Diffusion MRI is valuable in brainstem glioma genotyping with quantitative measurements of white matter tracts.

OBJECTIVES: To investigate the value of diffusion MRI (dMRI) in H3K27M genotyping of brainstem glioma (BSG). METHODS: A primary cohort of BSG patients with dMRI data (b = 0, 1000 and 2000 s/mm2) and H3K27M mutation information were included. A total of 13 diffusion tensor and kurtosis imaging (DTI; DKI) metrics were calculated, then 17 whole-tumor histogram features and 29 along-tract white matter (WM) microstructural measurements were extracted from each metric and assessed within genotypes. After feature selection through univariate analysis and the least absolute shrinkage and selection operator method, multivariate logistic regression was used to build dMRI-derived genotyping models based on retained tumor and WM features separately and jointly. Model performances were tested using ROC curves and compared by the DeLong approach. A nomogram incorporating the best-performing dMRI model and clinical variables was generated by multivariate logistic regression and validated in an independent cohort of 27 BSG patients. RESULTS: At total of 117 patients (80 H3K27M-mutant) were included in the primary cohort. In total, 29 tumor histogram features and 41 WM tract measurements were selected for subsequent genotyping model construction. Incorporating WM tract measurements significantly improved diagnostic performances (p < 0.05). The model incorporating tumor and WM features from both DKI and DTI metrics showed the best performance (AUC = 0.9311). The nomogram combining this dMRI model and clinical variables achieved AUCs of 0.9321 and 0.8951 in the primary and validation cohort respectively. CONCLUSIONS: dMRI is valuable in BSG genotyping. Tumor diffusion histogram features are useful in genotyping, and WM tract measurements are more valuable in improving genotyping performance. CLINICAL RELEVANCE STATEMENT: This study found that diffusion MRI is valuable in predicting H3K27M mutation in brainstem gliomas, which is helpful to realize the noninvasive detection of brainstem glioma genotypes and improve the diagnosis of brainstem glioma. KEY POINTS: • Diffusion MRI has significant value in brainstem glioma H3K27M genotyping, and models with satisfactory performances were built. • Whole-tumor diffusion histogram features are useful in H3K27M genotyping, and quantitative measurements of white matter tracts are valuable as they have the potential to improve model performance. • The model combining the most discriminative diffusion MRI model and clinical variables can help make clinical decision.

Fast and Efficient Atmospheric NO2 Collection for Isotopic Analysis by a 3D-Printed Denuder System.

Being major species of atmospheric reactive nitrogen, nitrogen oxides (NOx = NO + NO2) have important implications for ozone and OH radical formation in addition to nitrogen cycles. Stable nitrogen isotopes (δ15N) of NOx have been sought to track NOx emissions and NOx chemical reactivities in the atmosphere. The current atmospheric NOx collection methods for isotopic analysis, however, largely suffer from unverified collection efficiency and/or low collection speed (<10 L/min). The latter makes it difficult to study δ15N(NOx) in pristine regions with low NOx concentrations. Here, we present a three-dimensional (3D)-printed honeycomb denuder (3DP-HCD) system, which can effectively collect atmospheric NO2 (a major part of NOx) under a variety of laboratory and field conditions. With a coating solution consisting of 10% potassium hydroxide (KOH) and 25% guaiacol in methanol, the denuder system can collect NO2 with nearly 100% efficiency at flow rates of up to 70 L/min, which is 7 times higher than that of the existing method and allows high-resolution (e.g., diurnal or finer resolution) NO2 collection even in pristine sites. Besides, the δ15N of NO2 collected by the 3DP-HCD system shows good reproducibility and consistency with the previously tested method. Preliminary results of online NO oxidation by a chrome trioxide (CrO3) oxidizer for simultaneous NO and NO2 collection are also presented and discussed.

Brainstem tumors may increase the impairment of behavioral emotional cognition in children.

