Cortical Line Research Articles

Differences in fixation to young and elderly quadrilateral surfaces with anatomic quadrilateral surface plate (AQSP) based on cortical thickness morphological results

AimsWith relatively thinner cortical thickness, the management of acetabulum osteoporotic fractures in elderly patients is difficult. The aim of the research was to compare and present the morphological characteristics of the quadrilateral plate in young and elderly age groups, such as the area, and position distribution of the thin cortical thickness region, fracture lines maps, and propose a revised design plate for elderly patients based on these anatomic information.MethodsAs a retrospective research, acetabular fracture with one normal hemipelvises, including 110 men and 39 women, were collected to present the morphological characteristics of the quadrilateral region. The subjects were divided into three different age groups: Group I = 18–40 years (31.3 ± 6.6 years), Group II = 41–60 years (49.9 ± 5.3 years), and Group III ≥ 61 years (68.7 ± 6.8 years). The area of the quadrilateral surface, the area and position distribution of the thin cortical thickness region, the ratio and fracture lines maps were calculated and compared with Mimics in different groups.ResultsThe thin cortical thickness/width region area (TCWRA) was significantly increased in Group III compared with Group I and Group II. The ratio of TCWRA accounted for in the quadrilateral region was also significantly increased in Group III (≥ 61 years) compared with Group I (P = 0.01) and Group II (P = 0.011). None of the subjects had a component involving the “A” zone, thirty-three thin cortical thickness regions were located in the “B” zone, and one hundred and sixteen involved both zones of the quadrilateral plate (“A + B” zone). Furthermore, there were a significant differences in the fracture line distributions in three age groups. More fracture lines of elderly patients were located at anterior part (B zone) compared with Group I and Group II.ConclusionsIt was identified the area of thin cortical thickness region increased as age grown, and fracture lines were inclined to be more distributed in “B” zone in elderly patients. To meet the demands of acetabular fixation in different age groups, cortical thickness changes in young and elderly individuals should be given special attention when the quadrilateral surface plate is designed.Level of evidence Level IV, observational study.

Radiographic Landmarks for the Femoral Attachment of the Medial Patellofemoral Complex: A Cadaveric Study

To report the radiographic landmarks for the medial patellofemoral complex (MPFC) footprint on the medial femur and describe the difference between the radiographic positions corresponding to the medial quadriceps tendon femoral ligament (MQTFL) and medial patellofemoral ligament (MPFL) fibers. In 8 unpaired cadaveric knees, the MPFC footprint was exposed on the medial femur, and the proximal and distal boundaries of the footprint were marked. Lateral fluoroscopic images of the knee were obtained and analyzed using Image J. The proximal boundary corresponding to the MQTFL, the MPFC midpoint, and distal boundary corresponding to the MPFL were described radiographically and compared for differences in position. The proximal MQTFL footprint was 0.8 ± 0.6 mm anterior (P= .013) and 5.2 ± 1.8 mm proximal to the MPFC midpoint (P <.001), whereas the distal MPFL footprint was 0.8 ± 0.7 mm posterior (P= .012) and 5.9 ± 1.1 mm distal to the radiographic MPFC midpoint (P <.001). The radiographic point corresponding to the distal MPFL footprint was 0.8 ± 0.9 mm posterior (P= .011) and 11.1 ± 2.3 mm distal to the radiographic point of the proximal MQTFL footprint (P <.001). When using the point of intersection of the posterior cortical line and the proximal posterior condyle as a reference, 91.6% of all points correlating to the MQTFL, MPFC midpoint and MPFL, were within 10 mm in any direction from this radiographic landmark. On fluoroscopic imaging, the proximal MQTFL and distal MPFL fibers had significantly different radiographic positions from the MPFC midpoint on the femur. These findings should be considered when reconstructing specific components of the MPFC. As fluoroscopy is often used intraoperatively to guide graft placement, our findings may serve as a reference when differentiating the locations of the MPFL vs MQTFL on the femur for anatomic reconstruction.

Functionalized Boron Nanoparticles as Potential Promising Antimalarial Agents.

Boron nanoparticles (BNPs), functionalized with hydroxyl groups, were synthesized in situ by a cascade process, followed by bromination and hydrolyzation reactions. These functionalized BNPs, (Bm(OH)n), were characterized using 1H and 11B NMR spectra, Fourier-transform infrared (FT-IR) spectroscopy, inductively coupled plasma-optical emission spectroscopy (ICP-OES), transmission electron microscopy (TEM), dynamic light scattering (DLS), and X-ray photoelectron spectroscopy (XPS) methods. These nanoparticles were also evaluated in vitro for their antimalarial activity against Plasmodium falciparum (3D7 strain) with an IC50 value of 0.0021 μM and showed low toxicity to Uppsala 87 malignant glioma (U87MG) cell lines, malignant melanoma A375 cell lines, KB human oral cancer cell lines, rat cortical neuron cell lines, and rat fibroblast-like synoviocyte (FLS) cell lines.

