Supramarginal resection of skull base chordomas: proof of concept and preliminary outcomes.

OBJECTIVE: The mainstay of treatment for skull base chordoma (SBC) is maximal safe resection followed by radiotherapy. However, even after gross-total resection (GTR), the recurrence rate is high due to microscopic disease in the resection margins. Therefore, supramarginal resection (SMR) could be beneficial, as has been shown for sacral chordoma. The paradigm of postoperative radiation therapy for every patient has also begun to change, as molecular profiling has shown variability in the risk of recurrence. The aim of this study was to present the concept of SMR applied to SBC, along with an individualized decision for postoperative radiation therapy. METHODS: This is a retrospective analysis of all SBCs operated on by the senior author between 2018 and 2023. SMR was defined as negative histological margins of bone and/or dura mater, along with evidence of bone resection beyond the tumor margins in the craniocaudal and lateral planes on postoperative imaging. Tumors were classified into 3 molecular recurrence risk groups (group A, low risk; group B, intermediate risk; and group C, high risk). Postoperative radiation therapy was indicated in group C tumors, in group B chordomas without SMR, or in cases of patient preference. RESULTS: Twenty-two cases of SBC fulfilled the inclusion criteria. SMR was achieved in 12 (55%) cases, with a mean (range) amount of bone resection beyond the tumor margins of 10 (2-20) mm (+40%) in the craniocaudal axis and 6 (1-15) mm (+31%) in the lateral plane. GTR and near-total resection were each achieved in 5 (23%) cases. Three (19%) tumors were classified as group A, 12 (75%) as group B, and 1 (6%) as group C. Although nonsignificant due to the small sample size, the trends showed that patients in the SMR group had smaller tumor volumes (13.9 vs 19.6 cm3, p = 0.35), fewer previous treatments (33% vs 60% of patients, p = 0.39), and less use of postoperative radiotherapy (25% vs 60%, p = 0.19) compared to patients in the non-SMR group. There were no significant differences in postoperative CSF leak (0% vs 10%, p = 0.45), persistent cranial nerve palsy (8% vs 20%, p = 0.57), and tumor recurrence (8% vs 10%, p = 0.99; mean follow-up 15 months) rates between the SMR and non-SMR groups. CONCLUSIONS: In select cases, SMR of SBC appears to be feasible and safe. Larger cohorts and longer follow-up evaluations are necessary to explore the benefit of SMR and individualized postoperative radiation therapy on progression-free survival.

PU.1 induces tumor-associated macrophages promoting glioma progression through BTK-mediated Akt/mTOR pathway activation.

Glioma, the most common primary malignant brain tumor, is characterized by infiltrating immune cells that contribute to tumor progression and therapeutic resistance. Tumor-associated macrophages (TAMs) constitute a significant proportion of these infiltrating immune cells and have been implicated in glioma progression. However, the underlying molecular mechanisms by which TAMs promote glioma progression remain elusive. In this study, we investigated the role of PU.1, a crucial transcription factor involved in myeloid cell development, in glioma-associated macrophage polarization and activation. First, bioinformatics and analysis of clinical glioma samples demonstrated a positive correlation between PU.1 expression in TAMs and disease severity. Further experiments using in vitro coculture systems revealed that the expression of PU.1 is increased in glioma cells vs. control cells. Importantly, PU.1-overexpressing macrophages exhibited a protumorigenic phenotype characterized by enhanced migration, invasion, and proliferation. Mechanistically, we found that PU.1-induced activation of the Bruton tyrosine kinase (BTK) signaling pathway led to Akt/mTOR pathway activation in macrophages, which further enhanced their protumorigenic functions. Furthermore, pharmacological inhibition of the BTK or Akt/mTOR pathway reversed the protumorigenic effects of macrophages in vitro and impaired their ability to promote glioma progression in vivo. In conclusion, our study elucidates a novel mechanism by which PU.1 induces the polarization and activation of TAMs in the glioma microenvironment. We highlight the significance of BTK-mediated Akt/mTOR pathway activation in driving the protumorigenic functions of TAMs. Targeting PU.1 and its downstream signaling pathways in TAMs may provide a promising therapeutic strategy to suppress glioma progression and improve patient outcomes.

