Systemic Mastocytosis

A 64-year-old man was admitted to the hematology ward due to neutropenia and thrombocytopenia. The only symptom in the month preceding his admission, was significant weight loss. Based on clinical and laboratory investigations, specifically bone marrow aspiration and biopsy, the patient was diagnosed with aggressive systemic mastocytosis (WHO 2008 ICD-0 code 9741/3)

Comparison of first line molecular targeted therapies treatment in metastatic renal cell carcinoma: metanalysis

Better understanding of renal cell carcinogenesis has led to the development of molecular therapies targeting the VEGF and mTOR pathways, as well as immunotherapeutic agents (ICPIs) up-regulating the host immune response, resulting in significant improvement in overall survival and quality of life in patients with metastatic clear cell renal cell carcinoma (mccRCC).Objective. Direct and indirect comparison of targeted agents used in first-line treatment in mccRCC.Methods. A systematic literature review was conducted in order to identify randomized controlled studies (RCS) in the first-line therapy for mRCC. The outcomes analysed were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and some adverse events (AEs). A network meta-analysis was conducted comparing OS and PFS Hazard Ratios (HRs) and ORR and AEs Odds Ratios (ORs).Results. Treatment’s efficacy: Nivolumab/Ipilimumab (NIV/IPI) and sorafenib (SOR), compared to placebo, prolonged OS (HRs 0.63 and 0.77, respectively). Axitinib (AXI), cabozantinib (CAB), temsirolimus (TEM), pazopanib (PAZ), TEM/IFN and tivozanib (TIV) also prolonged OS, but not significantly (HRs 0.77, 0.80, 0.89, 0.91, 0.93 and 0.96, respectively). CAB, sunitinib (SUN), AXI, TIV, PAZ, SOR and EVE demonstrated significant superiority in terms of PFS (HRs 0.17, 0.36, 0.37, 0.39, 0.41, 0.48 and 0.50, respectively). As for ORR, CAB, NIV/IPI, AXI, PAZ, BEV/IFNα, SUN, TIV and SOR presented significant improvement, compared to placebo (ORs 27.99, 20.72, 16.39, 14.95, 11.87, 10.54, 9.75 and 6.01, respectively). Treatment’s safety: TEM, EVE, BEV and NIV/IPI have had the best profile of AEs G 3/4 (OR 1.88, 1.99, 2.14 and 2.64, respectively). AEs leading to discontinuation of therapy were lower in TIV, TEM and SOR (ORs 0.52, 1.17 and 1.27, respectively). Hypertension events occurred mostly with AXI, CAB, TIV, PAZ, SUN and SOR (OR 63.30, 10.94, 6.96, 7.06, 7.07 and 4.45, respectively). HFS developed in PAZ, SOR, CAB SUN and AXI (OR 152.89, 58.23, 55.59, 26.33 and 22.33, respectively) and diarrhea mostly in AXI and SOR (OR 7.59 and 4.29, respectively).Conclusions. According to the results of this meta-analysis, NIV/IPI and CAB are indicated, with cautiousness, for front-line therapy in intermediate and high risk patients with mccRCC. AXI (with cautiousness) , PAZ, SUN, SOR, BEV/IFN and TIV are mainly preferred as first-line therapy in favorable and intermediate risk patients with mccRCC.