PURPOSE: It remains unclear as to whether patients with brainstem tumor experience complex neuropsychiatric problems. In this cohort study, we specifically investigated behavioral, emotional and cognitive symptoms in pediatric patients with brainstem glioma and healthy individuals. METHODS: A total of 146 patients with pediatric brainstem tumors (aged 4-18 years old) and 46 age-matched healthy children were recruited to assess their behaviors and emotions examined by the Child Behavior Checklist. A variety of clinical factors were also analyzed. RESULTS: There were significant differences in most behavioral and emotional symptoms between pediatric patients and healthy subjects. Moreover, patients with pons tumors exhibited significantly higher scores than patients with medulla oblongata tumors (p = 0.012), particularly in concerning the syndrome categories of Withdrawn (p = 0.043), Anxious/depressed symptoms (p = 0.046), Thought Problems (p = 0.004), Attention deficits (p = 0.008), Externalizing problems (p = 0.013), and Aggressive behavior (p = 0.004). A tumor body located in the pontine (p = 0.01, OR = 4.5, 95% CI = 1.4-14.059) or DIPG in the midbrain (p = 0.002, OR = 3.818, 95% CI = 1.629-8.948) appears to act as a risk factor that is associated with more problems in patients with neuropsychiatric symptoms. CONCLUSIONS: Pediatric patients with brainstem tumors exhibit severe behavioral and emotional problems. Tumor invades the pontine and midbrain act a risk factor with more problems. It suggests that structural and functional abnormalities in the brainstem will cause prolonged behavioral problems and emotional-cognitive dysfunctions in young children.

Surgical management and clinical outcomes of cerebellar liponeurocytomas-a report of seven cases and a pooled analysis of individual patient data.

Cerebellar liponeurocytomas (CLPNs) are very rare, with very few studies on this disease. Their treatment protocol also remains unclear. To better understand the disease, we reviewed the clinical features and outcomes, and proposed a treatment protocol based on previously reported cases as well as cases from our institute. The clinical data were obtained from seven patients with pathologically confirmed CLPNs, who underwent surgical treatment at our institute between November 2011 and June 2021. We also reviewed the relevant literature and 75 patients with CLPNs were identified between September 1993 and June 2021. Risk factors for progression-free survival (PFS) were evaluated in the pooled cohort. Our cohort included four males and three females, with a mean age of 43.9 ± 14.5 years (range: 29-64 years). CLPNs were located in the lateral ventricle in three cases and in the cerebellum in four cases. All seven cases achieved gross total resection (GTR) and radiotherapy was administered to two cases. After a mean follow-up of 44.9 ± 44.4 months, all patients remained well, with no recurrence or death. Among the 75 patients reported in the literature, 35 were males and 40 were females, with a mean age of 46.2 ± 13.6 years (range: 6-77 years). Biopsy, GTR, and non-GTR were achieved in one (1.3%), 50 (66.7%), and 24 (32%) patients, respectively. Radiotherapy was administered to 16 cases and chemotherapy was administered to only one case. After a mean follow-up of 47.5 ± 51.5 months, three patients died and tumor recurrence occurred in 17 patients. Multivariate Cox analysis revealed that non-GTR predicted a poor PFS (p = 0.020), and postoperative radiotherapy could not prolong PFS (p = 0.708). Kaplan-Meier analysis also showed that GTR was significantly associated with longer PFS (p = 0.008), and postoperative radiotherapy could not prolong PFS (p = 0.707). PFS rates at 1, 5, 10 years were 92.7%, 78.0%, 23.8% respectively. CLPNs are very rare brain tumors. Although they have favorable clinical prognosis, the recurrence is relatively high. GTR should be the first choice for treatment and close follow-up is necessary. Postoperative radiotherapy could not improve PFS in this study. A larger cohort is needed to verify our findings.

Rapid measurements of curcumin from complex samples coupled with magnetic biocompatibility molecularly imprinted polymer using electrochemical detection.

