Critical appraisal of patient-specific implants for secondary post-traumatic orbital reconstruction.

In orbital reconstruction, a patient-specific implant (PSI) may provide accurate reconstruction in complex cases, since the design can be tailored to the anatomy. Several design options may be embedded, for ease of positioning and precision of reconstruction. This study describes a cohort of 22 patients treated for secondary orbital reconstruction with a PSI; one patient received two PSI. The preoperative clinical characteristics and implant design options used are presented. When compared to preoperative characteristics, the postoperative clinical outcomes showed significant improvements in terms of enophthalmos (P < 0.001), diplopia (P < 0.001), and hypoglobus (P = 0.002). The implant position in all previous reconstructions was considered inadequate. Quantitative analysis after PSI reconstruction showed accurate positioning of the implant, with small median and 90th percentile deviations (roll: median 1.3°, 90th percentile 4.6°; pitch: median 1.4°, 90th percentile 3.9°; yaw: median 1.0°, 90th percentile 4.4°; translation: median 1.4 mm, 90th percentile 2.7 mm). Rim support proved to be a significant predictor of roll and rim extension for yaw. No significant relationship between design options or PSI position and clinical outcomes could be established. The results of this study show the benefits of PSI for the clinical outcomes in a large cohort of secondary post-traumatic orbital reconstructions.

Registration-free workflow for electromagnetic and optical navigation in orbital and craniofacial surgery.

The accuracy of intra-operative navigation is largely dependent on the intra-operative registration procedure. Next to accuracy, important factors to consider for the registration procedure are invasiveness, time consumption, logistical demands, user-dependency, compatibility and radiation exposure. In this study, a workflow is presented that eliminates the need for a registration procedure altogether: registration-free navigation. In the workflow, the maxillary dental model is fused to the pre-operative imaging data using commercially available virtual planning software. A virtual Dynamic Reference Frame on a splint is designed on the patient's fused maxillary dentition: during surgery, the splint containing the reference frame is positioned on the patient's dentition. This alleviates the need for any registration procedure, since the position of the reference frame is known from the design. The accuracy of the workflow was evaluated in a cadaver set-up, and compared to bone-anchored fiducial, virtual splint and surface-based registration. The results showed that accuracy of the workflow was greatly dependent on tracking technique used: the workflow was the most accurate with electromagnetic tracking, but the least accurate with optical tracking. Although this method offers a time-efficient, non-invasive, radiation-free automatic alternative for registration, clinical implementation is hampered by the unexplained differences in accuracy between tracking techniques.

Surgical instrument to improve implant positioning in orbital reconstruction: a feasibility study.

Adequate positioning of an orbital implant during orbital reconstruction surgery is essential for restoration of the pre-traumatised anatomy, but visual appraisal of its position is limited by the keyhole access and protruding soft tissues. A positioning instrument that attaches to the implant was designed to provide feedback outside the orbit. The goal of this study was to evaluate the accuracy of placement with the instrument and compare it with the accuracy of placement by visual appraisal. Ten orbits in five human cadaver heads were reconstructed twice: once using visual appraisal and once using the instrument workflow. No significant improvement was found for the roll (5.8° vs 3.4°, respectively, p=0.16), pitch (2.1° vs 1.5°, p=0.56), or translation (2.9 mm vs 3.3 mm, p=0.77), but the yaw was significantly reduced if the instrument workflow was used (15.3° vs 2.9°, p=0.02). The workflow is associated with low costs and low logistical demands, and may prevent outliers in implant positioning in a clinical setting when intraoperative navigation or patient-specific implants are not available.

Intestinal CD8+ T cell responses are abundantly induced early in human development but show impaired cytotoxic effector capacities.

