Enrichment of Fat Grafts With Adipose-derived Stromal Cells for Breast Augmentation: A Randomized, Double-blind, Placebo-controlled Trial of Fat Graft Survival
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SUBMITTER: Vester-Glowinski P
PROVIDER: S-EPMC6750484 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
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Project description:BackgroundSurgical methods using implants were broadly selected for breast augmentation surgery until recently; however, owing to several associated problems, fat transplantation using adipose-derived stem/stromal cells (ADSCs) has been suggested as an alternative.ObjectivesThis study evaluated the clinical benefits of fat transplantation using ADSCs for breast augmentation.MethodsThe clinical effects were investigated in 105 patients who underwent breast augmentation with ADSCs and fat transplantation. Liposuction was performed in the abdominal and/or thigh regions; ADSCs were isolated from the fat, mixed with refined fat, and transplanted into each breast; and changes in the breast volume were measured.ResultsThe average increase in breast volume was approximately 185 mL at 2 weeks after operation. Fat engraftment rates were 85.1, 75.1, and 73.7% of augmented volumes after 1, 3, and 6 months, respectively. A total of 39 patients who received >60 million ADSCs exhibited a transplanted fat engraftment rate of 90.5% (average increase, 162 mL), whereas this rate was 68.9% (average increase, 115 mL) in 31 patients who received <60 million ADSCs.ConclusionsThis study demonstrates that breast augmentation with ADSCs and fat transplantation is effective. Surgical outcomes substantially improved with increased numbers of implanted ADSCs.Level of evidence 4
| S-EPMC7671271 | biostudies-literature
Project description:Autologous fat transfer (AFT) is a procedure for adipose tissue (AT) repair after trauma, burns, post-tumor resections and lipodystrophies still negatively impacted by the lack of graft persistence. The reasons behind this poor outcome are unclear and seem to involve damages in either harvested/transplanted mature adipocytes or on their mesenchymal progenitors, namely adipose stromal/stem cells (ASC), and due to post-transplant AT apoptosis and involution. A rabbit subcutaneous AT regeneration model was here developed to first evaluate graft quality at different times after implant focusing on related parameters, such as necrosis and vasculogenesis. Standard AFT was compared with a strategy where purified autologous ASC, combined with hyaluronic acid (HA), assisted AFT. Five million of autologous ex vivo isolated CD29+, CD90+, CD49e+ ASC, loaded into HA, enriched 1 ml of AT generating an early significant protective effect in reducing AFT necrosis and increasing vasculogenesis with a preservation of transplanted AT architecture. This beneficial impact of ASC assisted AFT was then confirmed at three months with a robust lipopreservation and no signs of cellular transformation. By a novel ASC assisted AFT approach we ensure a reduction in early cell death favoring an enduring graft performance possibly for a more stable benefit in patients.
| S-EPMC3775159 | biostudies-literature
Project description:BackgroundDysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia.MethodClozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale.ResultsWhen compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient.ConclusionsIn patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.
| S-EPMC4954262 | biostudies-literature
Project description:An important challenge in schizophrenia therapeutics is to develop an efficacious treatment for cognitive impairment. Acetylcholinesterase inhibitors, such as rivastigmine, have been studied for improving cognitive performance in these patients.Rivastigmine (uptitrated to 6 mg/day) was given as an add-on therapy to risperidone-treated stable schizophrenia patients in a randomized, double-blind, placebo-controlled design. Of 67 patients who met eligibility criteria, 55 were recruited into the study. Twenty-eight were assigned to rivastigmine and 27 to placebo. These patients completed tests of attention, executive functioning, verbal skills, verbal and visuospatial working memory, and psychomotor speed on five occasions: at baseline, and at the end of the 1st, 3rd, 6th, and 12th months.The groups were similar in terms of sociodemographic profile and baseline clinical characteristics (Positive and Negative Syndrome Scale and Clinical Global Impression-Severity). Contrary to expectations, rivastigmine patients showed poorer outcomes on several cognitive measures. Rivastigmine patients experienced also more psychological as well as neurological side effects. Core psychopathology ratings, however, did not differ between rivastigmine and placebo groups.Our study does not support the long-term use of rivastigmine as an augmentation agent in schizophrenia. Rivastigmine may be associated with higher incidence of psychological and neurological side effects in patients with schizophrenia.
