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BACKGROUND: The efficacy and safety of percutaneous transluminal pulmonary angioplasty (PTPA) for Takayasu arteritis-associated pulmonary hypertension (TA-PH) remain unclear. OBJECTIVES: To examine the efficacy and safety of PTPA in TA-PH. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials Library were searched from inception to August 18, 2022, for articles investigating the efficacy and safety of PTPA for TA-PH. The primary efficacy outcomes were pulmonary vascular resistance (PVR) changes from baseline to re-evaluation and 6-minute walking distance (6MWD). The safety outcome was procedure-related complications. RESULTS: Five articles comprising 104 patients with TA-PH who underwent PTPA were included. The scores of article quality, as assessed using the methodological index for nonrandomized studies tool, were high, ranging from 13 to 15 points. The pooled treatment effects of PVR (weighted mean difference [WMD]: -4.8 WU; 95% confidence interval [CI]: -6.0 to -3.5 WU; I2 = 0.0%), 6MWD (WMD: 101.9 m; 95% CI: 60.3-143.6 m; I2 = 70.4%) significantly improved. Procedure-related complications, which predominantly present as pulmonary artery injury and pulmonary injury, occurred in 32.0% of the included patients. Periprocedural death occurred in one patient (1.0%, 1/100). CONCLUSIONS: Patients with TA-PH could benefit from PTPA in terms of hemodynamics and exercise tolerance, at the expense of procedure-related complications. PTPA should be encouraged to enhance the treatment response in TA-PH. These findings need to be confirmed by further studies, ideally, randomized controlled trials. REGISTRATION: PROSPERO CRD42022354087.
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Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Arterite de Takayasu , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/diagnóstico por imagem , Resultado do Tratamento , Angioplastia/efeitos adversos , Hipertensão Arterial Pulmonar/complicaçõesRESUMO
Tumor microenvironment (TME) is a complex and dynamic evolving environment which facilitates tumor proliferation and progression. We aimed at investigating the characteristics of tumor microenvironment and its prognostic value in gliomas. Transcriptome data of 702 glioma samples from The Cancer Genome Atlas were included as training dataset, while 325 samples from Chinese Glioma Genome Atlas database and 268 samples from GSE16011 database were used to validate. We found that the infiltration of stromal and immune cell varied in gliomas of different grades and pathological types, and was associated with poor prognosis. Based on the gene expression profile, we constructed a TME-related signature (TMERS), which was closely related to clinical features and genomic variation of gliomas. In TMERS-high group, specific gene mutations and increased copy number alternations were observed. Kaplan-Meier survival and Cox regression analysis showed that TMERS was an independent prognostic indicator. Then we developed a nomogram prognostic model to predict 1-year, 3-year and 5-year survival of patients. Functional analysis confirmed that TMERS could reflect the status of glioma microenvironment, and immunological analysis showed that macrophages were significantly enriched in the TMERS-high group. We established a novel TME-related signature for predicting prognosis and provided new insights into immunotherapy.
