Tendon Transection Healing Can Be Improved With Adipose-Derived Stem Cells Cultured With Growth Differentiation Factor 5 and Platelet-Derived Growth Factor.

BACKGROUND: As hand surgeons, tendon injuries and lacerations are a particularly difficult problem to treat, as poor healing potential and adhesions hamper optimal recovery. Adipose-derived stem cells (ADSCs) have been shown to aid in rat Achilles tendon healing after a puncture defect, and this model can be used to study tendon healing in the upper extremity. We hypothesized that ADSCs cultured with growth differentiation factor 5 (GDF5) and platelet-derived growth factor (PDGF) would improve tendon healing after a transection injury. METHODS: Rat Achilles tendons were transected and then left either unrepaired or repaired. Both groups were treated with a hydrogel alone, a hydrogel with ADSCs, or a hydrogel with ADSCs that were cultured with GDF5 and PDGF prior to implantation. Tissue harvested from the tendons was evaluated for gene expression of several genes known to play an important role in successful tendon healing. Histological examination of the tendon healing was also performed. RESULTS: In both repaired and unrepaired tendons, those treated with ADSCs cultured with GDF5/PDGF prior to implantation showed the best tendon fiber organization, the smallest gaps, and the most organized blood vessels. Treatment with GDF5/PDGF increased expression of the protenogenesis gene SOX9, promoted cell-to-cell connections, improved cellular proliferation, and enhanced tissue remodeling. CONCLUSIONS: Adipose-derived stem cells cultured with GDF5/PDGF prior to implantation can promote tendon repair by improving cellular proliferation, tenogenesis, and vascular infiltration. This effect results in a greater degree of organized tendon healing.

A Novel Strategy to Enhance Microfracture Treatment With Stromal Cell-Derived Factor-1 in a Rat Model.

BACKGROUND: Microfracture is one of the most widely used techniques for the repair of articular cartilage. However, microfracture often results in filling of the chondral defect with fibrocartilage, which exhibits poor durability and sub-optimal mechanical properties. Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for mesenchymal stem cells (MSCs) and is expressed at high levels in bone marrow adjacent to developing cartilage during endochondral bone formation. Integrating SDF-1 into an implantable collagen scaffold may provide a chondro-conductive and chondro-inductive milieu via chemotaxis of MSCs and promotion of chondrogenic differentiation, facilitating more robust hyaline cartilage formation following microfracture. OBJECTIVE: This work aimed to confirm the chemoattractive properties of SDF-1 in vitro and develop a one-step method for incorporating SDF-1 in vivo to enhance cartilage repair using a rat osteochondral defect model. METHODS: Bone marrow-derived MSCs (BMSCs) were harvested from the femurs of Sprague-Dawley rats and cultured in low-glucose Dulbecco's modified Eagle's medium containing 10% fetal bovine serum, with the medium changed every 3 days. Passage 1 MSCs were analyzed by flow cytometry with an S3 Cell Sorter (Bio-Rad). In vitro cell migration assays were performed on MSCs by labeling cells with carboxyfluorescein diacetate, succinimidyl ester (CFDA-SE; Bio-Rad). For the microfracture model, a 1.6-mm-diameter osteochondral defect was created in the femoral trochleae of 20 Sprague-Dawley rats bilaterally until bone marrow spillage was seen under saline irrigation. One knee was chosen at random to receive implantation of the scaffold, and the contralateral knee was left unfilled as an empty control. Type I collagen scaffolds (Kensey Nash) were coated with either gelatin only or gelatin and SDF-1 using a dip coating process. The rats received implantation of either a gelatin-only scaffold (N = 10) or gelatin-and-SDF-1 scaffold (N = 10) at the site of the microfracture. Femurs were collected for histological analyses at 4- and 8-week time points post-operatively, and sections were stained with Safranin O/Fast Green. The samples were graded blindly by two observers using the Modified O'Driscoll score, a validated scoring system for chondral repair. A minimum of 10 separate grading scores were made per sample and averaged. Quantitative comparisons of cell migration in vitro were performed with one-way ANOVA. Cartilage repair in vivo was also compared among groups with one-way ANOVA, and the results were presented as mean ± standard deviation, with P-values < 0.05 considered as statistically significant. RESULTS: MSC migration showed a dose-response relationship with SDF-1, with an optimal dosage for chemotaxis between 10 and 100 ng/ml. After scaffold implantation, the SDF-1-treated group demonstrated complete filling of the cartilage defect with mature cartilage tissue, exhibiting strong proteoglycan content, smooth borders, and good incorporation into marginal cartilage. Modified O'Driscoll scores after 8 weeks showed a significant improvement of cartilage repair in the SDF-1 group relative to the empty control group (P < 0.01), with a trend toward improvement when compared with the gelatin-only-scaffold group (P < 0.1). No significant differences in scores were found between the empty defect group and gelatin-only group. CONCLUSION: In this study, we demonstrated a simple method for improving the quality of cartilage defect repair in a rat model of microfracture. We confirmed the chemotactic properties of SDF-1 on rat MSCs and found an optimized dosage range for chemotaxis between 10 and 100 ng/ml. Furthermore, we demonstrated a strategy to incorporate SDF-1 into gelatin-collagen I scaffolds in vivo at the site of an osteochondral defect. SDF-1-treated defects displayed robust hyaline cartilage resurfacing of the defect with minimal fibrous tissue, in contrast to the empty control group. The results of the in vitro and in vivo studies together suggest that SDF-1-mediated signaling may significantly improve the quality of cartilage regeneration in an osteochondral defect.