Curcumin widely exists in food, and rapid selective and accurate detection of curcumin have great significance in chemical industry. In this experiment, a new magnetic biocompatibility molecularly imprinted polymer was prepared with nontoxic and biocompatible Zein to adsorb curcumin selectively. The polymer has high biocompatibility, good adsorption capacity, and specific adsorption for curcumin. Combined with portable electrochemical workstations, the polymer can be used to detect curcumin rapidly and cost-effectively. Using curcumin as a template and Zein as the crosslinking agent, the polymers were synthesized on the surface of Fe3 O4 particles for solid phase extraction. The experimental results showed that the polymer reached large adsorption capacity (32.12 mg/g) with fast kinetics (20 min). The adsorption characteristic of the polymer followed the Langmuir isotherm and pseudo-second-order kinetic models. Hexacyanoferrate was used as electrochemical probe to generate signals, and the linear range was 5-200 µg/mL for measuring curcumin. The experimental analysis showed that the polymer was an ideal material for selective accumulation of curcumin from complex samples. This approach has been successfully applied to the determination of curcumin in food samples with electrochemical detection, indicating that this is a feasible and practical technique.

Deciphering the immunological and prognostic features of hepatocellular carcinoma through ADP-ribosylation-related genes analysis and identify potential therapeutic target ARFIP2.

BACKGROUND: Hepatocellular carcinoma is one of the most common malignancies, and its prognosis and treatment outcome cannot be accurately predicted. ADP-ribosylation (ADPR) is a post-translationa modification of proteins involved in protein trafficking and immune response. Therefore, it is necessary to explore the ADPR-related genes associated with the prognosis and therapeutic efficacy of hepatocellular carcinoma treatments. METHODS: We downloaded the data of hepatocellular carcinoma samples to identify ADPR-related genes as prognostic markers, and established a novel ADPR-related index (ADPRI) based on univariate and multivariate COX regression analyses. Patients' prognosis, clinical features, somatic variant, tumor immune microenvironment, chemotherapeutic response and immunotherapeutic response were systematically analyzed. Finally, the role of ARFIP2 in hepatocellular carcinoma cells was preliminarily explored in vitro. RESULTS: The ADPRI consisting of four ADPR related genes (ARL8B, ARFIP2, PARP12, ADPRHL1) was established to be a reliable predictor of survival in patients with hepatocellular carcinoma and was validated using external datasets. Compared with the low ADPRI group, the high ADPRI group presented higher levels of mutation frequency, immune infiltration and patients in high ADPRI group benefit more from immune checkpoint inhibitor treatment. In addition, we predicted some natural small molecule drugs as potential therapeutic targets for hepatocellular carcinoma. Finally, Knockdown of ARFIP2 inhibits the proliferation and migration of hepatocellular carcinoma cells by inducing the G1/S phase cell cycle arrest in HCC cells. CONCLUSIONS: The ADPRI can be used to accurately predict the prognosis and immunotherapeutic response of hepatocellular carcinoma patients and providing valuable insights for future precision treatment of patients with hepatocellular carcinoma.

Flexible Organic Photovoltaic-Powered Hydrogel Bioelectronic Dressing With Biomimetic Electrical Stimulation for Healing Infected Diabetic Wounds.

Electrical stimulation (ES) is proposed as a therapeutic solution for managing chronic wounds. However, its widespread clinical adoption is limited by the requirement of additional extracorporeal devices to power ES-based wound dressings. In this study, a novel sandwich-structured photovoltaic microcurrent hydrogel dressing (PMH dressing) is designed for treating diabetic wounds. This innovative dressing comprises flexible organic photovoltaic (OPV) cells, a flexible micro-electro-mechanical systems (MEMS) electrode, and a multifunctional hydrogel serving as an electrode-tissue interface. The PMH dressing is engineered to administer ES, mimicking the physiological injury current occurring naturally in wounds when exposed to light; thus, facilitating wound healing. In vitro experiments are performed to validate the PMH dressing's exceptional biocompatibility and robust antibacterial properties. In vivo experiments and proteomic analysis reveal that the proposed PMH dressing significantly accelerates the healing of infected diabetic wounds by enhancing extracellular matrix regeneration, eliminating bacteria, regulating inflammatory responses, and modulating vascular functions. Therefore, the PMH dressing is a potent, versatile, and effective solution for diabetic wound care, paving the way for advancements in wireless ES wound dressings.

Nano-scale surface morphology evolution of Cu/Ti thin films.

