Autologous Versus Alloplastic Reconstruction for Patients with Obesity: A Systematic Review and Meta-analysis.

BACKGROUND: Autologous flaps may have superior outcomes when compared to implant breast reconstruction in patients with obesity. To date, no published review has illustrated the superiority of autologous to implant-based reconstruction in this study group in terms of aesthetics outcomes and surgical complications. METHODS: A systematic search was conducted on PubMed, Cochrane, Google Scholar, and Embase from inception to December 31, 2020. Studies comparing the outcomes (patient satisfaction and complications) of autologous versus implant-based reconstruction in patients with BMI > 30 were selected. RESULTS: The search yielded 1633 articles, of which 76 were assessed in full text. A total of 12 articles fit inclusion for qualitative review; of them, 7 were meta-analyzed. Autologous reconstruction had a lower incidence of infection (OR 0.74 [95% CI 0.59, 0.92]), hematoma/seroma formation (OR 0.34 [95% CI 0.23, 0.49]), and reconstructive failure (OR 0.47 [95% CI 0.36, 0.62]), but not skin necrosis (OR 0.95 [95% CI 0.73, 1.25]) or wound dehiscence (OR 1.03 [95% CI 0.72, 1.49]) when compared to implant-based reconstruction. Deep vein thrombosis (DVT) and pulmonary embolism occurred more frequently with autologous versus alloplastic reconstruction (OR 2.21 [95% CI 1.09, 4.49] for DVT and OR 2.49 [95% CI 1.13, 5.48] for PE). BREASTQ scores were higher for the autologous breast reconstruction when compared to implant-based group, but failed to reach significance (p value >0.05). CONCLUSION: The current evidence in the literature suggests that autologous breast reconstruction has lower surgical complication rate when compared to implant-based reconstruction at the expense of higher risk of thrombotic complications for patients with BMI > 30. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Modulating the HSP90 control over NFκB/NLRP3/Caspase-1 axis is a new therapeutic target in the management of liver fibrosis: Insights into the role of TAS-116 (Pimitespib).

Aberrant activation of the NLRP3 inflammasome is recognized to induce a chronic inflammatory response in the liver, ultimately leading to hepatic fibrosis. HSP90 is suggested to regulate NLRP3 activation and its downstream signaling. This study is the first to explore the potential therapeutic role of pimitespib in mitigating liver fibrosis in rats. The results of the study revealed that pimitespib effectively suppressed hepatic inflammation and fibrogenesis by modulating HSP90's control over the NFκB/NLRP3/caspase-1 axis. In vitro experiments demonstrated that pimitespib reduced LDH levels and increased hepatocyte survival, whereas in vivo, it prolonged the survival of rats with hepatic fibrosis. Additionally, pimitespib exhibited improvements in the function and microscopic characteristics of rat livers. Pimitespib effectively inhibited NFκB, which serves as the priming signal for NLRP3 activation. Pimitespib's inhibitory effect on NLRP3, identified as an HSP90 client protein, plays a central role in the observed anti-fibrotic effect. The simultaneous inhibition of both priming and activation signals of NLRP3 by pimitespib led to a reduction in caspase-1 activity and subsequent suppression of the N-terminal fragment of gasdermin D, ultimately constraining hepatocyte pyroptotic cell death. These diverse effects were associated with a decrease in the transcription of inflammatory mediators IL-1ß, IL-18, and TNF-α, as well as the fibrogenic mediators TGF-ß, TIMP-1, PDGF-BB, and Col1a1. Moreover, pimitespib induced the expression of HSP70, which could further contribute to the repression of fibrosis development. In summary, our findings provide an evolutionary perspective on managing liver fibrosis, positioning pimitespib as a promising candidate for anti-inflammatory and antifibrotic therapy.