Assessment of changes in vessel area during needle manipulation in microvascular anastomosis using a deep learning-based semantic segmentation algorithm: A pilot study.

Appropriate needle manipulation to avoid abrupt deformation of fragile vessels is a critical determinant of the success of microvascular anastomosis. However, no study has yet evaluated the area changes in surgical objects using surgical videos. The present study therefore aimed to develop a deep learning-based semantic segmentation algorithm to assess the area change of vessels during microvascular anastomosis for objective surgical skill assessment with regard to the "respect for tissue." The semantic segmentation algorithm was trained based on a ResNet-50 network using microvascular end-to-side anastomosis training videos with artificial blood vessels. Using the created model, video parameters during a single stitch completion task, including the coefficient of variation of vessel area (CV-VA), relative change in vessel area per unit time (ΔVA), and the number of tissue deformation errors (TDE), as defined by a ΔVA threshold, were compared between expert and novice surgeons. A high validation accuracy (99.1%) and Intersection over Union (0.93) were obtained for the auto-segmentation model. During the single-stitch task, the expert surgeons displayed lower values of CV-VA (p < 0.05) and ΔVA (p < 0.05). Additionally, experts committed significantly fewer TDEs than novices (p < 0.05), and completed the task in a shorter time (p < 0.01). Receiver operating curve analyses indicated relatively strong discriminative capabilities for each video parameter and task completion time, while the combined use of the task completion time and video parameters demonstrated complete discriminative power between experts and novices. In conclusion, the assessment of changes in the vessel area during microvascular anastomosis using a deep learning-based semantic segmentation algorithm is presented as a novel concept for evaluating microsurgical performance. This will be useful in future computer-aided devices to enhance surgical education and patient safety.

Moyamoya Vasculopathy and Moyamoya-Related Systemic Vasculopathy: A Review With Histopathological and Genetic Viewpoints.

Systemic vasculopathy has occasionally been reported in cases of moyamoya disease (MMD). Since the pathological relationship between moyamoya vasculopathy (MMV) and moyamoya-related systemic vasculopathy (MMRSV) remains unclear, it was examined herein by a review of histopathologic studies in consideration of clinicopathological and genetic viewpoints. Although luminal stenosis was a common finding in MMV and MMRSV, histopathologic findings of vascular remodeling markedly differed. MMV showed intimal hyperplasia, marked medial atrophy, and redundant tortuosity of the internal elastic lamina, with outer diameter narrowing called negative remodeling. MMRSV showed hyperplasia, mainly in the intima and sometimes in the media, with disrupted stratification of the internal elastic lamina. Systemic vasculopathy has also been observed in patients with non-MMD carrying the RNF213 (ring finger protein 213) mutation, leading to the concept of RNF213 vasculopathy. RNF213 vasculopathy in patients with non-MMD was histopathologically similar to MMRSV. Cases of MMRSV have sometimes been diagnosed with fibromuscular dysplasia. Fibromuscular dysplasia is similar to MMD not only in the histopathologic findings of MMRSV but also from clinicopathological and genetic viewpoints. The significant histopathologic difference between MMV and MMRSV may be attributed to a difference in the original vascular wall structure and its resistance to pathological stress between the intracranial and systemic arteries. To understand the pathogeneses of MMD and MMRSV, a broader perspective that includes RNF213 vasculopathy and fibromuscular dysplasia as well as an examination of the 2- or multiple-hit theory consisting of genetic factors, vascular structural conditions, and vascular environmental factors, such as blood immune cells and hemodynamics, are needed.

Visual dysfunction and neurodegeneration caused by severe inflammatory optic neuropathy after coil embolization of a paraclinoid aneurysm: illustrative case.