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Glioma , Microambiente Tumoral , Glioma/patologia , Humanos , Imunoterapia , Prognóstico , Transcriptoma , Microambiente Tumoral/genéticaRESUMO
Background Subendocardial late gadolinium enhancement (LGE) detected with cardiac MRI in myocarditis represents a diagnostic dilemma, since it may resemble myocardial ischemia. Purpose To explore and compare the histopathologic characteristics and clinical features and outcomes in patients with myocarditis with and without subendocardial involvement at cardiac MRI. Materials and Methods This retrospective study evaluated 39 patients with myocarditis pathologically proven by means of either endomyocardial biopsy or explant pathologic findings between 2015 and 2020. Patients were divided into two groups according to cardiac MRI phenotype: 18 with subendocardial involvement (mean age ± standard deviation, 40 years ± 17; 10 women) and 21 with no subendocardial involvement (mean age, 35 years ± 11; six women). The median follow-up period was 784 days (interquartile range [IQR], 90-1123 days). The Student t test, Mann-Whitney U test, and univariable Cox regression were used for statistical analyses. Results In the 18 patients with subendocardial involvement, 12 (67%) had lymphocytic myocarditis and six (33%) had giant cell myocarditis. Patients with subendocardial involvement compared with those without subendocardial involvement had lower left ventricular ejection fraction (mean ± standard deviation, 27% ± 11 vs 41% ± 19; P = .004), larger LGE extent (median, 13% [IQR, 10%-22%] vs 5% [IQR, 2%-17%]; P < .001), higher rates of cardiac death or transplant (eight of 18 patients [44%] vs one of 21 patients [4.8%]; P = .006), higher probability of giant cell myocarditis (six of 18 [33%] vs one of 21 [4.8%]; P = .02), and more major adverse cardiovascular events (MACE) (15 of 18 [83%] vs seven of 21 [33%]; P = .002). In a subgroup of patients with comparable LGE extent (median, 15% vs 16%; P = .40) and left ventricular ejection fraction (median, 27% vs 31%; P = .26), the prognostic difference in terms of MACE remained (15 of 17 patients [88%] vs five of 10 [50%]; P = .02). Conclusion Subendocardial involvement detected with cardiac MRI in myocarditis indicated more severe clinical features, including a higher frequency of severe lymphocytic myocarditis or giant cell myocarditis and worse prognosis. © RSNA, 2021 See also the editorial by de Roos in this issue.
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Imageamento por Ressonância Magnética/métodos , Miocardite/diagnóstico por imagem , Miocardite/patologia , Adulto , Feminino , Coração/diagnóstico por imagem , Coração/fisiopatologia , Humanos , Masculino , Fenótipo , Estudos RetrospectivosRESUMO
BACKGROUND: Several studies have shown that members of the tumor necrosis factor (TNF) family play an important role in cancer immunoregulation, and trials targeting these molecules are already underway. Our study aimed to integrate and analyze the expression patterns and clinical significance of TNF family-related genes in gliomas. METHODS: A total of 1749 gliomas from 4 datasets were enrolled in our study, including the Cancer Genome Atlas (TCGA) dataset as the training cohort and the other three datasets (CGGA, GSE16011, and Rembrandt) as validation cohorts. Clinical information, RNA expression data, and genomic profile were collected for analysis. We screened the signature gene set by Cox proportional hazards modelling. We evaluated the prognostic value of the signature by Kaplan-Meier analysis and timeROC curve. Gene Ontology (GO) and Gene set enrichment analysis (GSEA) analysis were performed for functional annotation. CIBERSORT algorithm and inflammatory metagenes were used to reveal immune characteristics. RESULTS: In gliomas, the expression of most TNF family members was positively correlated. Univariate analysis showed that most TNF family members were related to the overall survival of patients. Then through the LASSO regression model, we developed a TNF family-based signature, which was related to clinical, molecular, and genetic characteristics of patients with glioma. Moreover, the signature was found to be an independent prognostic marker through survival curve analysis and Cox regression analysis. Furthermore, a nomogram prognostic model was constructed to predict individual survival rates at 1, 3 and 5 years. Functional annotation analysis revealed that the immune and inflammatory response pathways were enriched in the high-risk group. Immunological analysis showed the immunosuppressive status in the high-risk group. CONCLUSIONS: We developed a TNF family-based signature to predict the prognosis of patients with glioma. Video abstract.