Σημαντικές πρόοδοι στην κατανόηση των μηχανισμών καρκινογένεσης του καρκίνου του νεφρού άνοιξαν το δρόμο εφαρμογής μοριακά στοχευμένων θεραπειών (ΣΘ). Από το 2006 μέχρι σήμερα, έγιναν αποδεκτές (FDA/EMA) 13 ΣΘ για ασθενείς με μεταστατικό διαυγοκυτταρικό καρκίνο του νεφρού (mccRCC), εκ των οποίων 8 ως θεραπείες 1ης γραμμής. Οι ΣΘ βελτίωσαν σημαντικά τη συνολική επιβί-ωση και την ποιότητα ζωής των ασθενών με mccRCC.Σκοπός: Η σύγκριση, ως προς την αποτελεσματικότητα και ασφάλεια, ΣΘ που προτάθηκαν ως αρχική θεραπεία του mccRCC.Υλικό - Μεθοδολογία: Μετά συστηματική έρευνα της βιβλιογραφίας, αναγνωρίσθηκαν 19 τυχαιοποιημένες, ελεγχόμενες, πολυκεντρικές μελέτες, εκ των οποίων 12 ήταν φάσης ΙΙΙ και 7 φάσης ΙΙ. Τα ευρήματα των μελετών αυτών συγκρίθηκαν ως προς την αποτελεσματικότητα [συνολική επιβίωση(OS), επιβίωση χωρίς εξέλιξη νόσου (PFS ), αντικειμενική απάντηση (ORR)] και ως προς 5 κύριες ανεπιθύμητες ενέργειες (ΑΕs). Μετα-ανάλυση(ΜΑ) δικτύου (network meta-analysis) εφαρμόσθηκε για τη σύγκριση των Hazard Ratios (HRs) των OS και PFS, καθώς και για τη σύγκριση των Odds Rations (ORs) των ORR και των AEs.Αποτελέσματα: Ως προς την αποτελεσματικότητα των θεραπειών, σημαντική παράταση της OS ,σε σχέση με placebo, παρουσίασαν η nivolumab/ipilimumab (NIV/IPI) και η sorafenib (SOR)(HRs 0,63 και 0,77,αντίστοιχα). Η axitinib (AXI), cabozantinib (CAB), temsirolimus (TEM), pazopanib(PAZ), TEM/IFNα και tivozanib (TIV) παρουσίασαν οριακά μη σημαντική παράταση της OS. Οι άλλες θεραπείες παρουσίασαν μη σημαντικές διαφορές. Σημαντική παράταση της PFS παρουσίασαν η CAB (μεγαλύτερη παράταση), SUN, AXI, TIV, PAZ, SOR και EVE (HRs 0,17, 0,36, 0,37, 0,39,0,41, 0,48 και 0,50, αντίστοιχα). Σημαντική υπεροχή ως προς την ORR, σε σχέση με placebo, παρουσίασαν η CAB (μεγαλύτερη απάντηση), NIV/IPI, AXI, PAZ, BEV/IFNα, SUN, TIV και SOR (OR 27,99, 20,72, 16,39, 14,95, 11,87, 10,54, 9,75 και 6,01, αντίστοιχα). Ως προς τις AEs, το καλύτερο προφίλ ως προς AEs G≥3 είχαν η ΤΕΜ, EVE, BEV και NIV/IPI και ως προς τη διακοπή της θεραπείας, λόγω AEs, είχαν η TIV, TEM και SOR. Αυξημένη πιθανότητα εμφάνισης υπέρτασης παρουσίασαν η AXI, CAB, TIV, PAZ, SUN και SOR και εμφάνισης HFS η PAZ, SOR, CAB, SUN και AXI. Στατιστικά σημαντική πιθανότητα εμφάνισης διάρροιας παρουσίασαν η AXI και SOR (OR 5,59 και 4,29, αντίστοιχα). Συμπεράσματα: Κατά την ΜΑ, η NIV/IPI και CAB συνιστώνται, με επιφύλαξη, ως θεραπεία 1ης γραμμής, σε ασθενείς ενδιάμεσου και υψηλού κινδύνου. Κατά σειρά προτίμησης, η AXI (με επιφύλαξη), PAZ, SUN, SOR, BEV/IFNα και TIV συνιστώνται ως 1ης γραμμής θεραπείες σε mccRCC, ιδίως σε ασθενείς χαμηλού και ενδιάμεσου κινδύνου

