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Intrathecal targeted drug delivery provides effective relief for cancer-related pain. However, its validation in management of craniofacial pain remains much less widely practiced, mainly due to the localized diffusion of analgesic agent with current approach. Here, we report our experience of prepontine cisternal routine for placement and implantation of intrathecal targeted drug delivery in two cases of cancer-related craniofacial pain. Lumbar cannulation was applied and the intrathecal catheter tip was positioned at the prepontine cistern under fluoroscopic guidance during the surgical implantation. Postoperative imaging confirmed that the catheter tip was successfully placed in the prepontine cisternal space. Satisfactory control of pain was achieved after intrathecal therapy, with significant reduction of background and breakthrough cancer pain. None obvious complications were observed in this study. Thus, our novel intrathecal routine may provide an alternative option for craniofacial pain caused by tumor, who were insufficiently treated by oral analgesic agents.

The focus of neuro-oncology research has changed from histopathologic grading to molecular characteristics, and medical imaging routinely follows this change.To compare the diagnostic performance of amide proton transfer (APT) and four diffusion models in gliomas grading and isocitrate dehydrogenase (IDH) genotype.Prospective.A total of 62 participants (37 males, 25 females; mean age, 52 ± 13 years) whose IDH genotypes were mutant in 6 of 14 grade II gliomas, 8 of 20 of grade III gliomas, and 4 of 28 grade IV gliomas.APT imaging using sampling perfection with application optimized contrasts by using different flip angle evolutions (SPACE) and DWI with q-space Cartesian grid sampling were acquired at 3 T.The ability of diffusion kurtosis imaging, diffusion kurtosis imaging, neurite orientation dispersion and density imaging (NODDI), mean apparent propagator (MAP), and APT imaging for glioma grade and IDH status were assessed, with histopathological grade and genetic testing used as a reference standard. Regions of interest (ROIs) were drawn by two neuroradiologists after consensus.T-test and Mann-Whitney U test; one-way analysis of variance (ANOVA); receiver operating curve (ROC) and area under the curve (AUC); DeLong test. P value 0.05 was considered statistically significant.Compared with IDH-mutant gliomas, IDH-wildtype gliomas showed a significantly higher mean, 5th-percentile (APTAPT has higher diagnostic accuracy than DTI, DKI, MAP, and NODDI in glioma IDH genotype. APT1 TECHNICAL EFFICACY: Stage 2.

To introduce the surgical technique and clinical outcomes of arthroscopic anterior talofibular ligament (ATFL) repair using the Internal Brace and lasso-loop technique for chronic ankle lateral instability.A retrospective study was performed on 29 patients who underwent all-arthroscopic ATFL repair with the Internal Brace and lasso-loop technique from January to August 2020. The patients included 24 males and five females, with a mean age of 30.17 years. Through the accessory anterolateral (AAL) portal, we drilled the bone tunnels and fixed the tape with 4.75 mm and 3.5 mm "SwiveLock" anchors and reattached the torn ligament by the lasso-loop technique.All 29 patients underwent all-arthroscopic procedures smoothly without serious complications, such as infection and important nerve or vessel injuries. There were eight cases of lateral malleolar avulsion fractures and ten cases of talus cartilage injury. The visual analog scale (VAS), Karlsson-Peterson, Tegner, and American Orthopedic Foot and Ankle Society (AOFAS) scores were used to evaluate the clinical consequences. All the patients were followed up for 18.66 ± 4.85 months on average. The average pre-operative VAS score was 4.69 ± 1.04, which was significantly higher than the average post-operative VAS score of 1.14 ± 1.56. At the final follow-up appointments, the averages of Karlsson-Peterson, AOFAS, and Tenger scores were 75.83 ± 9.44, 88.31 ± 6.81, and 6.93 ± 1.79, respectively, which was significantly higher than that before the operation.This arthroscopic anterior talofibular ligament repair with the Internal Brace and lasso-loop technique achieves satisfactory clinical outcomes with the benefits of high safety and reliability for chronic ankle lateral instability.