Development of Lipidoid Nanoparticles for siRNA Delivery to Neural Cells.

Lipidoid nanoparticles (LNPs) are the delivery platform in Onpattro, the first FDA-approved siRNA drug. LNPs are also the carriers in the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines. While these applications have demonstrated that LNPs effectively deliver nucleic acids to hepatic and muscle cells, it is unclear if LNPs could be used for delivery of siRNA to neural cells, which are notoriously challenging delivery targets. Therefore, the purpose of this study was to determine if LNPs could efficiently deliver siRNA to neurons. Because of their potential delivery utility in either applications for the central nervous system and the peripheral nervous system, we used both cortical neurons and sensory neurons. We prepared siRNA-LNPs using C12-200, a benchmark ionizable cationic lipidoid along with helper lipids. We demonstrated using dynamic light scattering that the inclusion of both siRNA and PEG-lipid provided a stabilizing effect to the LNP particle diameters and polydispersity indices by minimizing aggregation. We found that siRNA-LNPs were safely tolerated by primary dorsal root ganglion neurons. Flow cytometry analysis revealed that Cy5 siRNA delivered via LNPs into rat primary cortical neurons showed uptake levels similar to Lipofectamine RNAiMAX—the gold standard commercial transfection agent. However, LNPs demonstrated a superior safety profile, whereas the Lipofectamine-mediated uptake was concomitant with significant toxicity. Fluorescence microscopy demonstrated a time-dependent increase in the uptake of LNP-delivered Cy5 siRNA in a human cortical neuron cell line. Overall, our results suggest that LNPs are a viable platform that can be optimized for delivery of therapeutic siRNAs to neural cells.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1208/s12248-021-00653-2.

MiR-16 exacerbates neuronal cell growth and inhibits cell apoptosis by targeting AKT3 in cerebral ischemia injury

Purpose: To evaluate the role of miR-16 in ischemic neuronal injury.Methods: An oxygen-glucose deprivation (OGD) model of ischemic neuronal injury was established in human brain cortical neuron HCN-2 cell line via hypoxic treatment. The mRNA or protein expressions of miR-16, AKT3, Bax and Bcl-2 were assessed by quantitative real time-polymerase chain reaction (qRTPCR) or western blot assay. Targetscan online software was applied to predict potential targets of miR-16. Cell proliferation was measured by CCK-8 assay while the relationship between miR-16 and AKT3 was determined by Luciferase reporter assay.Results: MiR-16 was overexpressed after OGD treatment. MiR-16 overexpression significantly promoted the proliferation of cortical neurons and inhibited their apoptosis, while miR-16 inhibition produced an opposite effect. The expression of AKT3 was increased after miR-16 inhibition, but it was decreased when miR-16 was overexpressed. In addition, luciferase reporter gene results showed that miR-16 targeted AKT3. Functional experiments showed that AKT3 overexpression reversed the effect of miR-16 overexpression on ischemic injury.Conclusion: MiR-16 regulates neuronal cell growth and cell apoptosis through AKT3 expression.These results present new potential therapeutic targets for the treatment of cerebral ischemic stroke.

A Novel Bispecific T Cell Engager (UMG2-BTCE) Targeting CD1a-CD3ε Is Effective Against Cortical-Derived Acute Lymphoblastic Leukemia

