ABSTRACT
The objectives of the present study were to evaluate (a) the feasibility of using stromal vascular fraction (SVF) and nanocrystalline hydroxyapatite (nHA) paste in combination for the treatment of segmental bone defect, (b) the quality of the callus produced, (c) the potential improvement of the autograft technique, and (d) the direct comparison of the biomaterial to the use of autogenous cancellous bone. Unilateral, segmental mid-diaphyseal bone defect was created on the right metatarsus of skeletally mature sheep animals (n = 24) under anesthesia (D0). Residual segments were stabilized by stainless-steel plates and appropriate screws. Defects were managed as follows: group A: use of nHA paste to filling, group B: use of autogenous bone graft mixed with nHA bone paste, placed in defect, group C: use of SVF mixed with nHA bone paste injected into defect, group D: use of bone graft and SVF with nHA paste before apposition in bone defect. SVF had been previously isolated from adipose tissue of the animals intra-operatively after digestion with collagenase solution and neutralization. Animals were evaluated clinically and by X-raying and ultrasonographic examination of the defect, at regular intervals, until D90. Ultrasonographic assessment performed along the length of the defect included calculation of the length of the bone defect and assessment of vascularization. SVF was successfully isolated from group C and D animals, with the average yield being 1.77 × 106 cells. The comparison of clinical scores (based on the 'Kaler scale') on each post-operative day indicated significant differences between the four groups on D1 to D30 (p < 0.01); the median clinical score within group A was 2.5 for D1-D30 and 1 for the entire period; respective scores for other groups were 1.5 (p = 0.07) and 0 (p = 0.033). Differences in radiographic assessment scores were significant for scores obtained on D60 (p = 0.049) and D90 (p = 0.006). There was a significant difference between the four groups in the length of the bone defect, as assessed ultrasonographically, for the entire length of the study; median values were 8, 8.5, 6, and 8 mm for groups A, B, C, and D, respectively (p = 0.008). There was a significance in the differences between median scores obtained during the histopathological examination: 2, 11, 13.5, and 12 for group A, B, C, and D (p = 0.022). There was an inverse correlation between the overall scores of histopathological evaluations and the length of the bone defect (observed on D90) (p < 0.0001) and a correlation between the overall scores and the radiographic assessment scores (obtained on D90) (p < 0.0001). This is the first study in which the efficacy of fresh autologous Stromal Vascular Fraction (SVF) from adipose tissue in enhancing bone healing in a long, weight-bearing, diaphyseal bone was evaluated. It is concluded that the lumbosacral region was an attractive site for harvesting adipose tissue, the use of SVF contributed to faster rehabilitation post-operatively, and SVF significantly enhanced bone formation; in general, the results indicated an osteogenic potential of SVF comparable to the gold standard autologous bone graft.
ABSTRACT
Background: This study aims to evaluate the efficacy of combined intraventricular and intravenous co-administration of colistin and tigecycline in the management of pan-drug resistant Acinetobacter baumannii meningitis/ventriculitis. Methods: In this case series we report 3 patients with healthcare-associated ventriculitis/meningitis caused by pan-drug resistant Acinetobacter baumannii that were treated with combined colistin and tigecycline administration through both intraventricular and intravenous routes. Results: All patients were administered colistin intraventricularly at a dose of 250.000 IU q.d. and intravenously at 9 million IU loading dose, followed after 12 hours by maintenance dose of 4.5 million IU every 12 hours and tigecycline intraventricularly at a dose of 10 mg b.i.d. and intravenously at 200 mg loading dose followed after 12 hours by 100 mg every 12 hours. In patients with a calculated creatinine clearance of less than 60 ml/min, according to the Cockcroft-Gault formula, the maintenance dose of colistin was reduced based on a modified formula. All patients had a favourable clinical and microbiological response with evidence of CSF sterilization. Conclusions: Taking advantage of the synergistic action of combined colistin and tigecycline through administration both intraventricularly and intravenously may be a promising salvage option for critically ill patients with pan-drug resistant A. baumannii CNS infection.