| S-EPMC5547865 | biostudies-other
Project description:BackgroundMultiple treatments for patients with major depressive disorder (MDD) have demonstrated efficacy, but up to one-third of individuals with MDD do not achieve symptomatic remission despite various interventions. Existing augmentation or combination strategies can have substantial safety concerns that may limit their application.MethodThis study investigated the antidepressant efficacy of a flexible dose of the dopamine agonist pramipexole as an adjunct to standard antidepressant treatment in an 8-week, randomized, double-blind, placebo-controlled trial conducted in a tertiary-level depression center. We randomized 60 outpatients (aged 18 to 75 years) with treatment-resistant nonpsychotic MDD (diagnosed according to DSM-IV) to either pramipexole (n = 30) or placebo (n = 30). Treatment resistance was defined as continued depression (Montgomery-Asberg Depression Rating Scale [MADRS] score ≥ 18) despite treatment with at least 1 prior antidepressant in the current depressive episode. Patients were recruited between September 2005 and April 2008. The primary outcome measure was the MADRS score.ResultsThe analyses that used a mixed-effects linear regression model indicated a modest but statistically significant benefit for pramipexole (P = .038). The last-observation-carried-forward analyses indicated that 40% and 33% of patients randomized to augmentation with pramipexole achieved response (χ(2) = 1.2, P = .27) and remission (χ(2) = 0.74, P = .61), respectively, compared to 27% and 23% with placebo; however, those differences were not statistically significant. Augmentation with pramipexole was well-tolerated, with no serious adverse effects identified.ConclusionFor patients who have failed to respond to standard antidepressant therapies, pramipexole is a safe and potentially efficacious augmentation strategy.Trial registrationClinicalTrials.gov identifier: NCT00231959.
| S-EPMC10034846 | biostudies-literature
Project description:Schizophrenia-spectrum disorders (SSD) are associated with increased inflammatory markers, both in brain and periphery. Augmentation with drugs that lower this pro-inflammatory status may improve clinical presentation. Simvastatin crosses the blood-brain barrier, has anti- inflammatory and neuroprotective effects and reduces metabolic syndrome. In this study, we investigated if 12 months of simvastatin augmentation can improve symptoms and cognition in patients with early SSD. This double-blind placebo-controlled trial included 127 SSD patients across the Netherlands, <3 years after their diagnosis. From these, 119 were randomly assigned 1:1 to simvastatin 40 mg (n = 61) or placebo (n = 58), stratified for sex and study site. Primary outcomes were symptom severity and cognition after 12 months of treatment. Depression, symptom subscores, general functioning, metabolic syndrome, movement disorders, and safety were secondary outcomes. Intention to treat analyses were performed using linear mixed models and ANCOVA. No main effect of simvastatin treatment was found on total symptom severity after 12 months of treatment as compared to placebo (X2(1) = 0.01, P = .90). Group differences varied over time (treatment*time X2(4) = 11.2; P = .025), with significantly lower symptom severity in the simvastatin group after 6 months (mean difference = -4.8; P = .021; 95% CI: -8.8 to -0.7) and at 24 months follow-up (mean difference = -4.7; P = .040; 95% CI: -9.3 to -0.2). No main treatment effect was found for cognition (F(1,0.1) = 0.37, P = .55) or secondary outcomes. SAEs occurred more frequently with placebo (19%) than with simvastatin (6.6%). This negative finding corroborates other large scale studies on aspirin, minocycline, and celecoxib that could not replicate positive findings of smaller studies, and suggests that anti-inflammatory augmentation does not improve the clinical presentation of SSD.
| S-EPMC8266622 | biostudies-literature
Project description:ObjectiveIntravenous N-methyl-d-aspartate (NMDA) antagonists have shown promising results in rapidly ameliorating depression symptoms, but placebo-controlled trials of oral NMDA antagonists as monotherapy have not observed efficacy. We conducted a randomized, double-blind, placebo-controlled trial of the NMDA antagonist memantine as an augmentation treatment for patients with DSM-IV major depressive disorder.MethodAdult outpatients with major depressive disorder and partial response or nonresponse to their current antidepressant (as indicated by a 17-item Hamilton Depression Rating Scale score of ≥ 16 at baseline) were randomized (from July 2006-December 2011) to add memantine (flexible dose 5-20 mg/d, with all memantine group participants reaching the dose of 20 mg/d) (n = 15) or placebo (n = 16) to their existing treatment for 8 weeks. The primary outcome, change in Montgomery-Asberg Depression Rating Score (MADRS), was evaluated with repeated-measures mixed effects models using last-observation-carried-forward methods. Secondary outcomes included other depression and anxiety rating scales, suicidal and delusional ideation, and other adverse effects.Results84% of participants completed the trial, including 93% of participants receiving memantine. Participants receiving memantine did not show a statistically or clinically significant change in MADRS scores compared to placebo, either over the entire study (β = 0.133, favoring placebo, P = .74) or at study completion (week 8 mean [SD] MADRS score change = -7.13 [6.61] [memantine]; -7.25 [11.14] [placebo]; P = .97). A minimal to small effect size (comparing change to baseline variability) favoring placebo was observed (Cohen d = 0.19). Similarly, no substantial effect sizes favoring memantine nor statistically significant between-group differences were observed on secondary efficacy outcomes.ConclusionsThis trial did not detect significant statistical or effect size differences between memantine and placebo augmentation among nonresponders or poor responders to conventional antidepressants. While the small number of participants is a limitation, this study suggests memantine lacks substantial efficacy as an augmentation treatment for major depressive disorder.Trial registrationClinicalTrials.gov identifier: NCT00344682.
