Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data

Purpose

The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury.

Methods

We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume.

Results

Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01–1.38; P?=?0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02–1.07; P?=?0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07–3.64; P?=?0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher V_T.

Conclusions

Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241).

     

People with chronic low back pain have poorer balance than controls in challenging tasks

Purpose: To compare the balance of individuals with and without chronic low back pain during five tasks.

Method: The participants were 20 volunteers, 10 with and 10 without nonspecific chronic low back pain, mean age 34?years, 50% females. The participants completed the following balance tasks on a force platform in random order: (1) two-legged stance with eyes open, (2) two-legged stance with eyes closed, (3) semi-tandem with eyes open, (4) semi-tandem with eyes closed and (5) one-legged stance with eyes open. The participants completed three 60-s trials of tasks 1–4, and three 30-s trials of task 5 with 30-s rests between trials. The center of pressure area, velocity and frequency in the antero-posterior and medio-lateral directions were computed during each task, and compared between groups and tasks.

Results: Participants with chronic low back pain presented significantly larger center of pressure area and higher velocity than the healthy controls (p?p?1.37 vs. effect size <0.64). There were no significant interactions between groups and tasks.

Conclusions: Individuals with chronic low back pain presented poorer postural control using center of pressure measurements than the healthy controls, mainly during more challenging balance tasks such as semi-tandem and one-legged stance conditions.

• Implications for Rehabilitation

• People with chronic low back had poorer balance than those without it.

• Balance tasks need to be sensitive to capture impairments.

• Balance assessments during semi-tandem and one-legged stance were the most sensitive tasks to determine postural control deficit in people with chronic low back.

• Balance assessment should be included during rehabilitation programs for individuals with chronic low back pain for better clinical decision making related to balance re-training as necessary.

     

Detection of Sialic Acid-Utilising Bacteria in a Caecal Community Batch Culture Using RNA-Based Stable Isotope Probing

Sialic acids are monosaccharides typically found on cell surfaces and attached to soluble proteins, or as essential components of ganglioside structures that play a critical role in brain development and neural transmission. Human milk also contains sialic acid conjugated to oligosaccharides, glycolipids, and glycoproteins. These nutrients can reach the large bowel where they may be metabolised by the microbiota. However, little is known about the members of the microbiota involved in this function. To identify intestinal bacteria that utilise sialic acid within a complex intestinal community, we cultured the caecal microbiota from piglets in the presence of ¹³C-labelled sialic acid. Using RNA-based stable isotope probing, we identified bacteria that consumed ¹³C-sialic acid by fractionating total RNA in isopycnic buoyant density gradients followed by 16S rRNA gene analysis. Addition of sialic acid caused significant microbial community changes. A relative rise in Prevotella and Lactobacillus species was accompanied by a corresponding reduction in the genera Escherichia/Shigella, Ruminococcus and Eubacterium. Inspection of isotopically labelled RNA sequences suggests that the labelled sialic acid was consumed by a wide range of bacteria. However, species affiliated with the genus Prevotella were clearly identified as the most prolific users, as solely their RNA showed significantly higher relative shares among the most labelled RNA species. Given the relevance of sialic acid in nutrition, this study contributes to a better understanding of their microbial transformation in the intestinal tract with potential implications for human health.     

Influence of Bleeding Risk on Outcomes of Radial and Femoral Access for Percutaneous Coronary Intervention: An Analysis From the GLOBAL LEADERS Trial

BackgroundRadial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding.MethodsPatients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days.ResultsIn the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; P_interaction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; P_interaction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant.ConclusionsOur findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating.     

Neuronal activity regulated pentraxin (narp) and GluA4 subunit of AMPA receptor may be targets for fluoxetine modulation

Fluoxetine is the foremost prescribed antidepressant. Drugs acting on monoaminergic system may also regulate glutamatergic system. Indeed, the investigation of proteins associated with this system, such as Narp (neuronal activity-dependent pentraxin) and GluA4 subunit of AMPA receptor may reveal poorly explored modulations triggered by conventional antidepressants. This study aimed to uncover neurochemical mechanisms underlying the chronic fluoxetine treatment, mainly by evaluating these protein targets in the prefrontal cortex and in the hippocampus. Mice received a daily administration of fluoxetine (0.1, 1 or 10 mg/kg, p.o.) or potable water (vehicle group) for 21 days. These animals were submitted to the forced swim test (FST) to verify antidepressant-like responses and the open-field test (OFT) to assess locomotor activity. Modulation of signaling proteins was analyzed by western blot. Chronic treatment with fluoxetine (1 and 10 mg/kg) was effective, since it reduced the immobility time in the FST, without altering locomotor activity. Fluoxetine 10 mg/kg increased CREB phosphorylation and BDNF expression in the prefrontal cortex and hippocampus. Noteworthy, in the hippocampus fluoxetine also promoted Akt activation and augmented Narp expression. In the prefrontal cortex, a significant decrease in the expression of the GluA4 subunit and Narp were observed following fluoxetine administration (10 mg/kg). The results provide evidence of novel molecular targets potentially involved in the antidepressant effects of fluoxetine, since in mature rodents Narp and GluA4 are mainly expressed in the GABAergic parvalbumin-positive (PV+) interneurons. This may bring new insights into the molecular elements involved in the mechanisms underlying the antidepressant effects of fluoxetine.

     

Evolving role of endoscopy in inflammatory bowel disease: Going beyond diagnosis

Inflammatory bowel disease, encompassing Crohn’s disease (CD) and ulcerative colitis, are chronic immune-mediated inflammatory bowel diseases (IBD) that primarily affect the gastrointestinal tract with periods of activity and remission. Large body of evidence exist to strengthen the prognostic role of endoscopic evaluation for both disease activity and severity and it remains the gold standard for the assessment of mucosal healing. Mucosal healing has been associated with improved clinical outcomes with prolonged remission, decreased hospitalization, IBD-related surgeries and colorectal cancer risk. Therefore, endoscopic objectives in IBD have been incorporated as part of standard care. With the known increased risk of colorectal cancer in IBD, although prevention strategies continue to develop, regular surveillance for early detection of neoplasia continue to be paramount in IBD patients’ care. It is thanks to evolving technology and visualization techniques that surveillance strategies are continuously advancing. Therapeutic endoscopic options in IBD have also been expanding, from surgery sparing therapies such as balloon dilation of fibrostenotic strictures in CD to endoscopic mucosal resection of neoplastic lesions. In this review article, we discuss the current evidence on the use of endoscopy as part of standard of care of IBD, its role in surveillance of neoplasia, and the role of interventional endoscopic therapies.