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Neoplasias Encefálicas , Glioma , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Humanos , Fatores de Necrose Tumoral/genética , Fatores de Necrose Tumoral/metabolismoRESUMO
AIMS: This study aimed to assess the clinical characteristics and long-term survival outcome in patients with Takayasu's arteritis-associated pulmonary hypertension (TA-PH). METHODS AND RESULTS: We conducted a nationally representative cohort study of TA-PH using data from the National Rare Diseases Registry System of China. Patients with pulmonary artery involvement who fulfilled the diagnostic criteria of Takayasu's arteritis and pulmonary hypertension were included. The primary outcome was the time from diagnosis of TA-PH to the occurrence of all-cause death. Between January 2007 and January 2019, a total of 140 patients were included, with a mean age of 41.4 years at diagnosis, and a female predominance (81%). Patients with TA-PH had severely haemodynamic and functional impairments at diagnosis. Significant improvements have been found in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and haemodynamic profiles in patients with TA-PH receiving drugs approved for pulmonary arterial hypertension. The overall 1-, 3-, and 5-year survival rates in TA-PH were 94.0%, 83.2%, and 77.2%, respectively. Predictors associated with an increased risk of all-cause death were syncope [adjusted hazard ratio (HR) 5.38 (95% confidence interval 1.77-16.34), P = 0.003], NT-proBNP level [adjusted HR 1.04 (1.03-1.06), P < 0.001], and mean right atrial pressure [adjusted HR 1.07 (1.01-1.13), P = 0.015]. CONCLUSION: Patients with TA-PH were predominantly female and had severely compromised haemodynamics. More than 80% of patients in our cohort survived for at least 3 years. Medical treatment was based on investigators' personal opinions, and no clear risk-to-benefit ratio can be derived from the presented data.
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Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Arterite de Takayasu , Adulto , Estudos de Coortes , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Estudos Retrospectivos , Arterite de Takayasu/complicações , Arterite de Takayasu/epidemiologiaRESUMO
BACKGROUND: Spinal arachnoid cysts are rare and have varied clinical manifestations depending on the affected spinal region and nerve roots. A complete cyst excision with fistula closure is the first choice of treatment. However, it might be difficult to localize the specific position of the fistula because previous images have no enhancements or the fistula is too tiny to be detected. CASE PRESENTATION: This case is a giant lumbar extradural arachnoid cyst. We administered a lumbar injection with contrast medium into subarachnoid space under digital subtraction angiography (DSA) and disclosed the fistula. Confirming the location of fistula enabled us to perform minimally invasive surgery to ligate the fistula. Surgical intervention for a spinal arachnoid cyst might encounter the problem of the formation of a postoperative cerebrospinal fluid (CSF) fistula. We propose the option of detecting the fistula preoperatively for minimal invasive surgery. Recurrence depends on the long-term follow-up, and more cases are needed to further evaluate our technique. CONCLUSIONS: The real-time contrast medium technique for spinal arachnoid cysts contributes to the complete ligation with minimally invasive surgery.
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Cistos Aracnóideos/cirurgia , Fístula/diagnóstico por imagem , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Doenças da Medula Espinal/cirurgia , Adulto , Fístula/cirurgia , Humanos , Região Lombossacral , Imageamento por Ressonância Magnética , Masculino , Complicações Pós-Operatórias/diagnóstico por imagemRESUMO
BACKGROUND: Standard fluoroscopic guidance (C-arm fluoroscopy) has been routinely used for intraoperative localization of spinal level for surgical removal of intraspinal tumour, while it is not suitable for selected patients, e.g. pregnant women, who need to avoid radiation exposure. Fusion imaging of real-time ultrasound (US) and magnetic resonance imaging (MRI) is a radiation-free technique which has been reported to have good localization accuracy in managing several conditions. CLINICAL PRESENTATION: A 37-year-old pregnant patient, presented with a progressively aggravating lower back pain for 20 days and was incapable of lying supine with lower extremities swelling for 1 week, was referred to our hospital in her 18th week of gestation. Lumbar MRI identified an L1 level intraspinal lesion, and surgery was planned. To avoid the ionizing radiation generated by fluoroscopy, volume navigation technique (VNT) based fusion imaging of US and MRI was used to localize the intraspinal lesion, which was removed entirely via minimally invasive interlaminar approach. Pathological examination confirmed the diagnosis of ependymoma of the conus medullaris. Her symptoms were largely relieved after the operation, and a healthy baby was delivered at the 40th week of pregnancy. CONCLUSION: We presented the first case of using VNT based fusion imaging of real-time US/MRI to guide the surgical resection of an intraspinal tumour. Future study with larger patient number is needed to validate this technique as an alternative to fluoroscopy in patients who need to avoid radiation exposure.
