Novel molecular subtypes of intracranial germ cell tumours expand therapeutic opportunities.

BACKGROUND: Intracranial germ cell tumours (IGCTs) are a rare group of malignancies that are clinically classified as germinomas and nongerminomatous germ cell tumours (NGGCTs). Previous studies have found that somatic mutations involving the MAPK/mTOR signalling pathway are common early events. However, a comprehensive genomic understanding of IGCTs is still lacking. METHODS: We established a cohort including over 100 IGCTs and conducted genomic and transcriptomic sequencing. RESULTS: We identified novel recurrent driver genomic aberrations, including USP28 truncation mutations and high-level copy number amplification of KRAS and CRKL caused by replication of extrachromosomal DNA. Three distinct subtypes associated with unique genomic and clinical profiles were identified with transcriptome analysis: immune-hot, MYC/E2F and SHH. Both immune-hot and MYC/E2F were predominantly identified in germinomas and shared similar mutations involving the RAS/MAPK signalling pathway. However, the immune-hot group showed an older disease onset age and a significant immune response. MYC/E2F was characterized by a younger disease onset age and increased genomic instability, with a higher proportion of tumours showing whole-genome doubling. Additionally, the SHH subtype was mostly identified in NGGCTs. CONCLUSIONS: Novel genomic aberrations and molecular subtypes were identified in IGCTs. These findings provide molecular basis for the potential introduction of new treatment strategies in this setting.

Chameleonic Reactivity of Imidoyl Sulfoxonium Ylides: Access to Functionalized Pyrroles and Dihydro-pyridines.

We have found a chameleonic reactivity of imidoyl sulfoxonium ylides. On the one hand, imidoyl sulfoxonium ylides react with electron-deficient reagents, such as alkynyl esters, to lead to the formation of 1,2-dihydro-pyridines. The methyl group attached to the sulfur atom acts as a methylene donor. On the other hand, imidoyl sulfoxonium ylides react with pyridinium 1,4-zwitterionic thiolates, which leads to the formation of functionalized pyrroles. Both transformations feature mild reaction conditions and good functional group tolerance.

The spatial distribution mechanism of PM2.5 and NO2 on the eastern coast of China.

The spatial distribution characteristics of multi-air pollutants and their impacts are difficult to quantify effectively. As PM2.5 and NO2 are the main air pollutants, it is of great significance to explore the spatial causes of their pollution and their interaction mechanism. This study used machine learning (LightGBM) and hot spot analysis to map the spatial distribution of PM2.5 and NO2 in Southwest Fujian (SWFJ) in 2018 and their key pollution areas. Then, the factors and interactive detection of geographical detectors were used to conduct a detailed analysis of the quantitative impact of potential factors such as human activities, terrain, air pollutants, and meteorology on PM2.5 and NO2 pollution. From this we can learn that 1. LightGBM has good stability for drawing the spatial distribution of PM2.5 and NO2. 2. The spatial mechanism of PM2.5 and NO2 can be effectively interpreted from a massive data and macro perspective. 3. A large amount of evidence shows that potential factors such as human activities, topography, air pollutants and meteorology have direct or indirect effects on PM2.5 and NO2 pollution in the SWFJ area. This includes the direct impact of local road traffic emissions on the distribution of PM2.5 and NO2 pollution, the digestion of both by vegetation, the mutual transformation of atmospheric pollutants themselves, and the impact of meteorological conditions. This study not only confirms the effectiveness of machine learning combined with geographical detectors to promote the study of regional air pollution mechanisms, but also confirms the feasibility of exploring the spatial distribution mechanisms of various air pollutants. Therefore, this study is of great significance for explaining the spatial distribution of PM2.5 and NO2, and can also provide reference for policy formulation to reduce regional PM2.5 and NO2 concentrations.

Identifying Tumor Microenvironment Biomarkers in Adherent and Cystic Vestibular Schwannomas.