Endoscopic endonasal pituitary sacrifice for select tumors with retrochiasmatic and/or retrosellar extension: surgical anatomy, operative technique, and case series.

OBJECTIVE: Tumors located in the retrochiasmatic region with extension to the third ventricle might be difficult to access when the pituitary-chiasmatic corridor is narrow. Similarly, tumor extension into the interpeduncular and retrosellar space poses a major surgical challenge. Pituitary transposition techniques have been developed to gain additional access. However, when preoperative pituitary function is already impaired or the risk of postoperative panhypopituitarism (PH) is considered to be particularly high, removal of the pituitary gland (PG) might be the preferred option to increase the working corridor. The aim of this study was to describe the relevant surgical anatomy, operative steps, and clinical experience with the endoscopic endonasal pituitary sacrifice (EEPS) and transsellar approach. METHODS: This study comprised anatomical dissections to highlight the relevant surgical steps and a retrospective case series reporting clinical characteristics, indications, and outcomes of patients who underwent EEPS. The surgical technique is as follows: both lateral opticocarotid recesses are exposed laterally, the limbus sphenoidale superiorly, and the sellar floor inferiorly. After opening the dura, the PG is detached circumferentially and mobilized off the medial walls of the cavernous sinuses. The descending branches of the superior hypophyseal artery are coagulated, and the stalk is transected. After removal of the PG, drilling of the dorsum sellae and bilateral posterior clinoidectomies are performed to gain access to the hypothalamic region, interpeduncular, and prepontine cisterns. RESULTS: From 2018 to 2023, 11 patients underwent EEPS. The cohort comprised mostly tuberoinfundibular craniopharyngiomas (n = 8, 73%). Seven (64%) patients had partial or complete anterior PG dysfunction preoperatively, while 4 (36%) had preoperative diabetes insipidus. Because of the specific tumor configuration, the chance of preserving endocrine function was estimated to be very low in patients with intact function. The main reasons for pituitary sacrifice were impaired visibility and surgical accessibility to the retrochiasmatic and retrosellar spaces. Gross-total tumor resection was achieved in 10 (91%) patients and near-total resection in 1 (9%) patient. Two (18%) patients experienced a postoperative CSF leak, requiring surgical revision. CONCLUSIONS: When preoperative pituitary function is already impaired or the risk for postoperative PH is considered particularly high, the EEPS and transsellar approach appears to be a feasible surgical option to improve visibility and accessibility to the retrochiasmatic hypothalamic and retrosellar spaces, thus increasing tumor resectability.

Can concentrated growth factor prevent postoperative complications of impacted third molar surgery? A split-mouth randomized double-blind trial.

OBJECTIVES: The purpose of the present study was to evaluate the effect of concentrated growth factor (CGF) on prevention of postoperative complications in the impacted third molar extraction. MATERIALS AND METHODS: A total of 25 healthy patients with symmetrical bilaterally impacted third molars (50 extraction sites) were enrolled in this split-mouth, randomized, double-blind clinical trial. Third molar extractions were performed in both sites of the mandible at the same appointment. Randomization was performed using a coin toss to choose the test and control sites. CGF was placed in the extraction socket and the socket was sutured (test group), while the contralateral socket was only sutured (control group). Each patient acted as their own control. The primary outcome were pain assessed by visual analog scale (VAS) and facial swelling on the1st, 3rd and 7th postoperative days. The secondary outcomes were bone healing in extraction sockets through alveolar bone height (ABH) and alveolar bone density (ABD) evaluated by cone beam computed tomography (CBCT) immediately after extraction and in the 3rd and 6th months. RESULTS: Twenty-five patients (12 female, 13 male; mean age 29.17) with bilateral impacted third molars participated in the study. A statistically significant reduction in pain was determined on the 3rd and 7th postoperative days in the CGF sites compared to the control sites while no statistically significant difference was found between the groups on the 1st postoperative day (3rd day, p = 0.009; 7th day, p = 0.039). There were no statistically significant differences in facial swelling and bone healing between the test and control groups at different time intervals, although the data obtained were slightly favoring the CGF group (p > 0.05). There were no serious adverse effects such as infection, alveolitis, paraesthesia, fracture through the follow-up period in all of the cases. CONCLUSION: The study has demonstrated the effect of CGF on relieving the severity of pain after the third molar extraction. CLINICAL RELEVANCE: Placement of CGF in the extraction socket could relieve postoperative pain and reduce patient discomfort after the third molar extraction. CGF is recommended during the third molar extraction due to its good biological effects, low cost and simple preparation procedures. TRIAL REGISTRATION NUMBER: ChiCTR2300077819.

