Minimally invasive surgeries for spontaneous hypertensive intracerebral hemorrhage (MISICH): a multicenter randomized controlled trial.

BACKGROUND: Intracerebral hemorrhage (ICH) is a common stroke type with high morbidity and mortality. There are mainly three surgical methods for treating ICH. Unfortunately, thus far, no specific surgical method has been proven to be the most effective. We carried out this study to investigate whether minimally invasive surgeries with endoscopic surgery or stereotactic aspiration (frameless navigated aspiration) will improve functional outcomes in patients with supratentorial ICH compared with small-bone flap craniotomy. METHODS: In this parallel-group multicenter randomized controlled trial conducted at 16 centers, patients with supratentorial hypertensive ICH were randomized to receive endoscopic surgery, stereotactic aspiration, or craniotomy at a 1:1:1 ratio from July 2016 to June 2022. The follow-up duration was 6 months. Patients were randomized to receive endoscopic evacuation, stereotactic aspiration, or small-bone flap craniotomy. The primary outcome was favorable functional outcome, defined as the proportion of patients who achieved a modified Rankin scale (mRS) score of 0-2 at the 6-month follow-up. RESULTS: A total of 733 patients were randomly allocated to three groups: 243 to the endoscopy group, 247 to the aspiration group, and 243 to the craniotomy group. Finally, 721 patients (239 in the endoscopy group, 246 in the aspiration group, and 236 in the craniotomy group) received treatment and were included in the intention-to-treat analysis. Primary efficacy analysis revealed that 73 of 219 (33.3%) in the endoscopy group, 72 of 220 (32.7%) in the aspiration group, and 47 of 212 (22.2%) in the craniotomy group achieved favorable functional outcome at the 6-month follow-up (P = .017). We got similar results in subgroup analysis of deep hemorrhages, while in lobar hemorrhages the prognostic outcome was similar among three groups. Old age, deep hematoma location, large hematoma volume, low preoperative GCS score, craniotomy, and intracranial infection were associated with greater odds of unfavorable outcomes. The mean hospitalization expenses were ¥92,420 in the endoscopy group, ¥77,351 in the aspiration group, and ¥100,947 in the craniotomy group (P = .000). CONCLUSIONS: Compared with small bone flap craniotomy, endoscopic surgery and stereotactic aspiration improved the long-term outcome of hypertensive ICH, especially deep hemorrhages. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02811614.

A patient-specific, interactive, multiuser, online mixed-reality neurosurgical training and planning system.

OBJECTIVE: Mixed-reality simulation is an emerging tool for creating anatomical models for preoperative planning. Its use in neurosurgical training (NT) has been limited because of the difficulty in real-time interactive teaching. This study describes the development of a patient-specific, interactive mixed-reality NT system. The authors took cases of intracranial tumor resection or neurovascular compression (NVC) as examples to verify the technical feasibility and efficacy of the mixed-reality NT system for residents' training and preoperative planning. METHODS: This study prospectively enrolled 40 patients who suffered from trigeminal neuralgia, hemifacial spasms, or intracranial tumors. The authors used a series of software programs to process the multimodal imaging data, followed by uploading the holographic models online. They used a HoloLens or a standard iOS device to download and display the holographic models for training. Ten neurosurgical residents with different levels of surgical experience were trained with this mixed-reality NT system. Change in surgical strategy was recorded, and a questionnaire survey was conducted to evaluate the efficacy of the mixed-reality NT system. RESULTS: The system allows the trainer and trainee to view the mixed-reality model with either a HoloLens or an iPad/iPhone simultaneously online at different locations. Interactive manipulation and instant updates were able to be achieved during training. A clinical efficacy validation test was conducted. The surgeons changed their exploration strategy in 48.3% of the NVC cases. For residents with limited experience in surgery, the exploration strategy for 75.0% of all patients with NVC was changed after the residents were trained with the mixed-reality NT system. Of the 60 responses for intracranial tumors, the trainee changed the surgical posture in 19 (31.7%) cases. The change of the location (p = 0.0338) and size (p = 0.0056) of craniotomy are significantly related to the experience of the neurosurgeons. CONCLUSIONS: The mixed-reality NT system is available for local or real-time remote neurosurgical resident training. It may effectively help neurosurgeons in patient-specific training and planning of surgery for cases of NVC and intracranial tumor. The authors expect the system to have a broader application in neurosurgery in the near future.