OBJECTIVE: A subset of vestibular schwannomas (VSs), including cystic tumors, have higher postoperative morbidity because of the presence of adhesions between the tumor, facial nerve (FN), and brainstem. We identify tumor microenvironment (TME) biomarkers to better classify these tumors and predict the degree of tumor adherence. STUDY DESIGN: Retrospective case series. SETTING: Tertiary skull base referral center. METHODS: Adult patients with cystic and solid VS matched in tumor size who underwent surgical resection were included. Expressions of seven biomarkers of extracellular matrix remodeling and tumor immune response were quantified via immunohistochemistry. The distribution of CD45+ immune cells was evaluated in intratumoral and perivascular compartments. The degree of tumor adherence was categorized as none, adherent to FN, or adherent to both FN and brainstem. RESULTS: Twenty-eight patients were included. Cystic VSs were significantly more adherent than solid VSs ( p = 0.02). Patients with adherent VS had shorter duration of symptoms and were more likely to undergo subtotal resection. In solid tumors, matrix metalloproteinase (MMP)-2 expression ( p = 0.02) and CD163+ macrophage infiltration ( p = 0.007) were correlated with tumor size. Linear discriminant analyses (LDAs) demonstrated MMP-2, MMP-14, CD80, CD163, and perivascular CD45 to be individually predictive of the degree of tumor adherence (all p < 0.05), with perivascular CD45 being the best independent predictor ( p = 0.005). An LDA model including these biomarkers demonstrated 100% accurate discrimination of all three levels of tumor adherence ( p = 0.04). CONCLUSIONS: Adherent VS have a distinct proinflammatory TME characterized by elevated MMP expression, enrichment of tumor-associated macrophages, and perivascular immune cell infiltration.

Comparison of Postoperative Outcomes in Cystic Versus Solid Vestibular Schwannoma in a Multi-institutional Cohort.

OBJECTIVE: Cystic vestibular schwannomas (cVSs) have more variable and less favorable clinical outcomes after microsurgical resection compared with solid VS (sVS). This study compares the preoperative presentation and postoperative outcomes between cVS and sVS. STUDY DESIGN: Retrospective cohort study. SETTING: Two tertiary skull base referral centers. METHODS: Consecutive adult patients who underwent VS resection from 2016 to 2021 were included. Univariate and multivariate analyses compared differences in baseline symptoms and postoperative outcomes between cVS and sVS. RESULTS: There were a total of 315 patients (64% female; mean age, 54 yrs) and 46 (15%) were cystic. cVS were significantly larger than sVS (maximum diameter, 28 vs. 18 mm, p < 0.001) and had higher rates of dysphagia and dysphonia preoperatively (p < 0.02). cVSs were more likely to undergo translabyrinthine resection (76 vs. 50%, p = 0.001) and have a higher rate of subtotal resection (STR) compared with sVS (30 vs. 13%, p = 0.003). At latest follow-up, fewer cVS achieved good facial nerve (FN) outcome (House-Brackmann [HB] I/II) (80 vs. 90%, p = 0.048). Subanalysis of cVS and sVS matched in tumor size, and surgical approach did not show differences in the rate of STR or FN outcomes (HB I/II, 82 vs. 78%, p = 0.79). CONCLUSION: In this large multi-institutional series, cVSs represent a distinct entity and are characterized by larger tumor size and higher incidence of atypical symptoms. Although cVSs were more likely to undergo STR and portend worse FN outcomes than sVSs, this may be due to their larger tumor size rather than the presence of the cystic component.

Why Do Cochlear Implant Candidates Defer Surgery? A Retrospective Case-Control Study.

OBJECTIVE(S): Despite undergoing thorough cochlear implant (CI) candidacy evaluation and counseling, some patients ultimately elect against implantation. This study sought to identify patient-related and socioeconomic factors predicting CI deferral. METHODS: A retrospective study of adult (≥18 years old) CI candidates presenting between 2007 and 2021 at a tertiary academic CI center was performed. The primary outcome was device implantation. Data collected included age, gender, hearing status, race, zip code of residence, median family income (MFI), distance traveled from the CI center, marital status, employment status, and insurance status. Multivariable binary logistic regression was performed to identify predictors of implantation. RESULTS: A total of 200 patients qualifying for CI were included, encompassing 77 adults deferring surgery (CI-deferred) and 123 consecutive adults electing for surgery (CI-pursued). Age, gender, hearing status, insurance type, employment status, distance from the implant center, and MFI were comparable between the groups (p > 0.05). Compared to CI-pursued patients, CI-deferred patients were more likely to be non-Caucasian (24.7% vs. 9.8%, p = 0.015) and unmarried (55.8% vs. 38.2%, p = 0.015). On multivariable logistic regression, older age (OR 0.981, 0.964-0.998, p = 0.027), African American race (OR 0.227, 0.071-0.726, p = 0.012), and unmarried status (OR 0.505, 0.273-0.935, p = 0.030) were independent predictors of implant deferral. CONCLUSION: This study demonstrates that increasing age at evaluation, African American race, and unmarried status are predictors for deferring CI surgery despite being implant candidates. These patients may benefit from increased outreach in the form of counseling, education, and social support prior to undergoing CI surgery. LEVEL OF EVIDENCE: 3 - retrospective study with internal control group Laryngoscope, 134:2857-2863, 2024.