BACKGROUND: Visual impairment due to delayed optic neuropathy is a rare complication of the endovascular treatment of paraclinoid aneurysms. An inflammatory response induced in the treated aneurysm wall is a known mechanism underlying this pathophysiology. The authors describe a case with severe and progressive optic neuropathy leading to neuronal degeneration and severe visual dysfunction. OBSERVATIONS: A 42-year-old female with a history of surgical clipping for a paraclinoid aneurysm presented with a recurrence. Although the patient was unaware of any visual dysfunction, a preoperative ophthalmological examination revealed mild inferior quadrantanopia in the left eye. The coil embolization procedure was uneventful; however, the following day, the patient experienced progressive visual impairment, which worsened despite the initiation of steroid therapy. Ophthalmological examination revealed a severe decrease in visual acuity and further deterioration of the visual field. Magnetic resonance imaging showed remarkable swelling and edema of the left optic nerve adjacent to the treated aneurysm. Despite continued steroid therapy, the patient's visual function did not recover well due to subsequent optic nerve degeneration. LESSONS: Optic neuropathy after endovascular procedures can lead to severe visual dysfunction. Careful management is essential, particularly when treating a symptomatic paraclinoid aneurysm, even if symptoms are only apparent on detailed examination.

Systemic immune-inflammation index in dural arteriovenous fistula: a feasible biomarker reflecting its clinical characteristics.

PURPOSE: The systemic immune-inflammation index (SII), a marker of systemic inflammation, can be calculated using peripheral blood tests. Although the SII has been reported as a feasible biomarker in various cerebrovascular diseases, no studies have explored in dural arteriovenous fistula (DAVF). A retrospective cohort study was performed to test whether the SII reflects the clinical characteristics of DAVF and whether this index could serve as a feasible biomarker. METHODS: This study included 28 patients who underwent endovascular treatment (39 sessions) for DAVF between 2014 and 2023. The SII was calculated using the following formula: platelet count multiplied by neutrophil count divided by lymphocyte count. We investigated the correlation between the SII and various clinical characteristics of DAVF, including symptom manifestation, and digital subtraction angiography findings. Additionally, we compared pre- and post-endovascular treatment changes in the SII. RESULTS: A significantly higher SII was observed in patients with multiple lesions, clinical symptoms (particularly aggressive symptoms), pseudophelebitic pattern (PPP), and sinus occlusion. Multivariate regression analysis revealed that the presence of symptoms (coefficient 270.9, P = 0.021) and PPP (coefficient 272.4, P = 0.017) were independent factors contributing to SII elevation. Notably, following endovascular treatment, there was a significant decrease in the elevated SII in patients whose symptoms resolved (P = 0.039) and where the DAVF was angiographically cured (P = 0.012). CONCLUSION: Elevation of the SII in patients with advanced DAVF and its decrease following endovascular treatment suggests that the SII reflects the disease condition and indicates its potential as a promising biomarker.

Predictive value of the hemispheric magnetic resonance angiography score on the development of indirect pial synangiosis after combined revascularization surgery for adult moyamoya disease.

PURPOSE: It is difficult to precisely predict indirect bypass development in the context of combined bypass procedures in moyamoya disease (MMD). We aimed to investigate the predictive value of magnetic resonance angiography (MRA) signal intensity in the peripheral portion of the major cerebral arteries for indirect bypass development in adult patients with MMD. METHODS: We studied 93 hemispheres from 62 adult patients who underwent combined direct and indirect revascularization between 2005 and 2019 and genetic analysis for RNF213 p.R4810K. The signal intensity of the peripheral portion of the major intracranial arteries during preoperative MRA was graded as a hemispheric MRA score (0-3 in the middle cerebral artery and 0-2 in the anterior cerebral and posterior cerebral arteries, with a high score representing low visibility) according to each vessel's visibility. Postoperative bypass development was qualitatively evaluated using MRA, and we evaluated the correlation between preoperative factors, including the hemispheric MRA score and bypass development, using univariate and multivariate analyses. RESULTS: A good indirect bypass was observed in 70% of the hemispheres. Hemispheric MRA scores were significantly higher in hemispheres with good indirect bypass development than in those with poor indirect bypass development (median: 3 vs. 1; p < 0.0001). Multiple logistic regression analysis revealed hemispheric MRA score as an independent predictor of good indirect bypass development (odds ratio, 2.1; 95% confidence interval, 1.3-3.6; p < 0.01). The low hemispheric MRA score (< 2) and wild-type RNF213 predicted poor indirect bypass development with a specificity of 0.92. CONCLUSION: Hemispheric MRA score was a predictive factor for indirect bypass development in adult patients who underwent a combined bypass procedure for MMD. Predicting poor indirect bypass development may lead to future tailored bypass surgeries for MMD.