Gastrointestinal viral infections are a major global cause of disease and mortality in infants. Cytotoxic CD8+ T cells are critical to achieve viral control. However, studies investigating the development of CD8+ T cell immunity in human tissues early in life are lacking. Here, we investigated the maturation of the CD8+ T cell compartment in human fetal, infant and adult intestinal tissues. CD8+ T cells exhibiting a memory phenotype were already detected in fetal intestines and increased after birth. Infant intestines preferentially harbored effector CCR7-CD45RA-CD127-KLRG1+/- CD8+ T cells compared to tissue-resident memory CD69+CD103+CD8+ T cells detected in adults. Functional cytotoxic capacity, including cytokine and granzyme B production of infant intestinal effector CD8+ T cells was, however, markedly reduced compared to adult intestinal CD8+ T cells. This was in line with the high expression of the inhibitory molecule PD-1 by infant intestinal effector CD8+ T cells. Taken together, we demonstrate that intestinal CD8+ T cell responses are induced early in human development, however exhibit a reduced functionality. The impaired CD8+ T cell functionality early in life contributes to tolerance during foreign antigen exposure after birth, however functions as an immune correlate for the increased susceptibility to gastrointestinal viral infections in infancy.

Digital surface scanning in flap perfusion.

Monitoring vascular perfusion of transferred tissue is essential in reconstructive surgery to recognize early flap failure. The aim of this study was to evaluate the ability of a digital surface scanner to detect vascular perfusion disorders through the monitoring of skin colour changes. A total of 160 surface scans of the forearm skin were performed with a TRIOS 3D scanner. Vascular compromise was simulated at different time-points by intermittent occlusion of the blood supply to the forearm skin (first the arterial blood supply and then the venous blood supply). Skin colour changes were examined according to the hue, saturation, and value colour scale. Colour differences were analysed with a paired t-test. Significant differences were observed between the colour of the normal skin and that of the vascular compromised skin (P<0.01). The surface scanner could distinguish between arterial occlusion and venous congestion (P<0.01). A digital surface scan is an objective, non-invasive tool to detect early vascular perfusion disorders of the skin.

Intraoperative imaging in orbital reconstruction: how does it affect the position of the implant?

Intraoperative imaging enables the surgeon to control the position of the implant during orbital reconstruction. Although it might improve surgical outcome and avoid the need for revision surgery, it may also increase the duration of the operation and the exposure to radiation. The goal of this study was to find out whether intraoperative imaging improves the position of the implant in reconstructions of the orbital floor and medial wall. Two surgeons reconstructed complex orbital fractures in 10 cadavers. After the reconstruction a computed tomographic scan was made to confirm the position of the implant and, if required, to make any adjustments. Scans were repeated until the surgeon was satisfied. The ideal position was ascertained by scans that were obtained before and after creation of the fractures. The position of the implant achieved was compared with that of the ideal position of the implant, and improved significantly for yaw (p=0.04) and roll (p=0.03). A mean of 1.6 scans was required for each reconstruction (maximum n=3). The main reason for alteration was the rotation roll. Intraoperative imaging significantly improves the position of the implant in fractures of the orbital floor and medial wall. The surgeon has quality control of its position during the reconstruction to restore the anatomical boundaries.

Splintless orthognathic surgery in edentulous patients-a pilot study.

The aim of this pilot study was to evaluate the accuracy and predictability of a splintless treatment protocol for edentulous patients undergoing orthognathic surgery in four consecutive cases. All operations were virtually planned, followed by computer-aided design of individual osteotomy guides and patient-specific fixation implants, which were three-dimensionally printed in titanium. In order to evaluate the discrepancy between the planned and the achieved postoperative result, the postoperative outcome was compared to the virtual treatment plan. Rotational and translational movement and discrepancies with the planned movements were quantified for the maxilla; the advancement was quantified for the mandible. For the maxilla, there was a mean translation discrepancy of 0.6mm. With regard to rotation, there was a mean discrepancy of 1.9°, 0.1°, and 0.4° for pitch, yaw, and roll, respectively. The mean discrepancy in translation of the mandible was 0.4mm. The results of this pilot study indicate that the splintless treatment protocol for orthognathic surgery in edentulous patients presented here is accurate and predictable.

Implant-oriented navigation in orbital reconstruction part II: preclinical cadaver study.