The Feasibility and Accuracy of Holographic Navigation with Laser Crosshair Simulator Registration on a Mixed-Reality Display.

Addressing conventional neurosurgical navigation systems' high costs and complexity, this study explores the feasibility and accuracy of a simplified, cost-effective mixed reality navigation (MRN) system based on a laser crosshair simulator (LCS). A new automatic registration method was developed, featuring coplanar laser emitters and a recognizable target pattern. The workflow was integrated into Microsoft's HoloLens-2 for practical application. The study assessed the system's precision by utilizing life-sized 3D-printed head phantoms based on computed tomography (CT) or magnetic resonance imaging (MRI) data from 19 patients (female/male: 7/12, average age: 54.4 ± 18.5 years) with intracranial lesions. Six to seven CT/MRI-visible scalp markers were used as reference points per case. The LCS-MRN's accuracy was evaluated through landmark-based and lesion-based analyses, using metrics such as target registration error (TRE) and Dice similarity coefficient (DSC). The system demonstrated immersive capabilities for observing intracranial structures across all cases. Analysis of 124 landmarks showed a TRE of 3.0 ± 0.5 mm, consistent across various surgical positions. The DSC of 0.83 ± 0.12 correlated significantly with lesion volume (Spearman rho = 0.813, p < 0.001). Therefore, the LCS-MRN system is a viable tool for neurosurgical planning, highlighting its low user dependency, cost-efficiency, and accuracy, with prospects for future clinical application enhancements.

Predictive factors of tinnitus after vestibular schwannoma surgery: a case-control study.

BACKGROUND: Tinnitus is very common in patients with vestibular schwannoma (VS). We analyzed the related factors of tinnitus after surgery. METHODS: One hundred seventy-three patients diagnosed with unilateral VS operated via the retrosigmoid approach were included in the study. All patients underwent relevant examinations and completed the THI scale before surgery and 6 months after surgery. The prognosis of tinnitus was evaluated according to the changes in THI. RESULTS: Of the 129 preoperative tinnitus patients, postoperative tinnitus resolved in 12.4%, improved in 29.5%, remained unchanged in 28.6%, and worsened in 29.5%. 18.2% of 44 patients without preoperative tinnitus appeared new-onset tinnitus postoperatively. Thirty-six patients never had tinnitus. Patients with smaller tumor sizes (≤ 3 cm) were more likely to experience preoperative tinnitus. Younger patients and those with serviceable hearing preoperatively were more likely to report their tinnitus unchanged or worsened. A new onset of postoperative tinnitus in the preoperative non-tinnitus group was found in better preoperative hearing function. CONCLUSIONS: In this study, 70% of patients had persistent tinnitus after vestibular schwannoma resection. The prognosis of tinnitus was influenced by age and preoperative hearing function. Tinnitus is a bothersome symptom and is often underestimated by doctors. Assessment of tinnitus is mandatory during the management of vestibular schwannoma.

Direct Performance of Triple-Stage Tandem Mass Spectrometry Analysis Using Dual-Direction Dipolar Excitation in a Digital Linear Ion Trap.

The ion trap mass spectrometer offers a unique advantage over other mass spectrometers by enabling multistage tandem mass spectrometry analysis with a single mass analyzer. It is employed to generate fragment ions through collision-induced dissociation (CID) usually by applying alternating current (AC) signals to a pair of electrodes for dipole excitation. The process of achieving double-stage tandem mass spectrometry analysis (MS/MS) in the mass spectrometer involves successive stages of injection, cooling, isolation, excitation, and scanning. For triple-stage tandem mass spectrometry analysis (MS/MS/MS), additional stages of isolation, cooling, and excitation need to be added based on the MS/MS analysis, resulting in a complex and time-consuming mass spectrometry workflow. In this study, a digital ion trap technology with the method of simultaneously applying dipole excitation signals to two pairs of electrodes in the ion trap was developed. This allows fragmentation of the precursor ion in one direction while exciting the first-generation product ions in the other direction, enabling direct acquisition of MS/MS/MS spectra. This approach simplifies the process of tandem mass spectrometry, as demonstrated by experimental studies on methamphetamine, which show that dual-direction excitation effectively reduces workflow and enhances the intensity of product ions. Additionally, the method of direct MS/MS/MS spectra achieved through dual-direction excitation in a digital ion trap mass spectrometer allows for a lower q value of the precursor ion owing to a pseudopotential well depth that is 1.648 times greater than that of a traditional sinusoidal ion trap. The experiments of analyzing high concentration n-butyl acetate and isobutyl acetate have shown that the implementation of MS/MS/MS analysis using dual-direction excitation can provide more mass spectral information and effectively distinguish between the two isomeric samples. The results of direct triple-stage spectra obtained by this technique for several typical volatile hazardous chemicals demonstrate the method's capability for rapid analysis and detection of such substances. In summary, the developed method of dual-directional excitation coupled with digital ion trap technology enables direct performance of triple-stage tandem mass spectrometry analysis, improving fragment ion intensities and providing more valuable mass spectral information. It offers advantages such as simplified workflows, faster analysis, and enhanced accuracy for analyzing compounds with low mass fragment ions.