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Ependimoma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neoplasias da Medula Espinal/diagnóstico por imagem , Cirurgia Assistida por Computador/métodos , Ultrassonografia/métodos , Adulto , Ependimoma/cirurgia , Feminino , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Gravidez , Medula Espinal/patologia , Medula Espinal/cirurgia , Neoplasias da Medula Espinal/cirurgia , Coluna Vertebral/cirurgiaRESUMO
OBJECT Posterior midline laminectomy or hemilaminectomy has been successfully applied as the standard microsurgical technique for the treatment of spinal intradural pathologies. However, the associated risks of postoperative spinal instability increase the need for subsequent fusion surgery to prevent potential long-term spinal deformity. Continuous efforts have been made to minimize injuries to the surrounding tissue resulting from surgical manipulations. The authors report here their experiences with a novel minimally invasive surgical approach, namely the interlaminar approach, for the treatment of lumbar intraspinal tumors. METHODS A retrospective review was conducted of patients at the Second Affiliated Hospital of Zhejiang University School of Medicine who underwent minimally invasive resection of lumbar intradural-extramedullary tumors. By using an operative microscope, in addition to an endoscope when necessary, the authors were able to treat all patients with a unilateral, paramedian, bone-sparing interlaminar technique. Data including preoperative neurological status, tumor location, size, pathological diagnosis, extension of resections, intraoperative blood loss, length of hospital stay, and clinical outcomes were obtained through clinical and radiological examinations. RESULTS Eighteen patients diagnosed with lumbar intradural-extramedullary tumors were treated from October 2013 to March 2015 by this interlaminar technique. A microscope was used in 15 cases, and the remaining 3 cases were treated using a microscope as well as an endoscope. There were 14 schwannomas, 2 ependymomas, 1 epidermoid cyst, and 1 enterogenous cyst. Postoperative radiological follow-up revealed complete removal of all the lesions and no signs of bone defects in the lamina. At clinical follow-up, 14 of the 18 patients had less pain, and patients' motor/sensory functions improved or remained normal in all cases except 1. CONClUSIONS When meeting certain selection criteria, intradural-extramedullary lumbar tumors, especially schwannomas, can be completely and safely resected through a less-invasive interlaminar approach using a microscope, or a microscope in addition to an endoscope when necessary. This approach was advantageous because it caused even less bone destruction, resulting in better postoperative spinal stability, no need for facetectomy and fusion, and quicker functional recovery for the patients. Individualized surgical planning according to preoperative radiological findings is key to a successful microsurgical resection of these lesions through the interlaminar space.
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Discotomia/métodos , Região Lombossacral/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neoplasias da Medula Espinal/cirurgia , Adulto , Idoso , Ependimoma/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurilemoma/cirurgia , Estudos Retrospectivos , Neoplasias da Medula Espinal/patologia , Resultado do TratamentoRESUMO
OBJECTIVE: Nucleotide metabolic reprogramming as a hallmark of cancer is closely related to the occurrence and progression of cancer. We aimed to comprehensively analyze the nucleotide metabolism-related gene set and clinical significance in gliomas. METHODS: The RNA sequencing data of 702 gliomas from the Cancer Genome Atlas (TCGA) dataset were included as the training set, and the RNA sequencing data from the other three datasets (CGGA, GSE16011, and Rembrandt) were used as independent validation sets. Survival curve, Cox regression analysis, time-dependent ROC curve and nomogram model were performed to evaluate prognostic power of signature. R language was the main tool for bioinformatic analysis and graphical work. RESULTS: Based on the expression profiles of nucleotide metabolism-related genes, consensus clustering identified two robust clusters with different prognosis. We then developed a nucleotide metabolism-related signature that was closely related to clinical, pathological, and genomic characteristics of gliomas. And ROC curve showed that our signature was a potential biomarker for mesenchymal subtype. Survival curve and Cox regression analysis revealed signature as an independent prognostic factor for gliomas. In addition, we constructed a nomogram model to predict individual survival. Finally, functional analysis showed that nucleotide metabolism not only affected cell division and cell cycle, but also was associated with immune response in gliomas. CONCLUSION: We developed a nucleotide metabolism-related signature to predict prognosis and provided new insights into the role of nucleotide metabolism in gliomas.
