Inflammatory markers in postoperative delirium (POD) and cognitive dysfunction (POCD): A meta-analysis of observational studies

<div><p>Background</p><p>The aim of this study was to summarize and discuss the similarities and differences in inflammatory biomarkers in postoperative delirium (POD) and cognitive dysfunction (POCD).</p><p>Methods</p><p>A systematic retrieval of literature up to June 2017 in PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure database, and the Wanfang database was conducted. Extracted data were analyzed with STATA (version 14). The standardized mean difference (SMD) and the 95% confidence interval (95% CI) of each indicator were calculated using a random effect model. We also performed tests of heterogeneity, sensitivity analysis, assessments of bias, and meta-regression in this meta-analysis.</p><p>Results</p><p>A total of 54 observational studies were included. By meta-analysis we found significantly increased C-reactive protein (CRP) (9 studies, SMD 0.883, 95% CI 0.130 to 1.637, <i>P</i> = 0.022 in POD; 10 studies, SMD -0.133, 95% CI -0.512 to 0.246, <i>P</i> = 0.429 in POCD) and interleukin (IL)-6 (7 studies, SMD 0.386, 95% CI 0.054 to 0.717, <i>P</i> = 0.022 in POD; 16 studies, SMD 0.089, 95% CI -0.133 to 0.311, <i>P</i> = 0.433 in POCD) concentrations in both POD and POCD patients. We also found that the SMDs of CRP and IL-6 from POCD patients were positively correlated with surgery type in the meta-regression (CRP: Coefficient = 1.555365, <i>P</i> = 0.001, 10 studies; IL-6: Coefficient = -0.6455521, <i>P</i> = 0.086, 16 studies).</p><p>Conclusion</p><p>Available evidence from medium-to-high quality observational studies suggests that POD and POCD are indeed correlated with the concentration of peripheral and cerebrospinal fluid (CSF) inflammatory markers. Some of these markers, such as CRP and IL-6, play roles in both POD and POCD, while others are specific to either one of them.</p></div

Meta-regression between the SMDs of peripheral CRP and IL-6 Levels before surgery and the potential sources of heterogeneity.

<p>Meta-regression between the SMDs of peripheral CRP and IL-6 Levels before surgery and the potential sources of heterogeneity.</p

Flow diagram of article selection.

<p>Flow diagram of article selection.</p

CRP (Peripheral) levels before surgery in patients with POD (A) and POCD (B).

<p>CRP (Peripheral) levels before surgery in patients with POD (A) and POCD (B).</p

S-100β (Peripheral) Levels Post-Surgery in Patients with POD (A) and POCD (B).

<p>S-100β (Peripheral) Levels Post-Surgery in Patients with POD (A) and POCD (B).</p

IL-6 (Peripheral) levels before surgery in patients with POD (A) and POCD (B).

<p>IL-6 (Peripheral) levels before surgery in patients with POD (A) and POCD (B).</p

Egger’s test results for publication and selective reporting bias.

<p>Egger’s test results for publication and selective reporting bias.</p

Results of the random-effects meta-analysis for the association between inflammatory markers and POD.

<p>Positive values indicate higher levels in POD patients; negative values indicate higher levels in control patients. CRP, C-reactive protein; IL-6, interleukin-6; S-100β, S-100 calcium binding protein beta subunit; NSE, neuron-specific enolase; IL-8, interleukin-8; IL-1β, interleukin-1 beta; TNF-α, tumor necrosis factor alpha; IGF-1, insulin-like growth factor-1; IL-10, interleukin-10; IL-1ra, interleukin-1 receptor antagonist; pre-op, pre-operation; post-op, post-operation; N, number of studies; SMD, standardized mean difference; CI, confidence interval.</p

Subgroup analyses for the assessment of impact of surgery type, anesthesia, and ethnicity on peripheral CRP and IL-6 levels perioperatively.

<p>Positive values indicate higher levels in POD/POCD patients; negative values indicate higher levels in control patients. All results are from random-effects models. pre-op, pre-operation; post-op, post-operation; N, number of studies; SMD, standardized mean difference; CI, confidence interval; *Data missing for N = 1 study.</p

Acoustics-Controlled Microdroplet and Microbubble Fusion and Its Application in the Synthesis of Hydrogel Microspheres

Droplet fusion technology is a key technology for many droplet-based biochemical medical applications. By integrating a symmetrical flow channel structure, we demonstrate an acoustics-controlled fusion method of microdroplets using surface acoustic waves. Different kinds of microdroplets can be staggered and ordered in the symmetrical flow channel, proving the good arrangement effect of the microfluidic chip. This method can realize not only the effective fusion of microbubbles but also the effective fusion of microdroplets of different sizes without any modification. Further, we investigate the influence of the input frequency and peak-to-peak value of the driving voltage on microdroplets fusion, giving the effective fusion parameter conditions of microdroplets. Finally, this method is successfully used in the preparation of hydrogel microspheres, offering a new platform for the synthesis of hydrogel microspheres