Caterina Riillo*and Daniele Caracciolo*equally contributed to the work.Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and orphan hematological disease derived from malignant transformation of thymic T cell precursors. At present, the prognosis of relapsed/refractory patients remains poor. While immunotherapy has significantly improved the outcome of B cell acute lymphoblastic leukemia (B-ALL), the lack of tumor-restricted T cell antigens hampers its efficacy in T-ALL. (Caracciolo D, Riillo C, et al. Therapeutic afucosylated monoclonal antibody and bispecific T-cell engagers for T-cell acute lymphoblastic leukemia. J Immunother Cancer. 2021) Therefore, the development of novel immune-therapeutics is eagerly awaited.CD1a is a cell surface glycoprotein restricted to cortical T-ALL subtype expressed only by cortical thymocytes and Langerhans's cells among human healthy tissue and might represent a valuable therapeutic target for the treatment of T-ALL. On this basis, we develop an asymmetric monovalent 2 +1 bispecific T cell engager (BTCE) derived from a novel humanized UMG2 mAb directed against an original CD1a epitope selectively expressed by cortical T-ALL cells.Methods.To evaluate if UMG2 recognizes a specific CD1a epitope, HEK293T cell line, negative for CD1a expression, has been transfected with a plasmid encoding for CD1a (HEK293T/CD1a) and with a negative control vector and UMG2 reactivity has been evaluated by flow cytometry. A competitive binding assay between UMG2 and commercially available CD1a antibodies was performed. The UMG2 expression profile was evaluated on healthy donor peripheral blood cells and on a panel of cortical T-ALL cell lines. To develop a UMG2 targeting immunotherapeutic construct with a limited unspecific T cell activation, an asymmetric 2+1 UMG2-CD3 bispecific T cell engager (BTCE) was generated using knobs into holes technology. UMG2-CD3 BTCE in vitro T cell-mediated activity was evaluated on HEK293T CD1a antigen-negative cell line, on HEK293T/CD1a, on patient-derived and T-ALL cell lines, co-cultured with healthy donors derived peripheral blood mononuclear cells (PBMCs), CD4/CD8 depleted and CD56 enriched lymphocytes at 10:1 E:T ratio.T cell activation, degranulation, proliferation, and pro-inflammatory cytokine secretion were assessed by flow cytometry on primary blasts and on T-ALL cells with effector lymphocytes.To evaluate UMG2-CD3 BTCE anti-tumor activity against CD1a expressing T-ALL cell line in vivo, Hu-PBMCs NSG mouse model was generated, and tumor growth was assessed by fluorescent imaging probe.ResultsUMG2 mAb recognizes a previously uncharacterized CD1a epitope and does not compete with any of the commercially available anti-CD1a mAbs. While a strong UMG2 reactivity is observed on both patient-derived samples and T-ALL cells, no binding is found on normal blood cells, indicating the tumor-restricted pattern of reactivity of UMG2.UMG2-CD3 BTCE specifically binds CD1a on leukemic cells and activates CD3ε downstream signaling pathway on T lymphocytes, as demonstrated by the concentration-dependent increase of T cell proliferation, cytotoxic degranulation (CD107a), expression of cell surface activation markers (CD25, CD69), and pro-inflammatory cytokine secretion (IL-2, TNF-α, IFN-γ).UMG2-CD3 BTCE mediates strong and concentration-dependent specific T cell re-directed cytotoxicity only on CD1a expressing leukemic cells in the presence of T lymphocytes. Minimal UMG2-CD3 BTCE residual anti-tumor activity is observed in CD4/CD8 depleted and CD56 enriched lymphocytes, while CD56 depleted and Fc-blocked PBMCs are able to induce an anti-T-ALL activity comparable to total PBMCs, demonstrating that UMG2-BTCE could not recruit monocytes and NK cells through Fc-FcyR interaction by reducing the risk of immune-mediated adverse events. Most importantly, in an in vivo of immune-humanized NSG mice engrafted with human T-ALL cells, UMG2-BTCE significantly inhibits tumor growth translating into the survival advantage of treated animals.Conclusion: Taken together, all these results provide a framework for the clinical development of UMG2-CD3 BTCE potentially offering a novel therapeutic path for cortical-derived T-ALL. DisclosuresNo relevant conflicts of interest to declare.

Atorvastatin does not ameliorate nephrogenic diabetes insipidus induced by lithium or potassium depletion in mice.

Acquired forms of nephrogenic diabetes insipidus (NDI) include lithium (Li)‐induced and hypokalemia‐induced NDI. Both forms are associated with AQP2 downregulation and collecting duct (CD) cellular remodeling. Statins are cholesterol‐lowering drugs appearing to increase AQP2 membrane‐translocation and improve urine concentration in other NDI models. We have investigated if statins are able to prevent or rescue the Li‐induced changes in mice and in a mouse cortical CD cell line (mCCDc1l). Biotinylation assays showed that acute (1hr) atorvastatin, simvastatin, or fluvastatin increased AQP2 membrane accumulation in mCCDc1l cells showing that the cell line responds to acute statin treatment. To see whether chronic statin treatment abolish the Li effects, mCCDc1l cells were treated with 48 h Li, combined Li/atorvastatin or combined Li/simvastatin. Li reduced AQP2, but combined Li/atorvastatin or Li/simvastatin did not prevent AQP2 downregulation. In mice, chronic (21 days) Li increased urine output and reduced urine osmolality, but combined Li/atorvastatin did not prevent these effects. In inner medulla (IM), Li reduced total AQP2 and increased pS261‐AQP2. Combined Li/atorvastatin did not abolish these changes. Atorvastatin did not prevent a Li‐induced increase in intercalated cells and proliferation in IM. In mice with already established NDI, atorvastatin had no effect on the Li‐induced changes either. Mice subjected to 14 days of potassium‐deficient diet developed polyuria and AQP2 downregulation in IM. Co‐treatment with atorvastatin did not prevent this. In conclusion, atorvastatin does not appear to be able to prevent or rescue Li‐NDI or to prevent hypokalemic‐induced NDI.

MiR‑497/MIR497HG inhibits glioma cell proliferation by targeting CCNE1 and the miR‑588/TUSC1 axis.