Intranasal Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Hypoxic-Ischemic Brain Injury.

Hypoxic-ischemic brain injury arises from inadequate oxygen delivery to the brain, commonly occurring following cardiac arrest, which lacks effective treatments. Recent studies have demonstrated the therapeutic potential of exosomes released from mesenchymal stem cells. Given the challenge of systemic dilution associated with intravenous administration, intranasal delivery has emerged as a promising approach. In this study, we investigate the effects of intranasally administered exosomes in an animal model. Exosomes were isolated from the cell supernatants using the ultracentrifugation method. Brain injury was induced in Sprague-Dawley rats through a transient four-vessel occlusion model. Intranasal administration was conducted with 3 × 108 exosome particles in 20 µL of PBS or PBS alone, administered daily for 7 days post-injury. Long-term cognitive behavioral assessments, biodistribution of exosomes, and histological evaluations of apoptosis and neuroinflammation were conducted. Exosomes were primarily detected in the olfactory bulb one hour after intranasal administration, subsequently distributing to the striatum and midbrain. Rats treated with exosomes exhibited substantial improvement in cognitive function up to 28 days after the insult, and demonstrated significantly fewer apoptotic cells along with higher neuronal cell survival in the hippocampus. Exosomes were found to be taken up by microglia, leading to a decrease in the expression of cytotoxic inflammatory markers.

Intracerebral transplantation of MRI-trackable autologous bone marrow stromal cells for patients with subacute ischemic stroke.

BACKGROUND: Ischemic stroke is one of the leading causes of death and neurological disability worldwide, and stem cell therapy is highly expected to reverse the sequelae. This phase 1/2, first-in-human study evaluated the safety, feasibility, and monitoring of an intracerebral-transplanted magnetic resonance imaging (MRI)-trackable autologous bone marrow stromal cell (HUNS001-01) for patients with subacute ischemic stroke. METHODS: The study included adults with severe disability due to ischemic stroke. HUNS001-01 cultured with human platelet lysates and labeled with superparamagnetic iron oxide was stereotactically transplanted into the peri-infarct area 47-64 days after ischemic stroke onset (dose: 2 or 5 × 107 cells). Neurological and radiographic evaluations were performed throughout 1 year after cell transplantation. The trial was registered at UMIN Clinical Trial Registry (number UMIN000026130). FINDINGS: All seven patients who met the inclusion criteria successfully achieved cell expansion, underwent intracerebral transplantation, and completed 1 year of follow-up. No product-related adverse events were observed. The median National Institutes of Health Stroke Scale and modified Rankin scale scores before transplantation were 13 and 4, which showed improvements of 1-8 and 0-2, respectively. Cell tracking proved that the engrafted cells migrated toward the infarction border area 1-6 months after transplantation, and the quantitative susceptibility mapping revealed that cell signals at the migrated area constantly increased throughout the follow-up period up to 34% of that of the initial transplanted site. CONCLUSIONS: Intracerebral transplantation of HUNS001-01 was safe and well tolerated. Cell tracking shed light on the therapeutic mechanisms of intracerebral transplantation. FUNDING: This work was supported by the Japan Agency for Medical Research and Development (AMED; JP17bk0104045 and JP20bk0104011).

Pre- and post-operative semicircular canal function evaluated by video head impulse test in patients with vestibular schwannoma.