This paper discusses solid-phase reaction, agglomeration and dendritic growth of Cu/Ti/Si thin films with different sublayer thickness, 70 nm Cu/20 nm Ti/Si and 20 nm Cu/70 nm Ti/Si, annealed using rapid thermal annealing (RTA) method at the temperature from 500 degrees C to 800 degrees C. The crystal structure is examined using XRD, and the surface morphology is measured by SEM and AFM. The sheet resistance is measured using four-point probe method. The dendritic patterns can be obtained in both thin films at high temperature but the density is not similar. For 70 nm Cu/20 nm Ti/Si thin films, Cu agglomerates at the annealed temperature upon to 700 degrees C and thin film is still crystalline after 800 degrees C. For 20 nm Cu/70 nm Ti/Si thin films, Cu agglomerated completely only after 500 degrees C and thin film has amorphous structure annealed after 800 degrees C.

The Interface Strengthening of Multi-Walled Carbon Nanotubes/Polylactic Acid Composites via the In-Loop Hybrid Manufacturing Method.

In this study, a new in-loop hybrid manufacturing method is proposed for fabricating multi-walled carbon nanotube (MWCNTs)/polylactic acid (PLA) composites. Molecular dynamics simulations were conducted in conjunction with experiments to reveal the mechanism of the proposed method for improving the interfacial performance of MWCNTs/PLA. The superposed gradients in the PLA chain activity and conformation due to the plasma-actuating MWCNTs promoted intermolecular interaction and infiltration between the MWCNTs and PLA chains, forming an MWCNTs-stress-transfer bridge in the direction perpendicular to the interlayer interface, and finally enhancing the performance of the composites. The experimental results indicated that the interfacial shear strength of the specimen fabricated using the proposed method increased by 30.50% to 43.26 MPa compared to those without the addition of MWCNTs, and this value was 4.77 times higher than that of the traditional manufacturing method, demonstrating the effectiveness of the proposed method in improving the interfacial properties of MWCNTs/PLA composites.

Improving the Mechanical Properties of CCFRPLA by Enhancing the Interface Binding Energy and Strengthening the Anti-Separation Ability of a PLA Matrix.

Additive manufacturing (AM) can produce almost any product shape through layered stacking. The usability of continuous fiber-reinforced polymers (CFRP) fabricated by AM, however, is restricted owing to the limitations of no reinforcing fibers in the lay-up direction and weak interface bonding between the fibers and matrix. This study presents molecular dynamics in conjunction with experiments to explore how ultrasonic vibration enhances the performance of continuous carbon fiber-reinforced polylactic acid (CCFRPLA). Ultrasonic vibration improves the mobility of PLA matrix molecular chains by causing alternative fractures of chains, promoting crosslinking infiltration among polymer chains, and facilitating interactions between carbon fibers and the matrix. The increase in entanglement density and conformational changes enhanced the density of the PLA matrix and strengthened its anti-separation ability. In addition, ultrasonic vibration shortens the distance between the molecules of the fiber and matrix, improving the van der Waals force and thus promoting the interface binding energy between them, which ultimately achieves an overall improvement in the performance of CCFRPLA. The bending strength and interlaminar shear strength of the specimen treated with 20 W ultrasonic vibration reached 111.5 MPa and 10.16 MPa, respectively, 33.11% and 21.5% higher than those of the untreated specimen, consistent with the molecular dynamics simulations, and confirmed the effectiveness of ultrasonic vibration in improving the flexural and interlaminar properties of the CCFRPLA.

Classification of Brainstem Gliomas Based on Tumor Microenvironment Status.

