Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis.

More than 40% of individuals will develop osteoarthritis (OA) during their lifetime, yet there are currently no licensed disease-modifying treatments for this disabling condition. Common polymorphic variants in ALDH1A2, which encodes the key enzyme for synthesis of all-trans retinoic acid (atRA), are associated with severe hand OA. Here, we sought to elucidate the biological significance of this association. We first confirmed that ALDH1A2 risk variants were associated with hand OA in the U.K. Biobank. Articular cartilage was acquired from 33 individuals with hand OA at the time of routine hand OA surgery. After stratification by genotype, RNA sequencing was performed. A reciprocal relationship between ALDH1A2 mRNA and inflammatory genes was observed. Articular cartilage injury up-regulated similar inflammatory genes by a process that we have previously termed mechanoflammation, which we believe is a primary driver of OA. Cartilage injury was also associated with a concomitant drop in atRA-inducible genes, which were used as a surrogate measure of cellular atRA concentration. Both responses to injury were reversed using talarozole, a retinoic acid metabolism blocking agent (RAMBA). Suppression of mechanoflammation by talarozole was mediated by a peroxisome proliferator-activated receptor gamma (PPARγ)-dependent mechanism. Talarozole was able to suppress mechano-inflammatory genes in articular cartilage in vivo 6 hours after mouse knee joint destabilization and reduced cartilage degradation and osteophyte formation after 26 days. These data show that boosting atRA suppresses mechanoflammation in the articular cartilage in vitro and in vivo and identifies RAMBAs as potential disease-modifying drugs for OA.

Facial synkinesis outcome measures: A systematic review of the available grading systems and a Delphi study to identify the steps towards a consensus.

INTRODUCTION: Facial synkinesis is characterised by abnormal and unintentional co-contractions of facial muscles caused by aberrant facial nerve healing, usually as a sequalae of facial palsy. The aim of this project is to propose a consensus for reporting this condition in the literature to facilitate the conduction of primary and secondary evidence studies, considering that no previous research has inquired in to this matter. METHODS: A systematic literature search was performed in MEDLINE and EMBASE databases, considering all the published articles on facial synkinesis. Studies that used a particular measuring system for this condition were included. Two authors independently assessed these articles focusing on the grading instruments utilised. The most commonly used instruments were analysed, and their basic components were incorporated in a modified Delphi survey, which was sent to a panel of experts. RESULTS: The systematic literature search retrieved 502 articles, of which 159 met the inclusion criteria. The two most commonly mentioned instruments were the House-Brackmann Scale and the Sunnybrook Facial Grading System. These were then followed by the Yanagihara scale, the Synkinesis Assessment Questionnaire, the eFace system and the Facial Clinimetric Evaluation. The modified Delphi study concluded that an ideal grading system for facial synkinesis should not only include a clinician-based evaluation of symmetry and signs of synkinesis, but also patient-reported symptoms. CONCLUSIONS: Considering the characteristics of the studies found in the literature, the Sunnybrook Facial Grading System fits best with the ideal synkinesis measuring instrument described by the panel of experts. However, in order to satisfy the need to include patient-reported outcomes, the use of the Facial Clinimetric Evaluation as an adjunct to the Sunnybrook Facial Grading System is proposed.

Comparing the Outcome of Different Biologically Derived Acellular Dermal Matrices in Implant-based Immediate Breast Reconstruction: A Meta-analysis of the Literatures.

BACKGROUND: Acellular dermal matrices (ADMs) have been used extensively in implant-based breast reconstruction. It was reported that due to the different sources and processing methods, the outcomes of ADMs in implant-based breast reconstructions are expected to differ. We designed this study to statistically analyze and discuss the outcome of 3 commonly used ADMs, Alloderm, Strattice, and Surgimend in implant-based breast reconstruction. METHODS: Comprehensive review of the literatures searched on electronic databases was done to identify studies published between 2006 and 2017 comparing the outcome of ADMs. Pooled random effect estimates for each complication and 95% confidence interval (CI) were calculated. One-way analysis of variance and Bonferroni test were used to compare statistical significance between and within groups, respectively. Multiple linear regression was done to include confounding factors and R statistic program for forest plot. RESULTS: Twenty-one studies met the inclusion with a total of 1,659, 999, and 912 breasts reconstructions in Alloderm, Strattice, and Surgimend, respectively. Seven complications extracted including major and minor infection, seroma, implant loss, hematoma, capsular contracture, and localized erythema. Pooled total complication rates were 23.82% (95% CI, 21.18-26.47%) in Strattice, 17.98% (95% CI, 15.49-20.47%) in Surgimend, 16.21% (95% CI, 14.44-17.99%) in Alloderm. Seroma rate was the highest in Strattice group (8.61%; 95% CI, 6.87-10.35%). There was no statistical significance between and within groups. CONCLUSION: Although Strattice exhibited a higher overall pooled complication rate compared with Alloderm and Surgimend, the incidence of individual complication varies between studies. A cost analysis of different ADMs may aid in choosing the type of ADMs to be used.