OBJECTIVES: To evaluate pre- and post-operative semicircular canal function in patients with vestibular schwannoma (VS) by the video Head Impulse Test (vHIT). METHODS: Nineteen patients with VS who underwent surgery were enrolled in this study. The gain in vestibulo-ocular reflex (VOR) and the degree of scatter in catch-up saccades were examined pre- and post-operatively for the semicircular canals in VS patients. RESULTS: Ten of 19 cases (52.6 %) with VS were defined as demonstrating both superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) impairment from the results of pre-operative vHIT. Hearing level and subjective vestibular symptoms showed significant correlations with pre-operative semicircular canal function. Compared to pre-operative vHIT results, VOR gains within 1 month after surgery were significantly reduced in all three canals; however, significant differences had disappeared in the anterior and posterior semicircular canals at 6 months after surgery. Cases of unknown origin had a significantly greater reduction in posterior semicircular canal function after surgery compared with those with disease of IVN origin. CONCLUSIONS: As vHIT could evaluate pre-operative vestibular nerve impairment, post-operative VOR gain reduction and the degree of vestibular compensation, semicircular canal function evaluated by vHIT provides a good deal of useful information regarding VS patients undergoing surgery compared to caloric testing, and vHIT should be performed pre- and post-operatively for patients with VS.

Impact of intraoperative cortical indocyanine green extravasation on local vasogenic edema immediately after direct revascularization in an adult with moyamoya disease: illustrative case.

BACKGROUND: Local vasogenic edema induced after direct revascularization in moyamoya disease (MMD) is associated with blood-brain barrier dysfunction, potentially leading to postoperative cerebral hyperperfusion (CHP) or delayed intracerebral hemorrhage. This phenomenon allows the leakage of fluids, proteins, and other substances from the blood vessels into the extracellular compartment. Typically, such edema is observed postoperatively rather than intraoperatively. OBSERVATIONS: A 48-year-old female with ischemic-onset MMD underwent revascularization on her left hemisphere with Suzuki's angiographic stage III. Direct bypass was successfully performed, as confirmed by intravenous indocyanine green (ICG) video angiography. Subsequently, ICG extravasation was observed near the anastomosis site, despite the absence of cortical injury or bleeding under white light microscopy. Postoperative radiological imaging showed reversible pure vasogenic edema in the corresponding area, with no evidence of CHP. The patient did not exhibit neurological deterioration and was discharged home on postoperative day 16. LESSONS: ICG, characterized by low molecular weight, water solubility, and high affinity with plasma proteins, can extravasate, serving as a direct indication of local vasogenic edema induced by direct revascularization in MMD. To enhance comprehension of the vulnerability of the blood-brain barrier in MMD, it is advisable to gather cases with prolonged observations of ICG video angiography after direct revascularization.

Differences between Acute Embolic and Atherosclerotic Middle Cerebral Artery Occlusion in Multiphase Arterial Spin-labeling Imaging.

Arterial spin-labeling magnetic resonance imaging (ASL-MRI) is widely used for evaluating collateral development in patients with acute ischemic stroke (AIS). This study aimed to characterize the findings of multiphase ASL-MRI between embolic and atherosclerotic large vessel occlusion (LVO) to aid in the differential diagnosis. Among 982 patients with AIS, 44 who were diagnosed with acute, symptomatic, and unilateral occlusion of the horizontal segment of the middle cerebral artery (MCA) were selected and categorized into embolic stroke (ES) and atherosclerosis (AT) groups. Using ASL-MRI (postlabeling delay [PLD] of 1.5, 2.0, and 2.5 s) at admission, the ipsilateral to contralateral ratio (ICR) of the signal intensity and its time-course increasing rate (from PLD 1.5 to 2.0 and 2.5, ΔICR) were measured and compared between the two groups. The mean ICR was significantly higher in the AT group than in the ES group (AT vs. ES: 0.49 vs. 0.27 for ICR1.5, 0.73 vs. 0.32 for ICR2.0, and 0.92 vs. 0.37 for ICR2.5). The ΔICR of PLD 1.5-2.0 (ΔICR2.0) and 2.5 (ΔICR2.5) were also significantly higher in the AT group than in the ES group (AT vs. ES: 50.9% vs. 26.3% for ΔICR2.0, and 92.6% vs. 42.9% for ΔICR2.5). Receiver operating characteristic curves showed moderate-to-strong discriminative abilities of each ASL-MRI parameter in predicting MCA occlusion etiology. In conclusion, multiphase ASL-MRI parameters may aid in differentiating intracranial LVO etiology during the acute phase. Thus, it is applicable to AIS management.

