A novel phosphocholine-mimetic inhibits a pro-inflammatory conformational change in C-reactive protein.

C-reactive protein (CRP) is an early-stage acute phase protein and highly upregulated in response to inflammatory reactions. We recently identified a novel mechanism that leads to a conformational change from the native, functionally relatively inert, pentameric CRP (pCRP) structure to a pentameric CRP intermediate (pCRP*) and ultimately to the monomeric CRP (mCRP) form, both exhibiting highly pro-inflammatory effects. This transition in the inflammatory profile of CRP is mediated by binding of pCRP to activated/damaged cell membranes via exposed phosphocholine lipid head groups. We designed a tool compound as a low molecular weight CRP inhibitor using the structure of phosphocholine as a template. X-ray crystallography revealed specific binding to the phosphocholine binding pockets of pCRP. We provide in vitro and in vivo proof-of-concept data demonstrating that the low molecular weight tool compound inhibits CRP-driven exacerbation of local inflammatory responses, while potentially preserving pathogen-defense functions of CRP. The inhibition of the conformational change generating pro-inflammatory CRP isoforms via phosphocholine-mimicking compounds represents a promising, potentially broadly applicable anti-inflammatory therapy.

An Analysis of the Implantable Doppler Probe for Postoperative Free-Flap Monitoring and Risk Factor Analysis for Revision Surgery in Facial Reanimation Surgery.

Background: Postoperative monitoring after free functional gracilis transfer for smile reconstruction in long-standing facial paralysis is challenging as clinical assessments are limited. Objective: In patients receiving free gracilis transfer for smile reconstruction, we compared the implantable Doppler probe with a handheld Doppler/intraoperative blood flow regarding the reliability in detecting perfusion compromised free flaps. Methods: In a retrospective cohort study we analyzed facial paralysis patients who, after free functional smile reconstruction, were postoperatively monitored using the implantable Doppler probe. Furthermore, we conducted a multiple logistic regression analysis on risk factors for vascular complications. Results: We included 119 patients who received 125 free functional gracilis transfers. The sensitivity of the implanted Doppler probe was 1.0 and the specificity 0.88. There were no false-negative results (negative predictive value = 1.0). The calculated positive predictive value was 0.41. We used a handheld Doppler device to verify signal changes. The combined positive predictive value of both tests was 0.91. Previous surgery in the surgical field was a risk factor for impaired blood flow. Conclusions: The implantable Doppler probe proved to be a reliable tool for postoperative monitoring of free functional gracilis transfer in facial reanimation surgery. Special care should be taken in preoperated patients.

Evaluation of a Novel Thiol-Norbornene-Functionalized Gelatin Hydrogel for Bioprinting of Mesenchymal Stem Cells.

Introduction: Three-dimensional bioprinting can be considered as an advancement of the classical tissue engineering concept. For bioprinting, cells have to be dispersed in hydrogels. Recently, a novel semi-synthetic thiolene hydrogel system based on norbornene-functionalized gelatin (GelNB) and thiolated gelatin (GelS) was described that resulted in the photoclick hydrogel GelNB/GelS. In this study, we evaluated the printability and biocompatibility of this hydrogel system towards adipose-tissue-derived mesenchymal stem cells (ASCs). Methods: GelNB/GelS was synthesized with three different crosslinking densities (low, medium and high), resulting in different mechanical properties with moduli of elasticity between 206 Pa and 1383 Pa. These hydrogels were tested for their biocompatibility towards ASCs in terms of their viability, proliferation and differentiation. The extrusion-based bioprinting of ASCs in GelNB/GelS-high was performed to manufacture three-dimensional cubic constructs. Results: All three hydrogels supported the viability, proliferation and chondrogenic differentiation of ASCs to a similar extent. The adipogenic differentiation of ASCs was better supported by the softer hydrogel (GelNB/GelS-low), whereas the osteogenic differentiation was more pronounced in the harder hydrogel (GelNB/GelS-high), indicating that the differentiation fate of ASCs can be influenced via the adaption of the mechanical properties of the GelNB/GelS system. After the ex vivo chondrogenic differentiation and subcutaneous implantation of the bioprinted construct into immunocompromised mice, the production of negatively charged sulfated proteoglycans could be observed with only minimal inflammatory signs in the implanted material. Conclusions: Our results indicate that the GelNB/GelS hydrogels are very well suited for the bioprinting of ASCs and may represent attractive hydrogels for subsequent in vivo tissue engineering applications.

Artificial Intelligence-Driven Video Analysis for Novel Outcome Measures After Smile Reanimation Surgery.

Background: Since facial paralysis is a dynamic condition, the analysis of still photographs is not sufficient for measurement of facial reanimation outcomes. This study aimed at evaluating an artificial intelligence (AI)-driven software as a novel video assessment tool for smile reanimation surgery and at comparing it with the Terzis score. Methods: Patients with facial paralysis undergoing smile reanimation surgery between January 2008 and April 2020 were eligible for this retrospective study. Inclusion criteria were at least 6 months of follow-up and availability of both pre- and post-operative video documentation. The software output was given as intensity score (IS) values between 0 and 1, representing emotions/action units (AUs) that are absent or fully present, respectively. Results: During the study period, 240 patients underwent facial reanimation surgery, of whom 63 patients met the inclusion criteria. Postoperatively, the median IS of the happiness emotion and lip corner puller AU increased significantly (p < 0.001). There was a positive correlation of Terzis score with the IS of happiness emotion (r = 0.8) and lip corner puller AU (r = 0.74). Conclusions: The novel AI-driven video analysis is strongly correlated with the Terzis score and shows promise for objective functional outcome evaluation after smile reanimation surgery.

The Edmonton Obesity Staging System Predicts Postoperative Complications After Abdominoplasty.

BACKGROUND: This study investigates the relationship between Edmonton Obesity Staging System (EOSS) and the occurrence of postoperative complications after abdominoplasty in massive weight loss patients. METHODS: A single-institution retrospective review of patients undergoing abdominoplasty between 2009 and 2019 after massive weight loss. Demographic data, laboratory findings, known risk factors for postoperative complications, as well as data on major and minor complications were extracted from the patient charts. Logistic regression models were used to investigate the relationship between the variables. RESULTS: Four hundred and five patients were included in the study. The prevalence of EOSS stages was: 0 (no comorbidities, N = 151, 37%), 1 (mild conditions, N = 40, 10%), 2 (moderate conditions, N = 149, 36%) and 3 (severe conditions, N = 70, 17%). Regression analysis showed that, controlling for body mass index (BMI), BMI Δ (maximal BMI - BMI at presentation), bariatric surgery, volume of resected tissue, and duration of surgery, EOSS stage significantly associated with the occurrence of postoperative complications. Compared with EOSS stage 0, EOSS stages 2 and 3 patients were associated with significantly more minor and major complications, respectively. The volume of resected tissue, BMI Δ, and age were associated with the occurrence of major complications. A regression model of comorbidities comprising the EOSS revealed a significant association of variables diabetes mellitus and hypertension with the occurrence of postoperative complications. CONCLUSIONS: Edmonton Obesity Staging System is a robust predictor of postoperative complications in abdominoplasty.