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.

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.

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.

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.

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.

Smoking cessation behavior in patients with a diagnosis of a non-communicable disease: The impact of perceived disease severity of and susceptibility to the disease.

INTRODUCTION: The Health Belief Model comprises two constructs influencing changed behaviors impacting on health, namely perceived severity and susceptibility. The aim of this study was to identify the impact of the combination of, or interactions between, these two constructs on quitting smoking in smokers with a diagnosis of a non-communicable disease (NCD). METHODS: From the large insurance claims database maintained by JMDC database (JMDC, Tokyo), we extracted data on 13284 participants who smoked. All participants were stratified according to their NCD diagnosis based on perceived severity and susceptibility as follows: Category I (high severity and high susceptibility) - acute myocardial infarction, and lung cancer; Category II (high severity and low susceptibility) - colorectal cancer, and stomach cancer; Category III (low severity and high susceptibility) - asthma, and transient ischemic attack; Category IV (low severity and low susceptibility) - appendicitis, and glaucoma. We performed multi-variable logistic regression analysis and calculated the proportion of those who were smoking at the first health check-up after the diagnosis and every three years thereafter. RESULTS: Using glaucoma as the reference, the adjusted odds ratios for smoking cessation were 14.2 (95% CI: 11.4-17.8) to 14.8 (95% CI: 12.5-17.4) in Category I; 4.5 (95% CI: 3.8-5.4) to 6.6 (95% CI: 5.4-8.0) in Category II; and 1.9 (95% CI: 1.7-2.1) to 2.8 (95% CI: 2.2-3.7) in Category III. In Categories I and II, the proportion of smokers rapidly decreased after diagnosis and mostly remained low thereafter. Smoking cessation rates for Categories I and II were not associated with readiness to improve lifestyles prior to NCD diagnosis. CONCLUSIONS: Our study confirms the significant impact of perceived severity of and susceptibility to the diagnosed disease on smoking cessation. The multiplicative effect of these two constructs at NCD diagnosis represents a 'teachable moment', a window of opportunity, for encouraging successful long-term smoking cessation.

The canonical E2Fs together with RETINOBLASTOMA-RELATED are required to establish quiescence during plant development.

Maintaining stable and transient quiescence in differentiated and stem cells, respectively, requires repression of the cell cycle. The plant RETINOBLASTOMA-RELATED (RBR) has been implicated in stem cell maintenance, presumably by forming repressor complexes with E2F transcription factors. Surprisingly we find that mutations in all three canonical E2Fs do not hinder the cell cycle, but similarly to RBR silencing, result in hyperplasia. Contrary to the growth arrest that occurs when exit from proliferation to differentiation is inhibited upon RBR silencing, the e2fabc mutant develops enlarged organs with supernumerary stem and differentiated cells as quiescence is compromised. While E2F, RBR and the M-phase regulatory MYB3Rs are part of the DREAM repressor complexes, and recruited to overlapping groups of targets, they regulate distinct sets of genes. Only the loss of E2Fs but not the MYB3Rs interferes with quiescence, which might be due to the ability of E2Fs to control both G1-S and some key G2-M targets. We conclude that collectively the three canonical E2Fs in complex with RBR have central roles in establishing cellular quiescence during organ development, leading to enhanced plant growth.

A Noonan-like pediatric patient with a de novo CBL pathogenic variant and an RNF213 polymorphism p.R4810K presenting with cardiopulmonary arrest due to left main coronary artery ostial atresia.

Left main coronary artery ostial atresia (LMCAOA) is an extremely rare condition. Here, we report the case of a 14-year-old boy with Noonan syndrome-like disorder in whom LMCAOA was detected following cardiopulmonary arrest. The patient had been diagnosed with Noonan syndrome-like disorder with a pathogenic splice site variant of CBL c.1228-2 A > G. He suddenly collapsed when he was running. After administering two electric shocks using an automated external defibrillator, the patient's heartbeat resumed. Cardiac catheterization confirmed the diagnosis of LMCAOA. Left main coronary artery angioplasty was performed. The patient was discharged without neurological sequelae. Brain magnetic resonance imaging revealed asymptomatic Moyamoya disease. In addition, RNF213 c.14429 G > A p.R4810K was identified. There are no reports on congenital coronary malformations of compound variations of RNF213 and CBL. In contrast, the RNF213 p.R4810K polymorphism has been established as a risk factor for angina pectoris and myocardial infarction in adults, and several congenital coronary malformations due to genetic abnormalities within the RAS/MAPK signaling pathway have been reported. This report aims to highlight the risk of sudden death in patients with RASopathy and RNF213 p.R4810K polymorphism and emphasize the significance of actively searching for coronary artery morphological abnormalities in these patients.

