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

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

The role of retinoic acid in cartilage mechanoflammation

Osteoarthritis (OA) is a highly prevalent condition that affects more than 40% of individuals over the course of their lifetime. There are currently no disease-modifying OA drug (DMOAD) licensed for the treatment of this disease. An Icelandic genome wide association study (GWAS) study identified common polymorphic variants in ALDH1A2, the gene which encodes the enzyme involved in the synthesis of all-trans retinoic acid (atRA), with severe hand OA. Subsequent data from our lab showed that atRA-responsive genes are downregulated on cartilage injury. Mechanical injury is one of the principal risk factors in the development of OA. Cartilage injury is known to activate downstream inflammatory signalling that is driven in a transforming growth factor activated-beta 1 (TAK1) dependent manner and thereby increase inflammatory gene regulation, in a process known as mechanoflammation. Talarozole (TLZ), a CYP26 inhibitor, which prevents the breakdown of atRA, suppresses the upregulation of inflammatory genes on cartilage injury. My project sought to identify the mechanism by which atRA-responsive genes were downregulated and determine how atRA suppressed mechanoflammation on cartilage injury. The downregulation of atRA-responsive genes on cartilage injury was mediated in both cytosolic phospholipase A2 (cPLA2) - and reactive oxygen species (ROS)-sensitive manner. TAK1 phosphorylation on cartilage injury was partially mediated in a nicotinamide adenine dinucleotide phosphate oxidase (NOX)-sensitive manner, whereas TAK1 was responsible for the partial phosphorylation of cPLA2 on cartilage injury. Apoptosis signal regulating kinase 1 (ASK1) was the key driver of mitogen activated protein kinases (MAPKs) (Jun N terminal kinase (JNK) and extracellular signal regulated kinase (ERK)) on cartilage injury and downstream inflammatory gene regulation. atRA suppressed mechanoflammation in a peroxisome proliferator activated receptor gamma (PPARG)-sensitive manner. These findings suggest that both boosting atRA level and ASK1 inhibition can suppress mechanoflammation in articular cartilage and identifies each pathway as targets for potential disease modifying drugs in the treatment of OA.</p

The role of retinoic acid in cartilage mechanoflammation

Osteoarthritis (OA) is a highly prevalent condition that affects more than 40% of individuals over the course of their lifetime. There are currently no disease-modifying OA drug (DMOAD) licensed for the treatment of this disease. An Icelandic genome wide association study (GWAS) study identified common polymorphic variants in ALDH1A2, the gene which encodes the enzyme involved in the synthesis of all-trans retinoic acid (atRA), with severe hand OA. Subsequent data from our lab showed that atRA-responsive genes are downregulated on cartilage injury. Mechanical injury is one of the principal risk factors in the development of OA. Cartilage injury is known to activate downstream inflammatory signalling that is driven in a transforming growth factor activated-beta 1 (TAK1) dependent manner and thereby increase inflammatory gene regulation, in a process known as mechanoflammation. Talarozole (TLZ), a CYP26 inhibitor, which prevents the breakdown of atRA, suppresses the upregulation of inflammatory genes on cartilage injury. My project sought to identify the mechanism by which atRA-responsive genes were downregulated and determine how atRA suppressed mechanoflammation on cartilage injury. The downregulation of atRA-responsive genes on cartilage injury was mediated in both cytosolic phospholipase A2 (cPLA2) - and reactive oxygen species (ROS)-sensitive manner. TAK1 phosphorylation on cartilage injury was partially mediated in a nicotinamide adenine dinucleotide phosphate oxidase (NOX)-sensitive manner, whereas TAK1 was responsible for the partial phosphorylation of cPLA2 on cartilage injury. Apoptosis signal regulating kinase 1 (ASK1) was the key driver of mitogen activated protein kinases (MAPKs) (Jun N terminal kinase (JNK) and extracellular signal regulated kinase (ERK)) on cartilage injury and downstream inflammatory gene regulation. atRA suppressed mechanoflammation in a peroxisome proliferator activated receptor gamma (PPARG)-sensitive manner. These findings suggest that both boosting atRA level and ASK1 inhibition can suppress mechanoflammation in articular cartilage and identifies each pathway as targets for potential disease modifying drugs in the treatment of OA

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