Halothane and sevoflurane did not impair LV relaxation, whereas propofol caused a mild impairment. However, the impairment by propofol was of a magnitude that is unlikely to cause clinical diastolic dysfunction.

During spontaneous breathing, early diastolic function improved in the sevoflurane but not in the propofol group. However, during positive pressure ventilation and balanced anaesthesia, there was no evidence of different effects caused by the two anaesthetics.

Intraoperative measurement of TDI in the anterior wall of the left ventricle is feasible and provides additional quantitative information on both regional and global systolic and diastolic function. We found changes in myocardial velocities indicating improvement in the systolic and impairment in the diastolic function of the anterior wall of the left ventricle immediately after mammary artery grafting.

Immune checkpoint blockade (ICB) has significantly improved the prognosis of cancer patients, but the majority experience limited benefit, evidencing the need for new therapeutic approaches. Upregulation of sialic acid-containing glycans, termed hypersialylation, is a common feature of cancer-associated glycosylation, driving disease progression and immune escape via the engagement of Siglec-receptors on tumor-infiltrating immune cells. Here, we show that tumor sialylation correlates with distinct immune states and reduced survival in human cancers. The targeted removal of Siglec-ligands in the tumor microenvironment, using an antibody-sialidase conjugate, enhances anti-tumor immunity and halts tumor progression in several mouse tumor models. Using single-cell RNA sequencing, we reveal desialylation mechanistically to repolarize tumor-associated macrophages (TAMs) and identify Siglec-E on TAMs as the main receptor for hypersialylation. Finally, we show genetic and therapeutic desialylation, as well as loss of Siglec- E, to synergize with ICB. Thus, therapeutic desialylation represents a novel immunotherapeutic approach, shaping macrophage phenotypes and augmenting the adaptive anti-tumor immune response.

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