Tissue Acceleration as a Novel Metric for Surgical Performance During Carotid Endarterectomy.

BACKGROUND AND OBJECTIVES: Gentle tissue handling to avoid excessive motion of affected fragile vessels during surgical dissection is essential for both surgeon proficiency and patient safety during carotid endarterectomy (CEA). However, a void remains in the quantification of these aspects during surgery. The video-based measurement of tissue acceleration is presented as a novel metric for the objective assessment of surgical performance. This study aimed to evaluate whether such metrics correlate with both surgeons' skill proficiency and adverse events during CEA. METHODS: In a retrospective study including 117 patients who underwent CEA, acceleration of the carotid artery was measured during exposure through a video-based analysis. Tissue acceleration values and threshold violation error frequencies were analyzed and compared among the surgeon groups with different surgical experience (3 groups: novice , intermediate , and expert ). Multiple patient-related variables, surgeon groups, and video-based surgical performance parameters were compared between the patients with and without adverse events during CEA. RESULTS: Eleven patients (9.4%) experienced adverse events after CEA, and the rate of adverse events significantly correlated with the surgeon group. The mean maximum tissue acceleration and number of errors during surgical tasks significantly decreased from novice, to intermediate, to expert surgeons, and stepwise discriminant analysis showed that the combined use of surgical performance factors could accurately discriminate between surgeon groups. The multivariate logistic regression analysis revealed that the number of errors and vulnerable carotid plaques were associated with adverse events. CONCLUSION: Tissue acceleration profiles can be a novel metric for the objective assessment of surgical performance and the prediction of adverse events during surgery. Thus, this concept can be introduced into futuristic computer-aided surgeries for both surgical education and patient safety.

Association of RNF213 polymorphism and cortical hyperintensity sign on fluid-attenuated inversion recovery images after revascularization surgery for moyamoya disease: possible involvement of intrinsic vascular vulnerability.

A cortical hyperintensity on fluid-attenuated inversion recovery images (FLAIR cortical hyperintensity (FCH)) is an abnormal finding after revascularization surgery for moyamoya disease. This study aimed to investigate the pathophysiology of FCH through genetic analyses of RNF213 p.R4810K polymorphism and perioperative hemodynamic studies using single-photon emission computed tomography. We studied 96 hemispheres in 65 adults and 47 hemispheres in 27 children, who underwent combined direct and indirect revascularization. Early or late FCH was defined when it was observed on postoperative days 0-2 and 6-9, respectively. FCH scores (range: 0-6) were evaluated according to the extent of FCH in the operated hemisphere. FCHs were significantly more prevalent in adult patients than pediatric patients (early: 94% vs. 78%; late: 97% vs. 59%). In pediatric patients, FCH scores were significantly improved from the early to late phase regardless of the RNF213 genotype (mutant median [IQR]: 2 [1-5] vs. 1 [0-2]; wild-type median: 4 [0.5-6] vs. 0.5 [0-1.75]). In adults, FCH scores were significantly improved in patients with the wild-type RNF213 allele (median: 4 [2-5.25] vs. 2 [2, 3]); however, they showed no significant improvement in patients with the RNF213 mutation. FCH scores were significantly higher in patients with symptomatic cerebral hyperperfusion than those without it (early median: 5 [4, 5] vs. 4 [2-5]; late median: 4 [3-5] vs. 3 [2-4]). In conclusion, the RNF213 p.R4810K polymorphism was associated with prolonged FCH, and extensive FCH was associated with symptomatic cerebral hyperperfusion in adult patients with moyamoya disease.