Emerging evidence has shown that microRNA (miR)-497 serves pivotal roles in tumorigenesis, cancer progression, metastasis and chemotherapy resistance in several types of cancer. In the present study, the expression and biological functions of miR-497 host gene (MIR497HG) were investigated in glioma tissue. The expression levels of miR-497 and MIR497HG were measured in glioma, adjacent non-cancerous and normal brain tissue and their association with the prognosis of patients with glioma were analyzed. The biological roles of miR-497 and MIR497HG were investigated in glioma cell lines. In addition, bioinformatics analysis, luciferase reporter assay and functional experiments were performed to identify and validate the downstream targets of miR-497 or MIR497HG. The expression levels of miR-497 and MIR497HG were downregulated in glioma tissue and cell lines compared with those in adjacent non-cancerous and normal brain tissue and normal human cortical neuron cell line. Patients with low miR-497 or MIR497HG expression levels exhibited a poor prognostic outcome. In addition, forced overexpression of miR-497 or MIR497HG significantly inhibited the proliferation and cell cycle progression of glioma cell lines. Furthermore, the results indicated that miR-497 and MIR497HG exerted their biological functions by direct targeting of cyclin E1 and miR-588/tumor suppressor candidate 1. In summary, the data indicated that miR-497 and MIR497HG served as tumor suppressors and may be used as potential therapeutic targets and prognostic biomarkers in glioma.

HDAC inhibition induces EMT and alterations in cellular iron homeostasis to augment ferroptosis sensitivity in SW13 cells

Epithelial-to-mesenchymal transition (EMT) is an essential mechanism for development and wound healing, but in cancer it also mediates the progression and spread of aggressive tumors while increasing therapeutic resistance. Adoption of a mesenchymal state is also associated with increased iron uptake, but the relationship between EMT and the key regulators of cellular iron metabolism remains undefined. In this regard, the human adrenal cortical carcinoma SW13 cell line represents an invaluable research model as HDAC inhibitor treatment can convert them from an epithelial-like (SW13-) cell type to a mesenchymal-like (SW13+) subtype. In this study we establish SW13 cells as a model for exploring the link between iron and EMT. Increased iron accumulation following HDAC inhibitor mediated EMT is associated with decreased expression of the iron export protein ferroportin, enhanced ROS production, and reduced expression of antioxidant response genes. As availability of redox active iron and loss of lipid peroxide repair capacity are hallmarks of ferroptosis, a form of iron-mediated cell death, we next examined whether HDAC inhibitor treatment could augment ferroptosis sensitivity. Indeed, HDAC inhibitor treatment synergistically increased cell death following induction of ferroptosis. The exact mechanisms by which HDAC inhibition facilitates cell death following ferroptosis induction requires further study. As several HDAC inhibitors are already in use clinically for the treatment of certain cancer types, the findings from these studies have immediate implications for improving iron-targeted chemotherapeutic strategies.

The radiographic relationship between the cortical overlap view (COV) and the tip of the greater trochanter

For proximal femoral nailing, choosing the proper entry point with the aid of C-arm imaging is crucial. Therefore, obtaining accurate radiological views that facilitate sound identification of the tip of the greater trochanter (GT) is of utmost importance. The aim of this study was to define a radiological view characterised by reproducible radiographic landmarks which will allow the reliable identification of the tip of the GT in the anteroposterior view. Anatomical and radiographic features of 16 cadaveric femurs were analysed. The cortical overlap view (COV), characterised by the radiological overlap of the density line of the piriform fossa and the intertrochanteric crest, was identified. It marks the rotation of the proximal femur at which the GT can be accurately identified and used to determine the desired entry point for a proximal femoral nail. Trainees and fully qualified orthopedic trauma surgeons were asked to identify the correct COV in radiological imaging series. Mean internal rotation of the femur to achieve a COV was 17.5° (range 12.8°–21.8°). In the COV the tip of the GT is the highest visible point and the mean distance from the cortical overlap line to the tip of the GT is 4.45 mm. Intra- and inter-rater reliability was high with ICC(2,k) = 0.932 and ICC(2,k) = 0.987 respectively. Trainees achieved higher rates of correct COV identification than specialists. There was no significant correlation between the internal rotation of the femur to achieve the COV and femoral antetorsion. In conclusion, the COV is a highly reproducible radiological view that is characterised by radiographic landmarks easy to recognise. It allows for accurate identification of the tip of the GT, which can be used by the surgeon as a reference to determine the desired entry point for an intramedullary nail.

Transcriptomic Analysis of HCN-2 Cells Suggests Connection among Oxidative Stress, Senescence, and Neuron Death after SARS-CoV-2 Infection.

According to the neurological symptoms of SARS-CoV-2 infection, it is known that the nervous system is influenced by the virus. We used pediatric human cerebral cortical cell line HCN-2 as a neuronal model of SARS-CoV-2 infection, and, through transcriptomic analysis, our aim was to evaluate the effect of SARS-CoV-2 in this type of cells. Transcriptome analyses revealed impairment in TXN gene, resulting in deregulation of its antioxidant functions, as well as a decrease in the DNA-repairing mechanism, as indicated by the decrease in KAT5. Western blot analyses of SOD1 and iNOS confirmed the impairment of reduction mechanisms and an increase in oxidative stress. Upregulation of CDKN2A and a decrease in CDK4 and CDK6 point to the blocking of the cell cycle that, according to the deregulation of repairing mechanism, has apoptosis as the outcome. A high level of proapoptotic gene PMAIP1 is indeed coherent with neuronal death, as also supported by increased levels of caspase 3. The upregulation of cell-cycle-blocking genes and apoptosis suggests a sufferance state of neurons after SARS-CoV-2 infection, followed by their inevitable death, which can explain the neurological symptoms reported. Further analyses are required to deeply explain the mechanisms and find potential treatments to protect neurons from oxidative stress and prevent their death.

