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Moyamoya vasculopathy secondary to various genetic disorders is classified as moyamoya syndrome (MMS). Recent studies indicate MMS occurs due to a combination of genetic modifiers and causative mutations for the primary genetic disorders. We performed whole-exome sequencing (WES) in 13 patients with various genetic disorders who developed MMS. WES successfully revealed the genetic diagnoses of neurofibromatosis type 1 (NF-1), Down syndrome, multisystemic smooth muscle dysfunction syndrome, Noonan syndrome, and alpha thalassemia. The previously reported modifier genes, RNF213 and MRVI1, were confirmed in the NF-1 and Down syndrome cases. Further analysis revealed rare hypomorphic variants in the causative genes of the primary disorders underlying MMS, such as Alagille syndrome and Rasopathies, conferred susceptibility to MMS. Genes involved in the development of pulmonary arterial hypertension (PAH), such as ABCC8 and BMPR2, were also identified as potential modifiers. The rare variants in the MMS and PAH genes were significantly enriched in the eight Japanese patients with MMS compared with the 104 Japanese individuals from the 1000 Genomes Project. Disease genes associated with the arterial occlusive conditions represented by those of Rasopathies and PAH may provide novel diagnostic markers and future therapeutic targets for MMS as well as moyamoya disease with an unknown cause.
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Secuenciación del Exoma , Enfermedad de Moyamoya , Humanos , Enfermedad de Moyamoya/genética , Femenino , Masculino , Adulto , Niño , Adolescente , Predisposición Genética a la Enfermedad , Persona de Mediana Edad , Preescolar , Ubiquitina-Proteína Ligasas/genética , Adulto Joven , Mutación , Adenosina Trifosfatasas/genética , Genes Modificadores , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/genética , Lactante , Neurofibromatosis 1/genéticaRESUMEN
General anesthesia is thought to suppress the immune system and negatively affect postoperative infection and the long-term prognosis of cancer. However, the mechanism underlying immunosuppression induced by general anesthetics remains unclear. In this study, we focused on propofol, which is widely used for sedation under general anesthesia and intensive care and examined its effects on the T cell function and T cell-dependent immune responses. We found that propofol suppressed T cell glycolytic metabolism, differentiation into effector T cells, and cytokine production by effector T cells. CD8 T cells activated and differentiated into effector cells in the presence of propofol in vitro showed reduced antitumor activity. Furthermore, propofol treatment suppressed the increase in the number of antigen-specific CD8 T cells during Listeria infection. In contrast, the administration of propofol improved inflammatory conditions in mouse models of inflammatory diseases, such as OVA-induced allergic airway inflammation, hapten-induced contact dermatitis, and experimental allergic encephalomyelitis. These results suggest that propofol may reduce tumor and infectious immunity by suppressing the T cell function and T cell-dependent immune responses while improving the pathogenesis and prognosis of chronic inflammatory diseases by suppressing inflammation.
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Linfocitos T CD8-positivos , Propofol , Propofol/farmacología , Animales , Ratones , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Ratones Endogámicos C57BL , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Inflamación/inmunología , Diferenciación Celular/efectos de los fármacos , Citocinas/metabolismo , Listeriosis/inmunología , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , FemeninoRESUMEN
PURPOSE: Surgical manipulation of the lungs increases the number of circulating tumor cells and the subsequent risk of metastasis in patients with lung cancer. This study investigated whether or not ligating the tumor-draining pulmonary vein first during lobectomy could improve the prognosis of these patients. METHODS: We retrospectively evaluated patients who underwent curative lobectomy for solitary nonsmall-cell lung carcinoma between January 2012 and December 2016. We divided the patients into the vein-first group, in which all associated pulmonary veins were dissected and severed before cutting the pulmonary artery, bronchus, or pulmonary fissure, and the other procedure group. RESULTS: Overall, we included 177 and 413 patients in the vein-first and other procedure groups, respectively. Propensity score matching yielded 67 pairs of patients. The 5-year overall survival (85.6% [95% confidence interval, 77.3-94.8%] vs. 69.4% [58.7-81.9%], P = 0.03%) and recurrence-free survival (73.4% [63.3-85.1%] vs. 53.5% [42.5-67.3%], P = 0.02) were significantly better in the vein-first group than in the other procedure group. The cumulative recurrence rate at 5 years post-surgery was significantly lower in the vein-first group than in the other procedure group (21.7% vs. 38.3%, P = 0.04). CONCLUSION: Our study suggests that ligating the pulmonary vein first during lobectomy for lung cancer can improve the overall survival, recurrence-free survival, and cumulative recurrence rate.