Mesenchymal Stem Cell-Specific and Preosteoblast-Specific Ablation of TSC1 in Mice Lead to Severe and Slight Spinal Dysplasia, Respectively

Background. TSC1-related signaling plays a pivotal role in intramembranous and endochondral ossification processes during skeletogenesis. This study was aimed at determining the significance of the TSC1 gene at different stages of spinal development. Materials and Methods. TSC1-floxed mice (TSC1flox/flox) were crossed with Prrx1-Cre or BGLAP-Cre transgenic mice or mesenchymal stem cell- and osteoblast-specific TSC1-deficient mice, respectively. Somatic and vertebral differences between WT and Prrx1-TSC1 null mice were examined at 4 weeks after birth. Results. No apparent body size abnormalities were apparent in newborn and 4-week- to 2-month-old mice with BGLAP-Cre driver-depleted TSC1. Vertebral and intervertebral discs displayed strong dysplasia in Prrx1-TSC1 null mice. In contrast, vertebrae were only slightly affected, and intervertebral discs from skeletal preparations displayed no apparent changes in BGLAP-TSC1 null mice. Conclusion. Our data suggest that the TSC1 gene is crucial for endochondral ossification during postnatal spine development but plays discriminative roles at different stages. Mesenchymal stem cell-specific ablation of TSC1 led to severe spinal dysplasia at early stages of endochondral ossification while osteoblast-specific deletion of TSC1 affected vertebrae slightly and had no detectable effects on intervertebral discs

Systematic Review and Meta-Analysis of Perioperative Intravenous Tranexamic Acid Use in Spinal Surgery

<div><p>Background</p><p>Tranexamic acid (TXA) is well-established as a versatile oral, intramuscular, and intravenous (IV) antifibrinolytic agent. However, the efficacy of IV TXA in reducing perioperative blood transfusion in spinal surgery is poorly documented.</p><p>Methodology</p><p>We conducted a meta-analysis of randomized controlled trials (RCTs) and quasi-randomized (qi-RCTs) trials that included patients for various spinal surgeries, such as adolescent scoliosis surgery administered with perioperative IV TXA according to Cochrane Collaboration guidelines using electronic PubMed, Cochrane Central Register of Controlled Trials, and Embase databases. Additional journal articles and conference proceedings were manually located by two independent researchers.</p><p>Results</p><p>Totally, nine studies were included, with a total sample size of 581 patients. Mean blood loss was decreased in patients treated with perioperative IV TXA by 128.28 ml intraoperatively (ranging from 33.84 to 222.73 ml), 98.49 ml postoperatively (ranging from 83.22 to 113.77 ml), and 389.21 ml combined (ranging from 177.83 to 600.60 ml). The mean volume of transfused packed cells were reduced by 134.55 ml (ranging 51.64 to 217.46) (95% CI; P = 0.0001). Overall, the number of patients treated with TXA who required blood transfusions was lower by 35% than that of patients treated with the comparator and who required blood transfusions (RR 0.65; 95% CI; 0.53 to 0.85; P<0.0001, I² = 0%). A dose-independent beneficial effect of TXA was observed, and confirmed in subgroup and sensitivity analyses. A total of seven studies reported DVT data. The study containing only a single DVT case was not combined.</p><p>Conclusions</p><p>The blood loss was reduced in spinal surgery patients with perioperative IV TXA treatment. Also the percentage of spinal surgery patients who required blood transfusion was significantly decreased. Further evaluation is required to confirm our findings before TXA can be safely used in patients undergoing spine surgery.</p></div

Risk of bias summary.

<p>review authors' judgments about each risk of bias item for each included study. + is “yes”, − is “no”, ? is “unclear”.</p

Method for study search and selection for inclusion.

<p>Method for study search and selection for inclusion.</p

Funnel plot to assess publication.

<p>Funnel plot to assess publication for the most frequently reported outcome –blood transfusion rate.</p

Forest plot diagram showing the effect of TXA on DVT.

<p>Forest plot diagram showing the effect of TXA on DVT.</p

Forest plot diagram showing the effect of TXA on total blood loss.

<p>The black diamond signifies that the mean difference is in favour of TXA. The size of each square depends on the weight of each study. A green square is given to continuous outcomes.</p