Predictors of osteoradionecrosis following irradiated tooth extraction

BackgroundTooth extraction post radiotherapy is one of the most important risk factors of osteoradionecrosis of the jawbones. The objective of this study was to determine the predictors of osteoradionecrosis (ORN) which were associated with a dental extraction post radiotherapy.MethodsA retrospective analysis of medical records and dental panoramic tomogram (DPT) of patients with a history of head and neck radiotherapy who underwent dental extraction between August 2005 to October 2019 was conducted.ResultsSeventy-three patients fulfilled the inclusion criteria. 16 (21.9%) had ORN post dental extraction and 389 teeth were extracted. 33 sockets (8.5%) developed ORN. Univariate analyses showed significant associations with ORN for the following factors: tooth type, tooth pathology, surgical procedure, primary closure, target volume, total dose, timing of extraction post radiotherapy, bony changes at extraction site and visibility of lower and upper cortical line of mandibular canal. Using multivariate analysis, the odds of developing an ORN from a surgical procedure was 6.50 (CI 1.37–30.91, p = 0.02). Dental extraction of more than 5 years after radiotherapy and invisible upper cortical line of mandibular canal on the DPT have the odds of 0.06 (CI 0.01–0.25, p < 0.001) and 9.47 (CI 1.61–55.88, p = 0.01), respectively.ConclusionExtraction more than 5 years after radiotherapy, surgical removal procedure and invisible upper cortical line of mandibular canal on the DPT were the predictors of ORN.

HGG-25. PRMT5 PROMOTES TUMOR GROWTH BY MAINTAINING STEMNESS OF PEDIATRIC HIGH-GRADE GLIOMA CELLS

BackgroundPediatric high-grade gliomas (pHGG) are aggressive tumors that together constitute the most common cause of childhood cancer mortality. Tumor stem cells that drive proliferation of pHGG resist chemotherapy and radiation, complicating treatment. The arginine methyltransferase PRMT5 maintains self-renewal in neural stem cells through epigenetic modifications. We hypothesized that PRMT5, which we identified as a potential driver of diffuse midline glioma (DMG) through an shRNA screen, plays a similar role in pHGG. MethodsUsing lentiviral delivery of shRNA, we knocked down (KD) PRMT5 in cortical pHGG and DMG cell lines and performed phenotypic, mechanistic and self-renewal assays. We irradiated PRMT5 KD and control cells to study sensitization. We orthotopically injected mice with PRMT5 KD pHGG cells, and with DMG cells in which PRMT5 was knocked out (KO) using CRISPR-Cas. ResultsIn cellular models of cortical pHGG and DMG, PRMT5 KD significantly reduced proliferation, inhibited cell cycle progression, increased apoptosis resistance, and decreased self-renewing cell frequency. A relative shift of PRMT5 from the cytoplasm to the nucleus accompanied differentiation induced by PRMT5 KD. Epigenetic changes accompanying PRMT5 KD included increased H3K27me3, a global transcription inhibitor, and decreased H3K27M expression in DMG. PRMT5 KD sensitized pHGG cells to radiation, increasing cell death 17–30%. PRMT5 KD/KO significantly increased survival in mice and decreased tumor aggressiveness and proliferation, but mice still died of tumor-related effects. ConclusionsPRMT5 maintains self-renewal and drives proliferation in preclinical pHGG models. In cellular and in vivo models, PRMT5 KD/KO produces epigenetic changes, including increased H3K27me3 levels and diminished H3K27M, that may reduce proliferation and self-renewal. Future work includes elucidation of the mechanisms by which PRMT5 produces the observed changes. Because PRMT5 KD/KO does not eliminate tumor growth, we plan to further study combining PRMT5 KD/KO and clinical-grade small molecule PRMT5 inhibitors with radiation and chemotherapeutic agents.

Is it possible to filter third molar cases with panoramic radiography in which roots surround the inferior alveolar canal? A comparison using cone-beam computed tomography

Inferior alveolar nerve (IAN) entrapment in third molar (M3) roots bears a significant risk for nerve injury. The aim of this study was to identify specific panoramic radiographic (PR) signs that can reliably identify IAN entrapment (IANE) root conformations. In a retrospective case-control study, 10 IANE and 218 non-IANE third molar risk cases were examined by PR and CBCT. The collected data included “classic” specific high-risk panoramic signs, number of M3 roots, extent of inferior alveolar canal (IAC)−root tip overlap, rotated position of M3 and impaction pattern. After bivariate analysis, sensitivity, specificity, positive and negative predictive values, positive likelihood ratios (LR+) and accuracy (AC) were calculated for the most significant predictive variables. Interruption of both cortical lines (LR+: 43.6; AC: 96.0%) and upward diversion of the IAC (LR+: 36.3; AC: 96.5%) were the most accurate single signs indicating IANE. Upward diversion combined with root darkening and interruption of the IAC (AC: 97.4%) and the combination of darkening with interruption and with a rotated M3 (LR+:130.8; AC: 97.8%) were the most accurate combinations predicting IANE. IANE may be correctly filtered with PR when focusing on the signs of upward diversion, darkening, interruption and rotated M3 position, especially in cases involving their multiple (≥3) presence. CBCT evaluation is highly recommended in these cases before partial and total tooth removals.