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Recurrencia Local de Neoplasia , Neumonectomía , Puntaje de Propensión , Venas Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Venas Pulmonares/cirugía , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neumonectomía/métodos , Estudios Retrospectivos , Masculino , Femenino , Ligadura/métodos , Anciano , Recurrencia Local de Neoplasia/epidemiología , Persona de Mediana Edad , Tasa de Supervivencia , PronósticoRESUMEN
Background: Intravenously administered indocyanine green (ICG) accumulates in lung tumors, facilitating their detection via a fluorescence spectrum measurement. This method aids in identifying tumor locations that are invisible to the naked eye. We aim to determine the optimal ICG dose and administration method for accurate tumor identification during lung resection surgeries, utilizing a novel ICG fluorescence spectroscopy system for precise tumor localization. Materials and Methods: ICG should be dissolved in the provided solution or distilled water and administered intravenously approximately 24 h before surgery, beginning with an initial dose of 0.5 mg/kg. If the tumor detection rate is insufficient, the dose may be gradually increased to a maximum of 5.0 mg/kg to determine the optimal dosage for effective tumor detection. This fluorescence spectroscopy during surgery may reveal additional lesions that remain undetected in preoperative assessments. The primary endpoint includes the correct diagnostic rate of tumor localization. The secondary endpoints include the measurement of the intraoperative ICG fluorescence spectral intensity in lung tumors, the assessment of the operability and safety of intraperitoneal ICG administrations, the measurement of the ICG fluorescence spectral intensity in surgical specimens, the comparison of the spectral intensity in lung tissues during collapse and expansion, the correlation between ICG camera images and fluorescence spectral intensity, and the comparison of fluorescence analysis results with histopathological findings. The trial has been registered in the jRCT Clinical Trials Registry under the code jRCTs011230037. Results and Conclusions: This trial aims to establish an effective methodology for localizing and diagnosing malignant lung tumors, thereby potentially improving surgical outcomes and refining treatment protocols.
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Background: Bilateral vertebral artery dissection aneurysm (VADA) is a rare condition that leads to severe stroke. However, the surgical strategy for its treatment is controversial because the pathology is very complicated and varies in each case. Here, we report a case of bilateral VADA that was successfully treated with staged bilateral VADA occlusion and low-flow bypass. Case Description: A Japanese man in his 40s presented with bilateral VADA with subarachnoid hemorrhage. He had only mild headaches without any other neurological deficits. Subsequently, the ruptured left VADA was surgically trapped. However, on postoperative day 11, the contralateral VADA enlarged. The right VADA was then proximally clipped via a lateral suboccipital approach. Furthermore, a superficial temporal artery-superior cerebellar artery bypass was performed through a subtemporal approach in advance to preserve cerebral flow in the posterior circulation. The bilateral VADA was obliterated, and the patient had an uneventful postoperative course during the 1-year and 6-month follow-up period. Conclusion: Bilateral VADA can be successfully treated with staged bilateral VADA obstruction and low-flow bypass. In this case, as the posterior communicating arteries were the fetal type and the precommunicating segments of the posterior cerebral arteries (P1) were hypoplastic, a low-flow bypass was used to supply the basilar and cerebellar arteries, except the posterior cerebral and posterior inferior cerebellar arteries. Furthermore, low-flow bypass is a less invasive option than high-flow bypass.
