Altered orientation dispersion index of white matter in individuals with insomnia during the COVID-19 pandemic: A study combining neuroimaging technique and Mendelian randomization.

STUDY OBJECTIVES: Coronavirus disease 2019 (COVID-19) can lead to insomnia. However, associations between COVID-19-caused insomnia and white matter (WM) changes are unclear. METHODS: All subjects had ever been infected with COVID-19. We investigated 89 insomniacs (29 chronic insomniacs, 33 new-onset insomniacs, 27 aggravated insomniacs) and 44 matched non-insomnia participants. Neurite orientation dispersion and density imaging (NODDI) was performed to identify micro-structural alterations of WM, and twelve scales related to sleeping status, memory, attention, learning, emotional status, and executive functions were used. Then, correlations between insomnia/cognitive-behavioral functions and diffusion metrics were tested. To eliminate influence of pre-COVID-19 factors on insomnia, causal relationships between COVID-19 and WM changes were validated by Mendelian randomization (MR) analysis. The significant brain regions of COVID-19-caused insomnia were intersected results of tract-based spatial statistics (TBSS) and MR analyses. RESULTS: Compared to non-insomnia group, insomnia group and its subgroups including post-COVID-19 aggravated or unchanged chronic insomnia group had higher orientation dispersion index (ODI) in extensive brain regions. The left superior longitudinal fasciculus (SLF), left posterior thalamic radiation (PTR), and left cingulate gyrus (CG) were specific brain regions in COVID-19-induced insomnia aggravation. After Bonferroni correction, partial correlation analyses within insomnia group showed that ODI in left SLF was positively correlated with Pittsburgh sleep quality index (PSQI), insomnia severity index (ISI), and self-rating anxiety scale (SAS) scores; ODI in the left PTR was positively correlated with PSQI and ISI scores. CONCLUSIONS: This study is a continuation of our previous research, which provided potential biomarkers for COVID-19-induced insomnia.

Impact of Epicardial Adipose Tissue on Right Cardiac Function and Prognosis in Pulmonary Arterial Hypertension.

BACKGROUND: Although epicardial adipose tissue (EAT) is linked to effects on survival in left-sided heart failure, the association between EAT and right-sided heart failure caused by pulmonary arterial hypertension (PAH) remains unknown. RESEARCH QUESTION: What are the potential impacts of EAT volume (EATV) on right ventricular function, biomarkers of myocardial injury, and long-term prognosis in patients with PAH?. STUDY DESIGN AND METHODS: A total of 135 age- and BMI-matched patients with PAH and 49 control subjects were included in this study. EATV was quantified by using cardiac magnetic resonance and was related to clinical correlates, N-terminal pro-brain natriuretic peptide, and cardiac function. Levels of EATV associated with the risk of clinical worsening were evaluated on a continuous scale (restricted cubic splines) and by previously defined centile categories with Cox proportional hazards regression models and Kaplan-Meier survival estimates. RESULTS: Compared with the control subjects, patients with PAH had a lower EATV (ln [EATV], 3.2 ± 0.8 mL vs 3.5 ± 0.7 mL; P = .034). The association of EATV with right ventricular end-diastolic volume (Pnonlinear = .001), right ventricular end-diastolic volume index (P < .001), right ventricular cardiac output (P = .003), N-terminal pro-brain natriuretic peptide (P = .030), and the risk of clinical worsening (P = .014) was U shaped. Compared with individuals with middle-level EATV, multivariable-adjusted hazard ratio for clinical worsening was 6.0 (95% CI, 1.3-27.8) for the individuals with low-level EATV and 6.8 (95% CI, 1.5-30.2) for high-level EATV in patients with PAH. INTERPRETATION: Patients with PAH had a decreased EATV compared with control subjects. EATV exhibited a U-shaped association with right ventricular function and biomarkers of myocardial injury in patients with PAH. Low and high levels of EATV might reduce long-term event-free survival in patients with PAH. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry; No. ChiCTR2100049804; www.chictr.org.cn.