Real-world impact of chemotherapy on overall survival in craniomaxillofacial osteosarcoma.

OBJECTIVES: The goal of this study was to identify the survival benefit of chemotherapy in craniomaxillofacial osteosarcoma (CMFO) patients based on a US population. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to select patients with CMFO from 1988 to 2016. Age and tumor size were grouped by X-tail. Cox analysis were used to estimate hazards ratios (HR) among patients. All of patients were divided into two cohorts by using Propensity Score Matching (PSM) method to evaluate the effect of chemotherapy. All prognostic factors were included in the nomograms which predict the median survival time. RESULTS: 410 patients were included in our study. The results of survival rate, Kaplan-Meier and Cox regression were showed no significant difference between the group of chemotherapy performed and the group without chemotherapy. PSM analysis also demonstrated the limited survival advantage of chemotherapy. Moreover, all factors were further incorporated to construct the novel nomograms and its concordance indices (C-index) for internal validation of OS prediction were 0.749 (95 %CI:0.731-0.767). CONCLUSIONS: Our study did not show the advantage of chemotherapy on the overall survival outcome of CMFO. Although neoadjuvant chemotherapy was currently recommended in clinical treatment, more rigorous randomized controlled trials are still needed. Nomograms would assist clinicians in making more accurate survival evaluation and choosing the optimal medical treatment.

The Temporoparietal Fascia Flap Transposition Technique for Ventral Skull Base Reconstruction: Anatomic Analysis and Surgical Application.

BACKGROUND AND OBJECTIVES: The temporoparietal fascia (TPF) flap is an alternative for revision endoscopic skull base reconstruction in the absence of the nasoseptal flap, and we aimed to investigate the anatomy and surgical application of TPF flap transposition in endoscopic endonasal surgery. METHODS: Six lightly embalmed postmortem human heads and 30 computed tomography angiography imaging scans were used to analyze the anatomic features of the TPF flap transposition technique. Three cases selected from a 512 endoscopic endonasal cases database were presented for the clinical application of the TPF flap. RESULTS: The TPF flap, composed by the deepest 3 scalp layers (galea aponeurotica, loose areolar connective tissue, and pericranium), can be harvested and then transposed through the infratemporal-maxillary-pterygoid tunnel to the ventral skull base. The superficial temporal artery as its feeding artery, gives frontal and parietal branches with similar diameter (1.5 ± 0.3 mm) at its bifurcation. The typical bifurcation was present in 50 sides (83.3%), with single (frontal) branch in 5 sides (8.3%), single (parietal) branch in 2 sides (3.3%), and multiple branches (>2) in 3 sides (5%). The transposed TPF flap was divided into 3 parts according to its anatomic location: (1) infratemporal part with an area of 19.5 ± 2.5 cm2, (2) maxillary part with an area of 23.7 ± 2.8 cm2, and (3) skull base part with an area of 44.2 ± 4 cm2. Compared with the nasoseptal flap, nasal floor flap, inferior turbinate flap, and extended septal flap, the coverage area of the skull base part of the TPF flap was significantly larger than any of them (P < .0001). CONCLUSION: The TPF flap technique is an effective alternative for endoscopic endonasal skull base reconstruction. The TPF flap could successfully cover large skull base defects through the infratemporal-maxillary-pterygoid tunnel.