Overloaded Orthopedic Force Induces Condylar Subchondral Bone Absorption by Stimulating Rat Mesenchymal Stem Cells Differentiating into Osteoclasts via mTOR-Regulated RANKL/OPG Secretion in Osteoblasts.

Appropriate orthopedic force led to bone remodeling of mandibular condyle, while overloaded orthopedic force (OOF) induced condylar bone absorption. Bone absorption is ascribed to the imbalanced activities between osteoclasts (OCs) and osteoblasts (OBs), mechanism of which remains unclear. This study aimed to observe the condylar changes induced by OOF by mandible advancement appliance and to further investigate the role of mammalian target of Rapamycin (mTOR) and RANKL/OPG in osteoclastic differentiation of stem cells in vivo and in vitro. In vivo, the results of micro-CT analysis indicated that condylar bone resorption was induced by OOF through mandibular advancement appliance for 2 weeks and worsened time dependently. Morphologically, cartilage thickness was reduced, subchondral cortical bone line appeared not continuous, and subchondral bone exhibited irregular-shaped and owned uneven surface. The bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were decreased accomplished with the increased trabecular separation (Tb.Sp) determined by micro-CT. In addition, based on immunofluorescent labeling, OOF activated both OCs and OBs, but osteoclastogenesis prevailed over osteogenesis. The mTOR activation and ratio of RANKL/OPG in OBs were elevated by OOF. In vitro, the results of western blot and polymerase chain reaction (PCR) consistently suggested that the mTOR and RANKL/OPG ratio were upregulated by overloaded mechanical stretch. Pretreatment with mTOR inhibitor, rapamycin, could attenuate the activation of mTOR and the secretion of RANKL in OBs. Interestingly, based on the Trap staining, the supernatant of OBs exposed to OOF could promote osteoclastic differentiation of mesenchymal stem cells (MSCs), while its role was weakened by inhibition of mTOR in OBs. Collectively, OOF induced condylar bone absorption; in the process, osteoclastogenesis was prominent than osteogenesis. The activation of mTOR and secretion of RANKL/OPG were enhanced by OOF and were involved in promoting MSCs differentiating into OCs.

A new fluoroscopic view for evaluation of anteromedial cortex reduction quality during cephalomedullary nailing for intertrochanteric femur fractures: the 30\xb0 oblique tangential projection

BackgroundAnteromedial cortex-to-cortex reduction is a key parameter for stable reconstruction of the fracture fragments during the intertrochanteric fracture fixation. This paper introduces the oblique fluoroscopic projection as a novel method to evaluate the quality of anteromedial cortical apposition.MethodsThree proximal femur specimens were marked with steel wires along five anatomic landmarks: Greater trochanter, Lesser trochanter, Intertrochanteric line, Anterolateral tubercle and the Anteromedial cortical line. After obtaining the standard femoral neck AP and lateral fluoroscopic images, the C-arm was rotated by every 5°increments until a clear tangential view of the antero-medial-inferior corner cortex was observed. 98 cases of intertrochanteric hip fractures were enrolled from April 2018 to October 2019. After fixation with the nails, the intra-operative anteromedial cortex reduction quality was evaluated from the AP, the true lateral, and the new anteromedial oblique fluoroscopic images. The fluoroscopic results were compared with the post-operative 3D-CT reconstruction images.ResultsThe specimen study showed that internal rotation of the C-arm to approximately 30 ° can remove all the obscure shadows and clearly display the antero-medial-inferior cortical tangent line. Clinically,the positive, neutral and negative apposition of different cortices via intra-operative fluoroscopic images showed79, 19 and 0 cases of medial cortical apposition in AP views; 2, 68 and 28 cases of anterior cortices in lateral views;and 22, 51 and 25cases of anteromedial cortical apposition in oblique views respectively. The post-operative 3D-CT reconstruction images revealed that the final anteromedial cortical contact was noted in 62 cases (63.3%), and lost in 36 cases (36.7%). The overall coincidence rate between intra-operative fluoroscopy and post-operative 3D-CT was 63.3% (62/98) in AP view,79.6% (78/98) in lateral view, and 86.7% (85/98) in oblique view(p < 0.001). Negative cortical apposition in oblique view was highly predictive of a final loss of cortical support on 3D CT (24/25 cases, 96%).And non-negative cortical apposition in oblique view was highly associated with true cortical support on 3D CT images (61/73 cases, 83.6%) (p < 0.001).ConclusionsBesides the AP and lateral projections, an anteromedial oblique view of 30° certifies to be a very useful means for evaluation of the fracture reduction quality of anteromedial cortical apposition.