Value for combination of T1WI star-VIBE with TWIST-VIBE dynamic contrast-enhanced MRI in distinguishing lung nodules. / T1WI star-VIBE增强结合TWIST-VIBE动态增强MRI对肺结节诊断的应用价值（英文）.

OBJECTIVES: With the increasing detection rate of lung nodules, the qualitative problem of lung nodules has become one of the key clinical issues. This study aims to evaluate the value of combining dynamic contrast-enhanced (DCE) MRI based on time-resolved imaging with interleaved stochastic trajectories-volume interpolated breath hold examination (TWIST-VIBE) with T1 weighted free-breathing star-volumetric interpolated breath hold examination (T1WI star-VIBE) in identifying benign and malignant lung nodules. METHODS: We retrospectively analyzed 79 adults with undetermined lung nodules before the operation. All nodules of patients included were classified into malignant nodules (n=58) and benign nodules (n=26) based on final diagnosis. The unenhanced T1WI-VIBE, the contrast-enhanced T1WI star-VIBE, and the DCE curve based on TWIST-VIBE were performed. The corresponding qualitative [wash-in time, wash-out time, time to peak (TTP), arrival time (AT), positive enhancement integral (PEI)] and quantitative parameters [volume transfer constant (Ktrans), interstitium-to-plasma rate constant (Kep), and fractional extracellular space volume (Ve)] were evaluated. Besides, the diagnostic efficacy (sensitivity and specificity) of enhanced CT and MRI were compared. RESULTS: There were significant differences in unenhanced T1WI-VIBE hypo-intensity, and type of A, B, C DCE curve type between benign and malignant lung nodules (all P<0.001). Pulmonary malignant nodules had a shorter wash-out time than benign nodules (P=0.001), and the differences of the remaining parameters were not statistically significant (all P>0.05). After T1WI star-VIBE contrast-enhanced MRI, the image quality was further improved. Compared with enhanced CT scan, the sensitivity (82.76% vs 80.50%) and the specificity (69.23% vs 57.10%) based on MRI were higher than that of CT (both P<0.001). CONCLUSIONS: T1WI star-VIBE and dynamic contrast-enhanced MRI based on TWIST-VIBE were helpful to improve the image resolution and provide more information for clinical differentiation between benign and malignant lung nodules.

Pre-operative MRI measurement of the Meckel's cave volume in percutaneous balloon compression of the trigeminal nerve.

OBJECTIVE: To explore the feasibility of measuring the volume of Meckel's cave by MRI before operation and its value in guiding percutaneous balloon compression (PBC) of trigeminal nerve (TN). METHODS: The pre-operative MRI and operative data of 31 patients, who underwent PBC of TN, were analyzed retrospectively. Axial scanning was performed using T2 weighted three-dimensional high-resolution MRI, and then coronal and sagittal images were reconstructed. Volumes of Meckel's cave were measured by two radiologists, and their consistence was assessed using intraclass correlation coefficient. Pearson and Spearman analyses were used to assess the correlations of the volumes of Meckel's cave among coronal, sagittal, and axial MRI images, and between that measured by MRI and the filling volume of operative balloon, respectively. Bland-Altman plot was used to assess their agreements. RESULTS: There was high consistency in volumes of Meckel's cave between the two radiologists with intraclass correlation coefficient from 0.921 to 0.962. High correlations and good agreements in volumes of Meckel's cave were obtained from the three orientations, with Pearson coefficients and differences of 0.96 and 0.01 ml (coronal vs sagittal), 0.95 and 0.01 ml (coronal vs axial), and 0.95 and 0.00 ml (sagittal vs axial), respectively. The moderate correlation and good agreements were also obtained between MRI and operative balloon volume (ρ = 0.448, p < 0.05; difference, 0.02 ml). CONCLUSION: It is feasible to measure the volume of Meckel's cave by MRI before operation, and it is of guiding significance for the individual selection of balloon filling volume in PBC of TN. ADVANCES IN KNOWLEDGE: This is the first study to investigate the relationships between the three-dimensional high resolution MRI images and the clinical volume of Meckel's cave. The high-resolution MRI method can help guide PBC of TN.