Tumor-associated macrophages confer colorectal cancer 5-fluorouracil resistance by promoting MRP1 membrane translocation via an intercellular CXCL17/CXCL22-CCR4-ATF6-GRP78 axis.

Chemotherapy represents a major type of clinical treatment against colorectal cancer (CRC). Aberrant drug efflux mediated by transporters acts as a key approach for tumor cells to acquire chemotherapy resistance. Increasing evidence implies that tumor-associated macrophages (TAMs) play a pivotal role in both tumorigenesis and drug resistance. Nevertheless, the specific mechanism through which TAMs regulate drug efflux remains elusive. Here, we discovered that TAMs endow CRC cells with resistance to 5-fluorouracil (5-FU) treatment via a cell-cell interaction-mediated MRP1-dependent drug efflux process. Mechanistically, TAM-secreted C-C motif chemokine ligand 17 (CCL17) and CCL22, via membrane receptor CCR4, activated the PI3K/AKT pathway in CRC tumor cells. Specifically, phosphorylation of AKT inactivated IP3R and induced calcium aggregation in the ER, resulting in the activation of ATF6 and upregulation of GRP78. Accordingly, excessive GRP78 can interact with MRP1 and promote its translocation to the cell membrane, causing TAM-induced 5-FU efflux. Taken together, our results demonstrated that TAMs promote CRC chemotherapy resistance via elevating the expression of GRP78 to promote the membrane translocation of MRP1 and drug efflux, providing direct proof for TAM-induced drug resistance.

Resection of corticotroph microadenomas invading the medial wall of the cavernous sinus in two cases of a primary and recurrent case of Cushing's disease.

Emerging evidence from multiple highly specialized groups continues to support a role for resection of the medial wall of the cavernous sinus when it is invaded by functional pituitary adenomas, to offer durable biochemical remission. The authors present two cases of Cushing's disease that underscore the power of this surgical technique in achieving remission in microadenomas that ectopically present in the cavernous sinus or have invaded the medial wall of the sinus. This video demonstrates key steps in the safe removal of the medial wall of the cavernous sinus and successful resection of tumor burden in the cavernous sinus for sustained postoperative remission. The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2323.

Oxidative stress in pituitary neuroendocrine tumors: Affecting the tumor microenvironment and becoming a new target for pituitary neuroendocrine tumor therapy.

Pituitary adenomas (PAs), or pituitary neuroendocrine tumors (PitNETs), are commonly found in the anterior pituitary gland. Although the majority of PitNETs are benign and stable, several tumors have malignant characteristics. The tumor microenvironment (TME) plays an important role in the process of tumorigenesis and is composed of several types of cells. Various cells in the TME are significantly affected by oxidative stress. It has been reported that immunotherapeutic strategies have good effects in several cancers. However, the clinical potential of immunotherapies in PitNETs has not yet been fully discussed. Oxidative stress can regulate PitNET cells and immune cells in the TME, thus affecting the immune status of the TME of PitNETs. Therefore, modulation of oxidative stress-regulated immune cells using a combination of several agents and the immune system to suppress PitNETs is a promising therapeutic direction. In this review, we systematically analyzed the oxidative stress process within PitNET cells and various immune cells to elucidate the potential value of immunotherapy.

The Pterygosphenoidal Triangle: Surgical Anatomy and Case Series in Endoscopic Endonasal Skull Base Surgery.