Investigating Deferral Rates in Cochlear Implantation: How Often Do Candidates Defer and Why?

OBJECTIVE: Evaluate the rate at which cochlear implant (CI) candidates decline surgery and identify associated factors. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Four hundred ninety-three CI candidates from July 1989 to December 2020 with complete demographic and socioeconomic data. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: Age, sex, race, marital and employment status, median household income percentile, distance-to-CI-center, and residence in a medically underserved county. RESULTS: Of the 493 CI candidates included, 80 patients (16.2%) declined surgery. Based on chart checking, the most common reason patients did not receive the implant was due to loss of follow-up (38%). African American patients were 73% less likely to undergo implantation compared with White patients (odds ratio [OR], 0.27 [0.11-0.68]; p = 0.005). Asian patients were 95% less likely to undergo implantation (OR, 0.05 [0.009-0.25]; p = 0.0003) compared with White patients. For every 1-year age increase, patients were 4% less likely to undergo implantation (OR, 0.96 [0.94-0.98]; p < 0.0001) and for every 10-year age increase, the patients were 33% less likely. Compared with their single counterparts, married patients were more likely to undergo implantation (OR, 1.87 [1.12-3.15]; p = 0.02). No differences were observed when comparing implanted and nonimplanted CI candidates in sex, employment status, distance-to-CI-center, or median family income percentile. A χ2 test of independence showed no association between receiving CIs and living in medically underserved counties ( χ2 = 2; N = 493; 0.3891; p = 0.53). CONCLUSIONS: Not infrequently, CI candidates decline surgery. Although demographic factors (race, age, and marital status) were associated with the cochlear implantation decision, socioeconomic factors (median family income and residence in a medically underserved community) were not. Perhaps cultural components of a patient's race have a larger impact on whether or not the patients get implanted.

Identification of immune-related candidate biomarkers in plasma of patients with sporadic vestibular schwannoma.

Vestibular schwannoma (VS) is an intracranial tumor arising from neoplastic Schwann cells and typically presenting with hearing loss. The traditional belief that hearing deficit is caused by physical expansion of the VS, compressing the auditory nerve, does not explain the common clinical finding that patients with small tumors can have profound hearing loss, suggesting that tumor-secreted factors could influence hearing ability in VS patients. We conducted profiling of patients' plasma for 66 immune-related factors in patients with sporadic VS (N > 170) and identified and validated candidate biomarkers associated with tumor size (S100B) and hearing (MCP-3). We further identified a nine-biomarker panel (TNR-R2, MIF, CD30, MCP-3, IL-2R, BLC, TWEAK, eotaxin, and S100B) with outstanding discriminatory ability for VS. These findings revealed possible therapeutic targets for VS, providing a unique diagnostic tool that may predict hearing change and tumor growth in VS patients, and may inform the timing of tumor resection to preserve hearing.

Using the Perimeter-Derived Diameter and Ellipticity Index of the Left Atrial Appendage Landing Zone to Predict Watchman Occluder Size.

Objective: The Watchman 2.5 occluder device is a useful device to treat atrial fibrillation (AF), and predicting the size of the Watchman 2.5 occluder device is important to the therapeutic efficacy. To use cardiac computed tomography angiography (CCTA) to predict the size of a Watchman 2.5 occluder device is a potential approach. Methods: The CCTA was used to individually plan the left atrial appendage (LAA) landing zone and measure the longest and shortest diameters, in addition to the perimeter. The average diameter, the perimeter-derived diameter (PDD), and the ellipticity index (EI) are then calculated from the above values. The longest diameter, the shortest diameter, the average diameter, and PDD of the landing zone were used to predict the occluder size. The size of the occluder was predicted using the longest diameter, the shortest diameter, the average diameter, and the PDD, which is then compared to the actual size. Results: There were differences between the predicted and actual values of the four groups, with the smallest variability in PDD (P = .007). There was a strong positive correlation between the four groups and the actual occluder size, with the strongest PDD correlation (r = 0.941, P < .001). The prediction accuracy ranged from 44.1% to 90.1% for different methods, with PDD having the highest prediction accuracy. The ROC curve of EI was predicted and plotted using the longest diameter method recommended in the Watchman's instructions, and the area under the curve was 0.905 (95%Confidence Interval (CI) 0.847-0.963), with a cut-off value of 1.198, a sensitivity of 88.9% and a specificity of 82.7%. LAAs with an EI<1.198 had similar accuracy in predicting occluder size, regardless of whether the longest diameter (93.94%) or PDD (87.88%) (P = .344) method was used. However, the kappa test showed poor agreement between the two methods (Kappa = 0.093). When EI ≥ 1.198 (n = 45), the accuracy of PDD in predicting occluder size was 93.33%, which is significantly higher than predictions of the longest diameter (28.9%) (P < .001). Conclusions: The longest diameter and the PDD methods predicted occluder size with a high degree of accuracy when the LAAs EI < 1.198; the PDD method is suggested to be a preferred method to treatAF.

