increased percentage of infiltrating CD82(+) lymphocytes was associated with better overall and progression-free survival. •Patients with higher percentages of PD1(+) tumor cells or PD1(+) infiltrating tumor lymphocytes, had a lower risk of death (OS) and/or relapse (PFS).•Patients with higher percentages CD8(+) infiltrating tumor lymphocytes demonstrated improved overall and progression-free survival. •We confirmed the prognostic value of the already known clinical and pathological parameters, such as disease stage, complete surgical resection and values of CEA and CA 19-9 tumor markers. •We found that tetraspanin CD81 promotes in vitro the proliferation rate of human colon cancer cells DLD1, CACO2 and HCT116. •We found that tetraspanin CD81 in vitro increases the motility of human colon cancer cells DLD1, CACO2 and HCT116. •We found that tetraspanin CD81 in vitro promotes tumorigenesis in DLD1 colon cancer cells. •We found that tetraspanin CD81 in vitro promotes cell cycle progression by positively influencing the expression of the transcription factors E2F1 and CDC6.•We observed a possible interaction of the tetraspanin CD81 with the signaling pathways of NF-κB, which, however, needs further investigation. In conclusion, we found by immunohistochemistry that tetraspanin CD82 has a protective role in the development and progression of colon cancer, as its expression in cancer tissues was associated with favorable clinicopathological characteristics of patients and increased survival. Similarly, PD1 expression was also identified as a positive prognostic factor by immunohistochemistry. Additionally, we observed by immunohistochemistry that the tetraspanin CD81 probably functions by suppressing the immune response in the tumor microenvironment in colon cancer, since infiltration of CD3(+) and CD8(+) T-lymphocytes was less prominent in patients with high CD81 expression in tumor cells. Finally, we found that tetraspanin CD81 contributes in vitro to the growth and progression of colon cancer, by promoting cancer cells’ proliferation and motility, while also positively regulating cell cycle progression.Η καρκινογένεση είναι μια πολύ-σταδιακή διαδικασία η οποία σε κυτταρικό επίπεδο περιλαμβάνει τη συσσώρευση γενετικών μεταλλάξεων, οι οποίες σε συνδυασμό με επιγενετικές τροποποιήσεις οδηγούν σε καθοριστικές μεταβολές στην γονιδιακή έκφραση και τη κυτταρική φυσιολογία, με αποτέλεσμα την ανεξέλεγκτη διαίρεση του κυττάρου και την απόκτηση μηχανισμών αποφυγής της απόπτωσης. Η ανάπτυξη και η εξέλιξη του καρκίνου ωστόσο αποτελεί μία περισσότερο περίπλοκη διαδικασία στην οποία συμβάλουν κύτταρα και άλλοι παράγοντες που είναι παρόντες στο μικροπεριβάλλον του όγκου, συμπεριλαμβανόμενου και του ανοσοποιητικού συστήματος του ξενιστή. Στους μοριακούς μηχανισμούς που σχετίζονται με την καρκινογένεση εμπλέκονται και τα μόρια της κυτταρικής επιφάνειας του συμπλέγματος διαφοροποίησης που είναι γνωστά ως τετρασπανίνες. Οι τετρασπανίνες είναι διαμεμβρανικές πρωτεΐνες που διαπερνούν τη μεμβράνη του κυττάρου με 4 α-έλικες και ρυθμίζουν πολλαπλές βιολογικές διεργασίες μέσω της ικανότητας τους να συγκεντρώνουν και να οργανώνουν συγκεκριμένους υποδοχείς και πρωτεΐνες σηματοδότησης σε μικρο-περιοχές στην επιφάνεια του κυττάρου. Οι πρωτεΐνες αυτές συνδυάζονται μεταξύ τους, καθώς και με μία σειρά άλλων διαμεμβρανικών και κυτταροπλασματικών πρωτεϊνών για να σχηματίσουν τις μεμβρανικές μικροεπικράτειες (μικροπεριοχές μοριακών συμπλεγμάτων εμπλουτισμένων με τετρασπανίνες -Tetraspanin Enriched Microdomains - TEMs). Αυτά τα πρωτεϊνικά συμπλέγματα αναφέρονται τους στη βιβλιογραφία ως δίκτυα τετρασπανινών (tetraspanin webs). Εξ ορισμού, ένα βασικό χαρακτηριστικό των τετρασπανινών είναι να οργανώνουν συγκεκριμένους υποδοχείς και πρωτεΐνες σηματοδότησης σε μεμβρανικές μικροεπικράτειες (microdomains) στην επιφάνεια των κυττάρων. Οι τετρασπανίνες έχουν λάβει ιδιαίτερης αναγνώρισης, καθώς