Gadolinium-based MR cisternography with prepontine cisternal routine for evaluating distribution pattern of intrathecal targeted drug delivery in pain management.

Gadolinium-based MR cisternography has been mainly applied in clinical evaluation of cerebrospinal fluid leaking, that is conducted by intrathecal administration of contrast media. Recently, we have reported one novel technique of intrathecal targeted drug delivery with prepontine cisternal routine to treat orofacial cancer pain. The aim of this study was to examine the distribution pattern of this intrathecal drug delivery strategy. Here, we introduce one case who suffered severe orofacial pain caused by sublingual gland tumor, and successfully attenuated by prepontine cisternal administration of analgesic agents. To assess the distribution of intrathecal drugs, postoperative MR images of brain, cervical, thoracic, and lumbar segments in axial, coronal, and sagittal planes were obtained after application of gadolinium. The perfusion rate of contrast medium was set at 0.01 mmol per hour for 24 hours prior to MR scanning. In the T1-weighted images, we can identify contrast spread not only locating around the site of the intrathecal catheter tip, but also concentrated to the lateral sides. None obvious side effect was found after intrathecal injection of contrast media. Thus, our finding demonstrated the local distribution phenomenon of intrathecal drugs through prepontine cisternal access, and the bilateral perfusion pattern may provide insights underlying the analgesic mechanism of trigeminal pain provided by this novel intrathecal therapy. Gadolinium-based MR cisternography may serve as a potential tool to confirm the therapeutic effect of intrathecal targeted drug delivery via prepontine cisternal routine in orofacial pain management.

Meniere's Disease Patients with Distinct Sac Pathoanatomic Findings React Differently to Endolymphatic Duct Blockage.

OBJECTIVES: To explore the possible difference in response to endolymphatic duct blockage (EDB) treatment in patients with Meniere's disease (MD) with distinct pathoanatomic characteristics of the sac. METHODS: In a total of 24 patients with MD receiving EDB treatment, the dynamics of the vertigo attack, hearing, vestibular function, and endolymph hydrops (EH) before surgery and 40 months following surgery in patients with normoplastic extraosseous portion of endolymphatic sac (eES) were compared with that in patients with atrophic eES. RESULTS: A higher prevalence of complete vertigo control, better cochlear and vestibular function, and lower endolymph to vestibule-volume ratio were found in patients with normoplastic eES than in those with atrophic eES. Moreover, the reversal of EH was found in a total of six patients in normoplastic eES group, but no reversal of EH was detected in the atrophic eES group after surgery. CONCLUSIONS: A difference in response to EDB treatment was shown in the MD patients with normoplastic eES and those with atrophic eES; the reversal of EH was found in the normoplastic eES group, but not in the atrophic eES group after surgery, suggesting two distinct pathologies in the eESs may underlie the pathogenesis of EH in two subgroups of MD patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2761-2769, 2023.

Prepontine cisternal routine for intrathecal targeted drug delivery in craniofacial cancer pain treatment: technical note.

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.

Arthroscopic anterior talofibular ligament repair with Internal Brace and lasso-loop technique for chronic ankle lateral instability.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging for Monitoring the Immune Response of Immunogenic Chemotherapy.

Objective: 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. 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. Results: At 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 (P<0.01), and a higher percentage of TUNEL staining (P < 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). Conclusions: The 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.

Diagnostic performance of gliomas grading and IDH status decoding A comparison between 3D amide proton transfer APT and four diffusion-weighted MRI models.