Chronological Volume Changes of the Temporal Muscle Pedicle Used for Encephalo-myo-synangiosis in Combined Revascularization for Moyamoya Disease: A Prospective Observational Study.

Although postoperative neurological events due to brain compression by the swollen temporal muscle are a rare complication, the chronological volume changes of the temporal muscle pedicle and their clinical impact have not yet been documented. This prospective observational study aimed to investigate the chronological volume changes in the temporal muscle pedicle in Moyamoya disease (MMD). Eighteen consecutive combined revascularization procedures using the temporal muscle were performed for symptomatic MMD in 2021. The postoperative pedicle volume was quantified using repeated computed tomography images on postoperative days (PODs) 0, 1, 7, 14, and 30. Postoperative neurological events with radiological evaluations and collateral development evaluated using magnetic resonance angiography obtained 6 months after surgery were studied. On average, the postoperative temporal muscle pedicle volume was most significantly increased by as much as 112% ± 9.6% on POD 7 (P < 0.001) and decreased by as little as 52% ± 21% on POD 30 (P < 0.0001) relative to POD 0. One exceptional patient (overall incidence, 5.6%) demonstrated postoperative transient neurological events due to brain compression by the swollen temporal muscle with decreased focal cerebral blood flow in the adjacent cortical area. The postoperative collateral development via direct and indirect revascularizations was confirmed in 16 (89%) and 12 (67%) hemispheres, respectively. All patients, except for one rebleeding case, showed independent outcomes at the mean latest follow-up period on 290 ± 96 days after surgery. Our observations confirmed the temporal profile of muscle pedicle volume changes after combined revascularization. Through routine attempts to avoid the unfavorable effects of temporal muscle swelling, combined revascularization can provide favorable outcomes in symptomatic MMD.

Standardization of the Definition and Surgical Management of Splenic Flexure Carcinoma by an International Expert Consensus Using the Delphi Technique: Room for Improvement?