Σύγκριση μοριακά στοχευμένων θεραπειών πρώτης γραμμής στο μεταστατικό καρκίνωμα του νεφρού - Μετανάλυση

Εισαγωγή: Σημαντικές πρόοδοι στην κατανόηση των μηχανισμών καρκινογένεσης του καρκίνου του νεφρού άνοιξαν το δρόμο εφαρμογής μοριακά στοχευμένων θεραπειών (ΣΘ). Από το 2006 μέχρι σήμερα, έγιναν αποδεκτές (FDA/EMA) 13 ΣΘ για ασθενείς με μεταστατικό διαυγοκυτταρικό καρκίνο του νεφρού (mccRCC), εκ των οποίων 8 ως θεραπείες 1ης γραμμής. Οι ΣΘ βελτίωσαν σημαντικά τη συνολική επιβί-ωση και την ποιότητα ζωής των ασθενών με mccRCC. Σκοπός: Η σύγκριση, ως προς την αποτελεσματικότητα και ασφάλεια, ΣΘ που προ-τάθηκαν ως αρχική θεραπεία του mccRCC. Υλικό - Μεθοδολογία: Μετά συστηματική έρευνα της βιβλιογραφίας, αναγνωρίσθη-καν 19 τυχαιοποιημένες, ελεγχόμενες, πολυκεντρικές μελέτες, εκ των οποίων 12 ήταν φάσης ΙΙΙ και 7 φάσης ΙΙ. Τα ευρήματα των μελετών αυτών συγκρίθηκαν ως προς την απολεσματικότητα [συνολική επιβίωση(OS), επιβίωση χωρίς εξέλιξη νόσου (PFS ), αντικειμενική απάντηση (ORR)] και ως προς 5 κύριες ανεπιθύμητες ενέργειες (ΑΕs). Μετα-ανάλυση(ΜΑ) δικτύου (network meta-analysis) εφαρμόσθηκε για τη σύγκριση των Hazard Ratios (HRs) των OS και PFS, καθώς και για τη σύγκριση των Odds Rations (ORs) των ORR και των AEs. Αποτελέσματα: Ως προς την αποτελεσματικότητα των θεραπειών, σημαντική παρά-ταση της OS ,σε σχέση με placebo, παρουσίασαν η nivolumab/ipilimumab (NIV/IPI) και η sorafenib (SOR)(HRs 0,63 και 0,77,αντίστοιχα). Η axitinib (AXI), cabozantinib (CAB), temsirolimus (TEM), pazopanib(PAZ), TEM/IFNα και tivozanib (TIV) παρουσία-σαν οριακά μη σημαντική παράταση της OS. Οι άλλες θεραπείες παρουσίασαν μη σημαντικές διαφορές. Σημαντική παράταση της PFS παρουσίασαν η CAB (μεγαλύ-τερη παράταση), SUN, AXI, TIV, PAZ, SOR και EVE (HRs 0,17, 0,36, 0,37, 0,39,0,41, 0,48 και 0,50, αντίστοιχα). Σημαντική υπεροχή ως προς την ORR, σε σχέση με placebo, παρουσίασαν η CAB (μεγαλύτερη απάντηση), NIV/IPI, AXI, PAZ, BEV/IFNα, SUN, TIV και SOR (OR 27,99, 20,72, 16,39, 14,95, 11,87, 10,54, 9,75 και 6,01, αντίστοιχα). Ως προς τις AEs, το καλύτερο προφίλ ως προς AEs G≥3 είχαν η ΤΕΜ, EVE, BEV και NIV/IPI και ως προς τη διακοπή της θεραπείας, λόγω AEs, είχαν η TIV, TEM και SOR. Αυξημένη πιθανότητα εμφάνισης υπέρτασης παρουσία-σαν η AXI, CAB, TIV, PAZ, SUN και SOR και εμφάνισης HFS η PAZ, SOR, CAB, SUN και AXI. Στατιστικά σημαντική πιθανότητα εμφάνισης διάρροιας παρουσίασαν η AXI και SOR (OR 5,59 και 4,29, αντίστοιχα). Συμπεράσματα: Κατά την ΜΑ, η NIV/IPI και CAB συνιστώνται, με επιφύλαξη, ως θεραπεία 1ης γραμμής, σε ασθενείς ενδιάμεσου και υψηλού κινδύνου. Κατά σειρά προτίμησης, η AXI (με επιφύλαξη), PAZ, SUN, SOR, BEV/IFNα και TIV συνιστώνται ως 1ης γραμμής θεραπείες σε mccRCC, ιδίως σε ασθενείς χαμηλού και ενδιάμεσου κινδύνου.Introduction. Better understanding of renal cell carcinogenesis has led to the deve-lopment of molecular therapies targeting the VEGF and mTOR pathways, as well as immunotherapeutic agents (ICPIs) up-regulating the host immune response, resu-lting in significant improvement in overall survival and quality of life in patients with metastatic clear cell renal cell carcinoma (mccRCC). Objective. Direct and indirect comparison of targeted agents used in first-line treat- ment in mccRCC. Methods. A systematic literature review was conducted in order to identify rando-mized controlled studies (RCS) in the first-line therapy for mRCC. The outcomes analysed were overall survival (OS), progression-free survival (PFS), objective respo-nse rate (ORR) and some adverse events (AEs). A network meta-analysis was conducted comparing OS and PFS Hazard Ratios (HRs) and ORR and AEs Odds Ratios (ORs). Results. Treatment’s efficacy: Nivolumab/Ipilimumab (NIV/IPI) and sorafenib (SOR), compared to placebo, prolonged OS (HRs 0.63 and 0.77, respectively). Axitinib (AXI), cabozantinib (CAB), temsirolimus (TEM), pazopanib (PAZ), TEM/IFN and tivozanib (TIV) also prolonged OS, but not significantly (HRs 0.77, 0.80, 0.89, 0.91, 0.93 and 0.96, respectively). CAB, sunitinib (SUN), AXI, TIV, PAZ, SOR and EVE demonstrated significant superiority in terms of PFS (HRs 0.17, 0.36, 0.37, 0.39, 0.41, 0.48 and 0.50, respectively). As for ORR, CAB, NIV/IPI, AXI, PAZ, BEV/IFNα, SUN, TIV and SOR presented significant improvement, compared to placebo (ORs 27.99, 20.72, 16.39, 14.95, 11.87, 10.54, 9.75 and 6.01, respectively). Treatment’s safety: TEM, EVE, BEV and NIV/IPI have had the best profile of AEs G 3/4 (OR 1.88, 1.99, 2.14 and 2.64, respectively). AEs leading to discontinuation of therapy were lower in TIV, TEM and SOR (ORs 0.52, 1.17 and 1.27, respectively). Hypertension events occurred mostly with AXI, CAB, TIV, PAZ, SUN and SOR (OR 63.30, 10.94, 6.96, 7.06, 7.07 and 4.45, respectively). HFS developed in PAZ, SOR, CAB SUN and AXI (OR 152.89, 58.23, 55.59, 26.33 and 22.33, respectively) and diarrhea mostly in AXI and SOR (OR 7.59 and 4.29, respectively). Conclusions. According to the results of this meta-analysis, NIV/IPI and CAB are indicated, with cautiousness, for front-line therapy in intermediate and high risk patients with mccRCC. AXI (with cautiousness) , PAZ, SUN, SOR, BEV/IFN and TIV are mainly preferred as first-line therapy in favorable and intermediate risk patients with mccRCC