Dietary Berberine and Ellagic Acid Supplementation Improve Growth Performance and Intestinal Damage by Regulating the Structural Function of Gut Microbiota and SCFAs in Weaned Piglets.

Early weaning is an effective method for improving the utilization rate of sows in intensive pig farms. However, weaning stress induces diarrhea and intestinal damage in piglets. Berberine (BBR) is known for its anti-diarrhea properties and ellagic acid (EA) is known for its antioxidant properties, however, whether their combination improves diarrhea and intestinal damage in piglets has not been studied, and the mechanism remains unclear. To explore the combined effects in this experiment, a total of 63 weaned piglets (Landrace × Yorkshire) were divided into three groups at 21 days. Piglets in the Ctrl group were treated with a basal diet and 2 mL saline orally, while those in the BE group were treated with a basal diet supplemented with 10 mg/kg (BW) BBR, 10 mg/kg (BW) EA, and 2 mL saline orally. Piglets in the FBE group were treated with a basal diet and 2 mL fecal microbiota suspension from the BE group orally, respectively, for 14 days. Compared with the Ctrl group, dietary supplementation with BE improved growth performance by increasing the average daily gain and average daily food intake and reducing the fecal score in weaned piglets. Dietary supplementation with BE also improved intestinal morphology and cell apoptosis by increasing the ratio of villus height to crypt depth and decreasing the average optical density of apoptotic cells; meanwhile, improvements also involved attenuating oxidative stress and intestinal barrier dysfunction by increasing the total antioxidant capacity, glutathione, and catalase, and upregulating the mRNA expressions of Occludin, Claudin-1, and ZO-1. Interestingly, the oral administration of a fecal microbiota suspension to piglets fed BE had similar effects to those of the BE group. According to 16S rDNA sequencing analysis, dietary supplementation with BE altered the composition of the microbiota, including firmicutes, bacteroidetes, lactobacillus, phascolarctobacterium, and parabacteroides, and increased the metabolites of propionate and butyrate. In addition, Spearman analysis revealed that improvements in growth performance and intestinal damage were significantly correlated with differential bacteria and short-chain fatty acids (SCFAs). In brief, dietary supplementation with BE improved the growth performance and intestinal damage by altering the gut microbiota composition and SCFAs in weaned piglets.

New insights into the cortex-to-stele ratio show it to effectively indicate inter- and intraspecific function in the absorptive roots of temperate trees.

The cortex-to-stele ratio (CSR), as it increases from thin- to thick-root species in angiosperms, is theorised to effectively reflect a compensation for the 'lag' of absorption behind transportation. But it is still not known if this compensatory effect exists in gymnosperm species or governs root structure and function within species. Here, anatomical, morphological, and tissue chemical traits of absorptive roots were measured in three temperate angiosperm and three gymnosperm species. Differences in the CSR and the above functional traits, as well as their intraspecific associations, were analyzed and then compared between angiosperms and gymnosperms. At the intraspecific level, the CSR decreased with increasing root order for all species. The expected functional indication of the CSR was consistent with decreases in specific root length (SRL) and N concentration and increases in the C to N ratio (C:N ratio) and the number of and total cross-sectional area of conduits with increasing root order, demonstrating that the CSR indicates the strength of absorption and transportation at the intraspecific level, but intraspecific changes are due to root development rather than the compensatory effect. These trends resulted in significant intraspecific associations between the CSR and SRL (R 2 = 0.36 ~ 0.80), N concentration (R 2 = 0.48 ~ 0.93), the C:N ratio (R 2 = 0.47 ~ 0.91), and the number of (R 2 = 0.21 ~ 0.78) and total cross-sectional area (R 2 = 0.29 ~ 0.72) of conduits in each species (p< 0.05). The overall mean CSR of absorptive roots in angiosperms was four times greater than in gymnosperms, and in angiosperms, the CSR was significantly higher in thick- than in thin-rooted species, whereas in gymnosperms, the interspecific differences were not significant (p > 0.05). This suggests that the compensation for the lag of absorption via cortex thickness regulation was stronger in three angiosperm species than in three gymnosperm species. In addition, there was poor concordance between angiosperms and gymnosperms in the relationships between CSRs and anatomical, morphological, and tissue chemical traits. However, these gymnosperm species show a more stable intraspecific functional association compared to three angiosperm species. In general, absorptive root CSRs could manifest complex strategies in resource acquisition for trees at both intra- and interspecific levels.

