Moyamoya syndrome after proton beam therapy in a pediatric patient with a pineal germ cell tumor and a germline polymorphism in RNF213.

The effects of RNF213, which leads to moyamoya disease susceptibility, on radiation-induced moyamoya syndrome (MMS) remain unknown. We report a case of MMS after proton beam therapy (PBT) was deployed to treat a brain tumor in a patient with an RNF213 polymorphism. An 8-year-old boy underwent whole ventricular and local PBT for a pineal germ cell tumor and was diagnosed with radiation-induced MMS 9 months later. He underwent right and left revascularization surgeries for cerebral hemodynamic compromise at 17- and 18-years of age, respectively. Genetic analysis revealed a heterozygous germline polymorphism RNF213 p.R4810K. This is the first report to suggest an association between RNF213 polymorphism and radiation-induced MMS.

Enhancing the immunogenicity of Wilms tumor 1 epitope in mesothelioma cells with immunoproteasome inhibitors.

The immunogenicity of cancer cells is influenced by several factors, including the expression of the major histocompatibility complex class I (MHC-I), antigen expression, and the repertoire of proteasome-produced epitope peptides. The malignant pleural mesothelioma cell line ACC-MEOS-4 (MESO-4) expresses high levels of MHC-I and Wilms tumor 1 (WT1) tumor antigens. Using a functional T cell reporter assay specific for the HLA-A*24:02 restricted WT1 epitope (WT1235, CMTWNQMNL), we searched for factors that augmented the immunogenicity of MESO-4, focusing on proteasomes, which have a central role in the antigen processing machinery. ONX-0914, a selective inhibitor of the immunoproteasome subunit ß5i, enhanced immunogenicity dose-dependently at low concentrations without cytotoxicity. In addition, CD8+ T lymphocytes recognizing WT1 showed greater cytotoxicity against MESO-4 pre-treated with ONX-0914. MESO-4 expresses a standard proteasome (SP) and immunoproteasome (IP). Notably, IP has distinct catalytic activity from SP, favoring the generation of antigenic peptides with high affinity for MHC-I in antigen-presenting cells and cancer cells. In vitro, immunoproteasome digestion assay and mass spectrometry analysis showed that IP cleaved WT1235 internally after the hydrophobic residues. Importantly, this internal cleavage of the WT1235 epitope was mitigated by ONX-0914. These results suggest that ONX-0914 prevents the internal destructive cleavage of WT1235 by IP, thereby promoting the specific presentation of the WT1 epitope by MESO-4. In conclusion, selective IP inhibitors might offer a means to modulate cancer cell immunogenicity by directing the presentation of particular tumor epitopes.

Surgical trends and outcomes of open, laparoscopic, and robotic colostomy reversal for benign disease.

BACKGROUND: Despite the increasing use of minimally invasive surgeries, the outcome benefits of adopting minimally invasive surgery for colostomy reversal remain unclear. We aimed to analyze nationwide trends in the use of minimally invasive surgery for colostomy reversal and compare patient outcomes between different surgical approaches. METHODS: The National Inpatient Sample was queried for patients who underwent colostomy reversal for benign disease from 2015 to 2021. National trends in the use of minimally invasive surgery for colostomy reversal were analyzed by Cochran-Armitage tests. Multivariable linear and logistic regressions accounting for hospital sample weights were developed to examine the association between operative approach (open, laparoscopic, and robotic) and patient outcomes, including hospital complications, length of stay, and hospital charges. RESULTS: A total of 23,260 patients underwent colostomy reversal: 18,880 (81.2%) open, 3,245 (14.0%) laparoscopic, and 1,135 (4.9%) robotic surgery. From 2015 to 2021, the proportion of robotic approaches increased >5-fold (range 2.1-12.5%; Ptrend < .001), whereas the increase in laparoscopic approaches was not significant (range 11.5-16.2%; Ptrend = .34). Multivariable analysis showed that the laparoscopic approach was associated with a lower incidence of pulmonary complications (adjusted odds ratio, 0.49; 95% confidence interval, 0.28-0.87), surgical-site infection (odds ratio, 0.37; 95% CI, 0.19-0.72), peritonitis/abdominal abscess (odds ratio, 0.45; 95% confidence interval, 0.26-0.78), and paralytic ileus (odds ratio, 0.67; 95% confidence interval, 0.48-0.92). The robotic approach was associated with a lower incidence of paralytic ileus (odds ratio, 0.58; 95% confidence interval, 0.33-0.99). Laparoscopic and robotic approaches were associated with 22.9% and 29.9% shorter length of stay, respectively. The robotic approach was associated with 33.0% greater hospital charge. CONCLUSIONS: This study observed a significant trend toward the increased use of robotics in colostomy reversal and potential clinical benefits with minimally invasive surgery. Robotic colostomy reversal, along with laparoscopic approach, may provide better postoperative recovery compared with the open approach; however, the utility of robotic surgeries needs to be reevaluated in the future, given the limited clinical benefits despite greater hospital charges.

Questioning the Correlation Between Incidence of Hirschsprung Disease And Indications for Rectal Biopsy.