Identifying G6PC3 as a Potential Key Molecule in Hypoxic Glucose Metabolism of Glioblastoma Derived from the Depiction of 18F-Fluoromisonidazole and 18F-Fluorodeoxyglucose Positron Emission Tomography.

Purpose: Glioblastoma is the most aggressive primary brain tumor, characterized by its distinctive intratumoral hypoxia. Sequential preoperative examinations using fluorine-18-fluoromisonidazole (18F-FMISO) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) could depict the degree of glucose metabolism with hypoxic condition. However, molecular mechanism of glucose metabolism under hypoxia in glioblastoma has been unclear. The aim of this study was to identify the key molecules of hypoxic glucose metabolism. Methods: Using surgically obtained specimens, gene expressions associated with glucose metabolism were analyzed in patients with glioblastoma (n = 33) who underwent preoperative 18F-FMISO and 18F-FDG PET to identify affected molecules according to hypoxic condition. Tumor in vivo metabolic activities were semiquantitatively evaluated by lesion-normal tissue ratio (LNR). Protein expression was confirmed by immunofluorescence staining. To evaluate prognostic value, relationship between gene expression and overall survival was explored in another independent nonoverlapping clinical cohort (n = 17) and validated by The Cancer Genome Atlas (TCGA) database (n = 167). Results: Among the genes involving glucose metabolic pathway, mRNA expression of glucose-6-phosphatase 3 (G6PC3) correlated with 18F-FDG LNR (P = 0.03). In addition, G6PC3 mRNA expression in 18F-FMISO high-accumulated glioblastomas was significantly higher than that in 18F-FMISO low-accumulated glioblastomas (P < 0.01). Protein expression of G6PC3 was consistent with mRNA expression, which was confirmed by immunofluorescence analysis. These findings indicated that the G6PC3 expression might be facilitated by hypoxic condition in glioblastomas. Next, we investigated the clinical relevance of G6PC3 in terms of prognosis. Among the glioblastoma patients who received gross total resection, mRNA expressions of G6PC3 in the patients with poor prognosis (less than 1-year survival) were significantly higher than that in the patients who survive more than 3 years. Moreover, high mRNA expression of G6PC3 was associated with poor overall survival in glioblastoma, as validated by TCGA database. Conclusion: G6PC3 was affluently expressed in glioblastoma tissues with coincidentally high 18F-FDG and 18F-FMISO accumulation. Further, it might work as a prognostic biomarker of glioblastoma. Therefore, G6PC3 is a potential key molecule of glucose metabolism under hypoxia in glioblastoma.

Moyamoya Syndrome Associated with Late-onset Idiopathic Aqueduct Stenosis Successfully Treated with Endoscopic Third Ventriculostomy.