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BACKGROUND: Schwannoma, a benign peripheral nerve sheath tumor, is perhaps only secondary to degenerative pathology as the most common lesion at neural foramen. The surgical dilemma here is either risking nerve injury because of inadequate exposure or the need for internal fixation because of facet joint sacrifice. OBJECTIVE: To evaluate the feasibility and safety of management of foraminal schwannomas by percutaneous full-endoscopic technique. METHODS: A single-center retrospective review was conducted on patients who underwent full-endoscopic resection of neural foraminal schwannomas. Tumors were grouped into either medial type or lateral type based on relevant location to the neural foramen, and respective surgical approaches were adopted. Data including preoperative neurological status, tumor size, surgery time, the extension of resection, and clinical outcomes were collected. The learning curve was plotted as surgical time/tumor size against case number. RESULTS: A total of 25 patients were treated between May 2015 and March 2022. Gross total resection was achieved in 24 patients, and near-total resection in 1 case, with 1 patient experienced transient voiding difficulty. No tumor recurrence or spinal instability was detected in the short-term follow-up (median follow-up 22 months, range 3 months-6 years). Surgical efficiency improved with the number of cases operated on and remained stable after the initial 10 cases. CONCLUSION: Percutaneous full-endoscopic technique is a safe and minimally invasive technique for the resection of foraminal schwannomas.
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Neoplasias de Bainha Neural , Neurilemoma , Neoplasias do Sistema Nervoso Periférico , Humanos , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Neurilemoma/diagnóstico por imagem , Neurilemoma/cirurgia , Neoplasias de Bainha Neural/patologia , EndoscopiaRESUMO
There is little known about the global burden of CVD attributable to ambient PM2.5 (referred to as CVD burden hereinafter) and its secular trend across different regions and countries. We aimed to evaluate the spatiotemporal trends in CVD burden at the global, regional and national levels from 1990 to 2019. Data on CVD burden including mortality and disability adjusted of life years (DALYs) from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019. Cases, the age-standardized rate of mortality (ASMR) and DALYs (ASDR) were estimated by age, sex and sociodemographic index (SDI). Estimated annual percentage change (EAPC) was calculated to evaluate the temporal changing in ASDR and ASMR from 1990 to 2019. In 2019, 2.48 million deaths and 60.91 million DALYs of CVD were attributed to ambient PM2.5 globally. Most CVD burden occurred in males, elderly and the middle SDI region. At national level, Uzbekistan, Egypt, and Iraq had the highest ASMR and ASDR. Despite remarkable increase in number of DALYs and deaths of CVD worldwide from 1990 to 2019, we observed nonsignificant change in ASMR (EAPC: 0.06, 95 % CI: -0.01, 0.13) and slight increment in ASDR (EAPC: 0.30, 95 % CI: 0.23, 0.37). The EAPCs of ASMR and ASDR were negatively associated with SDI in 2019, while the low-middle SDI region exhibited the fastest growth of ASMR and ASDR with EAPCs of 3.25 (95 % CI: 3.14, 3.37) and 3.36 (95 % CI: 3.22, 3.49), respectively. In conclusion, the global CVD burden attributable to ambient PM2.5 has largely increased over the past three decades. The population growth, aging and SDI contributed to the heterogeneity of spatial and temporal distribution. Enforcing policy to improving air quality is required to halt the growing burden of PM2.5 on health.