Purpose Some chemotherapeutics have been shown to induce both the release of damage-associated molecular patterns (DAMPs) and the production of type I interferon (IFN-I), leading to immunogenic cell death (ICD). However, the standard chemotherapy drug for glioma, temozolomide (TMZ), cannot induce ICD as it cannot activate IFN-I signaling. Moreover, inefficient delivery of immunostimulants across the blood-brain barrier (BBB) is the main obstacle to overcome in order to induce local immune responses in the brain. Methods A new oligonucleotide nanoformulation (Au@PP)/poly(I:C)) was constructed by coating gold nanoparticles (AuNPs) with methoxypolyethylene glycol (mPEG)-detachable (d)-polyethyleneimine (PEI) (Au@PP) followed by inducing the formation of electrostatic interactions with polyinosinic-polycytidylic acid (poly(I:C)). Intracranial GL261 tumor-bearing C57BL/6 mice were used to explore the therapeutic outcomes of Au@PP/poly(I:C) plus TMZ in vivo. The anti-tumor immune response in the brain induced by this treatment was analyzed by RNA sequencing and immunohistochemical analyses. Results Au@PP/poly(I:C) induced IFN-I production after endocytosis into glioma cells in vitro. Additionally, Au@PP/poly(I:C) was efficiently accumulated in the glioma tissue after intranasal administration, which allowed the nanoformulation to enter the brain while bypassing the BBB. Furthermore, Au@PP/poly(I:C) plus TMZ significantly improved the overall survival of the tumor-bearing mice compared with group TMZ only. RNA sequencing and immunohistochemical analyses revealed efficient immune response activation and T lymphocyte infiltration in the Au@PP/poly(I:C) plus TMZ group. Conclusion This study demonstrates that intranasal administration of Au@PP/poly(I:C) combined with TMZ induces ICD, thereby stimulating an in situ immune response to inhibit glioma growth.

This study provides an approach to estimating tympanic membrane perforation-induced hearing loss (HL) using a human middle ear model.Sixty-one cases of tympanic membrane perforation originating from fireworks were reported from the Ear-Nose-Throat Department. The otoscope, audiometry data and diagnosis records were organized, and gender, age, etiology, perforation size and diseased ear side were classified as independent variables. A multinomial regression model was used to analyze the potential effects of the variables on HL. Meanwhile, a human middle ear model was implemented to calculate the ensued HL resulting from different perforation areas and sites. In addition, linear regression models were used to establish functions between perforation size and HL.The audiometry data indicate that HL at high frequencies (f 2 kHz) is much more profound than that at the speech frequency band (f 1 kHz). Compared with mild HL (15 dB), mediate HL (15-30 dB) was correlated with the perforation area (p 0.05, 95% CI), while severe HL (30 dB) was affected by both perforation size and age (p 0.05, 95% CI). However, other factors, including gender and diseased ear side, do not show a statistically significant effect on HL. Furthermore, the Kruskal-Wallis test result reveals that HL at frequencies of 0.25 kHz ≤ f ≤ 8 kHz is strongly associated with the perforation size (p 0.05, 95% CI).It is conclusive that HL is positively proportional to the perforation size. However, HL is not correlated with the perforation site for small perforation areas of 10% (p 0.05, 95% CI).