Identification of Immune-Related Candidate Biomarkers in Plasma of Patients with Sporadic Vestibular Schwannoma: Candidate Plasma Biomarkers in Vestibular Schwannoma.

Vestibular schwannoma (VS) is intracranial tumor arising from neoplastic Schwann cells, causing hearing loss in about 95% of patients. The traditional belief that hearing deficit is caused by physical expansion of the VS, compressing the auditory nerve, does not explain the common clinical finding that patients with small tumors can have profound hearing loss, suggesting that tumor-secreted factors could influence hearing ability in VS patients. Here, we conducted profiling of patients' plasma for 67 immune-related factors on a large cohort of VS patients (N>120) and identified candidate biomarkers associated with tumor growth (IL-16 and S100B) and hearing (MDC). We identified the 7-biomarker panel composed of MCP-3, BLC, S100B, FGF-2, MMP-14, eotaxin, and TWEAK that showed outstanding discriminatory ability for VS. These findings revealed possible therapeutic targets for VS-induced hearing loss and provided a unique diagnostic tool that may predict hearing change and tumor growth in VS patients and may help inform the ideal timing of tumor resection to preserve hearing.

Construction of atrial fibrillation-related circRNA/lncRNA-miRNA-mRNA regulatory network and analysis of potential biomarkers.

BACKGROUND: The specific pathogenesis of atrial fibrillation (AF) remains unclear. In this study, we examined the expression of differential messenger RNAs (mRNAs), circular RNAs (circRNAs), and long-stranded noncoding RNAs (lncRNAs) from human peripheral blood mononuclear cells to initially construct a circRNA/lncRNA-miRNA-mRNA ceRNA regulatory network to explore the pathogenesis of AF and to screen for potential biomarkers. METHODS: A total of four pairs of AF cases and healthy subjects were selected to detect differentially expressed mRNAs, circRNAs, and lncRNAs in peripheral blood mononuclear cells by microarray analysis. And 20 pairs of peripheral blood from AF patients and healthy subjects were selected for validation of mRNA, circRNA, and lncRNA by quantitative real-time PCR (qRT-PCR).The relevant ceRNA networks were constructed by GO and KEGG and correlation analysis. RESULTS: The results showed that compared with healthy subjects, there were 813 differentially expressed mRNAs (DEmRNAs) in peripheral blood monocytes of AF, including 445 upregulated genes and 368 downregulated genes, 120 differentially expressed circRNAs (DEcircRNAs), including 65 upregulated and 55 downregulated, 912 differentially expressed lncRNAs (DElncRNAs), including 531 upregulated and 381 downregulated lncRNAs. GO and KEGG analysis of DERNA revealed the biological processes and pathways involved in AF. Based on microarray data and predicted miRNAs, a ceRNA network containing 34 mRNAs, 212 circRNAs, 108 lncRNAs, and 38 miRNAs was constructed. CONCLUSION: We revealed a novel ceRNA network in AF and showed that downregulated XIST, circRNA_2773, and CADM1 were negatively correlated with miR-486-5p expression and had a potential targeting relationship with miR-486-5p.

Outcomes After Transcutaneous Bone-Conduction Implantation in Adults and Children.