The inter-tumor heterogeneity of the tumor microenvironment (TME) and how it correlates with clinical profiles and biological characteristics in brainstem gliomas (BSGs) remain unknown, dampening the development of novel therapeutics against BSGs. The TME status was determined with a list of pan-cancer conserved gene expression signatures using a single-sample gene set enrichment analysis (ssGSEA) and was subsequently clustered via consensus clustering. BSGs exhibited a high inter-tumor TME heterogeneity and were classified into four clusters: "immune-enriched, fibrotic", "immune-enriched, non-fibrotic", "fibrotic", and "depleted". The "fibrotic" cluster had a higher proportion of diffuse intrinsic pontine gliomas (p = 0.041), and "PA-like" tumors were more likely to be "immune-enriched, fibrotic" (p = 0.044). The four TME clusters exhibited distinct overall survival (p < 0.001) and independently impacted BSG outcomes. A four-gene panel as well as a radiomics approach were constructed to identify the TME clusters and achieved high accuracy for determining the classification. Together, BSGs exhibited high inter-tumor heterogeneity in the TME and were classified into four clusters with distinct clinical outcomes and tumor biological properties. The TME classification was accurately identified using a four-gene panel that can potentially be examined with the immunohistochemical method and a non-invasive radiomics method, facilitating its clinical application.

Primary adult choroid plexus carcinomas: a single-center experience with a systematic review.

Objective: Primary adult choroid plexus carcinomas (PACPCs) are extremely rare brain tumors. The existing literature primarily comprises case reports, which limits our understanding of this uncommon disease. This study aims to describe the clinical characteristics and prognosis of PACPCs, as well as to identify optimal treatment strategies. Methods: We conducted a comprehensive analysis of clinical data from 7 patients with PACPCs who underwent surgical treatment at the Department of Neurosurgery, Beijing Tiantan Hospital, between March 2011 and March 2023. Additionally, a thorough search of the PubMed database was performed using the keywords "choroid plexus carcinoma" or "choroid plexus carcinomas" within the time frame of August 1975 to April 2023, which yielded a total of 28 identified cases. Subsequently, we evaluated risk factors for progression-free survival (PFS) and overall survival (OS) based on the pooled cases. Results: The pooled cohort, consisting of 7 cases from our institution and 28 cases from the literature, included 20 males and 15 females with a mean age of 44.3 ± 14.7 years (range: 21-73 years). Gross-total resection (GTR) and non-GTR were achieved in 22 (62.9%) and 13 (37.1%) patients, respectively. Radiotherapy and chemotherapy were administered to 29 (90.6%) and 13 (40.6%) patients, respectively. After a mean follow-up of 21.0 ± 26.7 months (range: 2-132 months), 18 patients were alive, and 11 patients had died. The multivariate Cox regression model demonstrated that non-GTR (HR 5.262, 95% CI 1.350-20.516, p=0.017) was a negative prognostic factor for OS. However, we did not find any risk factors for PFS. Conclusion: Complete surgical resection should be considered as the primary treatment approach for this rare disease. Chemotherapy and radiotherapy appear to have limited effectiveness in treating this condition. Further research with large cohorts is needed to validate our conclusions.

Establishment of an induced pluripotent stem cell line (JTUi003-A) from a patient with otosclerosis.

Otosclerosis is characterized by abnormal bone remodeling in the osseous labyrinth and progressive hearing loss. Although the etiology of otosclerosis is not fully understood, both environmental and genetic factors play important roles in its pathogenesis. Here, we generated an induced pluripotent stem cell line using episomal plasmid vectors from the peripheral blood mononuclear cells of a 48-year-old male with otosclerosis. The morphology and karyotype of the cells were normal. The expression of pluripotency markers was verified by mRNA and protein levels; the pluripotency state of the cell line was verified by successful differentiation into all three germ layers.

Posterior pilon fracture treated by opening the fibula fracture gap.

