Surgical treatment of nasal fractures may benefit from intraoperative 3D imaging.

This retrospective study aimed to assess the effects of the use of intraoperative three-dimensional (3D) imaging on outcomes in surgical treatment of nasal fractures. Furthermore, we investigated whether the use of intraoperative imaging improves outcomes and decreases the frequency of corrective surgeries compared to published literature. This retrospective descriptive study included patients who underwent operative treatment for nasal fractures with the use of intraoperative 3D imaging between January 2015 and January 2020 at a University Hospital. The primary outcome measure was patient satisfaction, which was assessed through patient charts about subjective esthetic problems and nasal obstruction. The secondary outcome measures were the number of intraoperative images and necessity of intra- and postoperative revisions. All the outcomes were evaluated using regression analysis. Of the 172 patients, secondary rhinoplasty and intraoperative revision were performed in 10 (6 %) and 93 (54 %) patients, respectively. Postoperatively, 19 (11 %) and 12 (7 %) patients complained of subjective esthetic problems and nasal obstruction, respectively. The intraoperative revision rate in patients undergoing surgical treatment of nasal fractures with intraoperative 3D imaging was >50 %. However, the incidence of postoperative secondary revision, nasal obstruction, and subjective esthetic problems was lower than that reported in the literature not having an intraoperative imaging. Our findings suggest that prompt quality control of the operative result enables immediate correction and prevents postoperative revision.

Two-screw osteosynthesis of the mandibular condylar head with different screw materials: a finite element analysis.

This study compared the biomechanical behavior of titanium, magnesium, and polylactic acid screws for two-screw osteosynthesis of mandibular condylar head fractures using finite element analysis. Von Mises stress distribution, fracture displacement, and fragment deformation were evaluated. Titanium screws performed the best in terms of carrying the highest load, resulting in the least fracture displacement and fragment deformation. Magnesium screws showed intermediate results, while PLA screws were found to be unsuitable with stress values exceeding their tensile strength. These findings suggest that magnesium alloys could be considered a suitable alternative to titanium screws in mandibular condylar head osteosynthesis.

Toll-Like Receptor 3 Mediates Aortic Stenosis Through a Conserved Mechanism of Calcification.

BACKGROUND: Calcific aortic valve disease (CAVD) is characterized by a phenotypic switch of valvular interstitial cells to bone-forming cells. Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors at the interface between innate immunity and tissue repair. Type I interferons (IFNs) are not only crucial for an adequate antiviral response but also implicated in bone formation. We hypothesized that the accumulation of endogenous TLR3 ligands in the valvular leaflets may promote the generation of osteoblast-like cells through enhanced type I IFN signaling. METHODS: Human valvular interstitial cells isolated from aortic valves were challenged with mechanical strain or synthetic TLR3 agonists and analyzed for bone formation, gene expression profiles, and IFN signaling pathways. Different inhibitors were used to delineate the engaged signaling pathways. Moreover, we screened a variety of potential lipids and proteoglycans known to accumulate in CAVD lesions as potential TLR3 ligands. Ligand-receptor interactions were characterized by in silico modeling and verified through immunoprecipitation experiments. Biglycan (Bgn), Tlr3, and IFN-α/ß receptor alpha chain (Ifnar1)-deficient mice and a specific zebrafish model were used to study the implication of the biglycan (BGN)-TLR3-IFN axis in both CAVD and bone formation in vivo. Two large-scale cohorts (GERA [Genetic Epidemiology Research on Adult Health and Aging], n=55 192 with 3469 aortic stenosis cases; UK Biobank, n=257 231 with 2213 aortic stenosis cases) were examined for genetic variation at genes implicated in BGN-TLR3-IFN signaling associating with CAVD in humans. RESULTS: Here, we identify TLR3 as a central molecular regulator of calcification in valvular interstitial cells and unravel BGN as a new endogenous agonist of TLR3. Posttranslational BGN maturation by xylosyltransferase 1 (XYLT1) is required for TLR3 activation. Moreover, BGN induces the transdifferentiation of valvular interstitial cells into bone-forming osteoblasts through the TLR3-dependent induction of type I IFNs. It is intriguing that Bgn-/-, Tlr3-/-, and Ifnar1-/- mice are protected against CAVD and display impaired bone formation. Meta-analysis of 2 large-scale cohorts with >300 000 individuals reveals that genetic variation at loci relevant to the XYLT1-BGN-TLR3-interferon-α/ß receptor alpha chain (IFNAR) 1 pathway is associated with CAVD in humans. CONCLUSIONS: This study identifies the BGN-TLR3-IFNAR1 axis as an evolutionarily conserved pathway governing calcification of the aortic valve and reveals a potential therapeutic target to prevent CAVD.

Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcome.

BACKGROUND: Reliable biomarkers for organ quality assessment during normothermic machine perfusion (NMP) are desired. ATP (adenosine triphosphate) production by oxidative phosphorylation plays a crucial role in the bioenergetic homeostasis of the liver. Thus, detailed analysis of the aerobic mitochondrial performance may serve as predictive tool towards the outcome after liver transplantation. METHODS: In a prospective clinical trial, 50 livers were subjected to NMP (OrganOx Metra) for up to 24.ßh. Biopsy and perfusate samples were collected at the end of cold storage, at 1.ßh, 6.ßh, end of NMP, and 1.ßh after reperfusion. Mitochondrial function and integrity were characterized by high-resolution respirometry (HRR), AMP, ADP, ATP and glutamate dehydrogenase analysis and correlated with the clinical outcome (L-GrAFT score). Real-time confocal microscopy was performed to assess tissue viability. Structural damage was investigated by histology, immunohistochemistry and transmission electron microscopy. FINDINGS: A considerable variability in tissue viability and mitochondrial respiration between individual livers at the end of cold storage was observed. During NMP, mitochondrial respiration with succinate and tissue viability remained stable. In the multivariate analysis of the 35 transplanted livers (15 were discarded), area under the curve (AUC) of LEAK respiration, cytochrome c control efficiency (mitochondrial outer membrane damage), and efficacy of the mitochondrial ATP production during the first 6.ßh of NMP correlated with L-GrAFT. INTERPRETATIONS: Bioenergetic competence during NMP plays a pivotal role in addition to tissue injury markers. The AUC for markers of outer mitochondrial membrane damage, ATP synthesis efficiency and dissipative respiration (LEAK) predict the clinical outcome upon liver transplantation. FUNDING: This study was funded by a Grant from the In Memoriam Dr. Gabriel Salzner Stiftung awarded to SS and the Tiroler Wissenschaftsfond granted to TH.

Embryology of the Abdominal Wall and Associated Malformations-A Review.

In humans, the incidence of congenital defects of the intraembryonic celom and its associated structures has increased over recent decades. Surgical treatment of abdominal and diaphragmatic malformations resulting in congenital hernia requires deep knowledge of ventral body closure and the separation of the primary body cavities during embryogenesis. The correct development of both structures requires the coordinated and fine-tuned synergy of different anlagen, including a set of molecules governing those processes. They have mainly been investigated in a range of vertebrate species (e.g., mouse, birds, and fish), but studies of embryogenesis in humans are rather rare because samples are seldom available. Therefore, we have to deal with a large body of conflicting data concerning the formation of the abdominal wall and the etiology of diaphragmatic defects. This review summarizes the current state of knowledge and focuses on the histological and molecular events leading to the establishment of the abdominal and thoracic cavities in several vertebrate species. In chronological order, we start with the onset of gastrulation, continue with the establishment of the three-dimensional body shape, and end with the partition of body cavities. We also discuss well-known human etiologies.

GCN5 contributes to intracellular lipid accumulation in human primary cardiac stromal cells from patients affected by Arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a genetic disease associated with sudden cardiac death and cardiac fibro-fatty replacement. Over the last years, several works have demonstrated that different epigenetic enzymes can affect not only gene expression changes in cardiac diseases but also cellular metabolism. Specifically, the histone acetyltransferase GCN5 is known to facilitate adipogenesis and modulate cardiac metabolism in heart failure. Our group previously demonstrated that human primary cardiac stromal cells (CStCs) contribute to adipogenesis in the ACM pathology. Thus, this study aims to evaluate the role of GCN5 in ACM intracellular lipid accumulation. To do so, CStCs were obtained from right ventricle biopsies of ACM patients and from samples of healthy cadaveric donors (CTR). GCN5 expression was increased both in ex vivo and in vitro ACM samples compared to CTR. When GCN5 expression was silenced or pharmacologically inhibited by the administration of MB-3, we observed a reduction in lipid accumulation and a mitigation of reactive oxygen species (ROS) production in ACM CStCs. In agreement, transcriptome analysis revealed that the presence of MB-3 modified the expression of pathways related to cellular redox balance. Altogether, our findings suggest that GCN5 inhibition reduces fat accumulation in ACM CStCs, partially by modulating intracellular redox balance pathways.