In orbital reconstruction, the acquired position of an orbital implant can be evaluated with the aid of intraoperative navigation. Feedback of the navigation system is only obtained after positioning of the implant: the implant's position is not tracked in real time during positioning. The surgeon has to interpret the navigation feedback and translate it to desired adjustments of the implant's position. In a previous study, a real-time implant-oriented navigation approach was introduced and the system's accuracy was evaluated. In this study, this real-time navigation approach was compared to a marker-based navigation approach in a preclinical set-up. Ten cadavers (20 orbital defects) were reconstructed twice, by two surgeons (total: 80 reconstructions). Implant positioning was significantly improved in the real-time implant-oriented approach in terms of roll (2.0° vs. 3.2°, P=0.03), yaw (2.2° vs. 3.4°, P=0.01) and translation (1.3mm vs. 1.8mm, P=0.005). Duration of the real-time navigation procedure was reduced (median 4.5 min vs. 7.5 min). Subjective appreciation of the navigation technique was higher for real-time implant-oriented navigation (mean 7.5 vs. 9.0). Real-time implant-oriented navigation feedback provides real-time, intuitive feedback to the surgeon, which leads to improved implant positioning and shortens duration of the navigation procedure.

The use of cranial resection templates with 3D virtual planning and PEEK patient-specific implants: A 3 year follow-up.

PURPOSE: The aim of this study was to evaluate the accuracy of resection templates in cranioplasties in order to facilitate a one-stage resection and cranial reconstruction. PATIENTS AND METHODS: In three cases, cranial resections were combined with direct reconstructions using the principles of computer-aided design, manufacturing, and surgery. The precision of the resection template was evaluated through a distance map, comparing the planned and final result. RESULTS: The mean absolute difference between the planned and actual reconstructed contour was less than 1.0 mm. After 3 years, no clinical signs of infection or rejection of the implants were present. The computed tomography scans showed no irregularities, and the aesthetic results remained satisfactory. CONCLUSION: One-stage resection and cranial reconstruction using a resection template, control template, and a prefabricated patient-specific implant of poly(ether-ether-ketone) (PEEK) proved to be a viable and safe method.

Microstructured beta-tricalcium phosphate for alveolar cleft repair: a two-centre study.

The current standard of care in alveolar cleft repair is timing the procedure in the mixed dentition stage and making use of autologous bone to restore the maxillary defect. Using a synthetic bone substitute bypasses the risk of donor site morbidity and reduces the operation time. In this study, the outcome of alveolar cleft repair using microporous beta-tricalcium phosphate (ß-TCP) was investigated in patients with unilateral cleft lip and palate. Twenty patients were enrolled prospectively in this study, divided between two centres. Continuity of the alveolar process, recurrence of oronasal fistulas, and eruption of teeth into the repaired cleft were evaluated at 1year postoperative. Also, cone beam computed tomography scans were analyzed using a volume-based semi-automatic segmentation protocol. No adverse events were reported. The mean residual bone volume in the repaired cleft at 1year postoperative was 65%. There was no recurrence of oronasal fistula. Furthermore, 90% of the teeth adjacent to the cleft erupted spontaneously and all patients showed a continuous alveolar process. Secondary alveolar grafting using microporous ß-TCP can safely be used in the clinical situation. Residual calcified tissue, canine eruption, and complication rates at the recipient site are comparable to those with autologous grafts.

Cyclists' eye movements and crossing judgments at uncontrolled intersections: An eye-tracking study using animated video clips.

Research indicates that crashes between a cyclist and a car often occur even when the cyclist must have seen the approaching car, suggesting the importance of hazard anticipation skills. This study aimed to analyze cyclists' eye movements and crossing judgments while approaching an intersection at different speeds. Thirty-six participants watched animated video clips with a car approaching an uncontrolled four-way intersection and continuously indicated whether they would cross the intersection first. We varied (1) car approach scenario (passing, colliding, stopping), (2) traffic complexity (one or two approaching cars), and (3) cyclist's approach speed (15, 25, or 35 km/h). Results showed that participants looked at the approaching car when it was relevant to the task of crossing the intersection and posed an imminent hazard, and they directed less attention to the car after it had stopped or passed the intersection. Traffic complexity resulted in divided attention between the two cars, but participants retained most visual attention to the car that came from the right and had right of way. Effects of cycling speed on cyclists' gaze behavior and crossing judgments were small to moderate. In conclusion, cyclists' visual focus and crossing judgments are governed by situational factors (i.e., objects with priority and future collision potential), whereas cycling speed does not have substantial effects on eye movements and crossing judgments.

