Polylactic acid (PLA, New-Fill s ; Medifill, London, UK and Dermic Labs, a division of Eventis, Strasbourg, France) injections into the deep dermis increase fibroblast numbers and collagen production. The substance is widely used in medical applications including cosmetic procedures. MethodsHIV-positive individuals with facial lipoatrophy (based on physician assessment) were randomized to immediate (weeks 0, 2 and 4) or delayed (weeks 12, 14 and 16) PLA given as three bilateral injections 2 weeks apart into the deep dermis overlying the buccal fat pad. Assessments included facial ultrasound, visual analogue scales, the Hospital Anxiety and Depression Scale (HADS) and assessment using photographs at weeks 0, 12 and 24. ResultsAll 30 patients completed 24 weeks of treatment. The median age of the patients was 41 years, with a mean of 80 months of nucleoside reverse transcriptase inhibitor (NRTI) therapy and a mean of 44 months of prior protease inhibitor (PI) therapy. The median CD4 count was 428-460 cells/mL, with 47% of patients in the immediate-treatment group and 93% of patients in the delayed-treatment groups witho50 HIV-1 RNA copies/mL at baseline. No differences in immunological, virological, biochemical, haematological or metabolic parameters emerged during the study. Injections were well tolerated with only two adverse events (cellulitis and bruising) recorded, one of which delayed treatment by 1 week. There were no discontinuations. Patient visual analogue assessments, photographic assessments, and anxiety and depression scores improved with treatment. At week 12, immediate-treatment patients had significantly better visual analogue scores (7 vs. 1, Po0.001) and lower anxiety scores (6 vs. 9, P 5 0.056) than delayed-treatment patients. Benefits on visual analogue and HADS scores persisted until week 24. ConclusionsPLA injections led to improvements in patient self-perception, anxiety and depression scores in individuals with facial lipoatrophy. Adverse events were uncommon. The benefits of PLA persisted for at least 18 weeks beyond the last injection.
Heterotopic ossification (HO) occurs secondary to trauma, causing pain and functional limitations. Identification of the cells that contribute to HO is critical to the development of therapies. Given that innate immune cells and mesenchymal stem cells are known contributors to HO, we sought to define the contribution of these populations to HO and to identify what, if any, contribution circulating populations have to HO. A shared circulation was obtained using a parabiosis model, established between an enhanced green fluorescent protein-positive/luciferase donor and a same-strain nonreporter recipient mouse. The nonreporter mouse received Achilles tendon transection and dorsal burn injury to induce HO formation. Bioluminescence imaging and immunostaining were performed to define the circulatory contribution of immune and mesenchymal cell populations. Histologic analysis showed circulating cells present throughout each stage of the developing HO anlagen. Circulating cells were present at the injury site during the inflammatory phase and proliferative period, with diminished contribution in mature HO. Immunostaining demonstrated that most early circulatory cells were from the innate immune system; only a small population of mesenchymal cells were present in the HO. We demonstrate the time course of the participation of circulatory cells in trauma-induced HO and identify populations of circulating cells present in different stages of HO. These findings further elucidate the relative contribution of local and systemic cell populations to HO.
PurposeHeterotopic ossification (HO) occurs in the setting of persistent systemic inflammation. The identification of reliable biomarkers can serve as an early diagnostic tool for HO, especially given the current lack of effective treatment strategies. Although serum biomarkers have great utility, they can be inappropriate or ineffective in traumatic acute injuries and in patients with fibrodysplasia ossificans progressiva (FOP). Therefore, the goal of this study is to profile the cytokines associated with HO using a different non-invasive source of biomarkers.MethodsSerum and saliva were collected from a model of trauma-induced HO (tHO) with hind limb Achilles’ tenotomy and dorsal burn injury at indicated time points (pre-injury, 48 h, 1 week, and 3 weeks post-injury) and a genetic non-trauma HO model (Nfatc1-Cre/caAcvr1fl/wt). Samples were analyzed for 27 cytokines using the Bio-Plex assay. Histologic evaluation was performed in Nfatc1-Cre/caAcvr1fl/wt mice and at 48 h and 1 week post-injury in burn tenotomy mice. The mRNA expression levels of these cytokines at the tenotomy site were also quantified with quantitative real-time PCR. Pearson correlation coefficient was assessed between saliva and serum.ResultsLevels of TNF-α and IL-1β peaked at 48 h and 1 week post-injury in the burn/tenotomy cohort, and these values were significantly higher when compared with both uninjured (p < 0.01, p < 0.03) and burn-only mice (p < 0.01, p < 0.01). Immunofluorescence staining confirmed enhanced expression of IL-1β, TNF-α, and MCP-1 at the tenotomy site 48 h after injury. Monocyte chemoattractant protein-1 (MCP-1) and VEGF was detected in saliva showing elevated levels at 1 week post-injury in our tHO model when compared with both uninjured (p < 0.001, p < 0.01) and burn-only mice (p < 0.005, p < 0.01). The Pearson correlation between serum MCP-1 and salivary MCP-1 was statistically significant (r = 0.9686, p < 0.001) Similarly, the Pearson correlation between serum VEGF and salivary VEGF was statistically significant (r = 0.9709, p < 0.05).ConclusionIn this preliminary study, we characterized the diagnostic potential of specific salivary cytokines that may serve as biomarkers for an early-stage diagnosis of HO. This study identified two candidate biomarkers for further study and suggests a novel method for diagnosis in the context of current difficult diagnosis and risks of current diagnostic methods in certain patients.
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