Moyamoya disease (MMD) is a rare idiopathic cerebrovascular disorder that causes transient ischemic attack (TIA) and ischemic stroke in the pediatric population. Herein, we report an extremely rare case of Moyamoya syndrome (MMS) and late-onset idiopathic aqueduct stenosis, a unique form of non-communicating hydrocephalus. A 17-year-old female presented with an intractable headache and occasional faintness. Pertinent medical history included a fourth ventricle epidermoid cyst without any evidence of aqueduct stenosis, which was surgically removed when she was two years of age. The patient subsequently experienced a TIA and was diagnosed with MMD at 14 years of age. Under the definitive diagnosis of MMS associated with a brain tumor, the patient underwent surgical revascularization of the symptomatic right hemisphere without complications. Although the ischemic symptoms resolved postoperatively, a medically intractable headache with occasional faintness persisted. Serial magnetic resonance imaging ultimately revealed newly developed non-communicating hydrocephalus due to acquired aqueduct stenosis at the age of 17. After careful exclusion of the development of either or both a periventricular anastomosis and vault moyamoya vessels along the surgical route using cerebral angiography, we performed an endoscopic third ventriculostomy (ETV) via the right anterior horn without complications. A complete resolution of her chronic headache with the shrinkage of the third ventriculomegaly was observed postoperatively. In cases of MMS associated with symptomatic aqueduct stenosis, transdural collaterals on the cranial vault and periventricular collaterals should be meticulously evaluated preoperatively using cerebral angiography to safely perform an ETV.

Increased CD44 expression in primary meningioma: its clinical significance and association with peritumoral brain edema.

OBJECTIVE: CD44 is a major cell surface receptor involved in cell adhesion and migration. The overexpression of CD44 is a poor prognostic factor in many neoplasms, including meningiomas. The aim of this study was to investigate the association between CD44 gene expression and clinical signatures of primary meningiomas. METHODS: CD44 gene expression was quantitatively evaluated by snap freezing tumor tissues obtained from 106 patients with primary meningioma. The relationships between CD44 expression and clinical signatures of meningiomas, including histological malignancy, tumor volume, and peritumoral brain edema (PTBE), were analyzed. PTBE was assessed using the Steinhoff classification (SC) system (from SC 0 to SC III). RESULTS: CD44 gene expression in WHO grade 2 and 3 meningiomas was significantly higher than that in grade 1 meningiomas. In addition, CD44 expression increased with the severity of PTBE. Particularly, among the grade 1 meningiomas or small-sized tumors (maximum tumor diameter < 43 mm), CD44 expression in tumors with severe PTBE (SC II or III) was significantly higher than that in tumors without or with mild PTBE (SC 0 or I). Multivariate logistic regression analysis also revealed that overexpression of CD44 was an independent significant factor of severe PTBE development in primary meningiomas. CONCLUSIONS: In addition to tumor cell aggressiveness, CD44 expression promotes the development of PTBE in meningioma. Since PTBE is a strong factor of tumor-related epilepsy or cognitive dysfunction in patients with meningioma, CD44 is thus a potential therapeutic target in meningioma with PTBE.

The prognostic values of plasma desmosines, crosslinking molecules of elastic fibers, in the disease progression of Moyamoya disease.

Moyamoya disease (MMD) is a cerebrovascular disease which is characterized by the chronic progression of steno-occlusive changes at the terminal portion of internal carotid arteries and the development of "moyamoya vessels." Dysregulation of the extracellular matrix is regarded as a key pathophysiology underlying unique vascular remodeling. Here, we measured the concentration of elastin crosslinkers desmosine and isodesmosine in the plasma of MMD patients. We aimed to reveal its diagnostic values of desmosines in the progression of steno-occlusive lesions. The concentrations of plasma desmosines were determined by liquid chromatography-tandem mass spectrometry. The temporal profiles of steno-occlusive lesions on magnetic resonance angiography were retrospectively evaluated, and the correlation between the progression of steno-occlusive changes in intracranial arteries and plasma desmosines concentrations was further analyzed. Plasma desmosines were significantly higher in MMD patients with disease progression compared to MMD patients without disease progression. Also, the incidence of disease progression was higher in MMD patients with plasma desmosines levels over limit of quantitation (LOQ) than those with plasma desmosines levels below LOQ. In conclusion, plasma desmosines could be potential biomarkers to predict the progression of steno-occlusive changes in MMD patients.