Aim: To review the indications for rectal mucosal/submucosal biopsy (RMSBx) used for diagnosing Hirschsprung's disease (HD) in pediatric patients. Methods: The medical records of all children between 1 and 15 years old assessed for chronic constipation between 2012 and 2022 were reviewed. Until the end of 2018, enema usage (E+) was a major indication for RMSBx. In 2019, laxative use for 3 months irrespective of enema use was added as an indication (L+). To determine the relevance of enema usage, L+ was subdivided by enema usage into (L+E+) and (L+E-) groups. The effect of changing the indications for RMSBx on the incidence of HD was investigated. Results: Of 562 eligible subjects, E+ = 410, L+ = 152; demographics are similar. RMSBx rate in E+ (E+RMSBx) was 36/410 (8.8%) and in L+ (L+RMSBx) was 42/152 (27.6%;) (P < .05). For L+RMSBx, 15/42 were L+E+ and 27/42 were L+E-. HD incidence in E+RMSBx was 8/36 (22.2%; E+HD) and in L+RMSBx was 13/42 (31.0%; L+HD) (p = ns). In L+RMSBx, HD incidence in L+E+ was 5/15 (33.3%; L+E+HD) and in L+E- was 8/27 (29.6%; L+E-HD) (P = ns). Differences in daily bowel motion frequency 6 months postoperatively were not statistically significant; E+HD (1.75/d) versus L+HD (2.03/d) and L+E+HD (1.60/day) versus L+E-HD (2.31/day). Unassisted voluntary defecation was confirmed 12 months postoperatively in 7/8 (87.5%) E+HD, 11/13 (84.6%) L+HD, 4/5 (80.0%) L+E+HD, and 7/8 (87.5%) L-E-HD; differences were not significant. Laxatives were still required in 2/8 (25.0%) E+HD, 3/13 (23.1%) L+HD, in 1/5 (20.0%) in L+E+HD, and 2/8 (25.0%) L+E-HD; differences were not significant. Conclusion: Incidence of HD was higher in L+HD, but not significantly different suggesting that indications for RMSBx have potential to influence incidence of HD and hint that the incidence of HD could actually be higher. Further assessment of additional indications is warranted to diagnose HD with greater accuracy.

Effective Smartphone Application Use for Postoperative Management of Moyamoya Disease.

Continuous and careful management is necessary after revascularization surgery for moyamoya disease (MMD). The postoperative information has been shared in person or by telephone and emails among doctors; however, this is not always efficient. We aimed to describe the feasibility of remote diagnosis and text chats using a smartphone application on postoperative MMD management. Twenty consecutive patients who underwent combined direct and indirect revascularization for MMD were prospectively investigated in this study. In ten patients, the operator viewed postoperative images uploaded on a smartphone screen using the Join application (Allm Inc., Tokyo, Japan). The doctors shared the radiological findings and treatment plans using the group text chat function and performed postoperative management. We evaluated the intermodality agreements of radiological findings between the smartphone screen and conventional viewer. Postoperative courses were compared between the two patient groups that used or did not use the application. All postoperative images were uploaded to the cloud server and the operator viewed them remotely on the smartphone screen without restriction of location. Detected abnormal findings were cerebral hyperperfusion (CHP), CHP-related watershed shift phenomenon, fluid-attenuated inversion recovery cortical hyperintensity, high signal intensity on diffusion-weighted imaging, CHP-related crossed cerebellar diaschisis, and hypoperfusion. Radiological agreement between the modalities was good in all cases, and additional findings were not obtained on the conventional viewer. The postoperative courses of the Join group were as good as those of the control group. Remote radiological diagnosis and text chat using a smartphone application were feasible and useful for efficient and safe postoperative MMD management.

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.

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.

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.

Non-invasive blood glucose estimation method based on the phase delay between oxy- and deoxyhemoglobin using visible and near-infrared spectroscopy.

Significance: Many researchers have attempted to estimate blood glucose levels (BGLs) noninvasively using near-infrared (NIR) spectroscopy. However, the optical absorption change induced by blood glucose is weak in the NIR region and often masked by interference from other components such as water and hemoglobin. Aim: Instead of using direct optical absorption by glucose, this study proposes an index calculated from oxy- and deoxyhemoglobin signals that shows a good correlation with BGLs while using conventional visible and NIR spectroscopy. Approach: The metabolic index, which is based on tissue oxygen consumption, was derived through analytical methods and further verified and reproduced in a series of glucose challenge experiments. Blood glucose estimation units were prototyped by utilizing commercially available smart devices. Results: Our experimental results showed that the phase delay between the oxy- and deoxyhemoglobin signals in near-infrared spectroscopy correlates with BGL measured by a conventional continuous glucose monitor. The proposed method was also confirmed to work well with visible spectroscopy systems based on smartphone cameras. The proposed method also demonstrated excellent repeatability in results from a total of 19 oral challenge tests. Conclusions: This study demonstrated the feasibility of non-invasive glucose monitoring using existing photoplethysmography sensors for pulse oximeters and smartwatches. Evaluating the proposed method in diabetic or unhealthy individuals may serve to further increase its practicality.

