The advent of pneumococcal conjugate vaccines led to the near disappearance of most of the included serotypes in high-income settings but also the rise of nonvaccine-type colonization and disease.... Show moreThe advent of pneumococcal conjugate vaccines led to the near disappearance of most of the included serotypes in high-income settings but also the rise of nonvaccine-type colonization and disease. Alternative strategies, using genetically conserved proteins as antigens, have been evaluated preclinically and clinically for years, so far unsuccessfully. One possible explanation for the failure of these efforts is that the choice of antigens may not have been sufficiently guided by an understanding of the gene expression pattern in the context of infection. Here, we present a targeted transcriptomic analysis of 160 pneumococcal genes encoding bacterial surface-exposed proteins in mouse models, human colonization, and human meningitis. We present the overlap of these different transcriptomic profiles. We identify two bacterial genes that are highly expressed in the context of mouse and human infection: SP_0282, an IID component of a mannose phosphotransferase system (PTS), and SP_1739, encoding RNase Y. We show that these two proteins can confer protection against pneumococcal nasopharyngeal colonization and intraperitoneal challenge in a murine model and generate opsonophagocytic antibodies. This study emphasizes and confirms the importance of studies of pneumococcal gene expression of bacterial surface proteins during human infection and colonization and may pave the way for the selection of a protein-based vaccine candidate. Show less
Westendorp, J.; Evers, A.W. M.; Stouthard, J.M.L.; Budding, J.; Wall, E.; Plum, N.M.F.; ... ; Vliet, L.M. van 2021
BackgroundMany complaints in medicine and in advanced illnesses are about communication. Little is known about which specific communications harm. This study explored the perspectives of patients... Show moreBackgroundMany complaints in medicine and in advanced illnesses are about communication. Little is known about which specific communications harm. This study explored the perspectives of patients with advanced cancer about potentially harmful communication behaviors by oncologists and helpful alternatives.MethodsAn online survey design was used that was based on literature scoping and patient/clinician/researcher input. Patients with advanced cancer (n = 74) reflected on the potential harmfulness of 19 communication situations. They were asked whether they perceived the situation as one in which communication could be harmful (yes/no). If they answered “yes,” they were asked whether they perceived the examples as harmful (yes/no) or helpful (yes/no) and to provide open comments. Results were analyzed quantitatively and qualitatively (content analysis).ResultsCommunication regarding information provision, prognosis discussion, decision-making, and empathy could be unnecessarily potentially harmful, and this occurred in various ways, such as making vague promises instead of concrete ones (92%), being too directive in decision-making (qualitative), and not listening to the patient (88%). Not all patients considered other situations potentially harmful (eg, introducing the option of refraining from anticancer therapy [49%] and giving too much [prognostic] information [60%]). Exploring each individual patients' needs/preferences seemed to be a precondition for helpful communication.ConclusionsThis article provides patient perspectives on oncologists' unnecessarily potentially harmful communication behaviors and offers practical tools to improve communication in advanced cancer care. Both preventable pitfalls and delicate challenges requiring an individualized approach, where exploration might help, are described. Although providing difficult and unwelcome news is a core task for clinicians, this study might help them to do so while preventing potentially unnecessary harm. Show less
Dellar, M.; Topp, C.; Pardo, G.; Prado, A. del; Fitton, N.; Holmes, D.S.T.; ... ; Wall, E. 2019