Intravenous Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Spinal Cord Injury by Regulating Neutrophil Extracellular Trap Formation through Exosomal miR-125a-3p.

Spinal cord injury (SCI) leads to devastating sequelae, demanding effective treatments. Recent advancements have unveiled the role of neutrophil extracellular traps (NETs) produced by infiltrated neutrophils in exacerbating secondary inflammation after SCI, making it a potential target for treatment intervention. Previous research has established that intravenous administration of stem cell-derived exosomes can mitigate injuries. While stem cell-derived exosomes have demonstrated the ability to modulate microglial reactions and enhance blood-brain barrier integrity, their impact on neutrophil deactivation, especially in the context of NETs, remains poorly understood. This study aims to investigate the effects of intravenous administration of MSC-derived exosomes, with a specific focus on NET formation, and to elucidate the associated molecular mechanisms. Exosomes were isolated from the cell supernatants of amnion-derived mesenchymal stem cells using the ultracentrifugation method. Spinal cord injuries were induced in Sprague-Dawley rats (9 weeks old) using a clip injury model, and 100 µg of exosomes in 1 mL of PBS or PBS alone were intravenously administered 24 h post-injury. Motor function was assessed serially for up to 28 days following the injury. On Day 3 and Day 28, spinal cord specimens were analyzed to evaluate the extent of injury and the formation of NETs. Flow cytometry was employed to examine the formation of circulating neutrophil NETs. Exogenous miRNA was electroporated into neutrophil to evaluate the effect of inflammatory NET formation. Finally, the biodistribution of exosomes was assessed using 64Cu-labeled exosomes in animal positron emission tomography (PET). Rats treated with exosomes exhibited a substantial improvement in motor function recovery and a reduction in injury size. Notably, there was a significant decrease in neutrophil infiltration and NET formation within the spinal cord, as well as a reduction in neutrophils forming NETs in the circulation. In vitro investigations indicated that exosomes accumulated in the vicinity of the nuclei of activated neutrophils, and neutrophils electroporated with the miR-125a-3p mimic exhibited a significantly diminished NET formation, while miR-125a-3p inhibitor reversed the effect. PET studies revealed that, although the majority of the transplanted exosomes were sequestered in the liver and spleen, a notably high quantity of exosomes was detected in the damaged spinal cord when compared to normal rats. MSC-derived exosomes play a pivotal role in alleviating spinal cord injury, in part through the deactivation of NET formation via miR-125a-3p.

Ommaya reservoir placement using ultrasound guidance via anterior fontanelle combined with frameless electromagnetic neuronavigation in patients with mucopolysaccharidosis type 2: Case reports and review of the literature.

Mucopolysaccharidosis type II (MPS II) results from the genetic deficiency of a lysosomal enzyme and is associated with central nervous system (CNS) dysfunction. In Japan, in addition to intravenous enzyme administration, intracerebroventricular enzyme delivery through the Ommaya reservoir has recently gained approval. Nevertheless, the ideal approach for safely implanting the reservoir into the narrow ventricles of infantile MPS II patients remains uncertain. In this report, we present two cases of successful reservoir placement in infantile MPS II patients using ultrasound guidance via the anterior fontanelle, coupled with flameless electromagnetic neuronavigation.

Long-term Outcomes of Combined Revascularization Surgery for Moyamoya Disease in the Elderly: A Single Institute Experience.

