Relationship Between Preoperative Plasma Fibrinogen Concentration, Perioperative Bleeding, and Transfusions in Elective Adult Spinal Deformity Correction.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: This study sought to investigate the relationship between preoperative (preop) fibrinogen, bleeding, and transfusion requirements in adult spinal deformity corrections. SUMMARY OF BACKGROUND DATA: Blood loss after major spinal reconstruction increases the risks and costs of surgery. Preoperative fibrinogen levels may predict intra- and postoperative blood loss. METHODS: Data were collected from clinic charts and hospital medical records of all 142 of a single surgeon's consecutive adult spine patients undergoing 7 or more levels deformity correction surgeries from January 2011 to December 2014. t tests were used to compare perioperative variables between patients with total blood loss in the upper quartile (≥1,000 mL) and the remaining patients. Similarly, patients receiving >2 units of packed red cells (PRCs) were compared with others. Analysis of variance was used to compare the blood loss between the patients' groups (quartiles) based on their preoperative fibrinogen concentration. RESULTS: Mean total blood loss was 847.9 (±543.6) mL. Overall, mean preoperative fibrinogen concentration was 254.8 (±82.9) mg/dL. Patients with lower fibrinogen concentration (<193 mg/dL) experienced significantly higher blood loss than those with higher concentrations (p < .05). Patients with transfusion >2 units PRC had significantly greater number of spinal levels treated, higher mean operative time, total blood loss and lower mean preoperative fibrinogen than those transfused 2 or fewer units PRC (p < .05). Total blood loss correlated significantly with preoperative fibrinogen concentration (r = -0.51, p < .05). All the thromboelastography (TEG) variables (G, K, and Angle) correlated significantly with preoperative fibrinogen (p < .05). CONCLUSIONS: In our cohort undergoing correction of adult spinal deformity, patients with preoperative fibrinogen level lower than 193 mg/dL had significantly higher bleeding than their counterparts. Perioperative transfusion requirements correlated moderately both with the blood loss and preoperative fibrinogen concentration. Incorporation of preoperative fibrinogen allows better prediction of total perioperative blood loss and may therefore guide the treatment team in use of ameliorating therapies. LEVEL OF EVIDENCE: Level IV.

Development of severe skeletal defects in induced SHP-2-deficient adult mice: a model of skeletal malformation in humans with SHP-2 mutations.

SHP-2 (encoded by PTPN11) is a ubiquitously expressed protein tyrosine phosphatase required for signal transduction by multiple different cell surface receptors. Humans with germline SHP-2 mutations develop Noonan syndrome or LEOPARD syndrome, which are characterized by cardiovascular, neurological and skeletal abnormalities. To study how SHP-2 regulates tissue homeostasis in normal adults, we used a conditional SHP-2 mouse mutant in which loss of expression of SHP-2 was induced in multiple tissues in response to drug administration. Induced deletion of SHP-2 resulted in impaired hematopoiesis, weight loss and lethality. Most strikingly, induced SHP-2-deficient mice developed severe skeletal abnormalities, including kyphoses and scolioses of the spine. Skeletal malformations were associated with alterations in cartilage and a marked increase in trabecular bone mass. Osteoclasts were essentially absent from the bones of SHP-2-deficient mice, thus accounting for the osteopetrotic phenotype. Studies in vitro revealed that osteoclastogenesis that was stimulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL) was defective in SHP-2-deficient mice. At least in part, this was explained by a requirement for SHP-2 in M-CSF-induced activation of the pro-survival protein kinase AKT in hematopoietic precursor cells. These findings illustrate an essential role for SHP-2 in skeletal growth and remodeling in adults, and reveal some of the cellular and molecular mechanisms involved. The model is predicted to be of further use in understanding how SHP-2 regulates skeletal morphogenesis, which could lead to the development of novel therapies for the treatment of skeletal malformations in human patients with SHP-2 mutations.

The effects of pineal gland transplantation on the production of spinal deformity and serum melatonin level following pinealectomy in the chicken.

Pinealectomy frequently produces spinal deformity in some animal models, but the precise biological mechanism of this phenomenon remains obscure. The current study investigated the effects of an autograft pineal body on the development of spinal deformity and serum melatonin (MLT) concentration after pinealectomy in the chicken. Thirty-six chickens (2 days of age) were divided into three equal groups. While the removal of the pineal gland was performed in groups B and C, a pineal body autograft was surgically implanted into the body wall musculature only in the pineal transplantation group (group C). Chickens in which no surgical intervention was performed served as intact controls (group A). Posteroanterior radiographs of the spines of the chickens were taken at the age of 8 weeks. These were used to determine Cobb angles and to measure the rib-vertebra angles (RVA) on the concave and convex sides of the curves, from which data the difference between the convex and concave RVA (the RVAD) was calculated. At the end of the study, serum MLT levels were determined using the enzyme-linked immunosorbent assay method, and histopathological examination of specimens from all the groups was performed. The results were compared using one-way analysis of variance followed by Duncan's test for pairwise comparisons or by the Kruskal-Wallis test followed by the Mann-Whitney U tests for comparisons between two groups. In this study, the serum MLT levels in groups B and C were significantly lower than those in group A ( P<0.05). However, scoliosis developed in only 7 of 12 (58%) in group B and 6 of 12 (50%) in group C. The average Cobb angle and RVAD in groups B and C were significantly larger than those found in group A ( P=0.000 and P=0.001, respectively). Interestingly, there were no significant differences in either serum MLT levels or development of scoliosis between groups B and C. From the results of the current study, it is evident that the intramuscular pineal gland transplantation following pinealectomy in young Hybro Broiler chickens has no significant effect on the development of spinal deformity and serum MLT level. In the light of this result, the role of MLT in the development of spinal deformity in chickens after pinealectomy remains controversial, and further investigations are warranted.