Lower cognitive function in older patients with lower muscle strength and muscle mass

Background: Low muscle strength and muscle mass are associated with adverse outcomes in older hospitalized patients. The aim of this study was to assess the association between cognitive functioning and muscle strength and muscle mass in hospitalized older patients. Methods: This prospective inception cohort included 378 patients aged 70 years or older. At admission patients were assessed for cognitive functioning by use of the Six-Item Cognitive Impairment Test (6-CIT). Muscle strength and muscle mass were assessed using handheld dynamometry and segmental multifrequency bioelectrical impedance analysis, within 48 h after admission and on day 7, or earlier on the day of discharge. Results: The data of 371 patients (mean age ± standard deviation 80.1 ± 6.4 years, 49.3% female) were available for analyses. The median (interquartile range) 6-CIT score was 4 (0-8) points. At admission, lower cognitive functioning was associated with lower muscle strength, lower skeletal muscle mass (SMM), lower appendicular lean mass, and lower SMM index. Cognitive functioning was not associated with change in muscle strength and muscle mass during hospitalization. Conclusion: This study further strengthens evidence for an association between lower cognitive functioning and lower muscle strength and muscle mass, but without a further decline during hospitalization

Shaping of natural killer cell antitumor activity by ex vivo cultivation

Natural killer (NK) cells are a promising tool for the use in adoptive immunotherapy, since they efficiently recognize and kill tumor cells. In this context, ex vivo cultivation is an attractive option to increase NK cells in numbers and to improve their antitumor potential prior to clinical applications. Consequently, various strategies to generate NK cells for adoptive immunotherapy have been developed. Here, we give an overview of different NK cell cultivation approaches and their impact on shaping the NK cell antitumor activity. So far, the cytokines interleukin (IL)-2, IL-12, IL-15, IL-18, and IL-21 are used to culture and expand NK cells. The selection of the respective cytokine combination is an important factor that directly affects NK cell maturation, proliferation, survival, distribution of NK cell subpopulations, activation, and function in terms of cytokine production and cytotoxic potential. Importantly, cytokines can upregulate the expression of certain activating receptors on NK cells, thereby increasing their responsiveness against tumor cells that express the corresponding ligands. Apart from using cytokines, cocultivation with autologous accessory non-NK cells or addition of growth-inactivated feeder cells are approaches for NK cell cultivation with pronounced effects on NK cell activation and expansion. Furthermore, ex vivo cultivation was reported to prime NK cells for the killing of tumor cells that were previously resistant to NK cell attack. In general, NK cells become frequently dysfunctional in cancer patients, for instance, by downregulation of NK cell activating receptors, disabling them in their antitumor response. In such scenario, ex vivo cultivation can be helpful to arm NK cells with enhanced antitumor properties to overcome immunosuppression. In this review, we summarize the current knowledge on NK cell modulation by different ex vivo cultivation strategies focused on increasing NK cytotoxicity for clinical application in malignant diseases. Moreover, we critically discuss the technical and regulatory aspects and challenges underlying NK cell based therapeutic approaches in the clinics