Three-dimensional position changes of the midface following Le Fort III advancement in syndromic craniosynostosis.

Little is known about the positional change of the Le Fort III segment following advancement. To study this, pre- and postoperative computed tomography scans of 18 craniosynosthosis patients were analyzed. The Le Fort III segment movement was measured by creating a reference coordinate system and by superpositioning the postoperative over the preoperative scan. On both the pre- and postoperative scans, four anatomical landmarks were marked: the most anterior point of the left and right foramen infraorbitale, the nasion, and the anterior nasal spine. A significant anterior movement of the four reference points was observed. No significant transversal differences were found. A significant difference between the anterior movement of the nasion and anterior nasal spine was found. In vertical dimension, there was a significant cranial movement of nasion in the study group. In addition, from all patients standardized lateral X-rays were viewed to determine the location and direction of force application that were linked to the outcomes of the three-dimensional movement of the nasion and anterior nasal spine (ANS) and the surgical technique. Conclusively, a significant advancement of the midface can be achieved with Le Fort III distraction osteogenesis in this specific patient group. Counterclockwise movement seemed to be the most dominant movement despite different modes of anchorage.

Monitoring antigen-specific biologics: current knowledge and future prospects.

An increasing number of antigen-specific biologics have been introduced into clinical practice, and the ones that arrived first have already reached the end of their patented life span. Despite the use of these agents for over a decade, individualized dosing is not standard practice. Most patients are treated according to treatment protocols, with a fixed dose administered at fixed time intervals. Although the between-subject variability in the volume of distribution is small, there is a moderate to high between-subject variability in the clearance of these biologics. The formation of neutralizing antidrug antibodies (ADAs) further contributes to the variability in the pharmacokinetics and pharmacodynamics. After the development of assays to detect biologic drug serum concentrations and ADA titers, the first clinical studies in immune-mediated diseases such as rheumatology, gastroenterology, and dermatology have now shown clear concentration-effect relationships. By monitoring the serum trough concentrations of biologics, patients with high drug exposure could be identified and dose reductions in those patients may lead to improved safety and substantial cost savings. Low biologic drug serum concentrations may be due to the development of ADAs, and if these are detected, a switch to an alternative treatment is indicated. We envision a vast expansion of therapeutic drug monitoring to support the use of biologics, and we urge the International Association of Therapeutic Drug Monitoring and Clinical Toxicology to embark on initiatives to investigate the contribution of therapeutic drug monitoring to this field.

Orbital change following Le Fort III advancement in syndromic craniosynostosis: quantitative evaluation of orbital volume, infra-orbital rim and globe position.

Patients with syndromic craniosynostosis suffering from shallow orbits due to midface hypoplasia can be treated with a Le Fort III advancement osteotomy. This study evaluates the influence of Le Fort III advancement on orbital volume, position of the infra-orbital rim and globe. In pre- and post-operative CT-scans of 18 syndromic craniosynostosis patients, segmentation of the left and right orbit was performed and the infra-orbital rim and globe were marked. By superimposing the pre- and post-operative scans and by creating a reference coordinate system, movements of the infra-orbital rim and globe were assessed. Orbital volume increased significantly, by 27.2% for the left and 28.4% for the right orbit. Significant anterior movements of the left infra-orbital rim of 12.0mm (SD 4.2) and right infra-orbital rim of 12.8mm (SD 4.9) were demonstrated. Significant medial movements of 1.7mm (SD 2.2) of the left globe and 1.5mm (SD 1.9) of the right globe were demonstrated. There was a significant correlation between anterior infra-orbital rim movement and the increase in orbital volume. Significant orbital volume increase has been demonstrated following Le Fort III advancement. The position of the infra-orbital rim was moved forward significantly, whereas the globe position remained relatively unaffected.