BACKGROUND: Surgical management of splenic flexure carcinoma remains controversial. OBJECTIVE: This study aimed to establish an expert international consensus on splenic flexure carcinoma management. DESIGN: A 3-round online-based Delphi study was conducted between September 2020 and April 2021. SETTING: The first round included 18 experts from 12 different countries. For the second and third rounds, each expert in the first round was asked to invite 2 more colorectal surgeons (n = 47). Out of 47 invited experts, 89% (n = 42) participated in the second and third rounds of the consensus. INTERVENTIONS: A total of 35 questions were created and sent via the online questionnaire tool. MAIN OUTCOME MEASURES: Levels of recommendation based on voting concordance were graded as follows: more than 75% agreement was defined as strong, between 50% and 75% as moderate, and below 50% as weak. RESULTS: There was moderate consensus on the definition of splenic flexure (55%) as 10 cm from either side where the distal transverse colon turns into the proximal descending colon. Also, experts recommended an abdominopelvic CT scan plus intraoperative exploration (moderate consensus, 72%) for tumor localization and cancer registry. Segmental colectomy was the preferred technique for the management of splenic flexure carcinoma in the elective setting (72%). Moderate consensus was achieved on the technique of complete mesocolic excision and central vascular ligation principles for splenic flexure carcinoma (74%). Only strong consensus was achieved on the surgical approach for minimally invasive surgery (88%). LIMITATIONS: Subjective decisions are based on individual expert clinical experience and not evidence based. CONCLUSIONS: This is the first internationally conducted Delphi consensus study regarding splenic flexure carcinoma. The definition of splenic flexure remains ambiguous. To more effectively compare oncologic outcomes among different cancer registries, guidelines need to be developed to standardize each domain and avoid arbitrary definitions. See Video Abstract at http://links.lww.com/DCR/C143 . ESTANDARIZACIN DE LA DEFINICIN Y MANEJO QUIRRGICO DEL CARCINOMA DE NGULO ESPLNICO ESTABLECIDO POR UN CONSENSO INTERNACIONAL DE EXPERTOS UTILIZANDO LA TCNICA DELPHI ESPACIO PARA MEJORAR: ANTECEDENTES:El tratamiento quirúrgico del cáncer de ángulo esplénico sigue siendo controvertido.OBJETIVO:Establecer un consenso internacional de expertos sobre el manejo del cáncer del ángulo esplénico.DISEÑO:Se condujo un estudio Delphi en línea de 3 rondas entre septiembre de 2020 y febrero de 2021.ESCENARIO:La primera ronda incluyó a 18 expertos de 12 países distintos. Para la segunda y tercera rondas, a cada experto de la primera ronda se le pidió que invitara a 2 cirujanos colorrectales más de su región (n = 47). De los 47 expertos invitados, el 89% (n = 42) participó en la segunda y tercera ronda del consenso.INTERVENCIONES:Se crearon y enviaron un total de 35 preguntas a través de la herramienta de cuestionario en línea.PRINCIPALES MEDIDAS DE RESULTADO:Los niveles de recomendación basados en la concordancia de votos fueron jerarquizados de la siguiente manera: más del 75% de acuerdo se definió como fuerte, entre 50 y 75% como moderado y por debajo del 50% como débil.RESULTADOS:Hubo un consenso moderado sobre la definición de ángulo esplénico (55%) como 10 cm desde cualquier lado donde el colon transverso distal se convierte en el colon descendente proximal. Así también, los expertos recomendaron la tomografía computarizada abdominopélvica más la exploración intraoperatoria (consenso moderado, 72%) para la localización del tumor y el registro del ángulo esplénico. La colectomía segmentaria fue la técnica preferida para el tratamiento del cáncer de ángulo esplénico en el caso de ser electivo (72%). Se logró un consenso moderado sobre la técnica de escisión completa del mesocolon y los principios de ligadura vascular a nivel central para el cáncer de ángulo esplénico (74%). Solo se logró un fuerte consenso sobre el abordaje quirúrgico para la cirugía mínimamente invasiva (88%).LIMITACIONES:Decisiones subjetivas basadas en la experiencia clínica de expertos individuales y no basadas en evidencia.CONCLUSIONES:Este es el primer estudio internacional de consenso Delphi realizado sobre el cáncer de ángulo esplénico. Si bien encontramos un consenso moderado sobre las modalidades de diagnóstico preoperatorio y el manejo quirúrgico, la definición de ángulo esplénico sigue siendo ambigua. Para comparar de manera más efectiva los resultados oncológicos entre diferentes registros de cáncer, se deben desarrollar pautas para estandarizar cada dominio y evitar definiciones arbitrarias. Consulte Video Resumen en http://links.lww.com/DCR/C143 . (Traducción-Dr. Osvaldo Gauto ).

Impact of RNF213 c.14576G>A Variant on the Development of Direct and Indirect Revascularization in Pediatric Moyamoya Disease.

BACKGROUND: Superficial temporal artery (direct) and encephalomyosynangiosis (indirect) revascularization may develop after combined bypass surgery in pediatric patients with moyamoya disease (MMD). However, arterial development varies widely among patients, and the underlying mechanisms remain unknown. OBJECTIVES: We evaluated the relationship between the development of donor arteries after bypass surgery in pediatric patients with MMD and the MMD-susceptibility gene variant c.14576G>A of ring finger protein (RNF) 213. METHODS: The data of pediatric patients with MMD (age <16 years at the time of surgery) treated with combined bypass surgery between September 2013 and April 2019 were consecutively analyzed. Quantitative measurements of the superficial temporal artery (STA), deep temporal artery (DTA), and middle meningeal artery (MMA) diameters with magnetic resonance angiography (MRA) source imaging were performed preoperatively and at 6-12 months postoperatively. The postoperative caliber change ratios (CCRs) were calculated. The relationship between CCRs and RNF213 c.14576G>A status was examined. RESULTS: Forty-eight hemispheres from 28 pediatric patients with MMD were examined. Three hemispheres belonged to patients with the AA genotype; 33 to patients with the AG genotype (AA/AG group); and 12 to patients with the GG genotype (GG group; wild type). The CCRs for the DTA were significantly higher in patients with RNF213 variant (AA/AG group; 2.5 ± 0.1) than in the GG group (2.0 ± 0.2) (p = 0.03), whereas the CCRs for the STA were significantly higher in the GG (1.6 ± 0.1) than in the AA/AG group (1.3 ± 0.6) (p = 0.02). There was no significant difference in the CCRs for the MMA and basilar artery between the groups. Other factors, including sex, age, and MRA grading, were not associated with the development of specific bypass development. CONCLUSIONS: The extent of collateral development associated with direct or indirect bypass was found to differ between the genotypes of the RNF213 c.14576G>A associated with pediatric MMD. This genetic variant correlates with the development of the disease and affects revascularization after bypass surgery in pediatric patients with MMD.

