Pedicle subtraction metallectomy with complex posterior reconstruction for fixed cervicothoracic kyphosis: illustrative case.

BACKGROUND: Iatrogenic cervical deformity is a devastating complication that can result from a well-intended operation but a poor understanding of the individual biomechanics of a patient's spine. Patient factors, such as bone fragility, high T1 slope, and undiagnosed myopathies often play a role in perpetuating a deformity despite an otherwise successful surgery. This imbalance can lead to significant morbidity and a decreased quality of life. OBSERVATIONS: A 55-year-old male presented to the authors' clinic with a chin-to-chest deformity and cervical myelopathy. He previously had an anterior C2-T2 fixation and a posterior C1-T6 instrumented fusion. He subsequently developed screw pullout at multiple levels, so the original surgeon removed all of the posterior hardware. The T1 cage (original corpectomy) severely subsided into the body of T2, generating an angular kyphosis that eventually developed a rigid osseous circumferential union at the cervicothoracic junction with severe cord compression. An anterior approach was not feasible; therefore, a 3-column osteotomy/fusion in the upper thoracic spine was planned whereby 1 of the T2 screws would need to be removed from a posterior approach for the reduction to take place. LESSONS: This case highlights the devastating effect of a hardware complication leading to a fixed cervical spine deformity and the complex decision making involved to safely correct the challenging deformity and restore function.

The ion channel TRPM7 regulates zinc-depletion-induced MDMX degradation.

Zinc deficiency has been linked to human diseases, including cancer. MDMX, a crucial zinc-containing negative regulator of p53, has been found to be amplified or overexpressed in various cancers and implicated in the cancer initiation and progression. We report here that zinc depletion by the ion chelator TPEN or Chelex resin results in MDMX protein degradation in a ubiquitination-independent and 20S proteasome-dependent manner. Restoration of zinc led to recovery of cellular levels of MDMX. Further, TPEN treatment inhibits growth of the MCF-7 breast cancer cell line, which is partially rescued by overexpression of MDMX. Moreover, in a mass-spectrometry-based proteomics analysis, we identified TRPM7, a zinc-permeable ion channel, as a novel MDMX-interacting protein. TRPM7 stabilizes and induces the appearance of faster migrating species of MDMX on SDS-PAGE. Depletion of TRPM7 attenuates, while TRPM7 overexpression facilitates, the recovery of MDMX levels upon adding back zinc to TPEN-treated cells. Importantly, we found that TRPM7 inhibition, like TPEN treatment, decreases breast cancer cell MCF-7 proliferation and migration. The inhibitory effect on cell migration upon TRPM7 inhibition is also partially rescued by overexpression of MDMX. Together, our data indicate that TRPM7 regulates cellular levels of MDMX in part by modulating the intracellular Zn2+ concentration to promote tumorigenesis.

Surgical management of symptomatic vertebral hemangiomas: A case report and literature review.

BACKGROUND: Vertebral hemangiomas (VHs) are common benign tumors that only rarely become symptomatic. There is a paucity of data regarding their surgical management and outcomes. Here, we reported a case involving an aggressive cervical VH, discussed its surgical management and outcomes, and reviewed the literature. METHODS: We assessed the clinical, radiological, and surgical outcomes for a patient with an aggressive cervical VH. We also performed a systematic review of the literature according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to describe surgical outcomes for symptomatic VH. RESULTS: A total of 154 studies including 535 patients with VH were included in the study. The majority of patients were female (62.8%), the average age was 43 years, and the thoracic spine was most commonly involved (80.6%). Utilizing Odom's criteria, outcomes were excellent in 81.7% (95% CI 73.2-90.2) of cases. For those presenting with myelopathy (P = 0.045) or focal neurological deficits (P = 0.018), outcomes were less likely to be excellent. Preoperative embolization was not associated with excellent outcome (P = 0.328). CONCLUSION: Surgical outcomes for VH are predominantly favorable, but aggressive VHs have the potential to cause significant residual postoperative neurological morbidity.

Activation of p53 and destabilization of androgen receptor by combinatorial inhibition of MDM2 and MDMX in prostate cancer cells.

Castration-resistant prostate cancer (CRPC) frequently develops after initial standard radiation and androgen deprivation therapy, leaving patients with limited further treatment options. Androgen receptor (AR) is a transcription factor that plays a key role in the initiation and progression of prostate cancer. p53, a major tumor suppressor that is rarely mutated in early-stages of prostate cancer, is often deregulated during prostate cancer progression. Here, we report an unusual co-amplification of MDM2 and MDMX, two crucial negative regulators of p53, in CRPC datasets. We demonstrate that combinatorial inhibition of MDM2 and MDMX, with nutlin-3 and NSC207895 respectively, has a profound inhibitory effect on cell proliferation of androgen-responsive, wild-type TP53 gene carrying prostate cancer cells LNCaP and 22Rv1. We further show that the combinatorial inhibition of MDM2 and MDMX not only activates p53, but also decreases cellular levels of AR and represses its function. Additionally, co-expression of MDM2 and MDMX stabilizes AR. Together, our results indicate that combinatorial inhibition of MDM2 and MDMX may offer a novel compelling strategy for prostate cancer therapy.