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In the hydrogenotrophic methanogenic pathway, formylmethanofuran dehydrogenase (Fmd) catalyzes the formation of formylmethanofuran through reducing CO2. Heterodisulfide reductase (Hdr) provides two low potential electrons for the Fmd reaction using a flavin-based electron-bifurcating mechanism. [NiFe]-hydrogenase (Mvh) or formate dehydrogenase (Fdh) complexes with Hdr and provides electrons to Hdr from H2 and formate, or the reduced form of F420, respectively. Recently, an Fdh-Hdr complex was purified as a 3-MDa megacomplex that contained Fmd, and its three-dimensional structure was elucidated by cryo-electron microscopy. In contrast, the Mvh-Hdr complex has been characterized only as a complex without Fmd. Here, we report the isolation and characterization of a 1-MDa Mvh-Hdr-Fmd megacomplex from Methanothermobacter marburgensis. After anion-exchange and hydrophobic chromatography was performed, the proteins with Hdr activity eluted in the 1- and 0.5-MDa fractions during size exclusion chromatography. Considering the apparent molecular mass and the protein profile in the fractions, the 1-MDa megacomplex was determined to be a dimeric Mvh-Hdr-Fmd complex. The megacomplex fraction contained a polyferredoxin subunit MvhB, which contains 12 [4Fe-4S]-clusters. MvhB polyferredoxin has never been identified in the previously purified Mvh-Hdr and Fmd preparations, suggesting that MvhB polyferredoxin is stabilized by the binding between Mvh-Hdr and Fmd in the Mvh-Hdr-Fmd complex. The purified Mvh-Hdr-Fmd megacomplex catalyzed electron-bifurcating reduction of [13C]-CO2 to form [13C]-formylmethanofuran in the absence of extrinsic ferredoxin. These results demonstrated that the subunits in the Mvh-Hdr-Fmd megacomplex are electronically connected for the reduction of CO2, which likely involves MvhB polyferredoxin as an electron relay.
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Dióxido de Carbono , Hidrógeno , Methanobacteriaceae , Methanobacteriaceae/metabolismo , Methanobacteriaceae/enzimología , Hidrógeno/metabolismo , Hidrógeno/química , Dióxido de Carbono/metabolismo , Dióxido de Carbono/química , Oxidorreductasas/metabolismo , Oxidorreductasas/química , Ferredoxinas/metabolismo , Ferredoxinas/química , Oxidación-Reducción , Proteínas Arqueales/metabolismo , Proteínas Arqueales/química , Proteínas Arqueales/genética , Electrones , Hidrogenasas/metabolismo , Hidrogenasas/químicaRESUMEN
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant form of vascular dysplasia. Genetic diagnosis is made by identifying loss-of-function variants in genes, such as ENG and ACVRL1. However, the causal mechanisms of various variants of unknown significance remains unclear. In this study, we analyzed 12 Japanese patients from 11 families who were clinically diagnosed with HHT. Sequencing analysis identified 11 distinct variants in ACVRL1 and ENG. Three of the 11 were truncating variants, leading to a definitive diagnosis, whereas the remaining eight were splice-site and missense variants that required functional analyses. In silico splicing analyses demonstrated that three variants, c.526-3C > G and c.598C > G in ACVRL1, and c.690-1G > A in ENG, caused aberrant splicing, as confirmed by a minigene assay. The five remaining missense variants were p.Arg67Gln, p.Ile256Asn, p.Leu285Pro, and p.Pro424Leu in ACVRL and p.Pro165His in ENG. Nanoluciferase-based bioluminescence analyses demonstrated that these ACVRL1 variants impaired cell membrane trafficking, resulting in the loss of bone morphogenetic protein 9 (BMP9) signal transduction. In contrast, the ENG mutation impaired BMP9 signaling despite normal cell membrane expression. The updated functional analysis methods performed in this study will facilitate effective genetic testing and appropriate medical care for patients with HHT.
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Telangiectasia Hemorrágica Hereditaria , Humanos , Telangiectasia Hemorrágica Hereditaria/genética , Endoglina/genética , Japón/epidemiología , Mutación , Pruebas Genéticas , Receptores de Activinas Tipo II/genéticaRESUMEN
Background. Robotic-assisted thoracic surgery (RATS) is now standard for lung cancer treatment, offering advantages over traditional methods. However, RATS's minimally invasive approach poses challenges like limited visibility and tactile feedback, affecting surgeons' navigation through com-plex anatomy. To enhance preoperative familiarization with patient-specific anatomy, we devel-oped a virtual reality (VR) surgical navigation system. Using head-mounted displays (HMDs), this system provides a comprehensive, interactive view of the patient's anatomy pre-surgery, aiming to improve preoperative simulation and intraoperative navigation. Methods. We integrated 3D data from preoperative CT scans into Perspectus VR Education software, displayed via HMDs for in-teractive 3D reconstruction of pulmonary structures. This detailed visualization aids in tailored preoperative resection simulations. During RATS, surgeons access these 3D images through Tile-ProTM multi-display for real-time guidance. Results. The VR system enabled precise visualization of pulmonary structures and lesion relations, enhancing surgical safety and accuracy. The HMDs offered true 3D interaction with patient data, facilitating surgical planning. Conclusions. VR sim-ulation with HMDs, akin to a robotic 3D viewer, offers a novel approach to developing robotic surgical skills. Integrated with routine imaging, it improves preoperative planning, safety, and accuracy of anatomical resections. This technology particularly aids in lesion identification in RATS, optimizing surgical outcomes.