The opportunity to treat older patients with Moyamoya disease (MMD) is increasing. However, the surgical outcomes after combined direct and indirect revascularization for elderly patients with MMD are not fully understood, especially for those ≥60 years old. This retrospective study examined 232 consecutive hemispheres of 165 adults with MMD who underwent combined revascularization. Clinical features and surgical outcomes were compared between the elderly (≥60 years) and nonelderly group (<60 years). Thirteen (5.6%, 64.4 ± 4.0 years old) and 219 hemispheres (94.4%, 40.2 ± 10.8 years old) were included in the elderly and nonelderly group, respectively. The proportion of clinical presentations before surgery did not differ. However, the prevalence of hypertension and hyperlipidemia was significantly higher in the elderly group than in the nonelderly group. Meanwhile, hyperthyroidism was observed only in the nonelderly group. No significant intergroup differences were observed in the incidence of perioperative complications occurring within four weeks postsurgery. Notably, the elderly group was more prone to develop perioperative intracerebral hemorrhage (odds ratio (OR) 3.14, 95% confidence interval (CI) 0.45-13.5) than the nonelderly group. During a median follow-up period of 7.8 years, the incidence of stroke recurrence occurring later than four weeks postsurgery was not significantly different between the groups (hazard ratio, 1.19; 95% CI 0.133-10.6). The prevalence of independent outcomes (76.9% vs. 90.4%, P = 0.14) and mortality (7.7% vs. 1.4%, P = 0.21) did not differ significantly between the elderly and nonelderly groups, respectively. Perioperative intracerebral hemorrhage may be common in the elderly and should be considered to achieve a favorable surgical outcome.

Deep learning-based video-analysis of instrument motion in microvascular anastomosis training.

PURPOSE: Attaining sufficient microsurgical skills is paramount for neurosurgical trainees. Kinematic analysis of surgical instruments using video offers the potential for an objective assessment of microsurgical proficiency, thereby enhancing surgical training and patient safety. The purposes of this study were to develop a deep-learning-based automated instrument tip-detection algorithm, and to validate its performance in microvascular anastomosis training. METHODS: An automated instrument tip-tracking algorithm was developed and trained using YOLOv2, based on clinical microsurgical videos and microvascular anastomosis practice videos. With this model, we measured motion economy (procedural time and path distance) and motion smoothness (normalized jerk index) during the task of suturing artificial blood vessels for end-to-side anastomosis. These parameters were validated using traditional criteria-based rating scales and were compared across surgeons with varying microsurgical experience (novice, intermediate, and expert). The suturing task was deconstructed into four distinct phases, and parameters within each phase were compared between novice and expert surgeons. RESULTS: The high accuracy of the developed model was indicated by a mean Dice similarity coefficient of 0.87. Deep learning-based parameters (procedural time, path distance, and normalized jerk index) exhibited correlations with traditional criteria-based rating scales and surgeons' years of experience. Experts completed the suturing task faster than novices. The total path distance for the right (dominant) side instrument movement was shorter for experts compared to novices. However, for the left (non-dominant) side, differences between the two groups were observed only in specific phases. The normalized jerk index for both the right and left sides was significantly lower in the expert than in the novice groups, and receiver operating characteristic analysis showed strong discriminative ability. CONCLUSION: The deep learning-based kinematic analytic approach for surgical instruments proves beneficial in assessing performance in microvascular anastomosis. Moreover, this methodology can be adapted for use in clinical settings.

Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial.

Importance: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke. Objective: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset. Design, Setting, and Participants: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were age 20 years or older, presence of acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 8-20 at baseline), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset. Data analysis was performed between May 9 and August 15, 2022. Exposure: Patients were randomly assigned to either intravenous MultiStem in 1 single unit of 1.2 billion cells or intravenous placebo within 18 to 36 hours of ischemic stroke onset. Main Outcomes and Measures: The primary end points were safety and excellent outcome at day 90, measured as a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Statistical analysis of efficacy was performed using the Cochran-Mantel-Haenszel test. Results: This study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 (range, 35-95) years, and more than half of patients were men (112 [54.4%]). There were no between-group differences in primary and secondary end points. The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (12 [11.5%] vs 10 [9.8%], P = .90; adjusted risk difference, 0.5% [95% CI, -7.3% to 8.3%]). The frequency of adverse events was similar between treatment groups. Conclusions and Relevance: In this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study. Trial Registration: ClinicalTrials.gov Identifier: NCT02961504.