BACKGROUND: The focus of neuro-oncology research has changed from histopathologic grading to molecular characteristics, and medical imaging routinely follows this change. PURPOSE: To compare the diagnostic performance of amide proton transfer (APT) and four diffusion models in gliomas grading and isocitrate dehydrogenase (IDH) genotype. STUDY TYPE: Prospective. POPULATION: 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. FIELD STRENGTH/SEQUENCE: 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. ASSESSMENT: 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. STATISTICAL TESTS: 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. RESULTS: Compared with IDH-mutant gliomas, IDH-wildtype gliomas showed a significantly higher mean, 5th-percentile (APT5 ), and 95th-percentile from APTw, the 95th-percentile value of axial, mean, and radial diffusivity from DKI, and 95th-percentile value of isotropic volume fraction from NODDI, and no significantly different parameters from DTI and MAP (P = 0.075-0.998). The combined APT model showed a significantly wider area under the curve (AUC 0.870) for IDH status, when compared with DKI and NODDI. APT5 was significantly different between two of the three groups (glioma II vs. glioma III vs. glioma IV: 1.35 ± 0.75 vs. 2.09 ± 0.93 vs. 2.71 ± 0.81). DATA CONCLUSION: APT has higher diagnostic accuracy than DTI, DKI, MAP, and NODDI in glioma IDH genotype. APT5 can effectively identify both tumor grading and IDH genotyping, making it a promising biomarker for glioma classification. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

A comparison of endolymphatic duct blockage, endolymphatic sac drainage and endolymphatic sac decompression surgery in reversing endolymphatic hydrops in Meniere's disease.

BACKGROUND: To explore the differences between endolymphatic duct blockage, endolymphatic sac drainage and endolymphatic sac decompression surgery in the reversal of endolymphatic hydrops (EH) in patients with intractable Meniere's disease (MD). METHODS: A total of 27 MD patients receiving endolymphatic duct blockage surgery (n = 10), endolymphatic sac drainage surgery (n = 9) and endolymphatic sac decompression surgery (n = 8) underwent gadolinium-enhanced inner ear magnetic resonance imaging (MRI) scans prior to, 2 weeks after and at > 12 months following surgery. RESULTS: In the group with endolymphatic duct blockage, 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 group with endolymphatic sac drainage, 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 except a recurrence of vestibular hydrops in 1 patient. All 4 patients exhibited a complete control of vertigo, but hearing improved in 1, worsened in 1 and remained unchanged in 2. In the group with endolymphatic sac decompression, both the second and third MRI examination revealed no reversal of EH. CONCLUSIONS: The present study has shown that both endolymphatic duct blockage surgery and endolymphatic sac drainage surgery have the potential to reduce EH in certain MD patients, but none of the patients receiving endolymphatic sac decompression surgery showed reversal of their EH.

A prospective study of dual-energy computed tomography for differentiating metastatic and non-metastatic lymph nodes of colorectal cancer.

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 (λHU), standardized iodine concentration (n△HU), iodine water ratio (nIWR), electron density value (nρeff), 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 λHU, n△HU, and nIWR values than non-metastatic nodes in both the arterial and venous phases (P<0.01). The area under curve (AUC), sensitivity, and specificity were 0.80, 80%, and 66% for λHU; 0.86, 70%, and 95% for n△HU; and 0.88, 71%, and 95% for nIWR in the arterial phase. There was no significant difference in electron density and effective Z values between metastatic and non-metastatic lymph nodes. CONCLUSIONS: DECT quantitative parameters may help differentiate between metastatic and normal lymph nodes in patients with CRC.

Application value of CAIPIRINHA-VIBE with MOCO in liver magnetic resonance examination.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Motion-corrected free-breathing late gadolinium enhancement combined with a gadolinium contrast agent with a high relaxation rate: an optimized cardiovascular magnetic resonance examination protocol.