ο ξεχωριστός μηχανισμός δράσης τους, τους επιτρέπει να έχουν πολλαπλές διαφορετικές λειτουργίες σε ένα κύτταρο ή/και μεταξύ διαφορετικών κυτταρικών τύπων. Οι τετρασπανίνες εμπλέκονται σε θεμελιώδεις κυτταρικές διεργασίες όπως ο πολλαπλασιασμός, η διαφοροποίηση και η μετανάστευση των κυττάρων. Επιπλέον, εμπλέκονται στην ενεργοποίηση, τον πολλαπλασιασμό, την ωρίμανση και την στόχευση διάφορων κυττάρων-τελεστών του ανοσοποιητικού συστήματος. Μεταξύ των βιολογικών διεργασιών που εμπλέκονται οι τετρασπανίνες υπάρχουν στοιχεία ότι ενέχονται στην καρκινογένεση καθώς και στην ανοσολογική απάντηση στο μικροπεριβάλλον του όγκου (11,28,70), ωστόσο, λόγω των πλειοτροπικών τους λειτουργιών, οι ακριβείς μοριακοί μηχανισμοί που διέπουν τη λειτουργία των τετρασπανινών και η συμβολή τους στην καρκινογένεση αλλά και στην ανοσολογική απάντηση δεν είναι πλήρως κατανοητοί. Στην οικογένεια των τετρασπανινών συγκαταλέγονται τα μόρια επιφανείας CD81 και CD82. Η τετρασπανίνη CD82 θεωρείται ότι δρα κατασταλτικά στην εξέλιξη του καρκίνου ενώ η τετρασπανίνη CD81 έχει ενοχοποιηθεί ότι προάγει την ανάπτυξη του όγκου, ωστόσο, δεδομένου των πλειοτροπικών τους λειτουργιών, η συμβολή τους στον καρκίνο του παχέος εντέρου παραμένει άγνωστη. Με την παρούσα πρόταση στοχεύουμε να διερευνήσουμε τον ρόλο τετρασπανινών CD81 και CD82 στην ανάπτυξη και εξέλιξη του καρκίνου του παχέος εντέρου αλλά και στην ανοσολογική απάντηση στο μικροπεριβάλλον του όγκου.Στην παρούσα διατριβή μελετήσαμε, σε ασθενείς με καρκίνο παχέος εντέρου, με τη χρήση ανοσοϊστοχημείας την έκφραση των τετρασπανινών CD81 και CD82 και των δεικτών PD1 και PDL1 σε καρκινικά κύτταρα και διηθούντα λεμφοκύτταρα, καθώς επίσης τη διήθηση του όγκου από CD3(+) και CD8(+) λεμφοκύτταρα. Για το σκοπό αυτό χρησιμοποιήθηκαν μονιμοποιημένοι ιστοί ασθενών σε μορφή TMAs. Τα ανοσοϊστοχημικά δεδομένα των ασθενών συσχετίστηκαν με τα κλινικο-εργαστηριακά τους χαρακτηριστικά. Εκτιμήσαμε επίσης την ολική επιβίωση και την επιβίωση ελεύθερης νόσου των ασθενών βάση των παθολογοανατομικών και κλινικο-εργαστηριακών τους χαρακτηριστικών. Σκοπός μας ήταν να αξιολογήσουμε το ρόλο καθενός από αυτά τα μόρια στον καρκίνο του παχέος εντέρου, ενεργώντας είτε ως καταστολείς, είτε ως προαγωγείς της καρκινογένεσης, καθώς και να προσδιορίσουμε την προγνωστική ή/και προβλεπτική τους αξία. Επιπλέον, μελετήσαμε τον ρόλο της τετρασπανίνης CD81 στην εξέλιξη (ανάπτυξη, κινητικότητα καρκινικών κυττάρων και δυνατότητα σχηματισμού όγκων) του καρκίνου του παχέος εντέρου in vitro, διερευνήσαμε πιθανούς μηχανισμούς δράσης και εξετάσαμε εάν η κανονική σηματοδοτική πορεία του NF-κΒ εμπλέκεται στην ρύθμιση της έκφρασης της CD81 στα καρκινικά κύτταρα παχέος εντέρου. Για το λόγο αυτό τροποποιήσαμε την έκφραση της CD81 στα καρκινικά κύτταρα παχέος εντέρου DLD1, HCT116, CACO2. Χρησιμοποιώντας ρετρο-ιικούς φορείς μπορέσαμε να μειώσουμε την έκφραση της CD81 στα κύτταρα DLD1, HCT116, CACO2 (με τη χρήση shRNA έναντιi της CD81), αλλά και να την αυξήσουμε στα κύτταρα HCT116, CACO2 (με τη χρήση ρετρο-ιικού φορέα που έφερε αντίγραφο του γονιδίου της CD81). Αποτελέσματα: •Παρατηρήσαμε χαμηλότερη έκφραση της τετρασπανίνης CD81 στα καρκινικά κύτταρα σε ασθενείς PS 0, έναντι PS 1 ή 2. •Παρατηρήσαμε χαμηλότερη έκφραση της τετρασπανίνης CD81 στα καρκινικά κύτταρα σε ασθενείς MMR-deficient έναντι MMR-proficient ασθενών.