ObjectiveTo evaluate the predictive value of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in the quantitative assessment of conventional chemotherapy-activated immune responses in mouse tumor models and clinics.MethodsA total of 19 subcutaneous tumor-bearing mice were randomly divided into treated and control groups. Both groups had orderly IVIM DWI examinations before and on days 6 and 12 after the administration of cyclophosphamide (CPA) or saline. Pathologic examinations were performed, including HE staining and immunohistochemistry (IHC). The expressions of immune-related genes in the tumor were measured by qPCR. In addition, six patients with breast cancer requiring neoadjuvant chemotherapy (NACT) also underwent functional MRI examinations and IHC to determine potential antitumor immune response.ResultsAt the end of the study, the CPA treatment group showed the lowest tumor volume compared to the control group. For pathological examinations, the CPA treatment group showed a lower percentage of CD31 staining (P < 0.01) and Ki-67 staining (PP < 0.01). The tumoral pseudodiffusion coefficient (D*) value showed a positive correlation with the CD31-positive staining rate (r = 0.729, P < 0.0001). The diffusion related parameters (D) value was positively correlated with TUNEL (r = 0.858, P < 0.0001) and negatively correlated with Ki-67 (r = -0.904, P < 0.0001). Moreover, a strong induction of the expression of the immune responses in the CPA treatment group was observed on day 12. D values showed a positive correlation with the Ifnb1-, CD8a-, Mx1-, Cxcl10- (r = 0.868, 0.864, 0.874, and 0.885, respectively, P < 0.0001 for all). Additionally, the functional MRI parameters and IHC results in patients with breast cancer after NACT also showed a close correlation between D value and CD8a (r = 0.631, P = 0.028).ConclusionsThe treatment response induced by immunogenic chemotherapy could be effectively evaluated using IVIM-DWI. The D values could be potential, sensitive imaging marker for identifying the antitumor immune response initiated by immunogenic chemotherapy.

Background: Traditional chemotherapeutic drugs have the potential to increase tumor cell immunogenicity by activating immunogenic cell death (ICD). The accumulation of preclinical and clinical evidence suggests that the success of neoadjuvant chemotherapy, immunogenic chemotherapy depends (at least in part) on their ability to stimulate anti-cancer immune responses. Although the pathological examination is the gold standard for detecting the antitumor immune response, it is invasive and cannot be performed repetitively. Hence, the aim of our study was to evaluate the predictive value of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in the quantitative assessment of conventional chemotherapy-activated immune responses in mouse tumor models and clinics.Methods: A total of 19 subcutaneous tumor-bearing mice were randomly divided into treated and control groups. Both groups had orderly IVIM DWI examinations before and on days 6 and 12 after the administration of cyclophosphamide (CPA) or saline. The expressions of immune-related genes in the tumor were measured by qPCR or detected by immunohistochemical assay. In addition, six patients with breast cancer requiring neoadjuvant chemotherapy also underwent functional MRI examinations. The primary statistical analysis methods were the Wilcoxon test of variance, correlation analysis, and the Kruskal-Wallis H test.Results: The tumoral pseudodiffusion coefficient (D*), the perfusion fraction (f), and the blood flow-related parameter (fD*) of the treatment group showed a trend that significantly decreased on day 6. Then, these values increased on day 12, while they displayed the opposite tendency in the control group. Compared with the control group, a strong induction of the expression of the immune responses in the CPA treatment group was observed on day 12. Additionally, the changes in functional MRI parameters in the six patients with breast cancer after neoadjuvant chemotherapy showed similar trends to those in the tumor-bearing mice in the CPA treatment group.Conclusions: The immune response induced by immunogenic chemotherapy could be effectively evaluated using IVIM-DWI. The D and D* values could be potential, sensitive imaging markers for identifying the antitumor immune response initiated by immunogenic chemotherapy.

This study aimed at establishing an evaluation methodology for aural discomfort induced by the interior pressure changes in high-speed trains running in tunnels. Experiments in pressure cabin, which can reveal the relationship between aural discomfort and pressure change, were discussed. Furthermore, a human middle ear model was used to simulate the vibration. The experimental conditions were considered as pressure loads, which were exerted on the tympanic membrane. Furthermore, the aural discomfort was hierarchically divided into four levels: ideal, good, bad, and worse. Four indicators, such as the tympanic membrane displacement and stress and the stapes footplate displacement and velocity, were used to establish the discomfort criteria. Logistic regression analysis was used to investigate the incidences of each level as well as to obtain the thresholds between levels. The outcomes have a p-value of less than 0.05; hence, the response results of the indicators are statistically significant. Additionally, the thresholds of the indicators were obtained and used to differentiate the aural discomfort levels. The intervals of the four indicators are (0,T1), (T1,Tc), (Tc,T3), and (T3,>T3) for the discomfort levels of ideal, good, bad, and worse, respectively. Moreover, the onset mechanism of aural sensations was revealed using the four indicators. It can be implied that large tympanic membrane and stapes footplate displacements tend to elicit ear complaints, such as fullness, otalgia, and vertigo, whereas the large stapes footplate velocity affects the onset of tinnitus and hearing loss.

