Faculty Bibliography

Glycation and the accumulation of advanced glycation end products (AGEs) are known to occur during normal aging but also in the progression of several diseases, such as diabetes. Diabetes type II and aging both lead to impaired wound healing. It has been demonstrated that macrophages play an important role in impaired wound healing, however, the underlying causes remain unknown. Elevated blood glucose levels as well as elevated methylglyoxal (MGO) levels in diabetic patients result in glycation and increase of AGEs. We used MGO to investigate the influence of glycation and AGEs on macrophages. We could show that glycation, but not treatment with AGE-modified serum proteins, increased expression of pro-inflammatory cytokines interleukin 1β (IL-1β) and IL-8 but also affected IL-10 and TNF-α expression, resulting in increased inflammation. At the same time, glycation reduced phagocytic efficiency and led to impaired clearance rates of invading microbes and cellular debris. Our data suggest that glycation contributes to changes of macrophage activity and cytokine expression and therefore could support the understanding of disturbed wound healing during aging and diabetes.

Figure 3 in the original article [1] is incorrect; labels for secondary outcomes have been shifted and do not correspond to the numbers reported in the table (Additional file 8). The corrected version can be seen ahead. This figure should be used over the figure 3 seen in the original article. This error does not affect the results, interpretation, or conclusion.

BACKGROUND:Identifying infection is critical in early sepsis screening. This study assessed whether biomarkers of endothelial activation and/or inflammation could improve identification of infection among Emergency Department (ED) patients with organ dysfunction. METHODS:We performed a prospective, observational study at two urban, academic EDs, between June 2016 and December 2017. We included admitted adults with 1) two systemic inflammatory response syndrome criteria and organ dysfunction, 2) systolic blood pressure < 90 mmHg, or 3) lactate ≥4.0 mmol/L. We excluded patients with trauma, transferred for intracranial hemorrhage, or without available blood samples. Treating ED physicians reported presence of infection (yes/no) at inpatient admission. Assays for angiopoietin-1, angiopoietin-2, soluble tumor necrosis factor receptor-1, interleukin-6, and interleukin-8 were performed using ED blood samples. The primary outcome was infection, adjudicated by paired physician review. Using logistic regression, we compared the performance of physician judgment, biomarkers, and physician judgment-biomarkers combination to predict infection. Area under the curve (AUC) and AUC 95% confidence intervals were estimated by bootstrap procedure. RESULTS:Of 421 patients enrolled, 306 patients met final study criteria. Of these, 154(50.3%) patients had infectious etiologies. Physicians correctly discriminated infectious from non-infectious etiologies in 239 (78.1%). Physician judgment performed moderately when discriminating infection (AUC 0.78, 95% CI: 0.74-0.82) and outperformed the best biomarker model, interleukin-6 alone, (AUC 0.71, 0.66-0.76). Physician judgment improved when including interleukin-6 (AUC 0.84, 0.79-0.87), with modest AUC improvement: 0.06 (0.03-0.08). CONCLUSIONS:In ED patients with organ dysfunction, plasma interleukin-6 may improve infection discrimination when added to physician judgment.

Previously, by targeting penicillin-binding protein 3, Pseudomonas-derived cephalosporinase (PDC), and MurA with ceftazidime-avibactam-fosfomycin, antimicrobial susceptibility was restored among multidrug-resistant (MDR) Pseudomonas aeruginosa. Herein, ceftazidime-avibactam-fosfomycin combination therapy against MDR P. aeruginosa clinical isolate CL232 was further evaluated. Checkerboard susceptibility analysis revealed synergy between ceftazidime-avibactam and fosfomycin. Accordingly, the resistance elements present and expressed in P. aeruginosa were analyzed using whole-genome sequencing and transcriptome profiling. Mutations in genes that are known to contribute to β-lactam resistance were identified. Moreover, expression of blaPDC, the mexAB-oprM efflux pump, and murA were upregulated. When fosfomycin was administered alone, the frequency of mutations conferring resistance was high; however, coadministration of fosfomycin with ceftazidime-avibactam yielded a lower frequency of resistance mutations. In a murine infection model using a high bacterial burden, ceftazidime-avibactam-fosfomycin significantly reduced the P. aeruginosa colony-forming units (CFUs), by approximately 2 and 5 logs, compared with stasis and in the vehicle-treated control, respectively. Administration of ceftazidime-avibactam and fosfomycin separately significantly increased CFUs, by approximately 3 logs and 1 log, respectively, compared with the number at stasis, and only reduced CFUs by approximately 1 log and 2 logs, respectively, compared with the number in the vehicle-treated control. Thus, the combination of ceftazidime-avibactam-fosfomycin was superior to either drug alone. By employing a "mechanism-based approach" to combination chemotherapy, we show that ceftazidime-avibactam-fosfomycin has the potential to offer infected patients with high bacterial burdens a therapeutic hope against infection with MDR P. aeruginosa that lack metallo-β-lactamases.

BACKGROUND:Current perioperative patient care aims to maintain homeostasis by attenuation of the stress response to surgery, as a more vigorous stress response can have detrimental effects on postoperative recovery. This systematic review and meta-analysis aims to assess the effect of perioperative music on the physiological stress response to surgery. METHODS:The Embase, Medline Ovid, Cochrane Central, Web of Science, and Google Scholar databases were searched from inception date until February 5, 2019, using a systematic literature search following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines for randomized controlled trials investigating the effect of music before, during, and/or after surgery in adult surgical patients on the stress response to surgery. Meta-analysis was performed using a random effects model and pooled standardized mean differences were calculated with 95% confidence intervals. This study was registered in the PROSPERO database (CRD42018097060). RESULTS: = 0). CONCLUSIONS:Perioperative music can attenuate the neuroendocrine stress response to surgery.

Hallberg et al. provide a limited literature review on the reversal of type 2 diabetes mellitus (T2DM) [...].