MYB3R-mediated and cell cycle-dependent transcriptional regulation of a tobacco ortholog of SCARECROW-LIKE28 in synchronized cultures of BY-2 cells.

Although it is well known that hierarchical transcriptional networks are essential for various aspects of plant development and environmental response, little has been investigated about whether and how they also regulate the plant cell cycle. Recent studies on cell cycle regulation in Arabidopsis thaliana identified SCARECROW-LIKE28 (SCL28), a GRAS-type transcription factor, that constitutes a hierarchical transcriptional pathway comprised of MYB3R, SCL28 and SIAMESE-RELATED (SMR). In this pathway, MYB3R family proteins regulate the G2/M-specific transcription of the SCL28 gene, of which products, in turn, positively regulate the transcription of SMR genes encoding a group of plant-specific inhibitor proteins of cyclin-dependent kinases. However, this pathway with a role in cell cycle inhibition is solely demonstrated in A. thaliana, thus leaving open the question of whether and to what extent this pathway is evolutionarily conserved in plants. In this study, we conducted differential display RT-PCR on synchronized Nicotiana tabacum (tobacco) BY-2 cells and identified several M-phase-specific cDNA clones, one of which turned out to be a tobacco ortholog of SCL28 and was designated NtSCL28. We showed that NtSCL28 is expressed specifically during G2/M and early G1 in the synchronized cultures of BY-2 cells. NtSCL28 contains MYB3R-binding promoter elements, so-called mitosis-specific activator elements, and is upregulated by a hyperactive form of NtmybA2, one of the MYB3R proteins from tobacco. Our study indicated that a part of the hierarchical pathway identified in A. thaliana is equally operating in tobacco cells, suggesting the conservation of this pathway across different families in evolution of angiosperm.

[Surgical Approaches to Pediatric Moyamoya Disease].

Moyamoya disease(MMD)is a chronic, occlusive cerebrovascular disease with unknown etiology, characterized by progressive stenosis of the internal carotid artery terminus and abnormal vascular network formation at the base of the brain. MMD has bimodal age distribution, with peaks in children and young adults, and surgical revascularization is a reasonable management choice for pediatric and adult patients with ischemic MMD. The superficial temporal artery-middle cerebral artery anastomosis with indirect pial synangiosis(combined revascularization)is a preferred surgical procedure for adult and pediatric MMD patients, providing early cerebral hemodynamic improvement and long-term favorable outcomes. Pediatric patients with MMD can present intrinsic postoperative hemodynamic complications, such as watershed shift ischemia and transient global hypoperfusion, even after successful revascularization. Therefore, perioperative management based on the early hemodynamic study is critical to avoid surgical complications, including perioperative cerebral infarction.

Outcomes of Combined Revascularization Surgery for Moyamoya Disease without Preoperative Cerebral Angiography.

OBJECTIVE: Cerebral angiography is the gold standard for diagnosing moyamoya disease (MMD), whereas magnetic resonance (MR) imaging/angiography is becoming more popular in the field of cerebrovascular disease due to its low invasiveness. Although there are concerns about using only MR imaging/angiography for preoperative analysis of MMD, considering the underestimation of pre-existing transdural collateral circulations and dangerous collaterals related to the risk of hemorrhage, we retrospectively reviewed our 10-year experience of MR imaging-first diagnosis and analyzed the perioperative outcomes. METHODS: We analyzed 160 consecutive direct/indirect combined revascularization procedures for MMD preoperatively assessed using MR imaging/angiography alone. Perioperative complications were assessed for up to 2 weeks after surgery. Locations of the lesions responsible for complications were further classified into the surgical field, the ipsilateral hemisphere outside the surgical field, and the contralateral hemisphere. RESULTS: Sixty-four revascularization procedures were performed in 38 children, and 96 procedures were performed in 68 adults. There was no difference in the incidence of perioperative ischemic complications between adults (6.3%) and pediatric patients (4.7%), but hemorrhagic complications were more frequently observed in adults (7.3%) than in children (0%) (P < 0.05). There was no specific lesion deviation for ischemic complications; however, hemorrhagic complications predominantly occurred in the surgical field. CONCLUSIONS: Direct/indirect combined revascularization surgery based on our preoperative diagnostic protocol with the MR-first strategy resulted in favorable outcomes in pediatric MMD patients with relatively low complication rates. However, the validity of the MR-first diagnostic protocol should be further evaluated in adult patients with MMD.