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In the last few decades, reduced-port video-assisted thoracic surgery (RP-VATS) has been developed to minimize surgical invasiveness. Nevertheless, VATS in children can occasionally be difficult because the lesion occupies a small thoracic cavity, limiting the working space. This study aimed to assess the feasibility of RP-VATS for the resection of mediastinal lesions in children in association with the tumor-to-thoracic height ratio (TTH ratio). We reviewed all patients aged ≤10 years who underwent resection for mediastinal lesions in our institute between January 2008 and August 2022. Patients who underwent diagnostic procedures were excluded from this study. The TTH ratio was calculated as tumor height divided by thoracic height. Seven patients in the RP-VATS group and six in the conventional procedures (multi-portal VATS or open surgery) group were included in this study. The TTH ratio was significantly lower in the RP-VATS group than in the conventional procedures group (median, 26.3% vs. 50.8%; P=0.007). The operating time (P=0.01) and duration of drainage (P=0.003) were significantly shorter and the blood loss (P=0.001) was significantly lower in the RP-VATS group than in the conventional procedures group. After adjusting for age, a lower TTH ratio was significantly associated with the completion of RP-VATS (odds ratio: 0.776; 95% confidence interval: 0.529-0.926; P=0.048). In conclusion, RP-VATS can be performed appropriately in carefully selected cases of pediatric mediastinal lesions. A low TTH ratio may predict the feasibility of RP-VATS. Further studies are warranted to determine the criteria for the indications of RP-VATS in children, so that more children can benefit from RP-VATS.
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It is unclear how rare RNF213 variants, other than the p.R4810K founder variant, affect the clinical phenotype or the function of RNF213 in moyamoya disease (MMD). This study included 151 Japanese patients with MMD. After performing targeted resequencing for all coding exons in RNF213, we investigated the clinical phenotype and statistically analyzed the genotype-phenotype correlation. We mapped RNF213 variants on a three-dimensional (3D) model of human RNF213 and analyzed the structural changes due to variants. The RNF213 p.R4810K homozygous variant, p.R4810K heterozygous variant, and wild type were detected in 10 (6.6%), 111 (73.5%), and 30 (19.9%) MMD patients, respectively. In addition, 15 rare variants were detected in 16 (10.6%) patients. In addition to the influence of the p.R4810K homozygous variant, the frequency of cerebral infarction at disease onset was higher in pediatric patients with other rare variants (3/6, 50.0%, P = 0.006) than in those with only the p.R4810K heterozygous variant or with no variants (2/51, 3.9%). Furthermore, on 3D modelling of RNF213, the majority of rare variants found in pediatric patients were located in the E3 module and associated with salt bridge loss, contrary to the results for adult patients. The clinical phenotype of rare RNF213 variants, mapped mutation position, and their predicted structural change differed between pediatric and adult patients with MMD. Rare RNF213 variants, in addition to the founder p.R4810K homozygous variant, can influence MMD clinical phenotypes or structural change which may contribute to the destabilization of RNF213.
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[Fe]-hydrogenase catalyzes the heterolytic cleavage of H2 and reversible hydride transfer to methenyl-tetrahydromethanopterin. The iron-guanylylpyridinol (FeGP) cofactor is the prosthetic group of this enzyme, in which mononuclear Fe(II) is ligated with a pyridinol and two CO ligands. The pyridinol ligand fixes the iron by an acyl carbon and a pyridinol nitrogen. Biosynthetic proteins for this cofactor are encoded in the hmd co-occurring (hcg) genes. The function of HcgB, HcgC, HcgD, HcgE, and HcgF was studied by using structure-to-function analysis, which is based on the crystal structure of the proteins and subsequent enzyme assays. Recently, we reported the catalytic properties of HcgA and HcgG, novel radical S-adenosyl methionine enzymes, by using an inâ vitro biosynthesis assay. Here, we review the properties of [Fe]-hydrogenase and the FeGP cofactor, and the biosynthesis of the FeGP cofactor. Finally, we discuss the expected engineering of [Fe]-hydrogenase and the FeGP cofactor.