OBJECTIVE: This prospective study investigated the feasibility of an optimized cardiovascular magnetic resonance (CMR) examination protocol using the motion-corrected (MOCO), balanced steady-state free precession (bSSFP), phase-sensitive inversion recovery (PSIR) sequence combined with a gadolinium contrast agent with a high relaxation rate in patients who cannot hold their breath. METHODS: Fifty-one patients with heart disease underwent CMR examinations twice and these were performed with different late gadolinium enhancement (LGE) imaging sequences (fast low-angle shot [FLASH] sequence vs. MOCO sequence) and different gadolinium contrast agents (gadopentetate dimeglumine vs. gadobenate dimeglumine) with a 48-hour interval. LGE image quality, total time spent in the whole study, and time taken to perform LGE imaging were compared for the two CMR examinations. RESULTS: LGE images with the MOCO bSSFP PSIR sequence showed significantly higher image quality compared with those with the segmented FLASH PSIR sequence. There was a significant difference between the total scan time for the two examinations and different LGE sequences. CONCLUSIONS: The MOCO bSSFP PSIR sequence effectively improves the quality of LGE images. Changing the CMR scanning protocol by combining the MOCO bSSFP PSIR sequence with a gadolinium contrast agent with a high relaxation rate effectively shortens the scan time.Clinical trial registration number: ChiCTR-ROC-17013978.

Modulation of hearing function following the downgrading or upgrading of endolymphatic hydrops in Meniere's disease patients with endolymphatic duct blockage.

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.

The Treatment of Cholesteatomas Involving the Antrum and Mastoid Using Transcanal Underwater Endoscopic Ear Surgery.

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.

Value of CT and three-dimensional reconstruction revealing specific radiological signs for screening causative high jugular bulb in patients with Meniere's disease.

BACKGROUND: The aim of the present study was to investigate the pathological features of vestibular aqueduct (VA) related high jugular bulb (HJB) and explore the possible cause-consequence relation between HJB and endolymphatic hydrops (EH), and the potential specific radiological signs for screening causative HJB in Meniere's disease (MD). METHODS: High-resolution computed tomography (HRCT) and three-dimensional reconstruction (3DRC) were used to detect the anatomical variables associated with VA and jugular bulb (JB) in hydropic and non-hydropic ears. The presence or absence of EH in the inner ear was determined by gadopentetate dimeglumine-enhanced magnetic resonance imaging. The presence of different types of HJB, the anatomical variables of the VA and JB and the three types of anatomical relationship between the VA and HJB were compared between the hydropic and non-hydropic ears using the χ2 or Fisher's exact tests. P < 0.05 was considered to indicate a statistically significant difference. RESULTS: JB was classified as: Type 1, no bulb; type 2, below the inferior margin of the posterior semicircular canal (PSCC); type 3, between the inferior margin of the PSCC and the inferior margin of the internal auditory canal (IAC); type 4, above the inferior margin of the IAC. There were no significant differences in the presence of types 1, 2 and 3 JB between two groups. The presence of type 4 JB, average height of the JB and prevalence of the non-visualization of the VA in CT scans showed significant differences between two groups. The morphological pattern between the JB and VA revealing by 3DRC was classified as: Type I, the JB was not in contact with the VA; type II, the JB was in contact with the VA, but the latter was intact without obstruction; type III, the VA was obliterated by HJB encroachment. There were no significant differences in the presence of type I and II between two groups. Type III was identified in 5 hydropic ears but no non-hydropic ears, with a significant difference observed between the two groups. CONCLUSION: The present results showed that JB height and non-visualization of the VA on Pöschl's plane could render patients susceptible to the development of EH. A jugular bulb reaching above the inferior margin of the IAC (type 4 JB) could obstruct VA, resulting in EH in a few isolated patients with MD. VA obliteration revealed by 3DRC, as a specific radiological sign, may have the potential for screening causative HJB in MD.

Intranasal Delivery of Immunotherapeutic Nanoformulations for Treatment of Glioma Through in situ Activation of Immune Response.

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.

Dynamics in Endolymphatic Hydrops & Symptoms in Meniere's Disease After Endolymphatic Duct Blockage, Preliminary Results.

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.

Assessment of hearing loss induced by tympanic membrane perforations under blast environment.

PURPOSES: This study provides an approach to estimating tympanic membrane perforation-induced hearing loss (HL) using a human middle ear model. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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).