BACKGROUND: Safe exposure of the lacerum segment of the carotid artery remains a challenge in endoscopic endonasal surgery. OBJECTIVE: To introduce the pterygosphenoidal triangle as a novel and reliable landmark for facilitating access to the foramen lacerum. METHODS: Fifteen colored silicone-injected anatomic specimens were dissected using an endoscopic endonasal approach to the foramen lacerum region in a stepwise manner. Twelve dried skulls were studied and 30 high-resolution computed tomography scans were analyzed to measure the borders and angles of the pterygosphenoidal triangle. Surgical cases incorporating the foramen lacerum exposure between July 2018 and December 2021 were reviewed to provide surgical outcomes of the proposed surgical technique. RESULTS: The pterygosphenoidal triangle is delineated by the pterygosphenoidal fissure medially and the vidian nerve laterally. The palatovaginal artery is located at the base of the triangle anteriorly, while the apex is formed by the pterygoid tubercle posteriorly, which leads to the anterior wall of the foramen lacerum and lacerum internal carotid artery. In the reviewed surgical cases, 39 patients underwent 46 foramen lacerum approaches for resection of pituitary adenoma (12 patients), meningioma (6 patients), chondrosarcoma (5 patients), chordoma (5 patients), or other lesions (11 patients). There were no carotid injuries or ischemic events. Near-total resection was achieved in 33 (85%) of 39 patients (gross-total in 20 [51%]). CONCLUSION: This study details the pterygosphenoidal triangle as a novel and practical anatomic surgical landmark for safe and effective exposure of the foramen lacerum in endoscopic endonasal surgery.

Periodontitis exacerbates atherosclerosis through Fusobacterium nucleatum-promoted hepatic glycolysis and lipogenesis.

AIMS: Positive associations between periodontitis (PD) and atherosclerosis have been established, but the causality and mechanisms are not clear. We aimed to explore the causal roles of PD in atherosclerosis and dissect the underlying mechanisms. METHODS AND RESULTS: A mouse model of PD was established by ligation of molars in combination with application of subgingival plaques collected from PD patients and then combined with atherosclerosis model induced by treating atheroprone mice with a high-cholesterol diet (HCD). PD significantly aggravated atherosclerosis in HCD-fed atheroprone mice, including increased en face plaque areas in whole aortas and lesion size at aortic roots. PD also increased circulating levels of triglycerides and cholesterol, hepatic levels of cholesterol, and hepatic expression of rate-limiting enzymes for lipogenesis. Using 16S ribosomal RNA (rRNA) gene sequencing, Fusobacterium nucleatum was identified as the most enriched PD-associated pathobiont that is present in both the oral cavity and livers. Co-culture experiments demonstrated that F. nucleatum directly stimulated lipid biosynthesis in primary mouse hepatocytes. Moreover, oral inoculation of F. nucleatum markedly elevated plasma levels of triglycerides and cholesterol and promoted atherogenesis in HCD-fed ApoE-/- mice. Results of RNA-seq and Seahorse assay indicated that F. nucleatum activated glycolysis, inhibition of which by 2-deoxyglucose in turn suppressed F. nucleatum-induced lipogenesis in hepatocytes. Finally, interrogation of the molecular mechanisms revealed that F. nucleatum-induced glycolysis and lipogenesis by activating PI3K/Akt/mTOR signalling pathway in hepatocytes. CONCLUSIONS: PD exacerbates atherosclerosis and impairs lipid metabolism in mice, which may be mediated by F. nucleatum-promoted glycolysis and lipogenesis through PI3K/Akt/mTOR signalling in hepatocytes. Treatment of PD and specific targeting of F. nucleatum are promising strategies to improve therapeutic effectiveness of hyperlipidaemia and atherosclerosis.

A YAP/TAZ-CD54 axis is required for CXCR2-CD44- tumor-specific neutrophils to suppress gastric cancer.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.

Refining the Anatomy of Percutaneous Trigeminal Rhizotomy: A Cadaveric, Radiological, and Surgical Study.