The influence of the degree of elongation to the displacements of structural walls with low-reinforced end-sections

The past few years, it has become explicit that failure due to transverse instability is difficult to be observed in actual structures after the event of seismic excitation, even if it is certain that it exists as phenomenon and can even lead to general collapse of structures. Consequently, because of the big importance of transverse instability and the role that plays in the seismic behavior and safety of constructions, a sedulous study is required about the mechanism of occurrence of this phenomenon and the factors that lead to its growth. The present work is experimental and consists of 5 test specimens of scale 1:3 simulating the boundary edges of structural walls. These specimens were reinforced with the same low longitudinal reinforcement ratio (1.79%). The degree of elongation applied was different for each specimen. The present paper tries to investigate the influence of the degree of elongation to the displacements and the modes of failure of test specimens

How does degree of elongation affect lateral buckling behavior of seismic walls?

It is considered logical to be expected that walls designed either with increased ductility requirements according to the Greek Concrete Code 2000 or designed to be in a high ductility category according to EC8: 2004, NZS 3101: 2006 and other modern international codes, present extensive tensile deformations, especially in the plastic hinge region of their base. Large tensile deformations are expected depending on the geometric characteristics and the level of ductility design of walls. Due to the cycling nature of loading, these tensile deformations can cause lateral instability of seismic walls depending on the size of tensile deformations. In the framework of the current work, it is experimentally investigated one of the most crucial parameters affecting the stability of structural walls, which is the degree of tensile strain of the longitudinal reinforcement of the extreme edges of load-bearing RC walls. The present paper tries to investigate the influence of the degree of tensile strain to the ultimate strength and the modes of failure of test specimens using 5 test specimens reinforced with the same longitudinal reinforcement ratio (3.19%) but strained to different degrees of elongation

The influence of the diameter of the longitudinal reinforcement of RC walls to their displacements against lateral instability

The possibility of failure because of lateral instability is limited significantly with the proper choice of an adequate thickness, which is specified by (most) modern seismic codes as a percentage of the height of the bottom storey. The current work investigates one parameter that may be affecting the stability of structural walls. This parameter is the diameter of the longitudinal reinforcement of the boundary edges of load-bearing walls. It contains an experimental research that tries to investigate the influence of the diameter of longitudinal reinforcement to the displacements of test specimens. It has to be noted that in order to examine experimentally the influence of the diameter of longitudinal reinforcement, test specimens of scale 1:3 simulating the boundary edges of structural walls were used. These specimens were reinforced with the same or almost the same longitudinal reinforcement ratios (2.68% - 2.79%) but had a different number of reinforcement bars of varying diameter. The diameters of bars which were used were equal to 8mm and 10mm. The specimens which were compared to each other contained (apart from bars of different diameter) a different number of bars and consequently a different way of placement of these bars at the wall end sections