Two-versus three-screw osteosynthesis of the mandibular condylar head: A finite element analysis.

Titanium screws are commonly used for osteosynthesis of mandibular condylar head fractures. Evidence suggests that the insertion of three screws may result in better fracture stability. Two screws only, on the other hand, could reduce adverse effects, mainly bone resorption. This study aimed to investigate the biomechanical differences in mandibular condylar head osteosynthesis with two versus three titanium screws using finite element analysis. A finite element model of the mandible with a right type P condylar head fracture fixed with two or three titanium screws was analyzed in ANSYS Mechanical. The geometry of the model assembly was constructed in ANSYS Spaceclaim. Biomechanical load boundary conditions were obtained from a validated musculoskeletal model in AnyBody Modeling System™. The preprocessing of the finite element model and mapping of the obtained boundary conditions was done in docq VIT. Fracture displacement, fragment deformation, von Mises stress distribution, and reaction forces within the screws were evaluated in ANSYS for three different loading scenarios. Finite element analysis showed similar results when comparing osteosynthesis with two versus three titanium screws for all three loading scenarios. Contralateral molar loading resulted in the highest stress on both the fracture and the screws with the maximum von Mises stress being found at the condylar neck. Stress concentration within the screws was found in the fracture gap and was higher in the lateral fragment. In all scenarios, maximum von Mises stress values were smaller when forces were distributed among three screws. However, stability was also adequate when two screws were used. Mandibular condylar head osteosynthesis with two titanium screws appears to provide sufficient fracture stability. Further clinical studies are needed to clarify the implications of these results.

Proximity of the middle meningeal artery and maxillary artery to the mandibular head and mandibular neck as revealed by three-dimensional time-of-flight magnetic resonance angiography.

PURPOSE: The close topographic relationship between vascular and osseous structures in the condylar and subcondylar region and marked variability in the arterial course has been revealed by both imaging and cadaveric studies. This study aimed to verify the previously published information in a large sample and to determine a safe surgical region. METHODS: We analyzed the three-dimensional time-of-flight magnetic resonance angiography images of 300 individuals. RESULTS: The mean distance between the middle meningeal artery and the apex of the condyle or the most medial point of the condyle was 18.8 mm (range: 11.2-25.9 mm) or 14.5 mm (range: 8.8-22.9 mm) respectively. The course of the maxillary artery relative to the lateral pterygoid muscle was medial in 45.7% of cases and lateral in 54.3%. An asymmetric course was evident in 66 patients (22%). The mean distance between the maxillary artery and condylar process at the deepest point of the mandibular notch was 6.2 mm in sides exhibiting a medial course (range: 3.7-9.8 mm) and 6.6 mm in sides exhibiting a lateral course (range: 3.9-10.4 mm). The distances were significantly influenced by age, gender, and the course of the maxillary artery. CONCLUSION: Our study emphasizes the marked inter- and intra-individual variability of the maxillary and middle meningeal arterial courses. We confirmed the proximity of the arteries to the condylar process. Extensive surgical experience and thorough preparation for each individual case are essential to prevent iatrogenic vascular injury.

Volumetric Evaluated Bone Resorption After Open Reduction and Internal Fixation of Condylar Head Fractures of the Mandible.

