The EORTC-55994 trial compared neoadjuvant chemotherapy (NACT) followed by radical surgery with concomitant chemoradiation (CCRT) in patients with Stage IB2-IIB cervical cancer. This trial took ...almost 12 years to recruit 626 patients with a median follow-up of 8.7 years.
PURPOSE
This multicenter trial by the European Organisation for Research and Treatment of Cancer Gynecological Cancer Group was motivated by conflicting evidence on the value of neoadjuvant chemotherapy before surgery compared with concomitant chemoradiotherapy (CCRT) in stage IB2-IIB cervical carcinoma.
METHODS
Between May 2002 and January 2014, 626 patients with International Federation of Gynecology and Obstetrics stage IB2-IIb were randomly assigned between neoadjuvant chemotherapy followed by surgery (NACT-S; n = 314) and standard CCRT (n = 312). The primary end point was 5-year overall survival (OS) rate. Secondary end points were progression-free survival, OS, toxicity, and health-related quality of life (HRQOL).
RESULTS
After a median follow-up of 8.7 years, 198 patients (31.6%) died. Age, stage, and cell type were balanced in both arms. Protocol treatment was completed in 223 of 314 (71%) patients in NACT-S and 257 of 312(82%) in CCRT arms. Main reasons for incomplete protocol treatment were toxicity (30 of 314; 9.6%) and progressive disease (21 of 314; 6.7%) in the NACT-S arm and toxicity (23 of 312; 7.4%) and patient refusal (13 of 312; 4.2%) in the CCRT arm. Additional radiotherapy after completed NACT-S was given to 107 patients (48%), and additional surgery to 20 patients (8%) after completed CCRT. Short-term adverse events (AEs) ≥grade 3 occurred more frequently with NACT-S (41% v 23%), and long-term AEs ≥grade 3 more often with CCRT (21% v 15%). The 5-year OS was not significantly different between NACT-S (72%; 95% CI, 66 to 77) and CCRT (76%; 95% CI, 70 to 80).
CONCLUSION
This trial failed to demonstrate superiority in favor of the NACT-S arm but resulted in acceptable morbidity and HRQOL in both arms.
Summary
The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post‐transplant ...outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X‐rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO2/FiO2 ≤ 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and ≥7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long‐term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized.
Background Allergic asthma is associated with chronic airway and systemic immune responses. Systemic responses include priming of peripheral blood eosinophils, which is enhanced after allergen ...challenge. In a subpopulation of asthmatic subjects, neutrophils are associated with bronchial inflammation. Objective We sought to monitor systemic granulocyte priming in allergic asthmatic subjects as a consequence of chronic and acute inflammatory signals initiated by allergen challenge. Methods Blood was taken at baseline and 6 to 24 hours after allergen challenge in asthmatic subjects with and without late asthmatic responses. Systemic granulocyte priming was studied by using expression of cellular markers, such as α-chain of Mac-1 (αm)/CD11b, L-selectin/CD62L, and an activation epitope present on FcγRII/CD32 recognized by monoclonal phage antibody A17. Results Eosinophils of asthmatic subjects have a primed phenotype identified by cell-surface markers. Neutrophils of these patients were subtly primed, which was only identified after activation with N-formyl-methionyl-leucyl-phenylalanine. After allergen challenge, an acute increase in eosinophil priming characterized by enhanced expression of activated FcγRII was found in patients experiencing a late asthmatic response and not in patients with a single early asthmatic response. In contrast, expression of αm/CD11b and L-selectin on granulocytes was not different between control and asthmatic subjects and was not affected by allergen challenge. Interestingly, expression of both adhesion molecules was positively correlated, and αm expression on eosinophils and neutrophils correlated positively with bronchial hyperresponsiveness. Conclusion Different phases, phenotypes, or both of allergic asthma are associated with distinct priming profiles of inflammatory cells in peripheral blood. Clinical implications Insight in differences of systemic innate responses will lead to better definition of asthma subtypes and to better designs of new therapeutic options.
In quantum information theory, the Schmidt rank is a fundamental measure for the entanglement dimension of a pure bipartite state. Its natural definition uses the Schmidt decomposition of vectors on ...bipartite Hilbert spaces, which does not exist (or at least is not canonically given) if the observable algebras of the local systems are allowed to be general C*-algebras. In this work, we generalize the Schmidt rank to the commuting operator framework where the joint system is not necessarily described by the minimal tensor product but by a general bipartite algebra. We give algebraic and operational definitions for the Schmidt rank and show their equivalence. We analyze bipartite states and compute the Schmidt rank in several examples: The vacuum in quantum field theory, Araki-Woods-Powers states, as well as ground states and translation invariant states on spin chains which are viewed as bipartite systems for the left and right half chains. We conclude with a list of open problems for the commuting operator framework.
Despite its popularity, several empirical and theoretical studies suggest that the quantum approximate optimization algorithm (QAOA) has persistent issues in providing a substantial practical ...advantage. So far, those findings mostly account for a regime of few qubits and shallow circuits. We find clear evidence for a `no free lunch'-behavior of QAOA on a general optimization task with no further structure; individual cases have, however, to be analyzed more carefully. We propose and justify a performance indicator for the deep-circuit QAOA that can be accessed by solely evaluating statistical properties of the classical objective function. We further discuss the various favorable properties a generic QAOA instance has in the asymptotic regime of infinitely many gates, and elaborate on the immanent drawbacks of finite circuits. We provide several numerical examples of a deep-circuit QAOA method based on local search strategies and find that - in alignment with our performance indicator - some special function classes, like QUBO, admit a favorable optimization landscape.
Background Allergic asthma is associated with chronic airway and systemic immune responses. Systemic responses include priming of peripheral blood eosinophils, which is enhanced after allergen ...challenge. In a subpopulation of asthmatic subjects, neutrophils are associated with bronchial inflammation. Objective We sought to monitor systemic granulocyte priming in allergic asthmatic subjects as a consequence of chronic and acute inflammatory signals initiated by allergen challenge. Methods Blood was taken at baseline and 6 to 24 hours after allergen challenge in asthmatic subjects with and without late asthmatic responses. Systemic granulocyte priming was studied by using expression of cellular markers, such as α-chain of Mac-1 (αm)/CD11b, L-selectin/CD62L, and an activation epitope present on FcγRII/CD32 recognized by monoclonal phage antibody A17. Results Eosinophils of asthmatic subjects have a primed phenotype identified by cell-surface markers. Neutrophils of these patients were subtly primed, which was only identified after activation with N-formyl-methionyl-leucyl-phenylalanine. After allergen challenge, an acute increase in eosinophil priming characterized by enhanced expression of activated FcγRII was found in patients experiencing a late asthmatic response and not in patients with a single early asthmatic response. In contrast, expression of αm/CD11b and L-selectin on granulocytes was not different between control and asthmatic subjects and was not affected by allergen challenge. Interestingly, expression of both adhesion molecules was positively correlated, and αm expression on eosinophils and neutrophils correlated positively with bronchial hyperresponsiveness. Conclusion Different phases, phenotypes, or both of allergic asthma are associated with distinct priming profiles of inflammatory cells in peripheral blood. Clinical implications Insight in differences of systemic innate responses will lead to better definition of asthma subtypes and to better designs of new therapeutic options.
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