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Hidrogenasas , Proteínas Hierro-Azufre , Hidrogenasas/metabolismo , Carbono/metabolismo , Proteínas Hierro-Azufre/química , Hierro/químicaRESUMEN
OBJECTIVE: The lateral supraorbital (LSO) approach is a minimally invasive craniotomy widely used in the surgical treatment of intracranial aneurysms (IAs). A protective bypass is considered a safety measure in high-risk and complex clipping procedures to maintain distal cerebral flow. However, the protective bypass has so far only been applied through a pterional or larger craniotomy. We aimed to describe the characteristics of the superficial temporal artery to middle cerebral artery (STA-MCA) bypass through the LSO craniotomy to treat complex IAs. METHODS: We retrospectively identified six patients with complex IAs who underwent clipping and a protective STA-MCA bypass through the LSO approach between January 2016 and December 2020. The STA donor artery was harvested through the same curvilinear skin incision with a small extension, and it was anastomosed to the opercular segment of the MCA. Subsequently, aneurysm clipping followed standardized steps. RESULTS: Anastomosis was successful in all patients. Despite requiring temporary occlusion of the parent artery, all aneurysms were successfully clipped without any neurological deterioration. CONCLUSIONS: A protective STA-MCA bypass is feasible through the LSO approach with certain technical modifications. This technique helps protect distal cerebral flow for safe clip placement in the treatment of complex IAs with the associated benefits of a less invasive craniotomy.
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Revascularización Cerebral , Aneurisma Intracraneal , Humanos , Arteria Cerebral Media/cirugía , Arterias Temporales/cirugía , Estudios Retrospectivos , Revascularización Cerebral/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/complicacionesRESUMEN
BACKGROUND: Symptomatic cerebral vasospasm after subarachnoid hemorrhage (SAH) is a significant cause of delayed cerebral ischemia that leads to poor outcomes. Selective intra-arterial administration of fasudil hydrochloride (IAF) has been adopted for its vasodilatory effect on spasm arteries to prevent delayed cerebral ischemia. However, its effect on clinical outcomes and predictive factors for good recovery are not fully understood. This study aimed to investigate the outcomes of selective IAF and identify predictive factors for good outcomes in patients with cerebral vasospasm after SAH. METHODS: A retrospective study of 36 patients with cerebral vasospasm following SAH who underwent selective IAF at our institution between January 2014 and May 2022 was conducted. We evaluated the improvements in neurological findings before and after selective IAF. Statistical analyses were performed to determine factors associated with good outcomes. RESULTS: Selective IAF improved the neurological findings in 26 patients (72.2%). Pre-therapeutic absence of cerebral infarction in more than 1/3 of the spasm artery perfusion area was significantly associated with an improvement in neurological findings (p < 0.0001). Furthermore, there was a tendency for a good outcome when the age was younger (p = 0.093), and the spasm was limited to peripheral vessels (p = 0.065). CONCLUSION: Our study indicates that selective IAF has a promising effect in improving symptomatic vasospasm, except when a large cerebral infarction exists in the spasm artery perfusion area. Early consideration of selective IAF could be recommended once patients experience symptomatic cerebral vasospasm after SAH.