Knockdown of ATRX enhances radiosensitivity in glioblastoma.

BACKGROUND: Glioblastoma are highly malignant type of primary brain tumors. Treatment for glioblastoma multiforme (GBM) generally involves surgery combined with chemotherapy and radiotherapy. However, the development of tumoral chemo- and radioresistance induces complexities in clinical practice. Multiple signaling pathways are known to be involved in radiation-induced cell survival. However, the role of alpha-thalassemia X-linked mutant retardation syndrome (ATRX), a chromatin remodeling protein, in GBM radioresistance remains unclear. METHODS: In the present study, the ATRX mutation rate in patients with glioma was obtained from The Cancer Genome Atlas, while its expression analyzed using bioinformatics. Datasets were also obtained from the Gene Expression Omnibus, and ATRX expression levels following irradiation of GBM were determined. The effects of ATRX on radiosensitivity were investigated using a knockdown assays. RESULTS: The present study demonstrated that the ATRX mutation rate in patients with GBM was significantly lower than that in patients with low-grade glioma, and that patients harboring an ATRX mutation exhibited a prolonged survival, compared with to those harboring the wild-type gene. Single-cell RNA sequencing demonstrated that ATRX counts increased 2 days after irradiation, with ATRX expression levels also increasing in U-251MG radioresistant cells. Moreover, the results of in vitro irradiation assays revealed that ATRX expression was increased in U-251MG cells, while ATRX knockdown was associated with increased levels of radiosensitivity. CONCLUSIONS: High ATRX expression levels in primary GBM may contribute to high levels of radioresistance. Thus ATRX is a potential target for overcoming the radioresistance in GBM.

Single-cell RNA-seq of in vitro expanded cells from cranial neural crest reveals a rare odontogenic sub-population.

Ecto-mesenchymal cells of mammalian tooth germ develops from cranial neural crest cells. These cells are recognised as a promising source for tooth development and regeneration. Despite the high heterogeneity of the neural crest, the cellular landscape of in vitro cultured cranial neural crest cells (CNCCs) for odontogenesis remains unclear. In this study, we used large-scale single-cell RNA sequencing to analyse the cellular landscape of in vitro cultured mouse CNCCs for odontogenesis. We revealed distinct cell trajectories from primary cells to passage 5 and identified a rare Alx3+/Barx1+ sub-population in primary CNCCs that differentiated into two odontogenic clusters characterised by the up-regulation of Pax9/Bmp3 and Lhx6/Dmp1. We successfully induced whole tooth-like structures containing enamel, dentin, and pulp under the mouse renal capsule using in vitro cultured cells from both cranial and trunk neural crests with induction rates of 26.7% and 22.1%, respectively. Importantly, we confirmed only cells sorted from odontogenic path can induce tooth-like structures. Cell cycle and DNA replication genes were concomitantly upregulated in the cultured NCCs of the tooth induction groups. Our data provide valuable insights into the cell heterogeneity of in vitro cultured CNCCs and their potential as a source for tooth regeneration.

Head model dataset for mixed reality navigation in neurosurgical interventions for intracranial lesions.