| S-EPMC4000742 | biostudies-literature
Project description:BackgroundSmall extracellular vesicles (sEVs) with genetic information secreted by cells play a crucial role in the cellular microenvironment. In this study, our purpose is to explore the characteristics of the small extracellular vesicles of human adipose-derived mesenchymal stromal cells (hADMSC-sEVs) and studied the role of hADMSC-sEVs in improving the survival rate of grafted fat.MethodsIn the present study, we used the transmission electron microscopy, nano-tracking analysis, nanoflow surface protein analysis, and zeta potential value to identify sEVs. SEVs' trajectory was traced dynamically to verify whether hADMSC-sEVs can be internalized into human umbilical vein endothelial cells (HUVECs) in vitro at different times. The angiogenic property of hADMSC-sEVs was observed by measuring the volume, weight, and histological analysis of the grafted fats in nude mouse models.ResultsOur research showed that the hADMSC-sEVs were sEVs with double-layer membrane structure and the diameter of which is within 30-150 nm. hADMSC-sEVs exert biological influence mainly through internalization into cells. Compared with the control group, the hADMSC-sEVs group had a significantly higher survival rate of grafted fat, morphological integrity, and a lower degree of inflammation and fibrosis. And immunohistochemistry showed that hADMSC-sEVs significantly increased the neovascularisation and the expression of CD34, VEGFR2, and Ki-67 in the graft tissue.ConclusionsAs a potential nanomaterial, hADMSC-sEVs have been explored in the field of cell-free application of stem cell technology. hADMSC-sEVs promoted the survival of grafted fats by promoting the formation of new blood vessels, which is another promising progress in the field of regenerative medicine. We believe that hADMSC-sEVs will have a broad application prospect in the field of regenerative medicine in the future.
| S-EPMC8091529 | biostudies-literature
Project description:ObjectiveThe authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.MethodThis was an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial conducted at three academic medical centers. Participants were 139 outpatients with persistent symptoms of major depression after an 8-week open-label trial of escitalopram (phase 1), randomly assigned in a 1:1 ratio to receive adjunctive ziprasidone (escitalopram plus ziprasidone, N=71) or adjunctive placebo (escitalopram plus placebo, N=68), with 8 weekly follow-up assessments. The primary outcome measure was clinical response, defined as a reduction of at least 50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D). The Hamilton Anxiety Rating scale (HAM-A) and Visual Analog Scale for Pain were defined a priori as key secondary outcome measures.ResultsRates of clinical response (35.2% compared with 20.5%) and mean improvement in HAM-D total scores (-6.4 [SD=6.4] compared with -3.3 [SD=6.2]) were significantly greater for the escitalopram plus ziprasidone group. Several secondary measures of antidepressant efficacy also favored adjunctive ziprasidone. The escitalopram plus ziprasidone group also showed significantly greater improvement on HAM-A score but not on Visual Analog Scale for Pain score. Ten (14%) patients in the escitalopram plus ziprasidone group discontinued treatment because of intolerance, compared with none in the escitalopram plus placebo group.ConclusionsZiprasidone as an adjunct to escitalopram demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.
| S-EPMC4843798 | biostudies-literature
Project description:Hops are the main components of beer that provide flavor and bitterness. Iso-α-acids, the bitter components of beer, have been reported to reduce body fat in humans, but the bitterness induced by effective doses of iso-α-acids precludes their acceptance as a nutrient. The matured hop bitter acids (MHBA) of oxidized hops appear to have a more pleasant bitterness compared to the sharper bitterness of iso-α-acids. While there has been little information concerning the identity of the MHBA compounds and their physiological effects, MHBA was recently found to be primarily composed of oxides derived from α-acids, and structurally similar to iso-α-acids. Here, we investigated the effects of matured hop extract (MHE) containing MHBA on reducing abdominal body fat in healthy subjects with a body mass index (BMI) of 25 to below 30 kg/m(2), classified as "obese level 1" in Japan or as "overweight" by the WHO.A randomized, double-blind, placebo-controlled parallel group study.Two hundred subjects (male and female aged 20 to below 65 years with a BMI of 25 or more and less than 30 kg/m(2)) were randomly assigned to two groups. During a 12-week ingestion period, the subjects in each group ingested daily 350 mL of test-beverage, either containing MHE (with 35 mg MHBA), i.e. the namely active beverage, or a placebo beverage without MHE. The primary endpoint was reduction of the abdominal fat area as determined by CT scanning after continual ingestion of MHE for 12 weeks.Compared to the placebo group, a significant reduction was observed in the visceral fat area after 8 and 12 w, and in the total fat area after 12 w in the active group. There was also a concomitant decrease in body fat ratio in the active group compared to the placebo group. No adverse events related to the test beverages or clinically relevant abnormal changes in the circulatory, blood and urine parameters were observed in either group.The present study suggests that continual ingestion of MHE safely reduces body fat, particularly the abdominal visceral fat of healthy overweight subjects.UMIN-CTR UMIN000014185.
| S-EPMC4784395 | biostudies-other