A systematic review of posterior pilon variant fractures.

Posterior pilon variant ankle fractures (PPVF) are a unique subtype of posterior malleolar fractures which have been a source of controversy and confusion in recent years. There has not been a thorough literature review previously written on the topic. Database searches of PubMed and Embase were conducted from inception until June 2023. The key words included "pilon variant," "posterior pilon variant," and "posterior pilon" fractures. Outcomes were evaluated by union time, rates of delayed union, nonunion, malunion, and complication. A total of 15 articles relevant to surgical repair of pilon variant fractures were included in the literature review. The unique mechanism of injury has been reported to involve both rotational and axial forces, leading to involvement of the posterior and medial aspects of the distal tibia. Pilon variant fractures can be suspected by several characteristics on radiographs and have a high confirmation rate via CT images. Multiple systems have been proposed to classify this fracture pattern, but there is no consensus on the ideal classification system. Surgically, direct fixation has shown better short-term clinical outcomes versus indirect fixation or no fixation. PPVF have a distinct fracture pattern involving the posterior and medial columns of the distal tibial plafond, and results from a mechanism intermediate to rotational and axial forces. These fractures are more severe than tri-malleolar fractures due to increased rates of articular impaction and incongruity. Future classification systems should focus on joint surface area and the tibial pilon column involved to avoid confusion with less severe posterior malleolar fractures.

Feasibility of stereotactic radiotherapy using a 1.5 T MR-linac: Multi-fraction treatment of pelvic lymph node oligometastases.

Online adaptive radiotherapy using the 1.5 Tesla MR-linac is feasible for SBRT (5 × 7 Gy) of pelvic lymph node oligometastases. The workflow allows full online planning based on daily anatomy. Session duration is less than 60 min. Quality assurance tests, including independent 3D dose calculations and film measurements were passed.

GPR3, GPR6, and GPR12 as novel molecular targets: their biological functions and interaction with cannabidiol.

The G protein-coupled receptors 3, 6, and 12 (GPR3, GPR6, and GPR12) comprise a family of closely related orphan receptors with no confirmed endogenous ligands. These receptors are constitutively active and capable of signaling through G protein-mediated and non-G protein-mediated mechanisms. These orphan receptors have previously been reported to play important roles in many normal physiological functions and to be involved in a variety of pathological conditions. Although they are orphans, GPR3, GPR6, and GPR12 are phylogenetically most closely related to the cannabinoid receptors. Using ß-arrestin2 recruitment and cAMP accumulation assays, we recently found that the nonpsychoactive phytocannabinoid cannabidiol (CBD) is an inverse agonist for GPR3, GPR6, and GPR12. This discovery highlights these orphan receptors as potential new molecular targets for CBD, provides novel mechanisms of action, and suggests new therapeutic uses of CBD for illnesses such as Alzheimer's disease, Parkinson's disease, cancer, and infertility. Furthermore, identification of CBD as a new inverse agonist for GPR3, GPR6, and GPR12 provides the initial chemical scaffolds upon which potent and efficacious agents acting on these receptors can be developed, with the goal of developing chemical tools for studying these orphan receptors and ultimately new therapeutic agents.

Cannabidiol, a novel inverse agonist for GPR12.

GPR12 is a constitutively active, Gs protein-coupled receptor that currently has no confirmed endogenous ligands. GPR12 may be involved in physiological processes such as maintenance of oocyte meiotic arrest and brain development, as well as pathological conditions such as metastatic cancer. In this study, the potential effects of various classes of cannabinoids on GPR12 were tested using a cAMP accumulation assay. Our data demonstrate that cannabidiol (CBD), a major non-psychoactive phytocannabinoid, acted as an inverse agonist to inhibit cAMP accumulation stimulated by the constitutively active GPR12. Thus, GPR12 is a novel molecular target for CBD. The structure-activity relationship studies of CBD indicate that both the free hydroxyl and the pentyl side chain are crucial for the effects of CBD on GPR12. Furthermore, studies using cholera toxin, which blocks Gs protein and pertussis toxin, which blocks Gi protein, revealed that Gs, but not Gi is involved in the inverse agonism of CBD on GPR12. CBD is a promising novel therapeutic agent for cancer, and GPR12 has been shown to alter viscoelasticity of metastatic cancer cells. Since we have demonstrated that CBD is an inverse agonist for GPR12, this provides novel mechanism of action for CBD, and an initial chemical scaffold upon which highly potent and efficacious agents acting on GPR12 may be developed with the ultimate goal of blocking cancer metastasis.

The MRI-Linear Accelerator Consortium: Evidence-Based Clinical Introduction of an Innovation in Radiation Oncology Connecting Researchers, Methodology, Data Collection, Quality Assurance, and Technical Development.

An international research consortium has been formed to facilitate evidence-based introduction of MR-guided radiotherapy (MR-linac) and to address how the MR-linac could be used to achieve an optimized radiation treatment approach to improve patients' survival, local, and regional tumor control and quality of life. The present paper describes the organizational structure of the clinical part of the MR-linac consortium. Furthermore, it elucidates why collaboration on this large project is necessary, and how a central data registry program will be implemented.

MRI/linac integration.

PURPOSE/OBJECTIVES: In radiotherapy the healthy tissue involvement still poses serious dose limitations. This results in sub-optimal tumour dose and complications. Daily image guided radiotherapy (IGRT) is the key development in radiation oncology to solve this problem. MRI yields superb soft-tissue visualization and provides several imaging modalities for identification of movements, function and physiology. Integrating MRI functionality with an accelerator can make these capacities available for high precision, real time IGRT. DESIGN AND RESULTS: The system being built at the University Medical Center Utrecht is a 1.5T MRI scanner, with diagnostic imaging functionality and quality, integrated with a 6MV radiotherapy accelerator. The realization of a prototype of this hybrid system is a joint effort between the Radiotherapy Department of the University of Utrecht, the Netherlands, Elekta, Crawley, U.K., and Philips Research, Hamburg, Germany. Basically, the design is a 1.5 T Philips Achieva MRI scanner with a Magnex closed bore magnet surrounded by a single energy (6 MV) Elekta accelerator. Monte Carlo simulations are used to investigate the radiation beam properties of the hybrid system, dosimetry equipment and for the construction of patient specific dose deposition kernels in the presence of a magnetic field. The latter are used to evaluate the IMRT capability of the integrated MRI linac. CONCLUSIONS: A prototype hybrid MRI/linac for on-line MRI guidance of radiotherapy (MRIgRT) is under construction. The aim of the system is to deliver the radiation dose with mm precision based on diagnostic quality MR images.