Demographic features in Unilateral Condylar Hyperplasia: An overview of 309 asymmetric cases and presentation of an algorithm.

PURPOSE: Unilateral Condylar Hyperplasia (UCH) is an acquired deformity of the mandible, which can highly influence the symmetry of the face due to its progressive nature. It is caused by growth resembling pathology in one of the mandibular condyles. Definition as well as classification is subject to discussion. The aim of this study is to evaluate a large cohort of alleged UCH patients, and to describe the clinical characteristics, demographic features, classification and follow up. Secondly an algorithm is presented, in order to achieve uniformity in diagnosis and treatment. PATIENTS AND METHODS: From 1994 to 2014 a database of consecutive patients from 3 maxillofacial departments (Academic Medical Center, Amsterdam; VU Medical Center, Amsterdam and Spaarne Gasthuis, Haarlem) with suspected UCH was set up. Patients were referred by orthodontists, dentists, general practitioners or maxillofacial surgeons. Demographic features, bonescan outcomes, laterality, classification and follow-up were noted. Secondarily, all patients were retrospectively diagnosed by one surgeon (JWN), using available documentation. Missing data and follow-up were additionally retrieved from orthodontic offices. RESULTS: 394 asymmetric patients were evaluated. In 309 (78%) patients, the diagnosis UCH was justified and SPECT data were available. The mean age at presentation was 20.3 years (SD ± 7.7, range 9.0-54.5 years). In 48% of the patients, the bonescan was positive. 80% of these patients received surgical treatment, of which 62% were treated with a condylectomy only, 33% were treated with condylectomy plus additive corrective surgery, and 5% underwent corrective surgery only. Of the patient group without positive bonescan 42% of the patients received surgical treatment: 34% condylectomy only, 15% condylectomy plus additive corrective surgery, and 51% corrective surgery only. In total (N = 309) 96 (31%) patients underwent condylectomy as only surgical treatment and 124 (40%) patients received no surgical treatment at all. Treatment could be finalized with orthodontic treatment without further surgery in 64% and 41% respectively. 96 patients were subject to comparison of the classification as noted by the clinician and the author (JWN). In only 72% of the cases, the secondary screening was in agreement with the initial classification. CONCLUSION: Based on this study not all (active) UCH patients require corrective (orthognathic) surgery. A (transoral) partial condylectomy for active patients is recommended, with a postoperative remodeling period of 6 months with or without orthodontic treatment. Second stage correcting surgery may be necessary upon evaluation, using general orthognathic diagnostic and planning procedures. It appears difficult to classify patients reliably using the available clinical and radiological documentation. Objectivity and quantification in the diagnostic process is necessary: uniformity in documentation and parameters. The attached documentation form and UCH treatment algorithm is recommended.

Implant-oriented navigation in orbital reconstruction. Part 1: technique and accuracy study.

Intraoperative navigation is frequently used to assess the position of the implant in orbital reconstruction. Interpretation of the feedback from the navigation system to a three-dimensional position of the implant needs to be done by the surgeon, and feedback is only gathered after the implant has been positioned. An implant-oriented navigation approach is proposed, with real-time intuitive feedback during insertion. A technical framework was set up for implant-oriented navigation, with requirements for planning, implant tracking, and feedback. A dedicated navigation instrument was designed and a software tool was developed in order to meet the technical requirements. An accuracy study was performed to investigate the accuracy of the method in comparison to the regular navigation pointer. A proof of concept was provided. The results showed a translation error of 1.12-1.15mm for implant-oriented navigation with regular registration (pointer 0.71-0.98mm) and 0.81mm with accurate registration (pointer 0.54mm). Rotational error was found to be small (<3°). Quantitative and intuitive qualitative feedback could be provided to the surgeon in real-time during insertion of an orbital implant. Following this proof of concept and accuracy study, the implications for the clinical workflow should be evaluated. An implant-oriented approach may form the foundation for augmented reality or robotic-aided implant insertion.