Objective: The purpose of the present study was to evaluate the dynamics of endolymphatic hydrops (EH) and symptoms in a group of patients who underwent endolymphatic duct blockage (EDB) for treatment of intractable Meniere's Disease (MD), and to explore a metric for verifying the effectiveness of EDB procedure.Methods: A total of 22 patients with intractable MD patients who underwent EDB participated in the present study. EH was visualized using locally enhanced inner ear magnetic resonance imaging (MRI) prior to and following surgery. The vestibular hydrops ratio (VHR) in the second MRI examination was compared with the pre-surgery recordings.Results: Following EDB, 6 patients exhibited complete or partial reversal of EH, complete control of vertigo spells and reported improvement in hearing; 13 patients showed no changes in EH or hearing, but 5 of these patients exhibited complete control of vertigo attacks, and the other 8 patients exhibited improved control of vertigo attacks. The final 3 patients showed an increase in EH, but symptomatic worsening in 2 patients, and symptomatic improvement in 1 patient. There was a significant difference in the average VHR prior to and following EDB. Postoperative VHR was positively correlated with the frequency of vertigo spells in the latest 6 months of follow-up and improvement of postoperative average hearing threshold.Conclusion: The decreased EH accompanying the reduction in vertigo attacks and hearing preservation may provide a metric for verifying the effectiveness of EDB treatment in patients with MD.

To explore the differences between endolymphatic duct blockage (EDB) and endolymphatic sac drainage (EDD) surgery in the reversal of endolymphatic hydrops (EH) in patients with intractable Meniere’s disease (MD). A total of 19 MD patients receiving EDB (n=10) and EDD (n=9) treatment underwent gadoliniumenhanced inner ear magnetic resonance imaging (MRI) scans prior to, 2 weeks after and at >12 months following surgery. In the EDB group, the second MRI revealed no changes in EH, whereas the third MRI revealed a reversal of vestibular EH in 3 patients and a downgrading of cochlear hydrops in 2 of these 3 patients, who presented with an improvement in their hearing and complete control of vertigo. In the EDD group, the second MRI showed a reversal of EH in 4 patients, and no changes in EH in the remaining 5 patients, whereas the third MRI showed that those 4 patients who presented with a reversal of EH at the second MRI stage remained unchanged, with the exception of one patient who experienced a recurrence of vestibular hydrops. All 4 patients exhibited a complete control of vertigo, although hearing improved in only 1 of them, worsened in 1 and remained unchanged in 2. The present study showed the reversal in EH was likely due to the delayed effect of surgery accompanied by an improvement in hearing in EDB group, whereas the reduction in the endolymph volume presented as an acute reversal of hydrops in EDD group without a causeeffect relationship with hearing function.

