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Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumour-like fibro-osseous lesion in the neuraxis including the spine. It is diagnosed by the presence of the following histological features: granular amorphous to chondromyxoid fibrillary cores with calcification/ossification, peripheral palisading of spindle to epithelioid cells, variable fibrous stroma, and foreign body reaction with multinucleated giant cells, as well as positive NF-L immunostaining. Spinal CAPNON is sometimes named as tumoural calcinosis that is tumour-like dystrophic calcification usually in the periarticular tissue and also described in calcified synovial cyst (CSC). We examined clinical, radiological and pathological features of five spinal CAPNONs and 21 spinal CSCs including three recurrent lesions. The results demonstrated some radiological and pathological overlaps between these two entities, as well as distinct features of each entity to be diagnosed. All CAPNONs showed the diagnostic histological features with NF-L positivity mainly in lesion cores and variable CD8+ T-cells. In contrast, CSCs exhibited the synovial lining and variable degenerative/reactive changes with some CAPNON-like features, but mostly no to occasionally limited NF-L positivity and less CD8+ T-cells with statistically significant differences between groups of CAPNONs and CSCs. Four CSCs contained CAPNON-like foci with the CAPNON diagnostic features including prominent NF-L positivity, and some transitional features from CSC to CAPNON. As the pathogenesis of CAPNON is likely reactive/degenerative in association with an inflammatory/immunological process involving NF-L protein deposition, our findings suggest the link between spinal CAPNON and CSC, with possible transition from CSC to CAPNON or CAPNON developing in reaction to CSC.

Background Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle. Owing to complex anatomy and high rates of morbidity, surgical management of large tumours is challenging. We seek to explore the clinical landscape of VS to identify predictors of outcome and help guide surgical decision making. Methods We retrospectively reviewed charts of patients who underwent primary surgery for VS between 2005 and 2020 at a quaternary referral center in Toronto, Canada. Mined data includes patient demographics, clinical presentation, radiological features, and treatment details. Regression modelling was used to identify predictors of tumour control, postoperative morbidity, and correlates of progression free survival (PFS). Results Two hundred and five tumours with sufficient data were included in our study. Syndromic NF2, large tumours (>3cm), subtotal resection (vs gross total resection), presence of edema on preoperative MRI, and preoperative trigeminal symptoms were all predictors of postoperative progression/need for further treatment; the latter four were also associated with shorter progression free survival. Extent of resection (EOR), tumour size, and Koos grade were independently predictive of postoperative progression/secondary intervention in multivariate models; however, only EOR was independently predictive of progression-free survival. EOR, tumour size, and patient age are each independently predictive of facial nerve outcome. Conclusions We comprehensively explore the clinical landscape of surgically treated vestibular schwannoma and highlight important outcome predictors and disease subgroups. This may have important implications in risk stratifying these challenging cases.

Background The endoscopic endonasal approach (EEA) has been increasing in popularity as an alternative to traditional transcranial and transorbital approaches in the treatment of orbital pathological entities. The purpose of the present study was to examine the outcomes of patients who had undergone EEA resection of orbital lesions at our center. Methods We performed a retrospective medical record review of patients who had undergone the EEA for resection of orbital lesions and orbital apex decompression from January 1, 2006 to December 1, 2019. For all the patients, the demographic data, presenting symptoms, symptom duration, imaging data, operative details, and postoperative outcomes were collected and reviewed. Results Nine patients underwent endoscopic endonasal resection of orbital lesions and orbital apex decompression at our center, including 6 male patients and 3 female patients. The mean age was 49.4 years, and the mean follow-up period was 3.8 years (range, 1–13.5 years). The orbital pathological lesions that were treated included nasopharyngeal carcinoma, hemangioma, fibrous dysplasia, IgG4 pseudotumor, inverted papilloma, angioleiomyoma, adenocarcinoma, and neuroendocrine paraganglioma metastasis. All the patients presented with exophthalmos of the affected orbit. Of the 9 patients, 5 presented with decreased visual acuity on examination. Postoperatively, 1 of these 5 patients had improved to baseline visual acuity, 3 had stable vision, and 1 had brief improvement before experiencing progressive visual decline 1 month postoperatively. Two patients presented with diplopia, and both improved postoperatively. Three patients experienced new, transient, and self-limiting postoperative diplopia. Conclusions For patients with orbital lesions causing compressive optic neuropathy, the endoscopic endonasal approach can be used as an alternative strategy in appropriately selected patients.

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.