BACKGROUND: Percutaneous trigeminal rhizotomy (PTR) is a widely used procedure for trigeminal neuralgia. However, comprehensive analyses that combine anatomic, radiological, and surgical considerations are rare. OBJECTIVE: To present high-quality anatomic dissections and radiological studies that highlight the technical nuances of this procedure. METHODS: Six silicon-injected postmortem heads underwent PTR. The surgical corridors were dissected, and the neurovascular relationships were studied. In addition, 20 dried human skulls and 50 computed tomography angiography and MRI scans were collected to study the anatomic relationships for a customized puncture corridor. RESULTS: The PTR corridor was divided into 3 segments: the buccal segment (length, 34.76 ± 7.20 mm), the inferior temporal fossa segment (length, 42.06 ± 6.92 mm), and the Meckel cave segment (length, 24.75 ± 3.34 mm). The puncture sagittal (α) and axial (ß) angles measured in this study were 38.32° ± 4.62° and 19.13° ± 2.82°, respectively. The precondylar reference line coincided with the foramen ovale in 75% of the computed tomography angiography scans, and the postcondylar line coincided with the carotid canal in 70% of the computed tomography angiography scans; these lines serve as the intraoperative landmarks for PTR. The ovale-carotid-pterygoid triangle, delineated by drawing a line from the foramen ovale to the carotid canal and the lateral pterygoid plate, is a distinguished landmark to use for avoiding neurovascular injury during fluoroscopy. CONCLUSION: Knowledge of the anatomic and radiological features of PTR is essential for a successful surgery, and a customized technical flow is a safe and effective way to access the foramen ovale.

Porphyromonas gingivalis induced UCHL3 to promote colon cancer progression.

Porphyromonas gingivalis (P. gingivalis), a Gram-negative oral anaerobe, was demonstrated to facilitate colonization and progression in colonic tumor, while the underlying mechanism still remains to be clarified. Here, we identified the proteome profile changed by P. gingivalis infection in HCT116 cells through label-free quantitative proteomics, and found that deubiquitinase UCHL3 was a key protein that response for P. gingivalis infection. By CCK8, colony formation, wound healing assays, and in vivo subcutaneous tumor mouse moudle, we proved that P. gingivalis could promote the proliferation and migration of colon cancer, while the process was inhibited by UCHL3 knock down. Through IP-MS, we identified GNG12 as the UCHL3 interacting protein. The protein level of GNG12 was significantly reduced when knock out UCHL3. Thus we propose that GNG12 is a substrate protein of UCHL3. Furthermore, we demonstrated that overexpression of GNG12 could restore the tumor inhibition effect caused by UCHL3 knock down, and UCHL3-GNG12 axis promote colon cancer progression via the NF-κB signal pathway. Collectively, this study unveiled that P. gingivalis infection up-regulated UCHL3 and stabilized its substrate protein GNG12 to activate the NF-κB signal pathway to promote colon cancer progression. Our study indicate that UCHL3 is a potential biomarker and therapeutic target for colon cancer which infected with P. gingivalis.

SLC11A1 as a stratification indicator for immunotherapy or chemotherapy in patients with glioma.

Background: Glioma is a fatal tumor originating from the brain, which accounts for most intracranial malignancies. Currently, Immunotherapy has turned into a novel and promising treatment in glioma patients. however, there are still few effective biomarkers to mirror the reaction to immunotherapy in patients with glioma. Therefore, we intended to elucidate the evaluable efficacy of SLC11A1 in glioma patients. Methods: In this study, samples from Shanghai General Hospital and data from TCGA, GEO, CGGA datasets were used to investigate and validate the relationship between SLC11A1 and the progression of glioma. We evaluated the predictive value of SLC11A1 on the prognosis of glioma with cox regression analysis. Then the relationship between immune infiltration and SLC11A1 was also analyzed. Ultimately, we performed the prediction on the immunotherapeutic response and therapeutic drugs according to the expression of SLC11A1. Results: Expression of SLC11A1 increased with progression and predicted unfavorable prognosis for glioma patients. The hazard ratio for SLC11A1 expression was 2.33 with 95% CI (1.92-2.58) (P < 0.001) in cox analysis. And based on expression, we found SLC11A1 stratified glioma patients into subgroups with different immune activation statuses. Moreover, we observed that patients with higher SLC11A1 levels companied with better immunotherapeutic response, while those with lower SLC11A1 levels may respond better to temozolomide. Conclusion: This study provided evidence that SLC11A1 was a novel prognostic marker and immunotherapy response indicator for gliomas. In some cases, SLC11A1 could be an effective marker for identifying patients who might benefit from immunotherapy or chemotherapy.