OBJECTIVE: To evaluate clinical and audiometric outcomes of adult and pediatric patients implanted with a semi-implantable transcutaneous active bone-conduction implant. STUDY DESIGN: Retrospective chart review. SETTING: Two tertiary referral centers. PATIENTS: Subjects implanted with the semi-implantable transcutaneous active bone-conduction implant called BoneBridge. INTERVENTION: Implantation of the BoneBridge and audiometric evaluations. MAIN OUTCOME MEASURES: Audiometric, clinical, and surgical outcomes as well as complications. RESULTS: Forty-two adults and 20 children were implanted for conductive or mixed hearing loss as well as single-sided deafness. Implantation significantly improved mean air-conduction pure-tone average from 72.8 ± 22.3 to 35 ± 9 dB in adults and from 65.7 ± 24.3 to 19.6 ± 8.2 dB in children (both p < 0.001). Word recognition score improved from 63.7 ± 38.8% to 85.6 ± 10.6% in adults and 57.8 ± 38% to 89.3 ± 10.1% in children (both p < 0.05). The rate of revision surgery was 11.3%, with four patients (6.5%) undergoing removal for device-related complications, two (3.2%) for complications associated with implantation, and one (1.6%) for device failure secondary to external trauma. CONCLUSIONS: In a large retrospective series consisting of both pediatric and adult patients, implantation with a transcutaneous active bone-conduction implant was found to be a reliable aural rehabilitation option for a variety of hearing loss etiologies.

The research hotspots and trends of volatile organic compound emissions from anthropogenic and natural sources: A systematic quantitative review.

Volatile organic compound (VOC) emissions have attracted wide attention due to their impacts on atmospheric quality and public health. However, most studies reviewed certain aspects of natural VOCs (NVOCs) or anthropogenic VOCs (AVOCs) rather than comprehensively quantifying the hotspots and evolution trends of AVOCs and NVOCs. We combined the bibliometric method with the evolution tree and Markov chain to identify research focus and uncover the trends in VOC emission sources. This study found that research mainly focused on VOC emission characteristics, effects on air quality and health, and VOC emissions under climate change. More studies concerned on AVOCs than on NVOCs, and AVOC emissions have shifted with a decreasing proportion of transport emissions and an increasing share of solvent utilization in countries with high emissions and publications (China and the USA). Research on AVOCs is imperative to develop efficient and economical abatement techniques specific to solvent sources or BTEX species to mitigate the detrimental effects. Research on NVOCs originating from human sources risen due to their application in medicine, while studies on sources sensitive to climate change grew slowly, including plants, biomass burning, microbes, soil and oceans. Research on the long-term responses of NVOCs derived from various sources to climate warming is warranted to explore the evolution of emissions and the feedback on global climate. It is worthwhile to establish an emission inventory with all kinds of sources, accurate estimation, high spatial and temporal resolution to capture the emission trends in the synergy of industrialization and climate change as well as to simulate the effects on air quality. We review VOC emissions from both anthropogenic and natural sources under climate change and their effects on atmospheric quality and health to point out the research directions for the comprehensive control of global VOCs and mitigation of O3 pollution.

Case report: Widely split P' waves in a patient with focal atrial tachycardia.

Background: Widely split P waves in sinus rhythm have been reported previously. However, widely split P' waves in focal atrial tachycardia (AT) on a surface electrocardiogram (ECG) have rarely been reported. The electrophysiological mechanism is relatively difficult to clarify, requiring a electrophysiological study. Case summary: A 67-year-old patient, who had undergone two radiofrequency ablations for atrial fibrillation, presented with recurrent palpitation. During the palpitation episode, the 12-lead ECG showed AT with a 3:1 atrioventricular conduction rate. P' waves were markedly prolonged in duration and widely split in morphology. An electrophysiological study showed that the tachycardia arose from the left atrial appendage (LAA) and was conducted through two distinct pathways. The impulse of one pathway was transmitted solely via the superior part of the atrium, including the Bachmann bundle. The second pathway was conducted via the coronary sinus and transmitted the impulse from the LAA to the ventricle. After the site showed that the earliest activation was ablated, repeated intravenous infusion of isoprenaline and programmed atrial stimulation did not induce tachycardia. Conclusion: Widely split P' waves in AT indicate intra- and interatrial conduction blocks, which can be easily overlooked due to the presence of low-voltage areas. Therefore, an electrophysiological study is crucial for identifying the origin of the tachycardia and elucidating the mechanistic details.

Auditory Brain Stem Response Predictors of Hearing Outcomes after Middle Fossa Resection of Vestibular Schwannomas.