PURPOSE: Decision making in the management of condylar head fractures remains difficult due to its dependency on multiple factors like fracture type, degree of dislocation, patient`s age and dental condition. As open reduction and internal fixation (ORIF) of condylar head fractures (CHFs) becomes more popular, the question of osteosynthesis removal is controversial. So far, information on volumetric changes after ORIF are available for a short-term period (<6 months) only. This study, therefore, was performed to assess bone resorption after condylar head fractures and to follow-up intermediate-term (>1 year) remodelling after removal of metallic osteosynthesis material. Furthermore clinical outcome was measured using Helkimo Index and put in relation with bone resorption. MATERIALS AND METHODS: A retrospective analysis of 19 patients who underwent open reduction and internal fixation of condylar head fractures at the University Hospital of Zürich between January 2016 and April 2018 using intraoperative cone-beam computed tomography repositioning control was conducted. The bone resorption on the condylar head was measured in the course after removal of osteosynthesis material by segmenting and superimposing of the postoperative 3D radiologic follow-up exam (T2) over the initial intraoperative cone-beam computed tomography (T1) using iPlan-CMF software. Complementary Helkimo index was assessed to put resorption rate in relation to clinical outcome. RESULTS: A total of 19 patients fulfilled the inclusion criteria. The mean follow-up time was 15.6 months and the mean bone resorption on the condylar head was -0.348cm3 or -15.29% of segmented condylar head. There was no correlation of clinical outcome and bone resorption. CONCLUSIONS: Helkimo index showed satisfying results; therefore, ORIF of condylar head fracture proves as a feasible treatment option. The mean bone resorption rate of -15.29% in the intermediate-term follow-up time (mean 15.6 months) is comparable to findings of other studies with short-term follow-up time (< 6 months). Thus, postinterventional remodeling activity and resorption seems highest in the first 4 to 6 postoperative months with little further resorption. In prevention of negative sequelae of protruding implants, timing of osteosynthesis material removal after this period of high bone remodeling activity is recommended. The resorption rate showed no correlation to clinical outcome.

Myogenic progenitor cell transplantation for muscle regeneration following hindlimb ischemia and reperfusion.

BACKGROUND: Muscle is severely affected by ischemia/reperfusion injury (IRI). Quiescent satellite cells differentiating into myogenic progenitor cells (MPC) possess a remarkable regenerative potential. We herein established a model of local application of MPC in murine hindlimb ischemia/reperfusion to study cell engraftment and differentiation required for muscle regeneration. METHODS: A clamping model of murine (C57b/6 J) hindlimb ischemia was established to induce IRI in skeletal muscle. After 2 h (h) warm ischemic time (WIT) and reperfusion, reporter protein expressing MPC (TdTomato or Luci-GFP, 1 × 106 cells) obtained from isolated satellite cells were injected intramuscularly. Surface marker expression and differentiation potential of MPC were analyzed in vitro by flow cytometry and differentiation assay. In vivo bioluminescence imaging and histopathologic evaluation of biopsies were performed to quantify cell fate, engraftment and regeneration. RESULTS: 2h WIT induced severe IRI on muscle, and muscle fiber regeneration as per histopathology within 14 days after injury. Bioluminescence in vivo imaging demonstrated reporter protein signals of MPC in 2h WIT animals and controls over the study period (75 days). Bioluminescence signals were detected at the injection site and increased over time. TdTomato expressing MPC and myofibers were visible in host tissue on postoperative days 2 and 14, respectively, suggesting that injected MPC differentiated into muscle fibers. Higher reporter protein signals were found after 2h WIT compared to controls without ischemia, indicative for enhanced growth and/or engraftment of MPC injected into IRI-affected muscle antagonizing muscle damage caused by IRI. CONCLUSION: WIT-induced IRI in muscle requests increased numbers of injected MPC to engraft and persist, suggesting a possible rational for cell therapy to antagonize IRI. Further investigations are needed to evaluate the regenerative capacity and therapeutic advantage of MPC in the setting of ischemic limb injury.

Bone tissue and histological and molecular events during development of the long bones.