Spotlight on clinical strategies of Chronic Internal Carotid Artery Occlusion: Endovascular interventions and external-intracarotid bypasses compared to conservative treatment.

Chronic internal carotid artery occlusion (CICAO) has high prevalence and incidence rates, and patients with CICAO can be completely asymptomatic, experience a devastating stroke or die. It is important to note that CICAO causes cerebrovascular accidents. Currently, the external carotid-internal carotid (EC-IC) bypass technique is used to treat CICAO. However, many clinical studies showed that EC-IC bypass was not beneficial for many patients with CICAO. Meanwhile, endovascular intervention treatment options for CICAO are evolving, and an increasing number of patients are undergoing endovascular intervention therapy. Accordingly, a review comparing both techniques is warranted. For this review, we searched PubMed and collected relevant case study reports comparing endovascular interventional therapy and internal and external cervical bypass surgeries to provide strategies for clinical treatment.

Ultrafine particles exposure is associated with specific operative procedures in a multi-chair dental clinic.

Air quality in dental clinics is critical, especially in light of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, given that dental professionals and patients are at risk of regular exposure to aerosols and bioaerosols in dental clinics. High levels of ultrafine particles (UFP) may be produced by dental procedures. This study aimed to quantify ultrafine particles (UFP) concentrations in a real multi-chair dental clinic and compare the levels of UFP produced by different dental procedures. The efficiency of a high-volume evacuator (HVE) in reducing the UFP concentrations during dental procedures was also assessed. UFP concentrations were measured both inside and outside of a dental clinic in Shanghai, China during a 12-day period from July to September 2020. Dental activities were recorded during working hours. The mean (±standard deviation) concentrations of indoor and outdoor UFP during the sampling period were 8,209 (±4,407) counts/cm3 and 15,984 (±7,977) counts/cm3, respectively. The indoor UFP concentration was much higher during working hours (10,057 ± 5,725 counts/cm3) than during non-working hours (7,163 ± 2,972 counts/cm3). The UFP concentrations increased significantly during laser periodontal treatment, root canal filling, tooth drilling, and grinding, and were slightly elevated during ultrasonic scaling or tooth extraction by piezo-surgery. The highest UFP concentration (241,136 counts/cm3) was observed during laser periodontal treatment, followed by root canal filling (75,034 counts/cm3), which showed the second highest level. The use of an HVE resulted in lower number concentration of UFP when drilling and grinding teeth with high-speed handpieces, but did not significantly reduce UFP measured during laser periodontal therapy. we found that many dental procedures can generate high concentration of UFP in dental clinics, which may have a great health impact on the dental workers. The use of an HVE may help reduce the exposure to UFP during the use of high-speed handpieces.

Short-Term Administration of HIV Protease Inhibitor Saquinavir Improves Skull Bone Healing with Enhanced Osteoclastogenesis.

