Synergistic Induction of Chicken Antimicrobial Host Defense Peptide Gene Expression by Butyrate and Sugars.

Antimicrobial resistance is a major concern to public health demanding effective alternative strategies to disease control and prevention. Modulation of endogenous host defense peptide (HDP) synthesis has emerged as a promising antibiotic alternative approach. This study investigated a potential synergy between sugars and butyrate in inducing HDP gene expression in chickens. Our results revealed that sugars differentially regulated HDP expression in both gene- and sugar-specific manners in chicken HD11 macrophage cells. Among eight mono- and disaccharides tested, all were potent inducers of avian ß-defensin 9 (AvBD9) gene (p<0.05), but only galactose, trehalose, and lactose obviously upregulated cathelicidin-B1 (CATHB1) gene expression. The expression of AvBD14 gene, on the other hand, was minimally influenced by sugars. Moreover, all sugars exhibited a strong synergy with butyrate in enhancing AvBD9 expression, while only galactose, trehalose, and lactose were synergistic with butyrate in CATHB1 induction. No synergy in AvBD14 induction was observed between sugars and butyrate. Although lactose augmented the expression of nearly all HDP genes, its synergy with butyrate was only seen with several, but not all, HDP genes. Mucin-2 gene was also synergistically induced by a combination of lactose and butyrate. Furthermore, lactose synergized with butyrate to induce AvBD9 expression in chicken jejunal explants (p<0.05). Mechanistically, hyper-acetylation of histones was observed in response to both butyrate and lactose, relative to individual compounds. Mitogen-activated protein kinase, NF-κB, and cyclic adenosine monophosphate signaling pathways were also found to be involved in butyrate- and lactose-mediated synergy in AvBD9 induction. Collectively, a combination of butyrate and a sugar with both HDP-inducing and barrier protective activities holds the promise to be developed as an alternative to antibiotics for disease control and prevention.

Impact of an intensivist-led multidisciplinary extended rapid response team on hospital-wide cardiopulmonary arrests and mortality.

OBJECTIVE: The effectiveness of rapid response teams remains controversial. However, many studied rapid response teams were not intensivist-led, had limited involvement beyond the initial activations, and did not provide post-ICU follow-up. The objective of this study was to examine the impact of implementing an intensivist-led multidisciplinary extended rapid response team on hospital-wide cardiopulmonary arrests and mortality. DESIGN: This was a pre-post rapid response team implementation study. SETTING: : Tertiary care academic center in Saudi Arabia. PATIENTS: A total of 98,391 patients in the 2-yr pre-rapid response team and 157,804 patients in the 3-yr post-rapid response team implementation were evaluated. INTERVENTION: The rapid response team was activated by any health care provider based on pre-defined criteria and a four-member intensivist-led multidisciplinary rapid response team responded to provide the necessary management and disposition. The rapid response team function was extended to provide follow-up until clinical stabilization. In addition, the rapid response team provided a mandatory post-ICU follow-up for a minimum of 48 hrs. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were cardiopulmonary arrests and mortality. After rapid response team implementation, non-ICU cardiopulmonary arrests decreased from 1.4 to 0.9 per 1,000 hospital admissions (relative risk, 0.68; 95% confidence interval, 0.53-0.86; p = 0.001) and total hospital mortality decreased from 22.5 to 20.2 per 1,000 hospital admissions (relative risk, 0.90; 95% confidence interval, 0.85-0.95; p < 0.0001). For patients who required admission to the ICU, there was a significant reduction in the Acute Physiology and Chronic Health Evaluation II scores after rapid response team implementation from 29.3 ± 9.3 to 26.9 ± 8.5 (p < 0.0001), with reduction in hospital mortality from 57.4% to 48.7% (relative risk, 0.85; 95% confidence interval, 0.78-0.92; p < 0.0001). Do-not-resuscitate orders for ward referrals increased from 0.7 to 1.7 per 1,000 hospital admissions (relative risk, 2.58; 95% confidence interval, 1.95-3.42; p < 0.0001) and decreased for patients admitted to ICU from the wards from 30.5% to 26.1% (relative risk, 0.86; 95% confidence interval, 0.74-0.99; p = 0.03). Additionally, ICU readmission rate decreased from 18.6 to 14.3 per 100 ICU alive discharges (relative risk, 0.77; 95% confidence interval, 0.66-0.89; p < 0.0001) and post-ICU hospital mortality from 18.2% to 14.8% (relative risk, 0.85; 95% confidence interval, 0.72-0.99; p = 0.04). CONCLUSION: The implementation of rapid response team was effective in reducing cardiopulmonary arrests and total hospital mortality for ward patients, improving the outcomes of patients who needed ICU admission and reduced readmissions and mortality of patients who were discharged from the ICU.

Compliance with DNR policy in a tertiary care center in Saudi Arabia.

INTRODUCTION: Do not resuscitate (DNR) is an important aspect of medical practice, although few studies from Arab Muslim countries address this issue. King Abdulaziz Medical City (KAMC), Saudi Arabia has a policy addressing all aspects of patient care at end of life. OBJECTIVE: To assess compliance of physicians with the current DNR policy. METHODS: A cohort study of data prospectively collected from 15/10/2008 through 15/01/2009 for patients where DNR was initiated. Patient charts were followed prospectively to observe DNR documentation completion. Data were analyzed in terms of frequencies and descriptive statistics, and the results expressed as percentages. RESULTS: DNR was initiated in 65 patients referred to the intensive care unit (ICU): 46.2% females, 53.8% males; age range 19-93 years, mean ± standard deviation (SD) 66.1 ± 16.0 years. DNR was initiated by ICU physician in 80% of cases and by most responsible physician (MRP) in 20% of cases. There was a delay (of more than 48 h) in completing MRP signature in 8 patients (12.3%), and no signature at all by the MRP in 13 patients (20%). Documentation of discussion with the family was absent in 53.8% of cases. CONCLUSIONS: ICU physicians have a role in initiating DNR. Mostly this issue is not addressed on admission. Documentation of DNR once initiated is still not up to the optimum level in 32.3% of cases, mainly due to MRP. Discussion with the patient's family was not well documented in the chart in more than half of cases.