Seismic design of R/C piers of hollow circular cross sections

Hollow circular cross sections are widely used in piers. However, it is known that they are especially sensitive against inelastic deformation and therefore their use should be avoided, when it comes to ductile seismic resistant bridge systems. Consequently, it is important that such sections are to be utilized in non-ductile systems, namely in cases where the numerical value of the behaviour factor q lies between 1 and 1.5. In such cases, there is a certain level of impact upon their design. As far as the flexural design of hollow circular R/C cross sections is concerned, it should be based on the yield strength of the tension zone rather than the maximum bending strength. The problem of the transverse spiral reinforcements and the question whether the active presence of an inner spiral is actually needed (given that the inner spiral can jeopardize the integrity of a structural element, when there are no additional restraint measures), are also affiliated with the flexural design. On the other hand, the shear design of such sections can be even more difficult, when it comes to both the determination of the transverse spiral reinforcements and the maximum shear strength, which is influenced by the curved struts of the virtual network mechanism. In this paper, a thorough analysis of the design of hollow circular R/C cross sections is attempted, given that the compliance criterion is the value of the flexural yield strength, rather than the maximum failure strength

Does degree of elongation affect displacements of structural walls?

The past few years, it has become explicit that failure due to transverse instability is difficult to be observed in actual structures after the event of seismic excitation, even if it is certain that it exists as phenomenon and can even lead to general collapse of structures. Consequently, because of the big importance of transverse instability and the role that plays in the seismic behavior and safety of constructions, a sedulous study is required about the mechanism of occurrence of this phenomenon and the factors that lead to its growth. The present work is experimental and consists of 5 test specimens of scale 1:3 simulating the boundary edges of structural walls. These specimens were reinforced with the same medium high longitudinal reinforcement ratio (3.19%). The degree of elongation applied was different for each specimen. The present paper tries to investigate the influence of the degree of elongation to the displacements and the modes of failure of test specimens

The influence of the degree of elongation to the displacements of seismic walls with maximum code-prescribed reinforcement ratio

It is expected that walls which were designed either with increased ductility requirements according to the Greek Concrete Code 2000 or were designed to be in a high ductility category according to EC8: 2004, NZS 3101: 2006 and other modern international codes, present extensive tensile deformations, especially in the plastic hinge region of their base. Depending on the geometric characteristics and the level of ductility design of walls, large tensile deformations are expected. These tensile deformations can cause their lateral instability depending on their size. Large width cracks, which are created as result of deep entry in the plastic region, are required to close, so that the in-plane flexural mode of wall can be completely developed at the reversal of loading sign. It is obvious that there should be a sufficient wall thickness, so that it is ensured that the compressive force can be developed in the compression zone of the wall cross-section without the event of out-of-plane buckling. A critical situation arises when at the reversal of the sign of moment, the cracks that emanate from tension (at the previous semi-cycle of loading) cannot close and thus, traverse buckling takes place, which leads the wall end section to lateral instability. The current work investigates one of the most basic parameters affecting the stability of structural walls, which is (apart from the wall thickness) the degree of tensile strain of the longitudinal reinforcement of the boundary edges of load-bearing walls. The present work is experimental. It has to be noted that in order to examine experimentally the influence of tensile strain, 5 test specimens of scale 1:3 simulating the boundary edges of structural walls were used. These specimens were reinforced with the maximum code-prescribed longitudinal reinforcement ratio (4.02%) and they all had the same reinforcement ratio. The degree of elongation which was applied was different for each specimen and it took values equal to 0‰, 10‰, 20‰, 30‰ and 50‰. The present article tries to investigate the influence of the degree of tensile strain to the displacements and the modes of failure of test specimens

Experimental and analytical research on the influence of the shear span ratio on the maximum shear strength of hollow circular R/C cross sections

This paper investigates a particular problem encountered in the design of reinforced concrete elements of circular hollow cross sections. Such problems still appear to be unclear, due to the fact that the current codes deal, al most exclusively, with the design of rectangular cross sections and no specific provisions are given for other cross sections. Hence, the design of such members is being dealt with either poor methods or with the use of methods that normally apply to rectangular cross sections. Specifically, the research deals with the influence of the shear span ratio on the maximum shear strength of reinforced concrete members with circular hollow cross sections. Six reinforced concrete specimens having a circular hollow cross section have been tested. lt was attempted to verify the accuracy of the proposed analytica(model, which estimates the shear strength for circular hollow R/C cross sections. The study was mainly focused on the shear span ratio, which is the dominant factor in the design of structural elements under shear loading. It is useful to be noted that R/C elements of thin hollow circular cross section are used in the case of bridge piers