BACKGROUND: Using immunomodulatory methods to address the challenging issue of craniofacial bone repair may be a potentially effective approach. The protease inhibitor saquinavir has been shown to inhibit the inflammatory response by targeting the toll-like receptor 4/myeloid differentiation primary response complex. Independently, inhibition of toll-like receptor 4 or myeloid differentiation primary response led to enhanced skull bone repair. Therefore, the authors aimed to investigate the effects of saquinavir on skull bone healing. METHODS: The effects of saquinavir on skull bone healing were assessed by means of gene expression, histology, immunohistochemistry, and tomography in a mouse calvarial defect model. Subsequently, the role of saquinavir in cell viability, migration, and osteogenic and osteoclastogenic differentiation was also evaluated in vitro. RESULTS: One-week saquinavir administration improved skull bone healing based on micro-computed tomographic and histomorphometric analyses. Compared to the vehicle control, 1-week saquinavir treatment (1) enhanced osteoclast infiltration (tartrate-resistant acid phosphatase staining) at day 7, but not at days 14 and 28; (2) induced more CD206 + M2 macrophage infiltration, but not F4/80 + M0 macrophages at days 7, 14, and 28; and (3) elevated osteoclastogenic gene RANKL (quantitative polymerase chain reaction) expression and other osteogenic and cytokine expression. Furthermore, in vitro data showed that saquinavir administration did not influence MC3T3-E1 cell migration or mineralization, whereas higher concentrations of saquinavir inhibited cell viability. Saquinavir treatment also enhanced the osteoclastic differentiation of bone marrow-derived precursors, and partially reversed high-mobility group box 1-driven osteoclastogenesis inhibition and elevated proinflammatory cytokine expression. CONCLUSION: The improved skull bone repair following short-term saquinavir treatment may involve enhanced osteoclastogenesis and modulated inflammatory response following skull injury. CLINICAL RELEVANCE STATEMENT: The authors' work demonstrates improved skull bone healing by short-term application of saquinavir, a drug traditionally used in the treatment of acquired immunodeficiency syndrome. As such, saquinavir may be repurposed for skeletal repair.

Anoikis resistance in diffuse glioma: The potential therapeutic targets in the future.

Glioma is the most common malignant intracranial tumor and exhibits diffuse metastasis and a high recurrence rate. The invasive property of glioma results from cell detachment. Anoikis is a special form of apoptosis that is activated upon cell detachment. Resistance to anoikis has proven to be a protumor factor. Therefore, it is suggested that anoikis resistance commonly occurs in glioma and promotes diffuse invasion. Several factors, such as integrin, E-cadherin, EGFR, IGFR, Trk, TGF-ß, the Hippo pathway, NF-κB, eEF-2 kinase, MOB2, hypoxia, acidosis, ROS, Hsp and protective autophagy, have been shown to induce anoikis resistance in glioma. In our present review, we aim to summarize the underlying mechanism of resistance and the therapeutic potential of these molecules.

Endoscopic Anatomy of the Zygomatic Nerve: Implications for the Endoscopic Transmaxillary Approach.

Introduction Understanding the anatomic features of the zygomatic nerve is critical for performing the endoscopic transmaxillary approach properly. Injury to the zygomatic nerve can result in facial numbness and corneal problems. Objective To evaluate the surgical anatomy of the zygomatic nerve and its segments from an endoscopic endonasal perspective for clinical implications of performing the endoscopic transmaxillary approach. Methods The origin, course, length, and segments of the zygomatic nerve were studied in four specimens from an endonasal perspective. Results The zygomatic nerve arises 4.1 ± 1.7 mm from the foramen rotundum of the maxillary nerve in the superolateral pterygopalatine fossa (PPF). According to its anatomic region in endonasal endoscopic surgery, we divided the zygomatic nerve into two segments: the PPF segment, from origin to the point of entry under Muller's muscle, which runs superolaterally to the inferior orbital fissure (IOF) (length, 4.6 ± 1.3 mm), and the IOF segment, starting at the entry point in Muller's muscle and terminating at the exit point in the IOF, which travels between Muller's muscle and the great wing of the sphenoid bone (length, 19.6 ± 3.6 mm). In the transmaxillary approach, the zygomatic nerve is a critical landmark in the superolateral PPF. Conclusion The zygomatic nerve travels in the PPF and the IOF; better visualization and preservation of this nerve during endonasal endoscopic surgery are crucial for successful outcomes.