Study on the precision of the robot-assisted sacroiliac screw placement

Objective: To evaluate the precision of the robot-assisted sacroiliac screw placement for posterior pelvis injury and the impacting factors. Methods: The clinical data of twenty-four cases of posterior pelvic fractures treated by percutaneous sacroiliac screw placement in Yantai shan Hospital from August 2016 to May 2018 were studied retrospectively. There were 17 males and 7 females with a mean age of 44.1 years (ranged from 17 to 71 years). According to AO classification, 17 cases were type B fractures (9 cases of type B1 and 8 type B2), and 7 cases were type C factures (3 cases of type C1, 2 type C2 and 2 type C3). All cases were treated by robot-assisted percutaneous sacroiliac screw placement (AO cannulated screws with a diameter of 7.3 mm). In the posterior pelvic surgeries for the 24 cases, 26 S(1) sacroiliac screws fixations and 18 S(2) sacroiliac screw fixations were placed in total, with single S(1) segmental fixation in 8 cases, single S(2) segmental fixation in 3 cases, S(1) and S(2) combined fixation in 13 cases, S(1) unidirectional one-sided fixation in 18 cases, S(1) bidirectional two-sided fixation in 3 cases, S(2) unidirectional one-sided fixation in 14 cases, S(2) bidirectional two-sided fixation in 2 cases and S(1) unidirectional double screws fixation in 2 cases. X-ray and CT examinations were taken for all 24 cases after operation. The visual analogue scale (VAS) of pain were performed before and after the operation. Results: All the sacroiliac screws were successfully implanted at once as planned with the assistance of the robot. The postoperative X-ray films and CT showed that none of the sacroiliac screws broke through the sacral body and the contralateral sacral wing's frontal cortex nor did they stray into the sacral canal and the intervertebral space. In 3 cases, the sacroiliac screws went closely against and wore out the front edge of iliac cortical density line and sacral alar slope and finally re-entered the sacral body. In 3 cases, sacroiliac screws touched upon the sacral nerve canals but did not break through the nerve canals. The mean VAS of pain was improved from 7.1 points (4-10 points) before the operation to 1.9 points (0-3 points) after. Conclusions: The robot-assisted sacroiliac screw placement shows high precision, and hence is worthy of clinical promotion; however the primary role of the surgeon could not be replaced.

Anatomical Mapping of the External Obturator Footprint: A Study In Cadavers with Implications for Direct Anterior THA.

BackgroundThe external obturator footprint in the trochanteric fossa has been suggested as a potential landmark for stem depth in direct anterior THA. Its upper border can be visualized during surgical exposure of the femur. A recent study reported that the height of the tendon has little variability (6.4 ± 1.4 mm) as measured on CT scans and that the trochanteric fossa is consistently visible on conventional pelvic radiographs. However, it is unclear where exactly the footprint of this tendon should be templated during preoperative planning so that it can be useful intraoperatively.Questions/purposesIn this study, we sought: (1) to provide instructions on exactly where to template the external obturator footprint on a preoperative planning radiograph, and (2) to confirm the small variability in height of the external obturator footprint found on CT scans in a cadaver study.MethodsTwo-dimensional (2-D) and three-dimensional (3-D) imaging was used to map the anatomy of the external obturator footprint. This dual approach was chosen because of their complementarity; conventional 2-D radiographs translate to clinical practice but 3-D navigation-based digitalization combined with CT allows for a better understanding of the cortical lines that comprise the outline of the trochanteric fossa. In 12 (four males, mean age 80 years, range 69 to 88) formalin-treated cadaveric lower extremities including the pelvis, the external obturator tendon was dissected, and the top and bottom end of its footprint marked with two small needles, and calibrated radiographs were taken. For another five (three males, mean age 75.7 years, range 61 to 91) fresh-frozen cadaveric lower extremities, including femoral reflective marker frames, CT scans were obtained and the exact location of the external obturator footprint was recorded using 3-D navigation-based digitalization. Qualitative analysis of both imaging modalities was used to develop instructions on where the external obturator footprint should be templated on a preoperative planning radiograph. Quantitative analysis of the dimensions of the external obturator footprint was performed.ResultsThe lowest point of the external obturator footprint was consistently found (± 1 mm) at the intersection of the vertical line comprised of the lateral wall of the trochanteric fossa and the oblique line formed by the intertrochanteric crest and therefore allows templating of this structure on the preoperative planning radiograph. The median (range) height of the footprint measured 6.4 mm and demonstrated small variability (4.7 to 7.6).ConclusionsWe suggest templating a 6.4-mm circle with its bottom on the intersection described above.Clinical RelevanceThe distance between the templated shoulder of the stem and the top of the circle can be used intraoperatively for guidance. Discrepancy should lead to re-evaluation of stem depth and leg length. Future work will investigate the usability, validity, and reliability of the proposed methodology in daily clinical practice.

