Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T). METHODS: In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn. RESULTS: From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocality (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death. CONCLUSION: s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Extended Penalty Coefficients For Elimination The Locking Effects In Moderately Thick Beam And Plate Finite Elements

The present paper is dedicated to presentation and energy verification of the methods of stabilization the strain energy by penalty coefficients. Verification of the methods is based on the consistency and ellipticity conditions to be satisfied by the finite elements. Three methods of stabilization are discussed. The first does not satisfy the above requirements. The second is consistent but cannot eliminate parasitic energy terms. The third method, proposed by the author, is based on the decomposition of the element stiffness matrix. The method can help to eliminate locking of the finite elements. For two-noded beam element with linear shape functions and exact integration a stabilized free of locking (and elliptical) element is received (equivalent to reduced integration element). Two plate finite elements are analyzed: four-noded rectangular element and DSG triangle. A new method of stabilization with the use of four independent parameters is proposed. The finite elements with this kind of stabilization satisfy the consistency condition. In the rectangular element it was not possible to eliminate one parasitic term of energy which appears during the procedure. For DSG triangle all parasitic terms of energy are eliminated. The penalty coefficients depends on the geometry of the triangle

On the influence of the size of certain weakness of foundation in the Westergaard problem

We wcześniejszej pracy autorów [3] zbadano wpływ pewnego typu osłabień podłoża pod płytą nawierzchni drogowej sztywnej w zagadnieniu Westergaarda [1,2], tj. określeniu maksymalnych ugięć i maksymalnych naprężeń w płycie prostokątnej sprężystej spoczywającej na podłożu Winklera w przypadku obciążenia kołem pojazdu w trzech położeniach: w narożu, na środku i przy krawędzi płyty. Jako osłabienie podłoża przyjęto jego brak na powierzchni prostokątnej równej 1/9 powierzchni płyty - w różnych położeniach względem płyty. Dla każdego z obciążeń określono najniekorzystniejsze położenia osłabienia podłoża. W tym artykule przedstawiono wyniki badania wrażliwości maksymalnych ugięć i maksymalnych naprężeń rozciągających na wielkość osłabienia podłoża w zdefiniowanych w pracy [3] najniekorzystniejszych położeniach. Analizowano jaki wpływ ma wielkość ubytku podłoża na rozważane wielkości. Przedstawiono plany warstwicowe maksymalnych naprężeń rozciągających w różnych wariantach zadania oraz wykresy zależności maksymalnych naprężeń i przemieszczeń w funkcji wielkości ubytku podłoża. Określono, przy jakich rozmiarach osłabienia podłoża może mieć ono istotny wpływ na wytrzymałość płyty. Przeprowadzone obliczenia wykonano z wykorzystaniem metody elementów skończonych, na bazie wcześniejszych doświadczeń modelowania.In the previous paper of the authors [3] the analysis of some regular weakness of the foundation in the Werstergaard problem was discussed. Maximum displacements and maximum stresses were considered. The weakness was 1/9 of the plate area in various positions. The most dangerous situations were defined. The present paper is an extension of previous considerations for the analysis of sensitivity of the results for the size of weakness. The results are presented in the form of maximal stress maps (for qualitative analysis) as well as the tables and graphs (for quantitative analysis). The plate was modeled with the use of the finite element method

Finite element of moderately thick arch - statics and free vibrations

Niniejszy artykuł dotyczy elementu skończonego łuku kołowego o średniej grubości (Ar2Ph2). W pracy pokazano sposób wyprowadzenia fizycznych” funkcji kształtu uwzględniających wpływ właściwości fizycznych materiału, geometrii przekroju poprzecznego i krzywizny łuku na jego deformację. Wykazano, że przy małym kacie rozwarcia elementu przechodzą one w odpowiednie funkcje elementu belkowego Timoshenki. Rozwiązano serię zadań z zastosowaniem prezentowanego elementu i otrzymano rozwiązania ścisłe w zakresie statyki oraz przybliżone wyniki w zagadnieniu drgań własnych. Wykazano dobrą zbieżność elementu w drugim typie zadań.The present paper is dedicated to the finite element of moderately thick arch (Ar2Ph2). So-called “physical” shape functions, stiffness matrix, load vector and mass matrix are derived. The shape functions are based on the displacement differential equations of the arch. The finite element is exact for static analysis. Convergence analysis for free vibration is presented with promising results