•Παρατηρήσαμε υψηλότερα ποσοστά διηθούντων CD81(+) λεμφοκυττάρων στους μη μεταστατικούς ασθενείς έναντι των μεταστατικών. •Παρατηρήσαμε αρνητική συσχέτιση ανάμεσα στην έκφραση της CD81 στα καρκινικά κύτταρα και τη διήθηση στο μικροπεριβάλλον του όγκου από CD3(+) και CD8(+) λεμφοκύτταρα •Παρατηρήσαμε ότι η έκφραση της τετρασπανίνης CD82 στους καρκινικούς ιστούς χάνεται στα υψηλότερα στάδια νόσου κατά TNM, με τους μεταστατικούς ασθενείς να παρουσιάζουν πολύ χαμηλότερα επίπεδα έκφρασης της CD82 έναντι των μη-μεταστατικών ασθενών. •Παρατηρήσαμε ότι ασθενείς με R1 ή R2 εκτομή παρουσίαζαν ελαττωμένη έκφραση της CD82 στους καρκινικούς ιστούς συγκριτικά με τους ασθενείς που είχαν R0 εκτομή. •Παρατηρήσαμε μειωμένη έκφραση της CD82 στους καρκινικούς ιστούς σε ασθενείς με αυξημένες τιμές καρκινικών δεικτών CEA και CA 19-9. •Παρατηρήσαμε ότι ασθενείς στους οποίους ο πρωτοπαθής όγκος εντοπίζεται δεξιά εκφράζουν ελαττωμένη CD82 στα καρκινικά κύτταρα, έναντι της αριστερής εντόπισης. •Παρατηρήσαμε μειωμένα ποσοστά CD82(+) λεμφοκυττάρων σε μεταστατικούς ασθενείς, σε ασθενείς με κακή γενική κατάσταση (PS 1 ή 2) και σε ασθενείς με αυξημένες τιμές καρκινικών δεικτών CEA και Ca 19-9. •Παρατηρήσαμε υψηλότερα ποσοστά PD1(+) καρκινικών κυττάρων στους μη-μεταστατικούς ασθενείς έναντι των μεταστατικών. •Παρατηρήσαμε υψηλότερο ποσοστό PD1(+) καρκινικών κύτταρων και λεμφοκυττάρων, σε ασθενείς με χαμηλούς καρκινικούς δείκτες CEA και CA 19-9. •Παρατηρήσαμε συσχέτιση μεταξύ των δεικτών CD82, CD81 και του δείκτη PD1 στα καρκινικά κύτταρα. •Παρατηρήσαμε θετική συσχέτιση μεταξύ των PD1(+) λεμφοκυττάρων και των CD81(+), CD82(+), CD3(+), CD8(+) λεμφοκυττάρων. •Παρατηρήσαμε υψηλότερα ποσοστά διηθούντων CD3(+) και CD8(+) λεμφοκυττάρων στους μη μεταστατικούς ασθενείς έναντι των μεταστατικών ασθενών. •Το ποσοστό των διηθούντων CD3 ή και CD8 Τ-λεμφοκυττάρων ήταν υψηλότερο στους ασθενείς με καλή γενική κατάσταση (PS0 έναντι PS1&2). •Ασθενείς με υψηλές τιμές CEA & Ca 19-9 παρουσίαζαν χαμηλότερα ποσοστά διηθούντων CD8-λεμφοκυττάρων. •Τα ποσοστά διήθησης των CD8 λεμφοκυττάρων ήταν υψηλότερα στους MMR-deficient ασθενείς. •Παρατηρήσαμε ότι η διήθηση από CD81(+) Τ-λεμφοκύτταρα μειώνει τον κίνδυνο θανάτου (OS) ή υποτροπής (PFS).•Παρατηρήσαμε ότι η αυξημένη έκφραση της τετρασπανίνης CD82 στα καρκινικά κύτταρα όσο και το αυξημένο ποσοστό διηθούντων CD82(+) λεμφοκυττάρων σχετίζεται με καλύτερη ολική επιβίωση και επιβίωση ελεύθερης νόσου. •Παρατηρήσαμε ότι οι ασθενείς που παρουσίαζαν υψηλή έκφραση του PD1, είτε στα καρκινικά κύτταρα, είτε στα διηθούντα λεμφοκύτταρα παρουσίαζαν μικρότερο κίνδυνο θανάτου (OS) ή/και υποτροπής (PFS). •Η διήθηση από CD8(+) λεμφοκύτταρα αναδείχθηκε ως θετικός προγνωστικός παράγοντας, προσδίδοντας σε ασθενείς με καρκίνο του παχέος εντέρου μειωμένο κίνδυνο υποτροπής και θανάτου. •Επιβεβαιώσαμε την προγνωστική αξία των ήδη γνωστών κλινικο-παθολογοανατομικών παραμέτρων, όπως το στάδιο της νόσου, την πλήρης χειρουργική εκτομή και τις τιμές των καρκινικών δεικτών CEA και CA 19-9. •Διαπιστώσαμε in vitro ότι η τετρασπανίνη CD81 προάγει στον ρυθμό πολλαπλασιασμού ανθρώπινων καρκινικών κυττάρων παχέος εντέρου. •Διαπιστώσαμε in vitro ότι τετρασπανίνη CD81 αυξάνει την κινητικότητα των ανθρώπινων καρκινικών κυττάρων παχέος εντέρου.•Διαπιστώσαμε in vitro ότι τετρασπανίνη CD81 προάγει την σχηματισμό όγκων στα καρκινικά κύτταρα παχέος εντέρου DLD1. •Διαπιστώσαμε in vitro ότι τετρασπανίνη CD81 προάγει την εξέλιξη του κυτταρικού κύκλου επηρεάζοντας θετικά την έκφραση του μεταγραφικού παράγοντα E2F1 και του CDC6. •Παρατηρήσαμε πιθανή αλληλεπίδραση της τετρασπανίνης CD81 με τα σηματοδοτικά μονοπάτια του NF-κΒ που όμως χρήζει περαιτέρω διερεύνησης.Συμπερασματικά, διαπιστώσαμε ότι η τετρασπανίνη CD82 έχει προστατευτικό ρόλο στην ανάπτυξη και εξέλιξη του καρκίνου του παχέος εντέρου, καθότι η έκφραση της στους καρκινικούς ιστούς συσχετίστηκε με ευνοϊκά κλινικο-παθολογοανατομικά χαρακτηριστικά των ασθενών και αυξημένη επιβίωση. Παρομοίως, η έκφραση του PD1 αναγνωρίστηκε επίσης ως θετικός προγνωστικός παράγοντας. Παράλληλα, παρατηρήσαμε ότι η τετρασπανίνη CD81 πιθανώς λειτουργεί καταστέλλοντας την ανοσιακή απόκριση στο μικροπεριβάλλον του όγκου στον καρκίνο του παχέος εντέρου. Τέλος, διαπιστώσαμε ότι η τετρασπανίνη CD81 συμβάλει στην ανάπτυξη και την εξέλιξη του καρκίνου του παχέος εντέρου in vitro, προάγοντας τον πολλαπλασιασμό και την κινητικότητα των καρκινικών κυττάρων, ενώ επίσης παρατηρήσαμε ότι ρυθμίζει θετικά την εξέλιξη του κυτταρικού κύκλου