Characterization of the Rapid Drop in Pulse Oximetry Reading After Intraoperative Administration of Methylene Blue in Open Thoracoabdominal Aortic Repairs.

This study evaluates the changes of oxygen saturation (SpO2) after intravenous administration of methylene blue in 103 patients undergoing open repair of thoracoabdominal aortic aneurysms. We found that SpO2 decreased by a median (interquartile range [IQR]) of 49% (37%-81%) <1 minute after methylene blue administration and recovered completely after approximately 6 minutes-median (IQR) of 270 seconds (180-510). A shorter time to nadir SpO2 was associated with a higher nadir (Spearman r [95% confidence interval {CI}], -0.32 [-0.50 to -0.13]; P = .001). Body surface area (BSA) was positively correlated with nadir SpO2 (Spearman r [95% CI], 0.36 [0.15-0.51]; P < .001).

High-dose versus low-dose opioid anesthesia in adult cardiac surgery: A meta-analysis.

STUDY OBJECTIVE: We performed a systematic comparison of high-dose and low-dose opioid anesthesia in cardiac surgery. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING: Operating room. PATIENTS: 1400 adult patients undergoing cardiac surgery using general anesthesia. INTERVENTIONS: All RCTs comparing the effects of various doses of intravenous opioids (morphine, fentanyl, sufentanil, and remifentanil) during adult cardiac surgery using general anesthesia published until May 2018 (full-text English articles reporting data from human subjects) were included. MEASUREMENTS: Primary outcome was intensive care unit (ICU) length of stay (LOS). Secondary outcomes were ventilation time, use of vasopressors, perioperative myocardial infarction, perioperative stroke, and hospital LOS. MAIN RESULTS: Eighteen articles were included (1400 patients). There was no difference in ICU LOS between studies using high or low dose of opioids (both short-acting and long-acting) (standard mean difference [SMD]-0.02, 95%CI: -0.15-0.11, P = 0.74). Similarly, there was no difference in secondary outcomes of ventilation time (SMD-0.27, 95%CI: -0.63-0.09, P = 0.14), use of vasopressors (OR 0.61, 95%CI: 0.29-1.30, P = 0.20), myocardial infarction (risk difference 0.00, 95% CI: -0.02-0.03, P = 0.70), stroke (RD 0.00, 95% CI: -0.01-0.01, P = 0.92) and hospital LOS (SMD 0.03, 95% CI: -0.26-0.33, P = 0.84). At meta-regression, there was no effect of age, gender, or type of opioid on the difference between groups. CONCLUSIONS: Our data suggest that low-dose opioids, both short acting and long acting, are safe and effective to use in adult cardiac surgery patients, independent of the clinical characteristics of the patients and the type of opioid used. In view of the current opioid epidemic, low-dose opioid anesthesia should be considered for cardiac surgery patients.