Background Spondylodiscitis is a challenging spinal disorder that requires surgical treatment only as a last resort. The use of various procedures and instruments remains controversial. In this retrospective study, we reported the safety and efficacy of a CaSO4 drug carrier system for the transforaminal lumbar interbody fusion (TLIF) procedure for lumbar pyogenic spondylodiscitis. Methods Thirty-four patients with lumbar spondylodiscitis underwent TLIF. CaSO4 beads carrying vancomycin and gentamycin were implanted in the trajectory of screws and disc spaces. We measured markers of inflammation, scores of neurologic recovery, and quality of life. The fusion status was assessed at final follow-up and the correction of local and total lordotic angle was calculated. Results The patients were followed up for at least 12 months (range, 12–24 months). At 3 months follow-up, C-reactive protein levels and erythrocyte sedimentation rate returned to normal with no relapse. Nineteen patients with American Spinal Injury Association grade D preoperatively returned to American Spinal Injury Association grade E. The improvement on the visual analog scale and Oswestry Disability Index was 66.9% and 84.9%, respectively. At 12 months follow-up, 67.6% of patients achieved definitive union. The corrections of total and local lordotic angle were 10.02° ± 8.77° and 7.7° ± 8.75°, respectively. The rate of achievement of satisfactory Kirkaldy-Willis functional criteria was 85.3%. Conclusions The combined use of single-level TLIF with a CaSO4 drug delivery system was safe and effective for treatment of pyogenic lumbar spondylodiscitis. The system promoted reduction of inflammation with limited fixed segments without a negative impact on fusion status. This procedure may be considered a novel choice for spondylodiscitis, with more efficacy and less invasion.

The Enhanced Permeability and Retention (EPR) effect has been recognized as the central paradigm in tumor-targeted delivery in the last decades. In the wake of this concept, nanotechnologies have reached phenomenal levels in research. However, clinical tumors display a poor manifestation of EPR effect. Factors including tumor heterogeneity, complicating tumor microenvironment, and discrepancies between laboratory models and human tumors largely contribute to poor efficiency in tumor-targeted delivery and therapeutic failure in clinical translation. In this article, approaches for evaluation of EPR effect in human tumor were overviewed as guidance to employ EPR effect for cancer treatment. Strategies to augment EPR-mediated tumoral delivery are discussed in different dimensions including enhancement of vascular permeability, depletion of tumor extracellular matrix and optimization of nanoparticle design. Besides, the recent development in alternative tumor-targeted delivery mechanisms are highlighted including transendothelial pathway, endogenous cell carriers and non-immunogenic bacteria-mediated delivery. In addition, the emerging preclinical models better reflect human tumors are introduced. Finally, more rational applications of EPR effect in other disease and field are proposed. This article elaborates on fundamental reasons for the gaps between theoretical expectation and clinical outcomes, attempting to provide some perspective directions for future development of cancer nanomedicines in this still evolving landscape.

Objectives The incidence of human brucellosis has risen dramatically in China with few reports regarding the operation on spinal brucellosis. In this retrospective study we introduced CaSO4drug delivery system into the TLIF surgical procedure and evaluated its clinical effectiveness and feasibility. Patients and Methods 36 patients with lumbar brucellosis were enrolled and treated by posterior transforaminal decompression, instrumentation and fusion. Prepared CaSO4 beads carrying doxycycline were placed into the disc space and around pedicle screws. The activity of infection and pain-related function scales were recorded. Neurologic and functional recovery was evaluated using ASIA and Kirkaldy-Willis scale. Segmental and overall lordotic angles were measured and fusion status was assessed at final follow up. Results The average follow-up period was 15.6 ± 3.73 months. The level of ESR and CRP returned to normal at 3 months post-op. 14 patients with ASIA grade D pre-op returned ASIA grade E with 3 months. The improvement of VAS and ODI was 82% and 85.8% at 3 months post-op. The corrections of segmental and overall lordotic angle were 5.98 ± 3.54° and 6.24 ± 7.93°. 69% of patients reached definitive union at 12 months after surgery. The satisfactory rate on Kirkaldy-Willis functional outcome criteria was 88.9%. Conclusion The use of CaSO4 drug delivery system during single-stage TLIF for spinal brucellosis was safe and showed no negative impacts on fusion status and neurological function recovery. Our results are promising and the drug delivery system may be considered as a choice for future treatment in spinal brucellosis or other spondylodiscitis.