[Multidisciplinary approach of facial injuries]. / Multidisciplinaire aanpak bij aangezichtsletsel.

BACKGROUND: Approximately one quarter of polytrauma patients has facial injuries, which usually lead to loss of form and function. Several specialties are involved in the acute and reconstructive phases of facial injuries, such as oral and maxillofacial surgery, otorhinolaryngology, plastic surgery, ophthalmology and dentistry. CASE DESCRIPTION: A 25-year-old man with severe facial injuries was brought to the shock room after sustaining high-energy trauma. He had a panfacial fracture that required reconstruction. This was done with two surgeries, with an interval of 4 days. The patient recovered successfully after this. CONCLUSION: Because of the complexity of facial trauma, many factors are involved in acute care and treatment. It is therefore important to designate one coordinating specialty to guide this process. The oral and maxillofacial surgeon plays a vital role in this.

Quantitative comparison of human intestinal mononuclear leukocyte isolation techniques for flow cytometric analyses.

Studies on immune cells derived from the human intestine are needed to understand the pathogenesis of gastrointestinal diseases and to develop novel treatment strategies. Isolation techniques to extract these immune cells from intestinal tissue are largely based on murine studies and comparative data on isolation from human intestine is scarce. In this study we evaluated cell yield, viability, and surface-molecule expression on mononuclear leukocytes, comparing three techniques to obtain a single immune cell suspension from human intestine; low concentrations of either the enzymes Collagenase D or Liberase TL, and enzyme-free mechanical dissociation with the Medimachine. Both enzymatic isolation techniques provided a higher cell yield than mechanical dissociation. Expression of surface molecules remained intact after Collagenase D treatment, while Liberase TL digestion resulted in a strong decrease in the expression of the CD4 receptor. Taken together, Collagenase D digestion provides the highest yield of mononuclear cells while keeping surface molecule expression intact.

Three-dimensional virtual simulation of alar width changes following bimaxillary osteotomies.

The aim of this study was to evaluate the accuracy of three-dimensional (3D) soft tissue simulation of nose width changes following bimaxillary osteotomies and to identify patient- and surgery-related factors that may affect the accuracy of simulation. Sixty patients (mean age 26 years) who underwent bimaxillary osteotomies participated in this study. Cone beam computed tomography scans were acquired preoperatively and at 1-year postoperative. The 3D hard and soft tissue rendered preoperative and postoperative virtual head models were superimposed, after which the maxilla and mandible were segmented and aligned to the postoperative position. The postoperative changes in alar width were simulated using a mass tensor model (MTM)-based algorithm and compared with the postoperative outcome. 3D cephalometric analyses were used to quantify the simulation error. The postoperative alar width was increased by 1.6±1.1mm and the mean error between the 3D simulation and the actual postoperative alar width was 1.0±0.9mm. The predictability was not correlated to factors such as age, sex, alar cinch suture, VY closure, maxillary advancement, or a history of surgically assisted rapid maxillary expansion. The MTM-based simulation model of postoperative alar width change was found to be reasonably accurate, although there is room for further improvement.

Pathophysiology of dyssynchrony: of squirrels and broken bones.

The genesis of cardiac resynchronisation therapy (CRT) consists of 'bedside' research and 'bench' studies that are performed in series with each other. In this field, the bench studies are crucial for understanding the pathophysiology of dyssynchrony and resynchronisation. In a way, CRT started with the insight that abnormal ventricular conduction, as caused by right ventricular pacing, has adverse effects. Out of this research came the ground-breaking insight that 'simple' disturbances in impulse conduction, which were initially considered innocent, proved to result in a host of molecular and cellular derangements that lead to a vicious circle of remodelling processes that facilitate the development of heart failure. As a consequence, CRT does not only correct conduction abnormalities, but also improves myocardial properties at many levels. Interestingly, corrections by CRT do not exactly reverse the derangements, induced by dyssynchrony, but also activate novel pathways, a property that may open new avenues for the treatment of heart failure.

