SERCA2a, Phospholamban, Sarcolipin, and Ryanodine Receptors Gene Expression in Children with Congenital Heart Defects

In animal models of conotruncal heart defects, an abnormal calcium sensitivity of the contractile apparatus and a depressed L-type calcium current have been described. Sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) is a membrane protein that catalyzes the ATP-dependent transport of Ca2+ from the cytosol to the SR. The activity of SERCA is inhibited by phospholamban (PLN) and sarcolipin (SLN), and all these proteins participate in maintaining the normal intracellular calcium handling. Ryanodine receptors (RyRs) are the major SR calcium-release channels required for excitation-contraction coupling in skeletal and cardiac muscle. Our objective was to evaluate SERCA2a (i.e., the SERCA cardiac isoform), PLN, SLN, and RyR2 (i.e., the RyR isoform enriched in the heart) gene expression in myocardial tissue of patients affected by tetralogy of Fallot (TOF), a conotruncal heart defect. The gene expression of target genes was assessed semiquantitatively by RT-PCR using the calsequestrin (CASQ, a housekeeping gene) RNA as internal standard in the atrial myocardium of 23 pediatric patients undergoing surgical correction of TOF, in 10 age-matched patients with ventricular septal defect (VSD) and in 13 age-matched children with atrial septal defect (ASD). We observed a significantly lower expression of PLN and SLN in TOF patients, while there was no difference between the expression of SERCA2a and RyR2 in TOF and VSD. These data suggest a complex mechanism aimed to enhance the intracellular Ca2+ reserve in children affected by tetralogy of Fallot

Efficacy and safety of posteromedial translation for correction of thoracic curves in adolescent idiopathic scoliosis using a new connection to the spine: the Universal Clamp

Correction of adolescent idiopathic scoliosis (AIS) has been reported with various systems. All-screw constructs are currently the most popular, but they have been associated with a significant decrease in thoracic kyphosis, with a potential risk of junctional kyphosis, not observed with hybrid constructs in the literature. In addition, it is important to weigh potential advantages of pedicle screw fixation against risks specific to its use. Because hybrid constructs are associated with a lower risk of complications and better sagittal correction than all-screw constructs, at present we use lumbar pedicle screws combined with a new sublaminar connection to the spine (Universal Clamps) at thoracic levels. The purpose of this study was to determine the efficacy and safety of the Universal Clamp (UC) posteromedial translation technique for correction of AIS. Seventy-five consecutive patients underwent posterior spinal fusion and hybrid instrumentation for progressive AIS. Correction was performed at the thoracic level using posteromedial translation. At the lumbar level, correction was performed using in situ contouring and compression/distractions maneuvers. A minimum 2-year follow-up was required. Medical data and radiographs were prospectively analyzed and compared using a paired t test. The average age at surgery was 15 years and 4 months (±19 months). The average number of levels fused was 12 ± 1.6. The mean follow-up was 30 ± 5 months. The average preoperative Cobb angle of the major curve was 60° ± 20°. The immediate postoperative major curve correction averaged 66 ± 13%. The average loss of correction of the major curve between the early postoperative assessment and latest follow-up was 3.5° ± 1.4°. The mean Cincinnati correction index was 1.7 ± 0.8 postoperatively, and 1.57 ± 1 at last follow up. The mean rotation of the apical vertebra was corrected from 23.3° ± 9° preoperatively to 7.3° ± 5° at last follow up (69% improvement, P < 0.0001). In the sagittal plane, the mean thoracic kyphosis improved from 23.8° ± 14.2° preoperatively to 32.3° ± 7.3° at last follow up. For the 68 patients who had a normokyphotic or a hypokyphotic sagittal modifier, thoracic kyphosis increased from 20.5° ± 9.9° to 31.8° ± 7.4°, corresponding to a mean kyphosis correction of 55% at last follow up. No intraoperative complication occurred and none of the patients developed proximal junctional kyphosis during the follow up. The principal limitation of the UC technique was the rate of proximal posterior prominence (14.6%), leading us to recommend the use of conventional claws at the upper extremity of the construct. The technique was safe, and reduced operative time, radiation exposure, and blood loss. While achieving correction of deformity in the coronal and axial planes equivalent to the best reported results of all-screw or previous hybrid constructs, the UC hybrid technique appears to provide superior correction in the sagittal plane. The excellent outcome in all three planes was maintained at 2 year follow up