Background Context Imaging modalities used to visualize spinal anatomy intraoperatively include X-ray studies, fluoroscopy, and computed tomography (CT). All of these emit ionizing radiation. Purpose Radiation emitted to the patient and the surgical team when performing surgeries using intraoperative CT-based spine navigation was compared. Study Design/Setting This is a retrospective cohort case-control study. Patient Sample Seventy-three patients underwent CT-navigated spinal instrumentation and 73 matched controls underwent spinal instrumentation with conventional fluoroscopy. Outcome Measures Effective doses of radiation to the patient when the surgical team was inside and outside of the room were analyzed. The number of postoperative imaging investigations between navigated and non-navigated cases was compared. Methods Intraoperative X-ray imaging, fluoroscopy, and CT dosages were recorded and standardized to effective doses. The number of postoperative imaging investigations was compared with the matched cohort of surgical cases. A literature review identified historical radiation exposure values for fluoroscopic-guided spinal instrumentation. Results The 73 navigated operations involved an average of 5.44 levels of instrumentation. Thoracic and lumbar instrumentations had higher radiation emission from all modalities (CT, X-ray imaging, and fluoroscopy) compared with cervical cases (6.93 millisievert [mSv] vs. 2.34 mSv). Major deformity and degenerative cases involved more radiation emission than trauma or oncology cases (7.05 mSv vs. 4.20 mSv). On average, the total radiation dose to the patient was 8.7 times more than the radiation emitted when the surgical team was inside the operating room. Total radiation exposure to the patient was 2.77 times the values reported in the literature for thoracolumbar instrumentations performed without navigation. In comparison, the radiation emitted to the patient when the surgical team was inside the operating room was 2.50 lower than non-navigated thoracolumbar instrumentations. The average total radiation exposure to the patient was 5.69 mSv, a value less than a single routine lumbar CT scan (7.5 mSv). The average radiation exposure to the patient in the present study was approximately one quarter the recommended annual occupational radiation exposure. Navigation did not reduce the number of postoperative X-rays or CT scans obtained. Conclusions Intraoperative CT navigation increases the radiation exposure to the patient and reduces the radiation exposure to the surgeon when compared with values reported in the literature. Intraoperative CT navigation improves the accuracy of spine instrumentation with acceptable patient radiation exposure and reduced surgical team exposure. Surgeons should be aware of the implications of radiation exposure to both the patient and the surgical team when using intraoperative CT navigation.

In recent years, correlation filters have achieved excellent performance in terms of accuracy and robustness for visual target tracking. However, it is still a challenging task to improve the tracking capability which can handle complex background and deal with target scale changes. In this paper, a new tracker based on the correlation filter framework with scale adaptation for visual target tracking is presented: 1) an effective scale adaptive scheme, which can solve the fixed template size with the basis of traditional correlation filter tracker, is proposed; 2) two powerful features including histogram of oriented gradient and color name, which can improve the overall tracking performance, are integrated together; 3) a high-confidence model updating strategy, which can avoid the model occlusion problem during model updating, is developed. The extensive experimental evaluations on OTB-2013 dataset have demonstrated that the developed novel tracker in our study can successfully outperform the other trackers on the benchmark dataset with 51 sequences. It is very promising for various challenging scenarios.

Background: Lung cancer rates for never-smoking women in Xuanwei and Fuyuan, China are among the highest in the world and have been attributed to use of “smoky” (bituminous) coal. However, the key carcinogenic components of coal that drive lung cancer risk here have not been identified. Methods: We conducted a population-based case-control study of lung cancer among 1015 never smoking female cases and 485 comparable controls and linked cancer risk through a multipollutant model to 43 household air pollution (HAP) chemicals and particulates measured in a comprehensive exposure study conducted in the same population. Exposures assessed included methylated polycyclic aromatic hydrocarbons (PAH), which have never been directly evaluated in an epidemiologic study of any cancer. Findings: The strongest detected risk of lung cancer was for 5-methylchrysene, a mutagenic and carcinogenic PAH. In contrast, neither benzo(a)pyrene, a standard marker of PAH exposure used in risk assessment, nor fine particulate matter (PM2.5), commonly used to evaluate health outcomes from outdoor air pollution, were associated with risk of lung cancer in multipollutant models. Interpretation: This is the first study to comprehensively evaluate lung cancer risk from HAP constituents estimated over the entire lifecourse. Given the global ubiquity of coal use domestically for indoor cooking and heating and commercially for electric power generation, our study suggests that more extensive monitoring of coal combustion products including methylated PAHs may be warranted to more accurately assess health risks and develop prevention strategies from this exposure. Funding Statement: Funding provided by the intramural research program of the National Cancer Institute. Declaration of Interests: Authors have no conflicts of interest to declare. Ethical Approval Statement: The study protocol was approved by the institutional review boards of the National Cancer Institute (NCI) and China National Environmental Monitoring Center.