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INTRODUCTION: We evaluated the effects of secondary bone grafting (SBG) on oral health-related and generic health-related quality of life (OHRQOL and HRQOL, respectively) in preadolescent orthodontic patients with alveolar bone defects. METHODS: We divided 101 orthodontic patients aged 8-10 years into 3 groups: 39 general orthodontic patients, 18 patients with orofacial clefts who did not require SBG, and 44 patients with alveolar defects who required SBG using particulate cancellous bone and marrow obtained from the iliac crest. The participants completed the self-report Child Perceptions Questionnaire (CPQ) and Paediatric Quality of Life Inventory (version 4.0) for OHRQOL and HRQOL, respectively, and their scores were assessed. The quality of life (QOL) of patients who required SBG was examined before, 1 month, and 6 months after SBG. The relationships between OHRQOL or HRQOL and potential patient factors were also evaluated. RESULTS: Physical HRQOL subscale scores worsened 1 month after SBG, whereas the total OHRQOL and HRQOL scores before and after SBG showed no significant changes. OHRQOL and HRQOL showed no significant differences among the 3 groups before SBG. The presence of oronasal fistula was associated with poorer OHRQOL in patients with cleft lip and/or palate. CONCLUSIONS: SBG and orthodontic treatment had a relatively small impact on the QOL of the preadolescent children in this study. Understanding the influence of SBG and patient factors on QOL would enable better treatment and care for these patients.
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Cerebrovascular bypass techniques are the current cornerstone methods to achieve cerebral revascularization for moyamoya disease or syndrome and select cases of vascular pathologies, such as intracranial atherosclerotic occlusive disease and complex aneurysms. Factors influencing bypass efficiency include graft patency, short temporary occlusion time, and precise anastomosis. On the basis of our senior author's vast experience with 1300 bypasses, we recommend performing the anastomosis with the minimal number of stitches as achievable to avoid stenosis of the artery's internal lumen that may occur with unnecessary, additional stitches, preserving patency. After completing the anastomosis, when a leak occurs between the sutures, cottonoid tamponade, hemostatic materials, or adding 1 or 2 sutures to the space is often enough to close the gap. However, additional suture placement can be difficult, which might cause stenosis of the anastomosis and reduce blood flow. In this video, we introduce a bipolar coagulation technique for remodeling the anastomosis orifices, as an alternative manner, when minor leakages occur between the knots (Video 1). We demonstrate this technique in an adult moyamoya disease patient who underwent a superficial temporal artery-to-middle cerebral artery bypass, in this case coagulation of the donor artery wall at the anastomosis made possible to adapt the edges of the donor artery precisely to the recipient artery wall by shrinking its redundancy between the stitches. The most important task is to coagulate the donor side orifice precisely with low-power bipolar coagulation and never coagulate the recipient artery. This coagulation technique is a simple alternative to stop further leakage, and it prevents placing an additional suture and reduces temporary occlusion time.
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Revascularización Cerebral , Hemostáticos , Enfermedad de Moyamoya , Adulto , Anastomosis Quirúrgica/métodos , Revascularización Cerebral/métodos , Constricción Patológica , Humanos , Enfermedad de Moyamoya/cirugíaRESUMEN
A 23-year-old man was referred to our department for chest abnormal shadow. Computed tomography (CT) of the chest revealed a well-defined 1.2 cm nodule in the S4 segment of the right middle lobe and a well-defined 1.8 cm nodule in the S10 segment of the right lower lobe. The patient was found to have a fracture in the left fifth rib due to the falling accident at playing snowboard, two months before. He was diagnosed with a benign tumor in the right middle lobe and the right lower lobe and was performed surgery. Thoracoscopy revealed a yellowish-brown tumor in the right middle lobe( S4) and a yellow-brown tumor in the right lower lobe( S10). Both lesions were diagnosed as clots by rapid intraoperative pathologic diagnosis. Histopathological diagnosis was an intrapulmonary hematoma.
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Enfermedades Pulmonares , Neoplasias Pulmonares , Traumatismos Torácicos , Adulto , Hematoma/diagnóstico por imagen , Hematoma/etiología , Hematoma/cirugía , Humanos , Pulmón/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Traumatismos Torácicos/complicaciones , Traumatismos Torácicos/diagnóstico por imagen , Traumatismos Torácicos/cirugía , Adulto JovenRESUMEN
Glucocorticoids (GCs), immunosuppressive, and anti-inflammatory agents have various effects on T cells. However, the long-term influence of GCs on the T cell-mediated immune response remain to be elucidated. We demonstrated that the administration of GC during the TCR-mediated activation phase induced long-lasting suppression of glycolysis, even after the withdrawal of GC. The acquisition of the effector functions was inhibited, while the expression of PD-1 was increased in CD8 T cells activated in the presence of GC. Furthermore, adoptive transfer experiments revealed that GC-treated CD8 T cells reduced memory T cell formation and anti-tumor activity. These findings reveal that GCs have long-lasting influence on the T cell-mediated immune response via modulation of T cell metabolism.
