Genetic risk for aortic aneurysm in adolescent idiopathic scoliosis

BACKGROUND: Scoliosis is a feature of several genetic disorders that are also associated with aortic aneurysm, including Marfan syndrome, Loeys-Dietz syndrome, and type-IV Ehlers-Danlos syndrome. Life-threatening complications of aortic aneurysm can be decreased through early diagnosis. Genetic screening for mutations in populations at risk, such as patients with adolescent idiopathic scoliosis, may improve recognition of these disorders. METHODS: The coding regions of five clinically actionable genes associated with scoliosis (COL3A1, FBN1, TGFBR1, TGFBR2, and SMAD3) and aortic aneurysm were sequenced in 343 adolescent idiopathic scoliosis cases. Gene variants that had minor allele frequencies of <0.0001 or were present in human disease mutation databases were identified. Variants were classified as pathogenic, likely pathogenic, or variants of unknown significance. RESULTS: Pathogenic or likely pathogenic mutations were identified in 0.9% (three) of 343 adolescent idiopathic scoliosis cases. Two patients had pathogenic SMAD3 nonsense mutations consistent with type-III Loeys-Dietz syndrome and one patient had a pathogenic FBN1 mutation with subsequent confirmation of Marfan syndrome. Variants of unknown significance in COL3A1 and FBN1 were identified in 5.0% (seventeen) of 343 adolescent idiopathic scoliosis cases. Six FBN1 variants were previously reported in patients with Marfan syndrome, yet were considered variants of unknown significance based on the level of evidence. Variants of unknown significance occurred most frequently in FBN1 and were associated with greater curve severity, systemic features of Marfan syndrome, and joint hypermobility. CONCLUSIONS: Clinically actionable pathogenic mutations in genes associated with adolescent idiopathic scoliosis and aortic aneurysm are rare in patients with adolescent idiopathic scoliosis who are not suspected of having these disorders, although variants of unknown significance are relatively common. CLINICAL RELEVANCE: Routine genetic screening of all patients with adolescent idiopathic scoliosis for mutations in clinically actionable aortic aneurysm disease genes is not recommended on the basis of the high frequency of variants of unknown significance. Clinical evaluation and family history should heighten indications for genetic referral and testing

Temporary use of shape memory spinal rod in the treatment of scoliosis

NiTinol shape memory alloy is characterized by its malleability at low temperatures and its ability to return to a preconfigured shape above its activation temperature. This process can be utilized to assist in scoliosis correction. The goal of this retrospective study was to evaluate the clinical and radiographic results of intraoperative use of shape memory alloy rod in the correction of scoliosis. From May 2002 to September 2006, 38 scoliosis patients (ranging from 50° to 120°; 22 cases over 70°) who underwent shape memory alloy-assisted correction in our institute were reviewed. During the operation, a shape memory alloy rod served as a temporary correction tool. Following correction, the rod was replaced by a rigid rod. The mean blood loss at surgery was 680 ± 584 ml; the mean operative time was 278 ± 62 min. The major Cobb angle improved from an average 78.4° preoperatively to 24.3° postoperatively (total percent correction 71.4%). In 16 patients with a major curve <70° and flexibility of 52.7%, the deformity improved from 58.4° preoperatively to 12.3° postoperatively (percent correction, 78.9%). In 22 patients with a major curve >70° and flexibility of 25.6%, the deformity improved from 94.1° preoperatively to 30.1° postoperatively (percent correction, 68.1%). Only one case had a deep infection. There were no neurologic, vascular or correction-related complications such as screw pullout or metal fracture. The study shows that the intraoperative use of a shape memory rod is a safe and effective method to correct scoliosis

Identification of 4-amino-thieno[2,3-d]pyrimidines as QcrB inhibitors in Mycobacterium tuberculosis

Antibiotic resistance is a global crisis that threatens our ability to treat bacterial infections, such as tuberculosis, caused b