OBJECTIVE The aim of this study was to evaluate the feasibility and safety of transcanal underwater endoscopic bone resection (TUEBR) of the external auditory canal (EAC) for the management of cholesteatoma involving the antrum and mastoid. STUDY DESIGN Retrospective case review. SETTING Tertiary referral center. PATIENTS Pediatric and adult patients with primary cholesteatoma extending to the antrum and mastoid who underwent transcanal endoscopic ear surgery (TEES) with TUEBR between March 2016 and June 2017. INTERVENTION A rigid 2.7 mm diameter, 18 cm length Hopkins-rod telescope with an endoscopic sheath was inserted in the EAC and continuously perfused with saline during the dissection. TUEBR was performed to expose extensive cholesteatoma by using a high speed drill with curved burrs and a protected shaft. Next, removal of visible disease, reconstruction of the resected EAC, ossiculoplasty, and tympanoplasty were accomplished with TEES. RESULTS There were no intra- or postoperative severe complications such as facial palsy and inner ear injury except one patient suffering from secondary labyrinthitis. There was a negative linear relationship (r = -0.909) between the procedure time and procedure number of TUEBR. There was a weak relationship (r = 0.224) between the procedure time of TUEBR and the degree of the extension of cholesteatoma into the antrum and mastoid. There were two cases with residual cholesteatoma at 12 and 22 months follow-up postoperatively. CONCLUSION TUEBR is a safe and efficient technique for the resection of EAC bone and transcanal exposure of extensive cholesteatoma that would otherwise require mastoid dissection.

Background To explore the ability of Dual-energy CT (DECT) to differentiate metastatic from non-metastatic lymph nodes in colorectal cancer (CRC). Methods Seventy-one patients with primary CRC underwent contrast-enhanced DECT imaging before surgery. The colorectal specimen was scanned after surgery, and lymph nodes were matched to the pathology report. The DECT quantitative parameters were analyzed: dual-energy curve slope value(λHU), standardized iodine concentration (n△HU), iodine water ratio (nIWR), electron density value (nρeff), and effective atom-number (nZ), for the metastatic and non-metastatic lymph node differentiation. Also, sensitivity and specificity analyses were performed by using receiver operating characteristic curve. Results One hundred and fifty lymph nodes including 66 non-metastatic and 84 metastatic lymph nodes were matched using the radiological-pathological correlation. Metastatic node had a significantly greater λHU, n△HU and nIWR values than non-metastatic node in both arterial and venous phases (P HU; 0.86, 69.70% and 95.24% for n△HU; 0.88, 71.21% and 95.24% for nIWR in the arterial phase. No significant difference was found in electron density and effective Z value for differentiation. Conclusion Dual-energy CT quantitative parameters may be helpful in diagnosing metastatic lymph nodes of CRC.

BACKGROUND: Colorectal cancer (CRC) is the third most common malignancy worldwide, and lymph node metastasis is considered to be a risk factor for local recurrence and a poor prognosis in colorectal cancer. However, there remains a lack of reliable and non-invasive biomarkers to identify the lymph node status of CRC patients preoperatively. The purpose of this study was to explore the ability of dual-energy computed tomography (DECT) to differentiate metastatic from non-metastatic lymph nodes in colorectal cancer. METHODS: Seventy-one patients with primary colorectal cancer underwent contrast-enhanced dual-energy computed tomography imaging preoperatively. The colorectal specimen was scanned postoperatively, and lymph nodes were matched to the pathology report. The following dual-energy computed tomography quantitative parameters were analyzed: dual-energy curve slope value (λ(HU)), standardized iodine concentration (n△HU), iodine water ratio (nIWR), electron density value (nρ(eff)), and effective atom-number (nZ), based on metastatic and non-metastatic lymph node differentiation. Also, sensitivity and specificity analyses were performed using receiver operating characteristic curves. RESULTS: In all patients, one hundred and fifty lymph nodes, including 66 non-metastatic and 84 metastatic lymph nodes, were matched using the radiological-pathological correlation. Metastatic nodes had significantly greater λ(HU), n△HU, and nIWR values than non-metastatic nodes in both the arterial and venous phases (P