BACKGROUND: Posterior pilon fracture is a relatively common clinical fracture involving the posterior articular surface of the distal tibia. Currently, this form of fracture is receiving increasing attention. The surgical approach and technique for the treatment of posterior pilon fractures are still controversial. The purpose of this retrospective study was to compare the clinical and imaging outcomes of pilon fractures after treatment with the open fibula fracture line (OFFL) surgical technique versus the traditional posterolateral approach (TPL). METHODS: A retrospective analysis of patients with posterior pilon fractures treated using the open fibula fracture line technique and the traditional posterolateral approach between January 2015 and March 2020. Thirty-one cases were included in the open fibula fracture line technique group and twenty-eight cases were included in the traditional posterolateral approach group. We used the Burwell-Charnley scale to assess the effectiveness of surgical repositioning. The clinical outcomes were evaluated using American Orthopaedic Foot & Ankle Society ankle-hind foot score (AOFAS) and visual analog score (VAS). RESULTS: The overall anatomic reduction rate was slightly better in the open fibula fracture line group than in the conventional posterolateral group (81% vs. 71%, p = 0.406), but there was no statistically significant difference between the two groups. There were no statistically significant differences between the two groups in terms of fracture healing time and time to full weight bearing (p > 0.05). At the final follow-up, the AOFAS functional score of the open fibula fracture line group was statistically superior to that of the conventional posterolateral group (p < 0.05). However, there was no statistical difference between the two groups in VAS pain scores at rest, during activity, and under weight bearing (p > 0.05). CONCLUSION: The trans-fibular fracture approach provides a better surgical option for specific types of posterior pilon fractures with a high rate of anatomic repositioning and a good near-term outcome. TRIAL REGISTRATION: Retrospective registration.

Bottom-Up and Top-Down Attention Impairment Induced by Long-Term Exposure to Noise in the Absence of Threshold Shifts.

Objective: We aimed to assess the effect of noise exposure on bottom-up and top-down attention functions in industrial workers based on behavioral and brain responses recorded by the multichannel electroencephalogram (EEG). Method: In this cross-sectional study, 563 shipyard noise-exposed workers with clinical normal hearing were recruited for cognitive testing. Personal cumulative noise exposure (CNE) was calculated with the long-term equivalent noise level and employment duration. The performance of cognitive tests was compared between the high CNE group (H-CNE, >92.2) and the low CNE group; additionally, brain responses were recorded with a 256-channel EEG from a subgroup of 20 noise-exposed (NG) workers, who were selected from the cohort with a pure tone threshold <25 dB HL from 0.25 to 16 kHz and 20 healthy controls matched for age, sex, and education. P300 and mismatch negativity (MMN) evoked by auditory stimuli were obtained to evaluate the top-down and bottom-up attention functions. The sources of P300 and MMN were investigated using GeoSource. Results: The total score of the cognitive test (24.55 ± 3.71 vs. 25.32 ± 2.62, p < 0.01) and the subscale of attention score (5.43 ± 1.02 vs. 5.62 ± 0.67, p < 0.001) were significantly lower in the H-CNE group than in the L-CNE group. The attention score has the fastest decline of all the cognitive domain dimensions (slope = -0.03 in individuals under 40 years old, p < 0.001; slope = -0.06 in individuals older than 40 years old, p < 0.001). When NG was compared with controls, the P300 amplitude was significantly decreased in NG at Cz (3.9 ± 2.1 vs. 6.7 ± 2.3 µV, p < 0.001). In addition, the latency of P300 (390.7 ± 12.1 vs. 369.4 ± 7.5 ms, p < 0.001) and MMN (172.8 ± 15.5 vs. 157.8 ± 10.5 ms, p < 0.01) was significantly prolonged in NG compared with controls. The source for MMN for controls was in the left BA11, whereas the noise exposure group's source was lateralized to the BA20. Conclusion: Long-term exposure to noise deteriorated the bottom-up and top-down attention functions even in the absence of threshold shifts, as evidenced by behavioral and brain responses.

Adult diffuse intrinsic pontine glioma: clinical, radiological, pathological, molecular features, and treatments of 96 patients.