The bones are of mesenchymal or ectomesenchymal origin, form the skeleton of most vertebrates, and are essential for locomotion and organ protection. As a living tissue they are highly vascularized and remodelled throughout life to maintain intact. Bones consist of osteocytes entrapped in a mineralized extracellular matrix, and via their elaborated network of cytoplasmic processes they do not only communicate with each other but also with the cells on the bone surface (bone lining cells). Bone tissue develops through a series of fine-tuned processes, and there are two modes of bone formation, referred to either as intramembranous or endochondral ossification. In intramembranous ossification, bones develop directly from condensations of mesenchymal cells, and the flat bones of the skull, the clavicles and the perichondral bone cuff develop via this process. The bones of the axial (ribs and vertebrae) and the appendicular skeleton (e.g. upper and lower limbs) form through endochondral ossification where mesenchyme turns into a cartilaginous intermediate with the shape of the future skeletal element that is gradually replaced by bone. Endochondral ossification occurs in all vertebrate taxa and its onset involves differentiation of the chondrocytes, mineralization of the extracellular cartilage matrix and vascularization of the intermediate, followed by disintegration and resorption of the cartilage, bone formation, and finally - after complete ossification of the cartilage model - the establishment of an avascular articular cartilage. The epiphyseal growth plate regulates the longitudinal growth of the bones, achieved by a balanced proliferation and elimination of chondrocytes, and the question whether the late hypertrophic chondrocytes die or transform into osteogenic cells is still being hotly debated. The complex processes leading to endochondral ossification have been studied for over a century, and this review aims to give an overview of the histological and molecular events, arising from the long bones' (e.g. femur, tibia) development. The fate of the hypertrophic chondrocytes will be discussed in the light of new findings obtained from cell tracking studies.

Surgical Outcomes of Orbital Fracture Reconstruction Using Patient-Specific Implants.

PURPOSE: Patient-specific implants (PSIs) are known to yield reliable outcomes in orbital wall fracture reconstruction (high precision, smoother operating techniques, and shorter surgical duration). This study analyzed the surgical error and clinical and esthetic outcomes of orbital reconstructions with PSIs. METHODS: This ambispective cohort study enrolled patients who underwent orbital reconstruction using PSIs between October 2016 and January 2018. The study end points were surgical error, indication and duration of surgery, long-term sequelae, revision surgeries, and surgical complications. Surgical error was analyzed by superimposing the postoperative implant position onto the preoperative virtual plan. Both qualitative (heat map) and quantitative (distance) measurements were obtained. RESULTS: Three patients were enrolled prospectively, and 23 were enrolled retrospectively. Indications for surgery were defect size (25 patients), diplopia (10 patients), impaired eye motility (4 patients), and significant enophthalmos (6 patients). At the last patient visit, there were 5 cases of diplopia, 1 case of exophthalmos, and 6 cases of slight enophthalmos of incremental degree. In terms of surgical error, a mean distance of 0.6 mm (95% confidence interval, 0.49 to 0.76), with a mean maximal distance of 3.4 mm (95% confidence interval, 2.79 to 4.02), was noted. No revision surgery was necessary. Lid malposition complications were not observed. However, 1 case each of symblepharon and scleral show were observed. No time-saving component was observed. CONCLUSIONS: PSI use in orbital reconstruction guarantees a preplanned 3-dimensional anatomical shape with a mean surgical error of just 0.6 mm. Our clinical results were similar to those of other protocols; however, warranting a complex 3-dimensional anatomical shape also in large orbital fractures with a low mean surgical error is feasible by using PSIs.

Customized Titanium Reconstruction of Orbital Fractures Using a Mirroring Technique for Virtual Reconstruction and 3D Model Printing.

PURPOSE: Early operative reconstruction using titanium mesh is a technique often used for preventing sequelae after an orbital fracture. We sought to examine the utility of patient-specific molding of the mesh with a biomodel via virtual mirroring of the nonaffected side. METHODS: We retrospectively assessed the clinical and radiological outcomes of orbital fracture reconstruction using a customized titanium mesh shaped on 3D-printed biomodels in 34 unilateral orbital fracture cases. Preoperative virtual orbital reconstruction images, using the mirroring technique, were superimposed on postoperative 3D images, and clinical data from patient charts were analyzed. Orbital reconstructions were rated, and the intention to revise results intraoperatively, or during inpatient or outpatient phases, was assessed by 2 consultants and 2 residents. RESULTS: We found that most fractures arose from falls of <3 meters or from interpersonal violence. Ophthalmic injuries included subconjunctival bleeding, ocular contusion, enophthalmos, and diplopia. Long-term sequelae at last followup were diplopia (8.8%) and mild enophthalmos (11.8%). CONCLUSION: Interrater reliabilities regarding consultants' intention to revise results were substantial to almost perfect at any time point. Therefore, using the mirroring technique for the virtual reconstruction of a fractured orbit and a 3D-printed biomodel to customize commercial titanium implants yields good and reliable results, enhances surgical precision, and decreases the need for intraoperative revision, as well as long-term sequelae of orbital fractures.

