Application of tapered endotracheal tube cuffs did not reduce hospital-acquired pneumonia incidence among ICU and postoperative patients. Further research should examine the impact of concomitant use of tapered cuffs with continuous cuff pressure monitoring and subglottic secretion drainage.

The protozoan parasite Giardia is a highly prevalent intestinal pathogen with a wide host range. Data obtained in mice, cattle and humans revealed the importance of IL-17A in the development of a protective immune response against Giardia. The aim of this study was to further unravel the protective effector mechanisms triggered by IL-17A following G. muris infection in mice, by an RNA-sequencing approach. C57BL/6 WT and C57BL/6 IL-17RA KO mice were orally infected with G. muris cysts. Three weeks post infection, intestinal tissue samples were collected for RNA-sequencing, with samples from uninfected C57BL/6 WT and C57BL/6 IL-17RA KO animals serving as negative controls. Differential expression analysis showed that G. muris infection evoked the transcriptional upregulation of a wide array of genes, mainly in animals with competent IL-17RA signaling. IL-17RA signaling induced the production of various antimicrobial peptides, such as angiogenin 4 and α- and β-defensins and regulated complement activation through mannose-binding lectin 2. The expression of the receptor that regulates the secretion of IgA into the intestinal lumen, the polymeric immunoglobulin receptor, was also dependent on IL-17RA signaling. Interestingly, the transcriptome data showed for the first time the involvement of the circadian clock in the host response following Giardia infection.

OBJECTIVES: Microaspiration of subglottic secretions is the main pathogenic mechanism for ventilator-associated pneumonia (VAP). Adequate inflation of the endotracheal cuff is pivotal to providing an optimal seal of the extraluminal airway. However, cuff pressure substantially fluctuates due to patient or tube movements, which can induce microaspiration. Therefore, devices for continuous cuff pressure control (CCPC) have been developed in recent years. The purpose of this systematic review and meta-analysis is to assess the effectiveness of CCPC in VAP prevention. DATA SOURCES: A systematic search of Embase, the Cochrane Central Register of Controlled Trials, and the International Clinical Trials Registry Platform was conducted up to February 2022. STUDY SELECTION: Eligible studies were randomized controlled trials (RCTs) and quasi-RCTs comparing the impact of CCPC versus intermittent cuff pressure control on the occurrence of VAP. DATA EXTRACTION: Random-effects meta-analysis was used to calculate odds ratio (OR) and 95% CI for VAP incidence between groups. Secondary outcome measures included mortality and duration of mechanical ventilation (MV) and ICU stay. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Eleven RCTs with 2,092 adult intubated patients were included. The use of CCPC was associated with a reduced risk of VAP (OR, 0.51). Meta-analyses of secondary endpoints showed no significant difference in mortality but significant differences in durations of MV (mean difference, –1.07 d) and ICU stay (mean difference, –3.41 d) in favor of CCPC. However, the risk of both reporting and individual study bias was considered important. The main issues were the lack of blinding, potential commercial conflicts of interest of study authors and high heterogeneity due to methodological differences between studies, differences in devices used for CCPC and in applied baseline preventive measures. Certainty of the evidence was considered “very low.” CONCLUSIONS: The use of CCPC was associated with a reduction in VAP incidence; however, this was based on very low certainty of evidence due to concerns related to risk of bias and inconsistency.

Giardia duodenalis is one of the most commonly found intestinal parasites in mammalian hosts. Infections can generally be cleared by mounting an adequate protective immune response that is orchestrated through IL-17A. This study was aimed to investigate if and how the intestinal microbiome affects the protective Th17 response against Giardia by analysing and comparing the immune response following a G. muris and G. duodenalis infection in antibiotic treated and untreated mice. Depletion of the intestinal flora by antibiotic treatment had a severe effect on the infection dynamics of both Giardia species. Not only duration of infection was affected, but also the parasite burden increased significantly. Markers associated with a protective immune response, such as IL-17A and mannose binding lectin 2 were still significantly upregulated following infection in the antibiotic-treated mice, despite the lack of protection. On the other hand, the antibiotic treatment significantly decreased the level of IgA in the intestinal lumen by affecting its transporter and by reducing the number of IgA+ B-cells at the Peyer’s patches. Furthermore, the depletion of the gut microbiota by antibiotics also significantly lowered the intestinal motility. The combination of these factors likely results in a decreased clearance of the parasite from the intestinal tract.

Giardia is an intestinal protozoan parasite that has the ability to infect a wide range of hosts, which can result in the clinical condition ‘giardiasis’. Over the years, experimental research has shown the crucial involvement of IL-17A to steer the protective immune response against Giardia . The development of the protective response, as reflected by a significant drop in cyst secretion, typically takes around 3 to 4 weeks. However, early-life infections often have a more chronic character lasting for several weeks or months. Therefore, the aim of the current study was to investigate the dynamics of a Giardia muris infection and the subsequent host immune response in neonatal mice infected 4 days after birth. The outcome of the study showed that a G . muris infection in pre-weaned mice failed to trigger a protective IL-17A response, which could explain the prolonged course of infection in comparison to older mice. Only after weaning, a protective intestinal immune response started to develop, characterized by an upregulation of IL-17A and Mbl2 and the secretion of parasite-specific IgA.