Objectives To analyze the relationship between preoperative and intraoperative auditory brain stem response (ABR) characteristics and hearing outcomes in patients with vestibular schwannomas (VS) undergoing hearing preservation (HP) surgery via a middle cranial fossa (MCF) approach. Design Prospective study. Setting Academic tertiary skull base referral center. Methods Pre- and postoperative pure-tone average (PTA) and word recognition score (WRS) were examined. Intraoperative ABR wave III latency, wave V latency, and amplitude were recorded. HP was defined as postoperative WRS ≥50%. Participants Adult patients with VS and WRS ≥50% who underwent MCF tumor resection between November 2017 and September 2019. Main Outcome Measures Postoperative hearing outcomes. Results Sixty patients were included. Mean tumor size was 9.2 mm (range, 3-17). HP rates were 56.7% for the cohort and 69.7% for tumors <10 mm. A complete loss of wave V was associated with an 82.9% increase in postoperative PTA ( p < 0.001) and 97.2% decrease in WRS ( p < 0.001), whereas a diminished wave V was correlated with 62.7% increase in PTA ( p < 0.001) and 55.7% decrease in WRS ( p = 0.006). A diminished or absent wave V, but not increased wave III/V latency or decreased wave V amplitude, was correlated with a decline in postoperative hearing class ( r = 0.735, p < 0.001). Receiver-operating characteristic analysis demonstrated that a stable wave V has the highest accuracy in predicting HP (sensitivity of 82.6%, specificity of 84.8%). Conclusion Of the examined preoperative and intraoperative ABR characteristics, a stable wave V intraoperatively was the strongest predictor of HP after MCF resection of VS. Level of Evidence Level III.

The Mechanism of Rac1 in Regulating HCC Cell Glycolysis Which Provides Underlying Therapeutic Target for HCC Therapy.

Aim: To explore the role of Rac1 on sorafenib resistance in hepatocellular carcinoma. Methods: CCK-8, wound healing assay, Transwell, and cell cycle assay were used to detect the tumor cells development. Cell viability was assessed by MTT. The glycolytic pathway was revealed by cellular metabolism assays. Result: We recovered that Rac1 upregulation was related to HCC patients' poorer prognosis. Forced expression of Rac1 promoted cell development and sorafenib chemoresistance in HCC cells. Rac1 inhibitor EHop-016 and sorafenib combination markedly prevented cell viability, G2/M phase cycle arrest, and apoptosis than single therapy. Furthermore, combination therapy decreased glycolysis in HCC cells. In vivo, the tumor growth was significantly prevented by combination therapy single therapy. Conclusion: Our research declares that Rac1 inhibition could block sorafenib resistance in HCC by decreasing glycolysis, which would provide an underlying target for HCC therapy.

Dispersed Bone Spicules as a Cause of Postoperative Headache after Retrosigmoid Vestibular Schwannoma Surgery: A Myth?

Objectives Dispersion of bone dust in the posterior fossa during retrosigmoid craniectomy for vestibular schwannoma (VS) resection could be a source of meningeal irritation and lead to development of persistent postoperative headaches (POH). We aim to determine risk factors, including whether the presence of bone spicules that influence POH after retrosigmoid VS resection. Design Present study is a retrospective case series. Setting The study was conducted at a tertiary skull-base referral center. Participants Adult patients undergoing VS resection via a retrosigmoid approach between November 2017 and February 2020 were included for this study. Main Outcome Measures Development of POH lasting ≥ 3 months is the primary outcome of this study. Results Of 64 patients undergoing surgery, 49 had complete data (mean age, 49 years; 53% female). Mean follow-up time was 2.4 years. At latest follow up, 16 (33%) had no headaches, 14 (29%) experienced headaches lasting <3 months, 19 (39%) reported POH lasting ≥3 months. Twenty-seven (55%) patients had posterior fossa bone spicules detectable on postoperative computed tomography (CT). Age, gender, body mass index, length of stay, tumor diameter, size of craniectomy, the presence of bone spicules, or the amount of posterior petrous temporal bone removed from drilling did not differ significantly between patients with POH and those without. On multivariate logistic regression, patients with POH were less likely to have preoperative brainstem compression by the tumor (odds ratio [OR] = 0.21, p = 0.028) and more likely to have higher opioid requirements during hospitalization (OR = 1.023, p = 0.045). Conclusion The presence of bone spicules in the posterior fossa on postoperative CT did not contribute to headaches following retrosigmoid craniectomy approach for VS resection.