Endoskeletal mineralization in chimaera and a comparative guide to tessellated cartilage in chondrichthyan fishes (sharks, rays and chimaera).

An accepted uniting character of modern cartilaginous fishes (sharks, rays, chimaera) is the presence of a mineralized, skeletal crust, tiled by numerous minute plates called tesserae. Tesserae have, however, never been demonstrated in modern chimaera and it is debated whether the skeleton mineralizes at all. We show for the first time that tessellated cartilage was not lost in chimaera, as has been previously postulated, and is in many ways similar to that of sharks and rays. Tesserae in Chimaera monstrosa are less regular in shape and size in comparison to the general scheme of polygonal tesserae in sharks and rays, yet share several features with them. For example, Chimaera tesserae, like those of elasmobranchs, possess both intertesseral joints (unmineralized regions, where fibrous tissue links adjacent tesserae) and recurring patterns of local mineral density variation (e.g. Liesegang lines, hypermineralized 'spokes'), reflecting periodic accretion of mineral at tesseral edges as tesserae grow. Chimaera monstrosa's tesserae, however, appear to lack the internal cell networks that characterize tesserae in elasmobranchs, indicating fundamental differences among chondrichthyan groups in how calcification is controlled. By compiling and comparing recent ultrastructure data on tesserae, we also provide a synthesized, up-to-date and comparative glossary on tessellated cartilage, as well as a perspective on the current state of research into the topic, offering benchmark context for future research into modern and extinct vertebrate skeletal tissues.

Radiologic Analysis of Surgically Treated Fractures of the Condylar Process by an Endoscopic-Assisted Transoral Approach.

PURPOSE: This study analyzed the radiologic outcomes of patients with unilateral mandibular condylar fractures treated with open reduction-internal fixation (ORIF) through a transoral approach. PATIENTS AND METHODS: In this retrospective study, the radiologic images of 40 patients who underwent open reduction-internal fixation through a transoral approach were presented to 2 independent examiners. All patients underwent the surgical procedure between January 2015 and December 2016 at the Department of Cranio-Maxillofacial Surgery at UniversitätsSpital Zürich and were included in a previous functional outcome study. The surgical results were analyzed and graded as poor, acceptable, or good. The examiners declared whether they would have made any intraoperative revisions if the radiologic information had been available. Finally, the examiners estimated the required duration of elastic intermaxillary fixation (IMF) from the radiologic images, which was compared with the actual duration. RESULTS: Fracture reduction was classified as good in 33 cases (82.5%), acceptable in 5 cases, and poor in 2 cases by one examiner and as good in 32 cases (80%), acceptable in 6 cases, and poor in 2 cases by the other examiner. The inter-rater reliability was determined to be good (Cohen κ = 0.92). Correct osteosynthesis placement was found in 19 cases by one examiner and in 21 cases by the other examiner, with good inter-rater reliability (κ = 0.8). Moderate inter-rater reliability (κ = 0.4) was found for the required duration of elastic IMF. Furthermore, the estimated elastic IMF duration matched the actual duration in fewer than half of the cases. CONCLUSIONS: It is feasible to achieve reliably good radiologic results when operating on condylar process fractures by a transoral approach with endoscopic assistance and angled instruments. Intraoperative 3-dimensional imaging enables instant quality control and prompts surgical revision if needed.

Associated Ophthalmic Injuries in Patients With Fractures of the Midface.

PURPOSE: Concomitant ophthalmic injuries are common in patients with facial fractures, though frequency varies widely in the literature. Major ophthalmic injuries can have drastic consequences for patients, and permanent visual impairment cannot be prevented in all cases. This study analyzed the frequency and distribution pattern of associated ophthalmic injuries in patients who received operative treatment for fractures of the midface. MATERIAL AND METHODS: The clinical information system was searched for patients with midface fractures that were treated operatively between December 2014 and November 2017. Demographic, fracture-related, and ophthalmic data were assessed and statistically analyzed. RESULTS: This study included 282 patients. The most common fracture types were zygomaticomaxillary complex fractures and orbital floor fractures. Falls and violence were the most common causes of fractures (43.3% and 24.5%, respectively). Chemosis and subconjunctival bleeding were the most common associated eye injuries. The most prevalent long-term eye injury was diplopia, which was identified in 18.4% of cases preoperatively. Postoperative diplopia persisted in 36 cases (12.8%) at 3-month follow-up. Optic neuropathy, enophthalmos, exophthalmos, and retrobulbar hematomas were identified infrequently. CONCLUSION: Minor ophthalmic injuries, including chemosis and subconjunctival bleeding, are more frequently associated with midface trauma. These minor injuries tend to heal quickly and without sequela. Major ophthalmic injuries, including retinal detachment, optic neuropathy, and retrobulbar hematomas, are identified less frequently. Special attention should be paid to patients with diplopia, as this condition may persist and have long-term occupational consequences. Therefore, close interdisciplinary collaboration is essential when treating patients with fractures of the midface to prevent permanent visual impairment.