Microvessel Density in Patients with Cutaneous Melanoma: An Up-to-Date Systematic Review and Meta-Analysis

Background. We conducted a meta-analysis, in order to appraise the effect of microvessel density (MVD) on the survival of patients with cutaneous melanoma. Methods. This study was conducted according to the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. A systematic literature search in electronic databases (MEDLINE, Web of Science, and Cochrane Central Register of Controlled Clinical Trials) was performed. Fixed Effects or Random Effects model was used, based on the Cochran Q test. Results. In total 9 studies (903 patients) were included. Pooled HR for overall survival (OS) and disease-free survival (DFS) were 2.62 (95% CI: 0.71–9.60, p=0.15) and 2.64 (95% CI: 0.82–8.47, p=0.10), respectively. Odds ratios of overall survival between high and low MVD groups, at 12 (1.45, 95% CI: 0.16–13.24), 36 (2.93, 95% CI: 0.63–13.59), and 60 (4.09, 95% CI: 0.85–19.77) months did not reach statistical significance. Significant superiority of low MVD group, in terms of DFS, at all time intervals (OR: 4.69, p<0.0001; OR: 2.18, p=0.004; OR: 7.46, p=0.01, resp.) was documented. Discussion. MVD does not affect the HR of OS and DFS. A strong correlation with DFS rates at 12, 36, and 60 months was recorded