OBJECTIVE: Unlike its pediatric counterpart, adult diffuse intrinsic pontine glioma (DIPG) remains largely unelucidated. In this study, the authors examined the clinical, radiological, pathological, molecular, and clinical aspects of 96 adult DIPGs. METHODS: The National Brain Tumor Registry of China (April 2013-December 2019) was used to collect data on radiologically diagnosed adult DIPG patients. Survival analysis was conducted using Kaplan-Meier curves and univariate and multivariate Cox regression. The chi-square test/Wilcoxon rank-sum test and multivariable logistic regression were used to examine the clinical and radiological characteristics of patients with long-term survival (LTS). Interaction analyses between clinical factors were also conducted. RESULTS: The median age at symptom onset was 33.5 years, and the median duration of symptoms was 4.5 months. The frequencies of H3K27M and IDH1 mutations were 37.2% and 26.5%, respectively. All adult DIPG patients had a median overall survival (OS) of 19.5 months, with 1-, 2-, and 3-year survival rates of 67.0%, 42.8%, and 36.0%, respectively. The median OS of 40 patients who did not undergo treatment was 13.4 months. Patients with H3K27M-mutant tumors had a poorer prognosis than those with IDH-mutant tumors (p < 0.001) and H3K27M(-)/IDH-wild-type tumors (p = 0.002), with a median OS of 11.4 months. The median OSs of patients with H3K27M-mutant tumors who received treatment and those who did not were 13.8 months and 7.5 months, respectively (p = 0.016). Among patients with and without a pathological diagnosis, H3K27M mutation (p < 0.001) and contrast enhancement on MRI (p = 0.003), respectively, imparted a worse prognosis. Treatments were the predictive factor for patients with H3K27M-mutant tumors (p = 0.038), whereas contrast enhancement on MRI was the prognostic factor for the H3K27M(-) group (p = 0.038). In addition, H3K27M mutation and treatment were significant predictors for patients with symptom duration ≤ 4 months (H3K27M, p = 0.020; treatment, p = 0.014) and tumors with no contrast enhancement (H3K27M, p = 0.003; treatment, p = 0.042). Patients with LTS were less likely to have cranial nerve palsy (p = 0.002) and contrast enhancement on MRI at diagnosis (p = 0.022). CONCLUSIONS: It is recommended that all adult DIPG patients undergo genomic testing for H3K27M and IDH mutations. Despite the low prevalence, additional study is needed to better characterize the efficacy of various treatment modalities in adults with DIPG.

White matter alterations in pediatric brainstem glioma: An national brain tumor registry of China study.

Background: Previous studies have identified alterations in structural connectivity of patients with glioma. However, white matter (WM) integrity measured by diffusion kurtosis imaging (DKI) in pediatric patients with brainstem glioma (BSG) was lack of study. Here, the alterations in WM of patients with BSG were assessed through DKI analyses. Materials and methods: This study involved 100 patients with BSG from the National Brain Tumor Registry of China (NBTRC) and 50 age- and sex-matched healthy controls from social recruitment. WM tracts were segmented and reconstructed using U-Net and probabilistic bundle-specific tracking. Next, automatic fiber quantitative (AFQ) analyses of WM tracts were performed using tractometry module embedded in TractSeg. Results: WM quantitative analysis identified alterations in DKI-derived values in patients with BSG compared with healthy controls. WM abnormalities were detected in the projection fibers involved in the brainstem, including corticospinal tract (CST), superior cerebellar peduncle (SCP), middle cerebellar peduncle (MCP) and inferior cerebellar peduncle (ICP). Significant WM alterations were also identified in commissural fibers and association fibers, which were away from tumor location. Statistical analyses indicated the severity of WM abnormality was statistically correlated with the preoperative Karnofsky Performance Scale (KPS) and symptom duration of patients respectively. Conclusion: The results of this study indicated the widely distributed WM alterations in patients with BSG. DKI-derived quantitative assessment may provide additional information and insight into comprehensively understanding the neuropathological mechanisms of brainstem glioma.

A Comparison of Chemotherapy Used with and without Apatinib for Patients with Ovarian Carcinoma Who Progressed after Standard Regimens: A Systematic Review and Meta-Analysis.

OBJECTIVE: This meta-analysis was conducted to compare the therapeutic efficacy and clinical safety of the combination therapy of apatinib plus chemotherapy with that of chemotherapy alone in patients with refractory or recurrent ovarian carcinoma (OC). METHODS: Relevant randomized controlled trials (RCT) or case-control studies (CCS) were identified by searching Chinese and English databases up to October 31, 2020. The risk of methodological bias tool and Newcastle-Ottawa scale (NOS) were used to assess trial quality. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the therapeutic effects and adverse drug reactions. Subgroup analyses of study type, study sample size, dosage of apatinib, and chemotherapy regimen between treatment group and control group were performed. Publication bias was assessed by funnel plot symmetry, Begg-Mazumdar test, and Egger test. The robustness of our results was presented by removing the trial one by one. RESULTS: Fifteen eligible studies covering 1,020 patients were included in this review and meta-analysis. Among these studies, 8 were RCTs, and 7 were CCSs. Compared with chemotherapy alone, apatinib plus chemotherapy significantly increased objective response rate (OR = 3.55; 95% CI 2.31 to 5.47), disease control rate (OR = 3.04; 95% CI 2.12 to 4.36), and overall survival (OR = 5.03; 95% CI 3.16 to 6.90). CONCLUSIONS: The combination treatment of apatinib plus chemotherapy provides better clinical benefits for OC patients when compared to chemotherapy alone and should be recommended for suitable patients with OC after the failure of standard regimens. However, further investigation into future large-scale prospective randomized research is still needed.