Does Zygomatic Complex Symmetry Differ Between Healthy Individuals and Surgically Treated Patients Using Intraoperative 3-Dimensional Cone Beam Computed Tomographic Imaging?

PURPOSE: Reconstruction of symmetry after zygomaticomaxillary complex (ZMC) fractures is essential for esthetic appearance as well as function. Therefore, this study aimed to analyze whether bony facial symmetry in patients surgically treated for unilateral ZMC fractures via intraoperative imaging differs from that of healthy individuals. PATIENTS AND METHODS: Retrospective and cross-sectional radiographic measurements of patients treated for unilateral ZMC fractures via intraoperative cone beam computed tomography (CBCT) were performed to evaluate the postoperative ZMC symmetry. The same number of healthy individuals without any history of midfacial trauma matched for age and gender served as the control group. Asymmetry of the ZMC was determined by measuring bilateral differences in the malar eminence position on CBCT. In addition, demographic statistics, etiology, and fracture type were analyzed. RESULTS: Analysis of 57 surgically treated patients and 57 healthy individuals with a mean age of 29 years was performed. No significant difference in the symmetry of the malar eminence position was observed between healthy individuals and patients treated for a unilateral ZMC fracture (P = .890). In one third of patients, corrections were needed after intraoperative CBCT control. CONCLUSIONS: The results of this study indicate that, on average, a ZMC asymmetry of 1.6 mm is observed in healthy individuals. Furthermore, the use of intraoperative CBCT for the treatment of dislocated ZMC fractures helps to achieve precise anatomic, symmetrical repositioning and is suggested to improve the quality of care.

miR-19a-3p containing exosomes improve function of ischaemic myocardium upon shock wave therapy.

AIMS: As many current approaches for heart regeneration exert unfavourable side effects, the induction of endogenous repair mechanisms in ischaemic heart disease is of particular interest. Recently, exosomes carrying angiogenic miRNAs have been described to improve heart function. However, it remains challenging to stimulate specific release of reparative exosomes in ischaemic myocardium. In the present study, we sought to test the hypothesis that the physical stimulus of shock wave therapy (SWT) causes the release of exosomes. We aimed to substantiate the pro-angiogenic impact of the released factors, to identify the nature of their cargo, and to test their efficacy in vivo supporting regeneration and recovery after myocardial ischaemia. METHODS AND RESULTS: Mechanical stimulation of ischaemic muscle via SWT caused extracellular vesicle (EV) release from endothelial cells both in vitro and in vivo. Characterization of EVs via electron microscopy, nanoparticle tracking analysis and flow cytometry revealed specific exosome morphology and size with the presence of exosome markers CD9, CD81, and CD63. Exosomes exhibited angiogenic properties activating protein kinase b (Akt) and extracellular-signal regulated kinase (ERK) resulting in enhanced endothelial tube formation and proliferation. A miRNA array and transcriptome analysis via next-generation sequencing were performed to specify exosome content. miR-19a-3p was identified as responsible cargo, antimir-19a-3p antagonized angiogenic exosome effects. Exosomes and target miRNA were injected intramyocardially in mice after left anterior descending artery ligation. Exosomes resulted in improved vascularization, decreased myocardial fibrosis, and increased left ventricular ejection fraction as shown by transthoracic echocardiography. CONCLUSION: The mechanical stimulus of SWT causes release of angiogenic exosomes. miR-19a-3p is the vesicular cargo responsible for the observed effects. Released exosomes induce angiogenesis, decrease myocardial fibrosis, and improve left ventricular function after myocardial ischaemia. Exosome release via SWT could develop an innovative approach for the regeneration of ischaemic myocardium.