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Background: Metabolic bariatric surgery the reduces risk of new-onset type 2 diabetes in individuals with obesity, but it is unclear whether the benefit varies by sex, age, or socioeconomic status. The aim was to assess the risk of new-onset type 2 diabetes after metabolic bariatric surgery in these subgroups. Methods: The Finnish Public Sector study, a follow-up study with matched controls nested in a large employee cohort, included patients without type 2 diabetes and with a diagnosis of obesity or self-reported BMI of at least 35 kg/m2. For each patient who had laparoscopic metabolic bariatric surgery (2008–2016), two propensity-score matched controls were selected. New-onset type 2 diabetes was ascertained from linked records from national health registries. Results: The study included a total of 917 patients and 1811 matched controls with obesity. New-onset type 2 diabetes was diagnosed in 15 of the patients who had metabolic bariatric surgery (4.1 per 1000 person-years) and 164 controls (20.2 per 1000 person-years). The corresponding rate ratio (RR) was 0.20 (95% c.i. 0.12 to 0.35) and the rate difference (RD) was −16.1 (−19.8 to −12.3) per 1000 person-years. The risk reduction was more marked in individuals of low socioeconomic status (RR 0.10 (0.04 to 0.26) and RD −20.6 (−25.6 to −15.5) per 1000 person-years) than in those with higher socioeconomic status (RR 0.35 (0.18 to 0.66) and RD −11.5 (−16.9 to −6.0) per 1000 person-years) (Pinteraction = 0.017). No differences were observed between sexes or age groups. Conclusion: Metabolic bariatric surgery was associated with a reduced risk of new-onset type 2 diabetes in men and women and in all age groups. The greatest benefit was observed in individuals of low socioeconomic status. The impact of metabolic bariatric surgery on the risk of new-onset type 2 diabetes was investigated in individuals with obesity. The findings indicate that metabolic bariatric surgery significantly reduces the risk of type 2 diabetes across sexes and age groups, with the most substantial benefit observed in individuals of low socioeconomic status. Lay Summary: Metabolic bariatric surgery reduces the risk of new-onset type 2 diabetes in individuals with obesity or severe obesity. The risk of new-onset type 2 diabetes after metabolic bariatric surgery varies between socioeconomic status subgroups. In this prospective study, new-onset type 2 diabetes occurred in 1.6% of 917 patients who underwent metabolic bariatric surgery and 9.1% of 1811 propensity score-matched controls. Risk reduction was more marked in individuals of low socioeconomic status. There were no differences between sex or age groups. The reduced risk of new-onset type 2 diabetes after metabolic bariatric surgery emphasizes the need to increase access to treatment in patients with severe obesity. As the preventive effect was most pronounced in individuals of low socioeconomic status associated with both greater burden of disease and worse access to healthcare, the findings need to be taken into account in health policies to reduce health inequalities. [ABSTRACT FROM AUTHOR]

Periprosthetic osteolysis remains as a major complication of total joint replacement surgery. Modulation of macrophage polarization with interleukin‐4 (IL‐4) has emerged as an effective means to limit wear particle‐induced osteolysis. The aim of this study was to evaluate the efficacy of local IL‐4 delivery in treating preexisting particle‐induced osteolysis. To this end, recently established 8 week modification of murine continuous femoral intramedullary particle infusion model was utilized. Subcutaneous infusion pumps were used to deliver polyethylene (PE) particles into mouse distal femur for 4 weeks to induce osteolysis. IL‐4 was then added to the particle infusion for another 4 weeks. This delayed IL‐4 treatment (IL‐4 Del) was compared to IL‐4 delivered continuously (IL‐4 Cont) with PE particles from the beginning and to the infusion of particles alone for 8 weeks. Both IL‐4 treatments were highly effective in preventing and repairing preexisting particle‐induced bone loss as assessed by μCT. Immunofluorescence indicated a significant reduction in the number of F4/80 + iNOS + M1 macrophages and increase in the number of F4/80 + CD206 + M2 macrophages with both IL‐4 treatments. Reduction in the number of tartrate resistant acid phosphatase + osteoclasts and increase in the amount of alkaline phosphatase (ALP) + osteoblasts was also observed with both IL‐4 treatments likely explaining the regeneration of bone in these samples. Interesting, slightly more bone formation and ALP + osteoblasts were seen in the IL‐4 Del group than in the IL‐4 Cont group although these differences were not statistically significant. The study is a proof of principle that osteolytic lesions can be repaired via modulation of macrophage polarization. [ABSTRACT FROM AUTHOR]

Macrophage‐mediated inflammatory reaction to implant wear particles drives bone loss around total joint replacements (TJR). Although most TJR recipients are elderly, studies linking wear particle‐activated macrophages and peri‐implant osteolysis have not taken into account the multiple effects that aging has on the innate immune system and, in particular, on macrophages. To address this, we compared the wear particle responses of bone marrow macrophages obtained from young (2‐month) and aged (18‐month) mice. Macrophages were polarized to M0, M1, or M2 phenotypes in vitro, challenged with titanium particles, and their inflammatory response was characterized at multiple time points by quantitative reverse‐transcription polymerase chain reaction and enzyme‐linked immunosorbent assay. In addition, age‐dependent changes in activation of transcription factor nuclear factor‐κB were analyzed by a lentiviral vector‐based luciferase reporter system. The particle stimulation experiment was further repeated using human primary macrophages isolated from blood donors of different ages. We found that the pro‐inflammatory responses were generally higher in macrophages obtained from young mice, but differences between the age groups remained small and of uncertain biological significance. Noteworthily, M2 polarization effectively suppressed the particle‐induced inflammation in both young and aged macrophages. These results suggest that aging of the innate immune system per se plays no significant role in the response of macrophages to titanium particles, whereas induction of M2 polarization appears a promising strategy to limit macrophage‐mediated inflammation regardless of age. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:405‐416, 2020 [ABSTRACT FROM AUTHOR]