Mixed reality navigation (MRN) technology is emerging as an increasingly significant and interesting topic in neurosurgery. MRN enables neurosurgeons to "see through" the head with an interactive, hybrid visualization environment that merges virtual- and physical-world elements. Offering immersive, intuitive, and reliable guidance for preoperative and intraoperative intervention of intracranial lesions, MRN showcases its potential as an economically efficient and user-friendly alternative to standard neuronavigation systems. However, the clinical research and development of MRN systems present challenges: recruiting a sufficient number of patients within a limited timeframe is difficult, and acquiring low-cost, commercially available, medically significant head phantoms is equally challenging. To accelerate the development of novel MRN systems and surmount these obstacles, the study presents a dataset designed for MRN system development and testing in neurosurgery. It includes CT and MRI data from 19 patients with intracranial lesions and derived 3D models of anatomical structures and validation references. The models are available in Wavefront object (OBJ) and Stereolithography (STL) formats, supporting the creation and assessment of neurosurgical MRN applications.

Large Accumulation of Collagen and Increased Activation of Mast Cells in Hearts of Mice with Hyperlipidemia / Grande Acúmulo de Colágeno e Aumento da Ativação de Mastócitos nos Corações de Ratos com Hiperlipidemia

Abstract Background: Hyperlipidemia, which is characterized by an elevation of lipids in the bloodstream, is a major risk factor for cardiac disease. Objectives: The present study investigated the role of fibrosis in the progression of hyperlipidemia in the mice heart, and whether mast cell activation was associated with the fibrosis process. Methods: Hyperlipidemia was produced in C57BL / 6 mice by feeding them on a high-fat diet for 8 weeks.To assess tissue fibrosis, picrosirius red staining was performed. Hematoxylin & eosin (H&E) staining was performed to identify the histopathological changes in the hearts. Immunohistochemistry was also accomplished to determine the localization of transforming growth factor (TGF)-β and α-smooth muscle actin (α-SMA). Western blotting was performed to analyze the expression of chymase, tryptase, TGF-β, α-SMA and activity of Wnt/β-catenin pathway. At the end, serum total cholesterol (TC) and triglycerides (TG) levels were measured. All the values were expressed as means ± SD, the statistical significance level adopted was 5%. Results: Hyperlipidemia mice showed significantly increased collagen deposition in the hearts compared with normal mice. In addition, H&E staining showed significant cellular degeneration. Cardiac muscle was arranged in disorder with fracture in mice of the model group. Immunohistochemistry and western blot analysis revealed that expression levels of tryptase, chymase, β-catenin, TGF-β and α-SMA were significantly increased in the hyperlipidemia mice compared with the control group. Conclusions: The results indicated that mast cell activation might induce cardiac fibrosis by tryptase and chymase in hyperlipidemia, which had a close relationship with the increased activity of TGF-β/Wnt/β-catenin pathway.

Resumo Fundamentos: A hiperlipidemia, que se caracteriza por uma elevação dos lipídeos na corrente sanguínea, é um importante fator de risco para a doença cardíaca. Objetivos: O presente estudo investigou o papel da fibrose na progressão da hiperlipidemia no coração do rato e se a ativação dos mastócitos estava associada ao processo de fibrose. Método: A hiperlipidemia foi produzida em ratos C57BL/6 alimentando-os com uma dieta rica em gordura durante 8 semanas. Para avaliar a fibrose tecidual, foi realizada coloração vermelha picro-Sirius. A coloração com hematoxilina e eosina (H & E) foi feita para identificar as alterações histopatológicas nos corações. A imuno-histoquímica também foi levada a cabo para determinar a localização do fator de crescimento transformante (TGF) -β e α-actina do músculo liso (α-SMA). O Western Blot foi realizado para analisar as expressões de quimase, triptase, TGF-β, α-SMA e a atividade da via Wnt / β-catenina. Finalmente, se mediram os níveis séricos de colesterol total (TC) e triglicerídeos (TG). Todos os valores foram expressos como média ± DP, o nível de significância estatística adotado foi de 5%. Resultados: Os ratos hiperlipidêmicos mostraram aumento significativo da deposição de colágeno nos corações em comparação com ratos normais. Além disso, a coloração de H & E mostrou degeneração celular significativa. O músculo cardíaco estava em desordem com ruptura de fibras em ratos do grupo modelo. A análise imuno-histoquímica e o Western Blot revelaram que os níveis de expressão de triptase, quimase, β-catenina, TGF-β e α-SMA estavam significativamente aumentados nos ratos hiperlipidêmicos em comparação com o grupo controle. Conclusões: Os resultados indicaram que a ativação de mastócitos pode induzir fibrose cardíaca por triptase e quimase em hiperlipidemia, a qual teve uma relação estreita com a atividade aumentada da via TGF-β / Wnt / β-catenina.