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Linfocitos T CD8-positivos/metabolismo , Glucocorticoides/farmacología , Glucosa/metabolismo , Inmunidad , Terapia de Inmunosupresión , Animales , Antígenos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Femenino , Glucólisis/efectos de los fármacos , Inmunidad/efectos de los fármacos , Memoria Inmunológica/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Prednisolona/farmacologíaRESUMEN
OBJECTIVE: Postoperative intracerebral hemorrhage (ICH) after direct bypass surgery for Moyamoya disease could contribute to neurologic deterioration. The aim of this study was to evaluate the effectiveness of 5-day bed rest in reducing the occurrence of postoperative ICH. METHODS: This study included 122 consecutive hemispheres in 87 Japanese adult MMD patients, composed of 80 control hemispheres from historical data and 42 hemispheres after 5-day bed rest. They all underwent direct bypass surgery. The incidence of postoperative ICH and neurologic deterioration assessed via the modified Rankin Scale were investigated and statistically analyzed. RESULTS: Postoperative ICH was observed in 9 out of the 80 (11.3%) control patients, but not in the 42 patients with 5-day bed rest. The incidence of postoperative ICH and neurologic deterioration via the modified Rankin Scale were significantly different between the 2 groups (P = 0.0268 and 0.0078, respectively). Univariate logistic analysis revealed that 5-day bed rest significantly reduced the incidence of postoperative ICH (P = 0.0048). CONCLUSIONS: Five-day bed rest after direct bypass surgery dramatically can reduce the incidence of postoperative ICH and neurologic deterioration after direct bypass surgery.
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Revascularización Cerebral , Enfermedad de Moyamoya , Adulto , Reposo en Cama/efectos adversos , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/prevención & control , Revascularización Cerebral/efectos adversos , Humanos , Enfermedad de Moyamoya/complicaciones , Enfermedad de Moyamoya/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Hemorragia Posoperatoria/complicaciones , Hemorragia Posoperatoria/epidemiología , Hemorragia Posoperatoria/prevención & controlRESUMEN
BACKGROUND: The endovascular treatment of large, wide-necked basilar apex aneurysms (BAAs) remains challenging. Although horizontal stent deployment across both P1 segments of the posterior cerebral arteries (PCAs) would be an optimal strategy in coil embolization of wide-necked BAAs, this is only feasible in cases with anatomically favorable access. In rare circumstances, large-diameter conduits of extracranial-intracranial (EC-IC) bypass can also provide a good access route for endovascular treatment of complex intracranial aneurysms. METHODS: We describe the technique of accessing the PCA via EC-IC bypass grafts and deploying a stent horizontally across the neck of BAA and its coil embolization. We provide a detailed technical review and describe some pitfalls of the procedure. RESULTS: Two patients underwent EC-IC bypass surgery prior to the treatment of a large, wide-necked BAA. The radial artery and saphenous vein were used as grafts, respectively. To facilitate coil embolization for a large BAA, a PCA-to-PCA horizontal stent was deployed via the bypass graft. Trans-cell and jailing techniques were used, respectively. Both aneurysms were completely occluded, and the patients were discharged without any neurological deficit. CONCLUSION: Horizontal stent deployment via EC-IC bypass grafts can be performed safely, providing proper closure of the aneurysmal neck and apposition to both PCAs, facilitating complete coil embolization.
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Embolización Terapéutica , Aneurisma Intracraneal , Embolización Terapéutica/métodos , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Arteria Cerebral Posterior , Stents , Resultado del TratamientoRESUMEN
Carbonate apatite (CO3 Ap), an inorganic component of human bone, has been clinically applied as an artificial bone substitute. In this study, the effects of the CO3 content in CO3 Ap on the replacement by new bone were studied by fabricating CO3 Ap granules containing 0.9-8.3 wt% of CO3 . The dissolution rate of CO3 Ap in a weak acidic solution, mimicking the Howship's lacunae, was rapid for the CO3 Ap granules containing a larger amount of CO3 . Histological analyses demonstrated the rapid resorption in CO3 Ap and replacement by natural bone tissue when the CO3 content was increased. Therefore, the CO3 content in CO3 Ap is a key factor that influences the replacement of the bone tissue.