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.

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.

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.

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.

Jasmonates, gibberellins, and powdery mildew modify cell cycle progression and evoke differential spatiotemporal responses along the barley leaf.

Barley (Hordeum vulgare) is an important cereal crop, and its development, defence, and stress responses are modulated by different hormones including jasmonates (JAs) and the antagonistic gibberellins (GAs). Barley productivity is severely affected by the foliar biotrophic fungal pathogen Blumeria hordei. In this study, primary leaves were used to examine the molecular processes regulating responses to methyl-jasmonate (MeJA) and GA to B. hordei infection along the leaf axis. Flow cytometry, microscopy, and spatiotemporal expression patterns of genes associated with JA, GA, defence, and the cell cycle provided insights on cell cycle progression and on the gradient of susceptibility to B. hordei observed along the leaf. Notably, the combination of B. hordei with MeJA or GA pre-treatment had a different effect on the expression patterns of the analysed genes compared to individual treatments. MeJA reduced susceptibility to B. hordei in the proximal part of the leaf blade. Overall, distinctive spatiotemporal gene expression patterns correlated with different degrees of cell proliferation, growth capacity, responses to hormones, and B. hordei infection along the leaf. Our results highlight the need to further investigate differential spatial and temporal responses to pathogens at the organ, tissue, and cell levels in order to devise effective disease control strategies in crops.

Diagnostic Value of Vessel Wall Imaging to Determine the Timing of Extracranial‒Intracranial Bypass for Moyamoya Syndrome Associated with Active Sjögren's Syndrome: A Case Report.

BACKGROUND: Sjögren's syndrome is a chronic autoimmune disorder that predominantly affects exocrine organs. It is characterized by an organ-specific infiltration of lymphocytes. The involvement of the major cerebral arteries in Sjögren's syndrome has rarely been reported. A recent study reported a case of successful extracranial-intracranial (EC-IC) bypass without complications, even in the active inflammatory state, although the optimal timing of such a bypass remains unclear. CASE DESCRIPTION: We here report the case of a 43-year-old woman presenting with acute ischemic stroke due to progressive middle cerebral artery (MCA) occlusion and signs of primary Sjögren's syndrome. During intensive immunosuppressive therapy for active Sjögren's syndrome, the patient was monitored using contrast-enhanced magnetic resonance vessel wall imaging (MR-VWI). A couple of intravenous cyclophosphamide injections combined with a methylprednisolone pulse and antiplatelet therapy resulted in clear resolution of vessel wall enhancement, which suggested remission of inflammatory vasculitis. Nevertheless, she still experienced a transient ischemic attack (TIA) due to decreased regional cerebral blood flow by MCA occlusion, as demonstrated by the conventional time-of-flight MR angiography and single-photon emission computed tomography. Considering the increased risk of further stroke, the decision was made to perform an EC-IC bypass as a treatment for medically uncontrollable hemodynamic impairment. Her postoperative course was uneventful without further repeated TIAs, and continued immunosuppressive therapy for Sjögren's syndrome provided effective management. CONCLUSIONS: Our findings emphasize the diagnostic value of contrast-enhanced MR-VWI in monitoring the effect of immunosuppressive therapy for the major cerebral artery vasculitis and in determining the timing of EC-IC bypass as a "rescue" treatment for moyamoya syndrome associated with active Sjögren's syndrome.

Carotid Endarterectomy for a Case with an Extremely Twisted Internal Carotid Artery.

The internal carotid artery (ICA) typically runs posterolaterally to the external carotid artery (ECA) at the level of the common carotid artery (CCA) bifurcation in the neck. The "twisted ICA" is an anatomical variation, wherein the ICA is medial to the ECA. Several studies on the twisted ICA have discussed its anatomical definition, incidence, clinical features, and surgical results in patients with luminal stenosis. Computed tomography angiography (CTA)-based analyses of surgically treated cohorts documented a twist angle, reaching up to 95°. Carotid endarterectomy (CEA) was successfully performed for these patients. This study reports a case of a significantly twisted ICA with severe luminal stenosis that was successfully treated with CEA. An 81-year-old male was incidentally diagnosed with asymptomatic right ICA stenosis based on magnetic resonance (MR) angiography. Three-dimensional (3D)-CTA showed that the ICA revealed 74% stenosis of the ICA, based on the North American Symptomatic Carotid Endarterectomy Trial criteria. The 3D-CTA showed the ICA medial to the ipsilateral ECA at the level of the CCA bifurcation in the neck. It extended proximally to the pharynx, and the twist angle was 102°. Black-blood MR of the carotid plaque exhibited a high intensity on T1-weighted imaging, indicating vulnerability. Intraoperatively, the position of the ICA was corrected using multiple hooks instead of a surgical retractor. He showed no permanent deficits, such as an ipsilateral cerebral infarction, although transient postoperative hoarseness was observed. This case report documented a significantly twisted ICA with luminal stenosis, successfully treated via CEA, by correcting the carotid position using multiple hooks with gentle manipulation.