Evaluation of anatomic landmarks and safe zones for screw placement in the atlas via the posterior arch

Several studies have evaluated quantitative anatomic data for direct lateral mass screw fixation. To analyze anatomic landmarks and safe zones for optimal screw placement through the posterior arc of the human atlas, morphometric parameters of 41 adult native human atlas specimens were quantitatively measured. Internal dimensions of the atlas (lateral mass, maximum and minimum intraosseous screw length), minimum height and width of the posterior arc and optimal screw insertion angles were defined on pQCT scans. By this, an optimal posterior screw insertion point (OIP) and a preferable screw direction (PSD) through the posterior arch into the lateral mass of C1 were defined. External dimensions (transverse and sagittal diameter) as well as the width of the mid-portion of C1 lateral mass were significantly higher in male specimens. The mean height of the posterior arch at the vertebral artery groove was 4.1 ± 0.8 mm in female and 4.6 ± 0.9 mm in male specimens. The optimal screw insertion point was located 21.6 ± 1.7 mm in female and 23.6 ± 2.3 mm in male lateral from the posterior tubercle of C1 (P < 0.01). The preferable screw direction was a mean medial inclination of 7.9 ± 1.9° in female and 7.3 ± 2.7° in male specimens and a mean rostral direction of 2.4 ± 1.8° in female and 3.1 ± 1.7° in male specimens. In conclusion, the presented study provides information for the use and design of upper cervical spine instrumentation techniques, such as screw placement to C1 via the posterior arch. The characterization of working areas and safe zones (OIP, PSD) might contribute to a minimization of screw malposition in this highly demanding instrumentation technique

Progressive liver, kidney, and heart degeneration in children and adults affected by TULP3 mutations.

Organ fibrosis is a shared endpoint of many diseases, yet underlying mechanisms are not well understood. Several pathways governed by the primary cilium, a sensory antenna present on most vertebrate cells, have been linked with fibrosis. Ciliopathies usually start early in life and represent a considerable disease burden. We performed massively parallel sequencing by using cohorts of genetically unsolved individuals with unexplained liver and kidney failure and correlated this with clinical, imaging, and histopathological analyses. Mechanistic studies were conducted with a vertebrate model and primary cells. We detected bi-allelic deleterious variants in TULP3, encoding a critical adaptor protein for ciliary trafficking, in a total of 15 mostly adult individuals, originating from eight unrelated families, with progressive degenerative liver fibrosis, fibrocystic kidney disease, and hypertrophic cardiomyopathy with atypical fibrotic patterns on histopathology. We recapitulated the human phenotype in adult zebrafish and confirmed disruption of critical ciliary cargo composition in several primary cell lines derived from affected individuals. Further, we show interaction between TULP3 and the nuclear deacetylase SIRT1, with roles in DNA damage repair and fibrosis, and report increased DNA damage ex vivo. Transcriptomic studies demonstrated upregulation of profibrotic pathways with gene clusters for hypertrophic cardiomyopathy and WNT and TGF-β signaling. These findings identify variants in TULP3 as a monogenic cause for progressive degenerative disease of major organs in which affected individuals benefit from early detection and improved clinical management. Elucidation of mechanisms crucial for DNA damage repair and tissue maintenance will guide novel therapeutic avenues for this and similar genetic and non-genomic diseases