Geographical Variation in Mental Hospital Discharges in Greece: A Nationwide Study (1999–2012)

Background: The primary goal of this study is to estimate the pattern of hospital discharges throughout Greece due to mental disorders between 1999 and 2012. Methods: Data for discharges were obtained from the Hellenic Statistical Authority. A sex- and age-adjusted proportional hospitalization ratio (PHR) was used to estimate the ratio between the hospitalizations in each prefecture and the overall hospitalizations. Additionally, age-adjusted admission rates and hospitalization days were calculated for each sex. Descriptive and time series analysis were conducted to understand the epidemiological characteristics and to investigate the trend of annual PHR, respectively. Correlation between disorders and sociodemographic characteristics was also tested. Global and local spatial analysis was conducted to assess the spatial homogeneity of disorders and to detect any clusters of similar values. Results: More males (55%) were hospitalized. Schizophrenic and other psychoses were stated as the primary diagnosis of discharges (54.3%) for mental disorders, contributing to the highest annual mean number of hospitalization-days for male (296.9) and female patients (341.0). Most patients were out of the workforce, and most patients with drug dependence (74.5%) and schizophrenia and other psychoses (55.9%) remained unmarried. Higher PHRs were discovered in the north, while schizophrenic and other psychoses (R = 0.492), affective psychoses (R = 0.534), senile and presenile organic psychotic conditions (R = 0.543) were correlated with alcohol consumption (p < 0.001). Conclusions: The study provides evidence of geographical variation of discharges due to mental disorders and a significant association between disorders and alcohol consumption, marriage status and absence of the workforce