Evaluation of the anterior mandibular donor site one year after secondary reconstruction of an alveolar cleft: 3-dimensional analysis using cone-beam computed tomography.

The aim of this study was to analyse changes in the volume of the chin after harvest of a bone graft for secondary reconstruction of an alveolar cleft. Cone-beam computed tomographic (CT) scans of 27 patients taken preoperatively, and immediately and one year postoperatively, were analysed, and 3-dimensional hard-tissue reconstructions made. The hard-tissue segmentation of the scan taken one year postoperatively was subtracted from the segmentation of the preoperative scan to calculate the alteration in the volume of bone at the donor site (chin). A centrally-orientated persistent concavity at the buccal side of the chin was found (mean (range) 160 (0-500) mm(3)). At the lingual side of the chin, a central concavity remained (mean (range) volume 20 (0-80) mm(3)). Remarkably, at the periphery of this concavity there was overgrowth of new bone (mean (range) volume 350 (0-1600) mm(3)). Re-attachment of the muscles of the tongue resulted in a significantly larger central lingual defect one year postoperatively (p=0.01). We also measured minor alterations in volume of the chin at one year. Whether these alterations influence facial appearance and long term bony quality is to be the subject of further research.

4-hydroxytamoxifen trans-represses nuclear factor-kappa B activity in human osteoblastic U2-OS cells through estrogen receptor (ER)alpha, and not through ER beta.

Estrogens are important mediators of bone homeostasis, and postmenopausal estrogen replacement therapy is extensively used to prevent osteoporosis. The biological effects of estrogen are mediated by receptors belonging to the superfamily of steroid/thyroid nuclear receptors, estrogen receptor (ER)alpha and ER beta. ER alpha, not only trans-activates target genes in a hormone-specific fashion, but it can also neutralize other transcriptional activators, such as nuclear factor (NF)-kappa B, causing repression of their target genes. A major mechanism by which estrogens prevent osteoporosis seems to be repression of transcription of NF-kappa B target genes, such as the osteoclast-activating cytokines interleukin-6 and interleukin-1. To study the capacity of both ERs in repression of NF-kappa B signaling in bone cells, we first carried out transient transfections with ER alpha or ER beta of the human osteoblastic U2-OS cell line, in which endogenous NF-kappa B was stimulated by tumor necrosis factor alpha. Repression by ER alpha was already observed without 17 beta-estradiol, whereas addition of the ligand increased repression to 90%. ER beta, however, was able to repress NF-kappa B activity only in the presence of ligand. Because it is known that some antiestrogens can also display tissue-specific agonistic properties, 4-hydroxytamoxifen was tested for its capacity in repressing NF-kappa B activity and was found to be active (albeit less efficient than 17 beta-estradiol) and, interestingly, only with ER alpha. The pure antagonist ICI 164,384 was incapable of repressing through any ER subtypes. Deletion analysis and the use of receptor ER alpha/ER beta-chimeras showed that the A/B domain, containing activation function-1, is essential for this suppressive action. Next, we developed stable transfectants of the human osteoblastic U2-OS cell line containing ER alpha or ER beta in combination with an NF-kappa B luciferase reporter construct. In these cell lines, repression of NF-kappa B activity was only mediated through ER alpha and not through ER beta. These findings offer new insights into the specific role of both ER subtypes in bone homeostasis and could eventually help in developing more specific medical intervention strategies for osteoporosis.

Quantitative determination of sodium-o-[(2,6-dichlorophenyl)-amino]phenylacetate (diclofenac) in human blood plasma or serum.

A rapid method for the estimation of sodium-(o-[(2,6-dichlorophenyl)-amino]-phenyl)-acetate (diclofenac-Na, Voltaren) used in the treatment of rheumatic diseases, in human blood plasma is described. The substance is extracted from acidified plasma with dichloromethane and acetylated after evaporation of the organic solvent, whereupon quantitation is performed by gas-liquid chromatography on a 10% OV-17 column, F.I. detection.