Contribution of Audiogram Classification in Evaluating Vestibular Dysfunction in Sudden Sensorineural Hearing Loss With Vertigo.

Object: We aimed to identify the relationship between vertigo symptoms and the involvement of vestibular dysfunction in sudden sensorineural hearing loss (SSNHL) and the contribution of audiogram classification. Methods: A total of 50 patients with unilateral SSNHL were retrospectively divided into the vertigo group and non-vertigo group depending on the presence of vertigo. The involved vestibular end organs (VEOs) were verified by a battery of vestibular function tests including video head impulse test (vHIT), cervical vestibular-evoked myogenic potential (cVEMP), and ocular VEMP (oVEMP). The correlations of audiogram configurations, initial pure-tone average (PTA), number of involved VEOs, prognosis (complete recovery rate), and vestibular functions were analyzed between the two groups. Additionally, the vestibular functions in a subgroup of profound SSNHL patients were further compared within groups with or without vertigo. Results: Significant differences in the initial audiogram configurations (p = 0.033) and the abnormal rates of the posterior semicircular canal (PSC) (p = 0.035) and oVEMP (p = 0.046) were found between the two groups. The number of involved VEOs was related to the initial PTA in the vertigo group (p = 0.002, r = 0.541) and non-vertigo group (p = 0.042, r = 0.446). The prognosis was related to the abnormal rate of cVEMP and the number of involved VEOs in both vertigo group (p = 0.008, r = 0.482; p = 0.039, r = 0.385, respectively) and non-vertigo group (p = 0.016, r = 0.520; p = 0.022, r = 0.495, respectively), and it was especially related to the audiogram configurations in the vertigo group (p < 0.001, r = 0.692). However, after classification by audiogram configurations, there was no statistical difference in the abnormal rates of all vestibular function tests or the number of involved VEOs between the profound SSNHL patients with or without vertigo. Conclusion: The relationship between the involvement of vestibular dysfunction and vertigo symptoms in patients with SSNHL was significantly different before and after audiogram classification. When evaluating the vestibular dysfunction in SSNHL patients, more attention should be paid to the audiogram configuration.

Steroid Administration Approach for Idiopathic Sudden Sensorineural Hearing Loss: A National Survey in China.

OBJECTIVE: To optimize a protocol for the steroid administration approach for idiopathic sudden sensorineural hearing loss (ISSNHL) in China. METHODS: A questionnaire was distributed to otolaryngologists. The data on demographics, indications for first-line and salvage treatment, such as intratympanic administration of steroids (ITS) and postauricular steroids (PAS), and procedures were analyzed. RESULTS: 74 respondents used oral steroids, 112 used intravenous injections, 10 used ITS and 6 used PAS as a monotherapy for first-line treatment, and 135 used ITS or PAS in conjunction with oral or intravenous injection as a first-line treatment. Of the 249 respondents who used ITS, 97.19% adopted it as salvage therapy. The most commonly used steroid was 0.5 ml dexamethasone at 5 mg/ml and the most common side effect was pain. Of the 174 respondents who used PAS, 94.25% used it as salvage therapy. The most commonly used steroid was 0.5 ml methylprednisolone mixed with 0.5 ml lidocaine. CONCLUSIONS: The obtained data suggested that intravenous injection of steroids was the most popular treatment for ISSNHL and that ITS or PAS were used as a salvage treatment in China.