To compare the image quality of VIBE sequence using controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA-VIBE) and using generalized autocalibrating partially parallel acquisitions (GRAPPA-VIBE) in liver magnetic resonance examination, and to evaluate the effect of non-rigid 3D-registration motion correction (MOCO) combined with CAIPIRINHA-VIBE on liver spatial location registration.A total of 85 patients underwent pre-contrast GRAPPA-VIBE and CAIPIRINHA-VIBE breath-hold scan in the mask phase, and then underwent CAIPIRINHA-VIBE breath-hold scan in arterial phase, portal vein phase and delay phase after administration. After the scanning of four phases of CAIPIRINHA-VIBE completed, 3D images without and with MOCO of each phase were automatically generated. The images quality of GRAPPA-VIBE and CAIPIRINHA-VIBE without MOCO in the mask phase was scored subjectively by two physicians. The number of slices at the top of the diaphragm in the arterial phase was taken as the base slice, and that in the other stages subtracted with the base slice for CAIPIRINHA without and with MOCO. The range of diaphragm movement in each phase was counted by + N/- N statistics.The image quality and the scores of CAIPIRINHA-VIBE were significantly higher than those of GRAPPA-VIBE in respiratory motion artifact suppression, liver edge sharpness and intrahepatic vascular sharpness (p 0.05). The spatial position consistency of the liver with MOCO is significantly better than that without MOCO.CAIPIRINHA-VIBE with MOCO can be used instead of conventional GRAPPA-VIBE sequence in upper abdominal MRI enhancement examination, especially for patients with poor breath-hold.

The objective of this study is to investigate the effects of ligament and tendon detachment on human middle ear sound transfer. For this purpose, a geometric human middle ear model was reconstructed based on the computed tomography scanning data of the temporal bones from healthy adult volunteers. For the ear model, pars tensa was assumed to be fit for a 5-parameter Maxwell model and inverse method was used to obtain the necessary coefficients. Furthermore, frequency response method was implemented to investigate the vibration behaviors of tympanic membrane umbo and stapes footplate under an acoustic stimulus of 90 dB within 0.2–8 kHz. Meanwhile, nine patterns of fractured ligaments and tendons, whose effects on the middle ear sound transfer function were simulated by setting free the nodes of the ligaments and tendons of interest. The results indicate that the displacement of tympanic membrane umbo and stapes footplate as well as the velocity transfer function lies within the bounds of the published experimental data. The detachments of ligaments or tendons except for lateral mallear ligament may incur both gains as much as 15 dB and losses of –8 dB in the velocity of stapes footplate at low frequencies ( f≤ 1 kHz), while no significant changes were observed at high frequencies ( f > 1 kHz). However, detachment of the ligaments or tendons induces tiny changes in the displacement of stapes footplate at the frequencies of 0.2–8 kHz.

The present study was to investigate the dynamics of endolymphatic hydrops (EH) and hearing function, and explore whether the hearing loss is caused by EH alone and whether the hearing function can be modulated by changes in the EH. The extent of EH visualized by gadolinium (Gd)-enhanced inner ear magnetic resonance imaging, hearing thresholds and the summating potential/action potential ratio (-SP/AP ratio) of electrocochleography (ECochG) were recorded prior to and following surgery in 22 patients with intractable Meniere's disease (MD) who underwent endolymphatic duct blockage (EDB). The difference value of the hearing threshold and -SP/AP ratio was significantly positively correlated with the difference value of the endolymph to vestibule-volume ratio (EVVR) and grading of cochlear hydrops between prior to and following surgery. Among patients with a decreased EVVR, the average hearing threshold and -SP/AP ratio was significantly decreased following surgery, as compared to that prior to surgery. Six out of seven patients with a hearing improvement (≥10-dB decline) and 4/5 patients with a negative conversion of EcochG showed downgrading of their hydrops in the cochlea and/or vestibule. By contrast, among patients with an increased EVVR, the average hearing threshold and -SP/AP ratio tended to increase following EDB, as compared with that prior to surgery. One out of two patients with a hearing deterioration (≥10-dB elevation) showed upgrading of her hydrops in both cochlea and vestibule. The present results showed the downgrading of cochlear and/or vestibular hydrops accompanied by the downregulation of the hearing threshold and -SP/AP ratio of EcochG, as well as the upgrading of cochlear and/or vestibular hydrops that tended to upregulate the hearing threshold and -SP/AP ratio of EcochG; this suggested that hearing loss is likely to be caused by hydrops and that the impaired hearing function be modulated by changes in the hydrops.