Minimally invasive robot-assisted direct pars repair: illustrative cases.

BACKGROUND: Robot-assisted techniques are increasingly integrated into the field of spine surgery, with the potential benefits of increased accuracy and reduced radiation exposure. The objective of this study was to describe the technique of minimally invasive robot-assisted direct pars repair with 2 case illustrations. OBSERVATIONS: An 18-year-old male and a 42-year-old male, both with bilateral L5 spondylolysis, underwent successful minimally invasive L5 direct pars repairs with robotic assistance after conservative measures failed, and their cases are presented herein. LESSONS: A robot-assisted direct pars repair is a safe and effective technique for treating bilateral lumbar spondylolysis. The integration of robot-assisted techniques in spine surgery has the potential to improve outcomes, decrease surgical time, and reduce the amount of radiation exposure to operating room staff. https://thejns.org/doi/10.3171/CASE2415.

Surgical management of a multilevel thoracolumbar aneurysmal bone cyst.

Aneurysmal bone cysts (ABCs) are primary bone tumours that rarely occur in the spine and generally affect one vertebral level in adolescents. Here, we present an unusual case of a multilevel thoracolumbar ABC, which presented a unique surgical challenge due to its infiltrative and destructive nature. A teenage male presented with back pain, paresthesias and a mildly spastic gait. MRI of the thoracolumbar spine revealed an expansive, multicystic mass extending from the left T12-L1 vertebral bodies into adjacent musculature. The patient underwent a two-stage surgical approach with decompression of the spinal cord and instrumentation to stabilise the vertebral column. The first stage involved posterior decompression, laminectomy and facetectomies, followed by pedicle-based instrumentation from T10 to L3. This was followed by a vertebrectomy and anterior stabilisation with an expansile cage from T11 to L2. A gross total resection was achieved with the patient maintaining full neurological function.

The multidrug resistance transporter P-glycoprotein confers resistance to ferroptosis inducers.

Aim: Ferroptosis is a non-apoptotic form of cell death caused by lethal lipid peroxidation. Several small molecule ferroptosis inducers (FINs) have been reported, yet little information is available regarding their interaction with the ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp, ABCB1) and ABCG2. We thus sought to characterize the interactions of FINs with P-gp and ABCG2, which may provide information regarding oral bioavailability and brain penetration and predict drug-drug interactions. Methods: Cytotoxicity assays with ferroptosis-sensitive A673 cells transfected to express P-gp or ABCG2 were used to determine the ability of the transporters to confer resistance to FINs; confirmatory studies were performed in OVCAR8 and NCI/ADR-RES cells. The ability of FINs to inhibit P-gp or ABCG2 was determined using the fluorescent substrates rhodamine 123 or purpuin-18, respectively. Results: P-gp overexpression conferred resistance to FIN56 and the erastin derivatives imidazole ketone erastin and piperazine erastin. P-gp-mediated resistance to imidazole ketone erastin and piperazine erastin was also reversed in UO-31 renal cancer cells by CRISPR-mediated knockout of ABCB1. The FINs ML-162, GPX inhibitor 26a, and PACMA31 at 10 µM were able to increase intracellular rhodamine 123 fluorescence over 10-fold in P-gp-expressing MDR-19 cells. GPX inhibitor 26a was able to increase intracellular purpurin-18 fluorescence over 4-fold in ABCG2-expressing R-5 cells. Conclusion: Expression of P-gp may reduce the efficacy of these FINs in cancers that express the transporter and may prevent access to sanctuary sites such as the brain. The ability of some FINs to inhibit P-gp and ABCG2 suggests potential drug-drug interactions.

The Multidrug Resistance Transporter P-glycoprotein Confers Resistance to Ferroptosis Inducers.

Ferroptosis is a form of cell death caused by direct or indirect inhibition of glutathione peroxidase 4 that leads to lethal lipid peroxidation. Several small molecule ferroptosis inducers (FINs) have been reported, yet little information is available regarding resistance mechanisms, particularly their interaction with the ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp, ABCB1) and ABCG2. Given the role that ABC transporters play in absorption, distribution, and excretion of many drugs, characterizing these interactions could provide information regarding oral bioavailability and brain penetration and may predict drug-drug interactions. Using ferroptosis-sensitive A673 cells transfected to express P-gp or ABCG2, we found that P-gp overexpression was able to confer resistance to FIN56 and the erastin derivatives imidazole ketone erastin and piperazine erastin. Results were confirmed with OVCAR8-derived NCI/ADR-RES cells that overexpress P-gp, where the P-gp inhibitor valspodar completely inhibited resistance to the FINs. P-gp-mediated resistance to imidazole ketone erastin and piperazine erastin was also reversed in UO-31 renal cancer cells by CRISPR-mediated knockout of ABCB1. At a concentration of 10 µM, the FINs ML-162, GPX inhibitor 26a, and PACMA31 were able to increase intracellular rhodamine 123 fluorescence over 10-fold in P-gp-expressing MDR-19 cells and GPX inhibitor 26a was able to increase intracellular purpurin-18 fluorescence over 4-fold in ABCG2-expressing R-5 cells. Expression of P-gp may reduce the efficacy of these FINs in cancers that express the transporter and may prevent access to sanctuary sites such as the brain. The ability of some FINs to inhibit P-gp and ABCG2 suggests potential drug-drug interactions.