Predicting Bone Marrow Edema and Fracture Age in Vertebral Fragility Fractures Using MDCT.

OBJECTIVE. The purpose of this study was to evaluate whether CT features can predict bone marrow edema (BME) on MRI and fracture age in vertebral fragility fractures. MATERIALS AND METHODS. A total of 189 thoracolumbar compression fractures in 103 patients (14 men, 89 women; mean age, 76 years) imaged with both spine CT and MRI were retrospectively included. The presence and extent of BME were assessed on MRI to divide fractures into those with and without BME. The group with BME was then classified for subgroup analysis into fractures with extensive BME (comprising 50% or more of the vertebral body) and those with BME comprising less than 50% of the vertebral body. On CT, five features (presence of cortical or endplate fracture line, presence of trabecular fracture line, presence of condensation band, change in trabecular attenuation, and width of paravertebral soft-tissue change) were analyzed. RESULTS. All five CT findings were predominantly seen in fractures with BME (p < 0.001). Elevated trabecular attenuation, presence of a cortical or endplate fracture line, and paravertebral soft-tissue width showed excellent diagnostic indication for fractures with BME (ROC AUCs: 0.990, 0.976, and 0.950, respectively). In the subgroup with extensive BME, paravertebral soft-tissue width was significantly higher, whereas the change in trabecular attenuation was lower compared with those with BME comprising less than 50% of the vertebral body (p < 0.001). When BME was present, fracture age was not significantly different between the two subgroups, and only greater trabecular attenuation elevation was predictive of older fracture age on linear mixed model analyses (p < 0.001). Interobserver agreement was good for the trabecular fracture line factor and excellent for all other factors. CONCLUSION. CT features accurately correlate with the presence and extent of BME in vertebral fragility fractures. Elevation of trabecular attenuation was the only significant image predictor of fracture age.

Trochlear dysplasia influences patellotrochlear index when measuring patella alta

Objectives:Patella alta is a risk factor for patellar instability and its recurrence after treatment. The patellotrochlear index (PTI) is a measurement used to quantify patella alta, describing patellar engagement in the trochlea through an index of trochlear overlap with patellar articular surface based on sagittal imaging. Values less than 20% have been reported to indicate patella alta, yet this measurement has primarily been described in normal knees. Trochlear dysplasia is also a common risk factor in patellar instability and can affect the length of the trochlea. Therefore the purpose of this study was to compare PTI measurements in knees with and without trochlear dysplasia, and to describe its relationship with trochlear length.Methods:Knees with trochlear dysplasia (defined by trochlear depth<4mm) based on CT imaging were identified from a series of knees with symptomatic patellar instability and compared to age- and gender matched asymptomatic controls. Measurements of patellar height including PTI and Caton Deschamps Index (CDI) were performed, as well as additional measurements of trochlear dysplasia including lateral trochlear inclination [LTI] and sulcus angle [SA]. Trochlear length was quantified using a previously described method of trochlear center-edge angle (TCEA) measurement, an angle between the posterior femoral cortical line with its intersection with Blumensaat’s line to the most proximal margin of the trochlea, with a smaller angle indicating more proximal extension of the trochlea. TCEA was measured at the central, medial, and lateral trochlea. Measurements were compared between dysplastic and control groups using t-test. Linear and multivariate regression analyses were performed to assess the relationship between PTI and measurements of trochlear dysplasia.Results:21 knees with trochlear dysplasia (13 female and 8 male) were included in this study, and were compared with 21 age- and gender-matched controls. In the dysplastic group, trochlear depth (TD) was 0.7+/-2.4mm vs 6.8+/-2.5mm (p<0.001) in the control group, SA was 154.2+/-11.5 degrees vs 134.0+/-8.3 degrees (p<0.001), and LTI was 12.1+/-6.2 vs 23.7+/-4.4 degrees (p<0.001) . Despite CDI being greater in the symptomatic group (1.19+/-0.23 vs 1.06+/-0.19, p=0.053), PTI was greater (with more overlap) in the symptomatic group (34.92+/-15.23% vs 25.43+/-21.55%, p=0.076). In the symptomatic group, the trochlear groove extended more proximally at the central (TCEA 58.4 degrees vs 68.6 degrees, p<0.001) and medial aspects (68.9 degrees vs 77.9 degrees, p<0.001). In dysplastic knees, PTI demonstrated a weak negative correlation with TCEA (R=-0.40) and with LTI (R=-0.45).Conclusion:In this study, knees with trochlear dysplasia had a PTI of 35% vs 25% in the control group, indicating greater patellar engagement despite having greater measurements of patella alta based on CDI (1.19 vs 1.06). PTI correlated with increased proximal extension of the trochlea which may account for the greater patellofemoral overlap. As abnormal trochlear length can associated with supratrochlear spurs, greater values on PTI may not necessarily indicate functional patellofemoral engagement. Further studies are needed to identify the functional relationship between trochlear length and patella alta.