In-vitro radiation exposure study. To determine the radiation exposure to the eyes, extremities, and deep tissue during percutaneous pedicle screw placement. Image-guided minimally invasive spinal surgery is typically performed with the use of fluoroscopy, exposing the surgeon and patient to ionizing radiation. The radiation dose to the surgeon has not been reported and risk to the surgeon performing this procedure over the long term is uncertain. Percutaneous pedicle screws were placed in a cadaveric specimen from L2-S1 bilaterally using a cannulated pedicle screw system. Two fluoroscopes were used in the anteroposterior and lateral planes. The surgeon wore a thermolucent dosimeter ring on the right hand and badge over the left chest beneath the lead apron. Complete surgical time was recorded and a computed tomography scan was performed to assess screw placement. Radiation exposure was measured for total time of fluoroscopy use; average exposure per screw, surgical level, and dose to the eyes was calculated. This data was used to define the safety of percutaneous pedicle screw placement. Total fluoroscope time for placement of 10 percutaneous pedicle screws was 4 minutes 56 seconds (29 s per screw). The protected dosimeter recorded less than the reportable dose. The ring dosimeter recorded 103 mREM, or 10.3 mREM per screw placed. All screws were within the bone confines with acceptable trajectory. Exposure to the eyes was 2.35 mREM per screw. On the basis of this data, percutaneous pedicle screw placement seems to be safe. A surgeon would exceed occupational exposure limit for the eyes and extremities by placing 4854 and 6396 screws percutaneously, respectively. Lead protected against radiation exposure during screw placement. The “hands-off” technique used in this study is recommended to minimize radiation exposure. Lead aprons, thyroid shields, and leaded glasses are recommended for this procedure.

Historically, creating patient-derived models of lower-grade glioma (LGG) has been challenging, contributing to few experimental platforms that support laboratory-based investigations of this disease. Although organoid modeling approaches have recently been employed to create in vitro models of high-grade glioma (HGG), it is unknown whether this approach can be successfully applied to LGG. In this study, we developed an optimized protocol for the establishment of organoids from LGG primary tissue samples by utilizing physiologic (5%) oxygenation conditions and employed it to produce the first known suite of these models. To assess their fidelity, we surveyed key biological features of patient-derived organoids using metabolic, genomic, histologic, and lineage marker gene expression assays. Organoid models were created with a success rate of 91% (n = 20/22) from primary tumor samples across glioma histological subtypes and tumor grades (WHO Grades 1–4), and a success rate of 87% (13/15) for WHO Grade 1–3 tumors. Patient-derived organoids recapitulated stemness, proliferative, and tumor-stromal composition profiles of their respective parental tumor specimens. Cytoarchitectural, mutational, and metabolic traits of parental tumors were also conserved. Importantly, LGG organoids were maintained in vitro for weeks to months and reanimated after biobanking without loss of integrity. We report an efficient method for producing faithful in vitro models of LGG. New experimental platforms generated through this approach are well positioned to support preclinical studies of this disease, particularly those related to tumor immunology, tumor-stroma interactions, identification of novel drug targets, and personalized assessments of treatment response profiles.

Genome-wide single nucleotide polymorphism (SNP) association studies recently identified four SNPs (rs10757274, rs2383206, rs2383207, and rs10757278) on chromosome 9p21 that were associated with coronary artery disease (CAD) and myocardial infarction (MI) in Caucasian populations from northern Europe and North America. Our aim was to determine whether these SNPs were associated with MI in a southern Europe/Mediterranean population. We employed a case–control association design involving 416 MI patients and 308 non-MI controls from Italy. Significant allelic association was identified between all four SNPs and MI. The association remained significant after adjusting for covariates for MI (P = 0.007–0.029). One risk haplotype (GGGG; P = 0.028) and one protective haplotype (AAAA; P = 0.047) were identified. Genotypic association analysis demonstrated that the SNPs conferred susceptibility to MI most likely in a dominant model (P = 0.0007–0.013). When the case cohort was divided into a group of MI patients with a family history (n = 248) and one group without it (n = 168), the positive, significant association was identified only in the group with the family history. These results indicate that chromosome 9p21 confers risk for development of MI in an Italian population.

5-aminolevulinic acid (5-ALA) is a porphyrin precursor in the heme synthesis pathway. When supplied exogenously, certain cancers consume 5-ALA and convert it to the fluorogenic metabolite protoporphyrin IX (PpIX), causing tumor-specific tissue fluorescence. Preoperative administration of 5-ALA is used to aid neurosurgical resection of high-grade gliomas such as glioblastoma, allowing for increased extent of resection and progression free survival for these patients. A subset of gliomas, especially low-grade tumors, do not accumulate PpIX intracellularly or readily fluoresce upon 5-ALA administration, making gross total resection difficult to achieve in diffuse lesions. We review existing literature on 5-ALA metabolism and PpIX accumulation to explore potential mechanisms of 5-ALA-induced glioma tissue fluorescence. Targeting the heme synthesis pathway and understanding its dysregulation in malignant tissues could aid the development of adjunct therapies to increase intraoperative fluorescence after 5-ALA treatment.

A prospective clinical research article. The primary goals were to determine (1) radiation exposure to the spine surgeon with the use of an intraoperative 3-dimensional imaging system and (2) to define the safe distance from the computed tomographic scanner. Intraoperative radiation exposure to the spinal surgeon has been assessed during 2-dimensional fluoroscopy but has not been investigated during intraoperative 3-dimensional imaging. Ten patients undergoing lumbar or thoracolumbar fusion were enrolled in a prospective trial to determine the radiation exposure to a spine surgeon standing in the substerile room, with the use of the O-ARM Imaging System (Medtronic, Memphis, TN). A thermolucent digital dosimeter was worn at chest level without a lead apron. Dosimeter readings and distance from the spine surgeon were recorded. Average surgeon exposure was 44.22 ± 17.4 μrem (range: 17.71–70.76 μrem). The mean distance from the O-ARM was 4.56 ± .32 m, and the surgeon was exposed for an average of 19.6 ± 5.7 seconds (range: 8.05–28.7 s). The annual number of necessary procedures required to surpass the exposure limit, according to the data presented here, would be 113,071 operations using O-ARM. Hence, the number of necessary procedures for O-ARM use is predicted to be 1,130,710 annual procedures to reach the occupational exposure limits for extremity, skin, and all other organs and 339,213 procedures to reach the limits for the lens of eye. Radiation exposure is minimal to the surgical team during routine use of the O-ARM imaging system. The number of procedures required to surpass occupational exposure limits is high if using appropriate distance from the O-ARM.