Geographical Variation in Mental Hospital Discharges in Greece: A Nationwide Study (1999&ndash;2012)

Background: The primary goal of this study is to estimate the pattern of hospital discharges throughout Greece due to mental disorders between 1999 and 2012. Methods: Data for discharges were obtained from the Hellenic Statistical Authority. A sex- and age-adjusted proportional hospitalization ratio (PHR) was used to estimate the ratio between the hospitalizations in each prefecture and the overall hospitalizations. Additionally, age-adjusted admission rates and hospitalization days were calculated for each sex. Descriptive and time series analysis were conducted to understand the epidemiological characteristics and to investigate the trend of annual PHR, respectively. Correlation between disorders and sociodemographic characteristics was also tested. Global and local spatial analysis was conducted to assess the spatial homogeneity of disorders and to detect any clusters of similar values. Results: More males (55%) were hospitalized. Schizophrenic and other psychoses were stated as the primary diagnosis of discharges (54.3%) for mental disorders, contributing to the highest annual mean number of hospitalization-days for male (296.9) and female patients (341.0). Most patients were out of the workforce, and most patients with drug dependence (74.5%) and schizophrenia and other psychoses (55.9%) remained unmarried. Higher PHRs were discovered in the north, while schizophrenic and other psychoses (R = 0.492), affective psychoses (R = 0.534), senile and presenile organic psychotic conditions (R = 0.543) were correlated with alcohol consumption (p &lt; 0.001). Conclusions: The study provides evidence of geographical variation of discharges due to mental disorders and a significant association between disorders and alcohol consumption, marriage status and absence of the workforce

Microvessel Density (MVD) in Patients with Osteosarcoma: A Systematic Review and Meta-Analysis

A meta-analysis was designed and conducted to estimate the effect of tumoral microvessel density (MVD) on the survival of patients with osteosarcoma. There was no difference between high and low MVD regarding the overall (OS) and disease-free (DFS) survival. Low MVD tumors displayed a lower DFS at the third year of follow-up. Although primary metastases did not affect the mean MVD measurements, tumors with a good chemotherapy response had a higher MVD value. Although no significant differences between tumoral MVD, OS and DFS were found, good adjuvant therapy responders had a significant higher vascularization pattern.</p

Facing internet fake-medicine and web para-pharmacy in the total absence of official recommendations from medical societies

Purpose: Internet fake information, parapharmacy and counterfeit drugs are a market of hundreds of billion dollars. Misleading internet data decrease patients' compliance to medical care, promote use of questionable and detrimental practices, and jeopardize patient outcome. This is particularly harmful among cancer patients, especially when pain and nutritional aspects are considered. Provision of Web recommendations for the general audience (patients, relatives, general population) from official medical-providers might be useful to outweigh the detrimental internet information produced by non-medical providers. Methods: 370 oncology and anesthesiology related societies were analyzed. Our objective was to evaluate the magnitude of web-recommendation for cancer cachexia and cancer pain for the general audience provided by official medical organizations' web sites at global level. Results: Magnitude of web-recommendations at global level was surprisingly scant both for coverage and consistency. Seven official medical societies provided updated web-recommendation for cancer cachexia to their patients/family members, and 15 for cancer pain. Scantiness was unrelated by continent, developmental index, oncology tradition, economic-geographic area and society type scrutinized. Conclusions: Patients need expert advice when exposed to fake internet information largely dominated by paramedical market profits. In this era of "new media" the patients' net-education represents a new major educational challenge for medical societies

Clinically Silent Small Vessel Disease of the Brain in Patients with Obstructive Sleep Apnea Hypopnea Syndrome

Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with increased risk of cerebrovascular disease. The aim of the present study was to investigate the association between the presence of the small vessel disease (SVD) of the brain in patients with OSAHS. The study included 24 patients with moderate to severe OSAHS and 34 healthy volunteers. All the subjects underwent magnetic resonance imaging (MRI) of the brain, in order to sought periventricular white matter (PVWM), deep white matter (DWM) and brainstem SVD. Among patients with OSAHS, 79.1% had SVD (grade 1–3, Fazekas score) in DWM and 91.7% in PVWM while 22.4% had brainstem—white matter hyperintensities (B-WMH). Patients with OSAHS had a much higher degree of SVD in the DWM and PVWM compared to the control group (p &lt; 0.001). The multivariate analysis showed an independent significant association of OSAHS with SVD (DWM and PVWM) (p = 0.033, OR 95% CI: 8.66 (1.19–63.08) and: p = 0.002, OR 95% CI: 104.98 (5.15–2141)). The same analysis showed a moderate association of OSAHS with B-WMH (p = 0.050, OR 15.07 (0.97–234.65)). Our study demonstrated an independent significant association of OSAHS with SVD and a moderate association of OSAHS with B-WMH

Facing internet fake-medicine and web para-pharmacy in the total absence of official recommendations from medical societies

Purpose: Internet fake information, parapharmacy and counterfeit drugs are a market of hundreds of billion dollars. Misleading internet data decrease patients' compliance to medical care, promote use of questionable and detrimental practices, and jeopardize patient outcome. This is particularly harmful among cancer patients, especially when pain and nutritional aspects are considered. Provision of Web recommendations for the general audience (patients, relatives, general population) from official medical-providers might be useful to outweigh the detrimental internet information produced by non-medical providers. Methods: 370 oncology and anesthesiology related societies were analyzed. Our objective was to evaluate the magnitude of web-recommendation for cancer cachexia and cancer pain for the general audience provided by official medical organizations' web sites at global level. Results: Magnitude of web-recommendations at global level was surprisingly scant both for coverage and consistency. Seven official medical societies provided updated web-recommendation for cancer cachexia to their patients/family members, and 15 for cancer pain. Scantiness was unrelated by continent, developmental index, oncology tradition, economic-geographic area and society type scrutinized. Conclusions: Patients need expert advice when exposed to fake internet information largely dominated by paramedical market profits. In this era of "new media" the patients' net-education represents a new major educational challenge for medical societies

Cancer pain ... who cares? : International and national patterns of evidence-based global guide-lines recommendations for physicians on the Web (2011 vs. 2018)

Purpose: Although pain is a common event during treatment of cancer, its assessment and management remains suboptimal in everyday clinical practice at global level. Methods: Considering both the important role of Internet in daily life and that clinical guidelines are important for translating evidence in clinical practice, we performed a prospective study to scrutinize the magnitude of updated evidence-based cancer-pain guideline recommendation for physicians on the web. Changes over-time at a global level were scrutinized at two time points: 2011 for baseline and 2018 at first follow-up. Both anesthesiology and oncology societies were analyzed. Results: In 2011 we scrutinized 181,00 WebPages and 370 eligible societies were identified; 364 of these were eligible for analyses both in 2011 and 2018. The magnitude of cancer pain updated and evidence-based guideline recommendations on the web for health care providers was extremely low at global level and at any time point considered 1.1% (4/364) in 2011 and 4.7% (17364) in 2018. Continental and intercontinental patterns, National's highest developmental index, oncology tradition and economic-geographic areas were not found to influence cancer pain web-guideline provision. In 2018, pain &amp; supportive care societies provided the highest rate of updated evidence-based cancer-pain guidelines for clinicians. Only 3/25 medical oncology societies and 1/34 radiation oncology societies, provided own or e-link (to other societies) evidence-based guidelines in their websites. Conclusions: Major medical oncology and radiation oncology societies - at global level - fail to produce updated cancer pain recommendations for their physicians, with most of these providing no or inconsistent or outdated guidelines