Discontinuation of tyrosine kinase inhibitors in pediatric chronic myeloid leukemia.

BACKGROUND: The feasibility of tyrosine kinase inhibitor (TKI) discontinuation in pediatric chronic myeloid leukemia (CML) remains to be fully elucidated. PROCEDURES: TKI was prospectively discontinued in patients who were diagnosed with CML at <20 years of age, treated with TKI for ≥3 years, and sustained molecular response 4.0 (MR4.0) for ≥2 years. Molecular relapse was defined as a single loss of major molecular response (MMR) (BCR-ABL1IS >0.1%). Relapsed patients resumed the same TKI therapy administered before discontinuation. RESULTS: Twenty-two patients with chronic-phase CML were enrolled, and the median ages at diagnosis and at TKI discontinuation were 9 (range: 1-14) years and 16 (5-26) years, respectively. The median follow-up time after TKI discontinuation was 37 months (range: 24-41 months). The median duration of TKI treatment before discontinuation was 100 (42-178) months, and that of MR4.0 was 53.5 (25-148) months. The treatment-free remission (TFR) rate at 12 months was 50.0% (90% confidence interval: 31.7%-65.8%). Eleven patients experienced loss of MMR within 4 months after TKI discontinuation and resumed TKI as originally prescribed. No progression was observed, and all 11 patients regained MR4.0 after TKI resumption. No patient had a withdrawal syndrome. The quality-of-life analysis suggested that successful TFR may improve academic performance in some patients. In patients who discontinued TKI therapy before puberty, the possibility of improvement in growth velocity upon TKI discontinuation was observed. CONCLUSIONS: TKI could be discontinued safely in patients with pediatric CML showing a sustained deep MR.

Impact of RNF213 founder polymorphism (p.R4810K) on the postoperative development of indirect pial synangiosis after direct/indirect combined revascularization surgery for adult Moyamoya disease.

Direct superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis combined with indirect pial synangiosis provides favorable surgical collaterals for Moyamoya disease (MMD), especially in adults; however, factors leading to the development of each direct and indirect collateral are not well documented.We aimed to investigate the association between RNF213 founder polymorphism (p.R4810K) and each direct and indirect collateral development. By qualitative and quantitative evaluations of direct and indirect surgical collaterals using time-of-flight MR angiography, postoperative development of each type of bypass was evaluated independently into two categories. Multivariate logistic regression analysis was performed to study the contributing factors for the development of each surgical collateral. Excellent development of postoperative direct and indirect bypass was observed in 65 hemispheres (70%) by qualitative evaluation, which was confirmed by quantitative evaluation. Multivariate logistic regression analysis of excellent indirect bypass development revealed a significant positive correlation with the p.R4810K (odds ratio, OR4.0; 95%-confidence interval, CI 1.2-16), advanced MR angiographic stage (OR9.5; 95%CI 1.7-73), and preoperative middle meningeal artery caliber (OR6.8; 95%CI 1.8-35), but a significant negative correlation was found with the excellent direct bypass development (OR0.17; 95%CI 0.03-0.75). No significant correlation was observed between excellent direct bypass development and the p.R4810K (OR0.95; 95%CI 0.37-2.4).In conclusion, excellent development of indirect collaterals after STA-MCA anastomosis combined with indirect pial synangiosis occurs more frequently in adult MMD with the RNF213 founder polymorphism, suggesting a role of the p.R4810K variant for marked in-growth of indirect collaterals and the utility of preoperative genetic analysis.