METABOLIC CHANGES AFTER SURGICAL SUBCUTANEOUS FAT REMOVAL

Background: There is increasing demand for both surgical (SSFR) and nonsurgical (NSSFR) subcutaneous fat removal procedures for achieving immediate improvements in physical appearance. However, their metabolic effects remain unclear. Aims: Firstly, to review the current state of knowledge on the metabolic changes after SSFR and identify any literature gaps. Secondly, to examine the magnitude and sustainability of these changes and explore the impact of prior obesity surgery on changes in glucose homeostasis after SSFR. Methods: An umbrella review was conducted to identify knowledge gaps, and implications for future research. Then, twin dose response meta-analyses (DRMA) were performed to examine the degree and duration of these metabolic changes after SSFR & NSSFR procedures. This was followed by a commentary paper that highlights the need to examine additional sources of population heterogeneity, which could alter the metabolic trajectory after SSFR. Next, a novel index of glucose excursion was validated which was then used subsequently in a quasi-experimental pilot study to examine changes in glucose homeostasis after SSFR in comparison to the impact of prior obesity surgery. Results: The umbrella review revealed that current literature is not conclusive; however, they suggest some metabolic benefits without a clear clinical significance. The DRMAs reported that SSFR is safe and may exert a transient metabolic benefit in body composition, adipokines, inflammation, blood pressure and lipid profile. However, only improvements in insulin sensitivity lasted beyond 6 months. On the other hand, NSSFR exerts a sustained effect on body composition for up to two months, but with a worsening in lipid profile in the first two weeks. The commentary paper highlighted the need to examine the independent metabolic effect of SSFR and history of bariatric surgery (irrespective of their body mass index and diabetic status). The quasi experiment validated Doi's weighted average glucose as a measure of post-load glucose excursion. Also reported that SSFR resulted in improvement in insulin resistance without affecting post-load glucose excursion, but that a history of obesity surgery was associated with an additional effect on glucose excursion, possibly due to sustained improvement of beta-cell function. Conclusion: SSFR appears to be associated with favorable metabolic changes, particularly an improvement in insulin sensitivity. Further studies that examine these changes from a hormonal perspective can broaden our knowledge of metabolic sequelae associated with sudden removal of subcutaneous fat and help us understand mechanisms underpinning the link between obesity and metabolic diseases. This could potentially identify new therapeutic targets

A meta-review of meta-analyses and an updated meta-analysis on the efficacy of chloroquine and hydroxychloroquine in treating COVID19 infection

Objective: To synthesize the findings presented in systematic reviews and meta-analyses as well as to update the evidence using a meta-analysis in evaluating the efficacy and safety of CQ and HCQ with or without Azithromycin for the treatment of COVID19 infection.Methods: The design of this meta-review followed the Preferred Reporting Items for Overviews of Systematic Reviews including harms checklist (PRIO-harms). A comprehensive search included several electronic databases in identifying all systematic reviews and metaanalyses as well as experimental studies which investigated the efficacy and safety of CQ, HCQ with or without antibiotics as COVID19 treatment. Findings from the systematic reviews and meta-analyses were reported using a structured summary including tables and forest plots. The updated meta-analysis of experimental studies was carried out using the distributional assumption-free quality effects model. Risk of bias was assessed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool for reviews and the MethodologicAl STandard for Epidemiological Research (MASTER) scale for the experimental studies. The main outcome for both the meta-review and the updated meta-analysis was mortality. Secondary outcomes included transfer to the intensive care unit (ICU) or mechanical ventilation, worsening of illness, viral clearance and the occurrence of adverse events. Results: A total of 13 reviews with 40 primary studies comprising 113,000 participants were included. Most of the primary studies were observational (n=27) and the rest were experimental studies. Two meta-analyses reported a high risk of mortality with similar ORs of 2.5 for HCQ with Azithromycin. However, four other meta-analyses reported contradictory results with two reporting a high risk of mortality and the other two reporting no significant association between HCQ with mortality. Most reviews reported that HCQ with or without Azithromycin had no significant effect on virological cure, disease exacerbation or the risk of transfer to the ICU, need for intubation or mechanical ventilation. After exclusion of studies that did not meet the eligibility criteria, the updated meta-analysis contained eight experimental studies (7 RCTs and 1 quasiexperimental trial), with a total of 5279 participants of whom 1856 were on either CQ/HCQ or combined with Azithromycin. CQ/HCQ with or without Azithromycin was significantly associated with a higher risk of adverse events. HCQ was not effective in reducing mortality transfer to the ICU, intubation or need for mechanical ventilation virological cure (RR 1.0, 95%CI 0.9-1.2, I2 =55%, n=5 studies) nor disease exacerbation (RR 1.2, 95%CI 0.3-5.0, I2 =29%, n=3 studies). Conclusion: There is conclusive evidence that CQ and HCQ, with or without Azithromycin are not effective in treating COVID-19 or its exacerbation