Spinal fractures in the setting of diffuse idiopathic skeletal hyperostosis conservatively treated via orthosis: illustrative cases.

BACKGROUND: Fractures in patients with diffuse idiopathic skeletal hyperostosis (DISH) are considered highly unstable injuries with high risk for neurological injury. Surgical intervention is the standard of care for these patients to avoid secondary spinal cord injuries. Despite this, certain cases may necessitate a nonoperative approach. Herein within, the authors describe three cases of cervical, thoracic, and lumbar fractures in the setting of DISH that were successfully treated via orthosis. OBSERVATIONS: The authors present three cases of fractures in patients with DISH. A 74-year-old female diagnosed with an acute fracture of a flowing anterior osteophyte at C6-C7 treated with a cervical orthosis. A 78-year-old male with an anterior fracture of the ankylosed T7-T8 vertebrae managed with a Jewett hyperextension brace. Finally, a 57-year-old male with an L1-L2 disc space fracture treated with a thoraco-lumbo-sacral orthosis. All patients recovered successfully. LESSONS: In certain cases, conservative treatment may be more appropriate for fractures in the setting of DISH as an alternative to the surgical standard of care. Most fractures in the setting of DISH are unstable, therefore it is necessary to manage these patients on a case-by-case basis.

H3.3-G34 mutations impair DNA repair and promote cGAS/STING-mediated immune responses in pediatric high-grade glioma models.

Pediatric high-grade gliomas (pHGGs) are the leading cause of cancer-related deaths in children in the USA. Sixteen percent of hemispheric pediatric and young adult HGGs encode Gly34Arg/Val substitutions in the histone H3.3 (H3.3-G34R/V). The mechanisms by which H3.3-G34R/V drive malignancy and therapeutic resistance in pHGGs remain unknown. Using a syngeneic, genetically engineered mouse model (GEMM) and human pHGG cells encoding H3.3-G34R, we demonstrate that this mutation led to the downregulation of DNA repair pathways. This resulted in enhanced susceptibility to DNA damage and inhibition of the DNA damage response (DDR). We demonstrate that genetic instability resulting from improper DNA repair in G34R-mutant pHGG led to the accumulation of extrachromosomal DNA, which activated the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway, inducing the release of immune-stimulatory cytokines. We treated H3.3-G34R pHGG-bearing mice with a combination of radiotherapy (RT) and DNA damage response inhibitors (DDRi) (i.e., the blood-brain barrier-permeable PARP inhibitor pamiparib and the cell-cycle checkpoint CHK1/2 inhibitor AZD7762), and these combinations resulted in long-term survival for approximately 50% of the mice. Moreover, the addition of a STING agonist (diABZl) enhanced the therapeutic efficacy of these treatments. Long-term survivors developed immunological memory, preventing pHGG growth upon rechallenge. These results demonstrate that DDRi and STING agonists in combination with RT induced immune-mediated therapeutic efficacy in G34-mutant pHGG.

Temporary Internal Bracing for Pediatric Odontoid Synchondrosis Fracture.

Children are predisposed to injuries of the upper cervical spine given their relatively immature osteology, ligamentous laxity, underdeveloped musculature, and larger ratios of head to body mass. Odontoid process fractures involving the synchondroses are among the most common of these injuries. Though many of these fractures can be treated conservatively with external bracing, fractures with significant displacement that are unable to be reduced require operative management. In these cases, most patients undergo C1-2 posterior fusion with arthrodesis with permanent limitation to atlantoaxial range of motion (ROM). Here, we present a novel operative approach to manage odontoid synchondrosis fractures with temporary internal bracing via C1-2 posterior instrumentation without arthrodesis. We saw a three-year-old female who presented after a motor vehicle collision with a displaced odontoid synchondrosis fracture that was unable to be adequately reduced in a closed fashion. In an attempt to preserve maximal atlantoaxial ROM, temporary internal bracing was carried out with excellent results.