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Doenças Cardiovasculares , Idoso , Masculino , Humanos , Doenças Cardiovasculares/epidemiologia , Carga Global da Doença , Percepção Social , Envelhecimento , Material Particulado , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Background: Various inherited traits contribute to the overall risk of venous thromboembolism (VTE). In addition, the epidemiology of thrombophilia in the East-Asian VTE population remains unclear; thus, we aimed to assess the proportion of hereditary thrombophilia via a meta-analysis. Methods: Publications from PubMed, EMBASE, web of science, and Cochrane before December 30, 2022, were searched. Studies from Japan, Korea, China, Hong Kong, Taiwan, Singapore, Thailand, Vietnam, Myanmar, and Cambodia were included. Congenital thrombophilia was described as diseases including protein C (PC) deficiency, protein S (PS) deficiency, antithrombin (AT) deficiency, factor (F)V Leiden (FVL), and prothrombin G20210A mutations. Studies were selected by 2 reviewers for methodological quality analysis. A random-effects model was used for the meta-analysis, assuming that estimated effects in the different studies are not identical. Results: Forty-four studies involving 6453 patients from 7 counties/regions were included in the meta-analysis. The prevalence of PC, PS, and AT deficiencies were 7.1%, 8.3%, and 3.8%, respectively. Among 2924 patients from 22 studies, 5 patients were carriers of FVL mutation. Among 2196 patients from 10 studies, 2 patients were carriers of prothrombin G20210A mutation in a Thailand study. Conclusion: The prevalence of PC, PS, and AT deficiencies was relatively high, while a much lower prevalence of FVL and prothrombin G20210A mutations were identified in East-Asian patients with VTE. Our data stress the relative higher prevalence of PC, PS, and AT deficiencies for thrombophilia in the East-Asian VTE population.
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Because the 6-minute walking test (6MWT) is a self-paced submaximal test, the 6-minute walking distance (6MWD) is substantially influenced by individual effort level and physical condition, which is difficult to quantify. We aimed to explore the optimal indicator reflecting the perceived effort level during 6MWT. We prospectively enrolled 76 patients with pulmonary arterial hypertension and 152 healthy participants; they performed 2 6MWTs at 2 different speeds: (1) at leisurely speed, as performed in daily life without extra effort (leisure 6MWT) and (2) an increased walking speed, walking as the guideline indicated (standard 6MWT). The factors associated with 6MWD during standard 6MWT were investigated using a multiple linear regression analysis. The heart rate (HR) and Borg score increased and oxygen saturation (SpO2) decreased after walking in 2 6MWTs in both groups (all p <0.001). The ratio of difference in HR before and after each test (ΔHR) to HR before walking (HRat rest) and the difference in SpO2 (ΔSpO2) and Borg (ΔBorg) before and after each test were all significantly higher in both groups after standard 6MWT than after leisure 6MWT (all p <0.001). Multiple linear regression analysis revealed that ΔHR/HRat rest was an independent predictor of 6MWD during standard 6MWT in both groups (both p <0.001, adjusted R2 = 0.737 and 0.49, respectively). 6MWD and ΔHR/HRat rest were significantly lower in patients than in healthy participants (both p <0.001) and in patients with cardiac functional class III than in patients with class I/II (both p <0.001). In conclusion, ΔHR/HRat rest is a good reflector of combined physical and effort factors. HR response should be incorporated into 6MWD to better assess a participant's exercise capacity.
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Hipertensão Arterial Pulmonar , Humanos , Frequência Cardíaca , Teste de Caminhada , Caminhada/fisiologia , Análise de Regressão , Teste de Esforço , Tolerância ao ExercícioRESUMO
PURPOSE: This study aimed to evaluate the diagnostic performance of convolutional neural network (CNN) models in Chiari malformation type I (CMI) and to verify whether CNNs can identify the morphological features of the craniocervical junction region between patients with CMI and healthy controls (HCs). To date, numerous indicators based on manual measurements are used for the diagnosis of CMI. However, the corresponding postoperative efficacy and prognostic evaluations have remained inconsistent. From a diagnostic perspective, CNN models may be used to explore the relationship between the clinical features and image morphological parameters. METHODS: This study included a total of 148 patients diagnosed with CMI at our institution and 205 HCs were included. T1-weighted sagittal magnetic resonance imaging (MRI) images were used for the analysis. A total of 220 and 355 slices were acquired from 98 patients with CMI and 155 HCs, respectively, to train and validate the CNN models. In addition, median sagittal images obtained from 50 patients with CMI and 50 HCs were selected to test the models. We applied original cervical MRI images (CI) and images of posterior cranial fossa and craniocervical junction area (CVI) to train the CI- and CVI-based CNN models. Transfer learning and data augmentation were used for model construction and each model was retrained 10 times. RESULTS: Both the CI- and CVI-based CNN models achieved high diagnostic accuracy. In the validation dataset, the models had diagnostic accuracy of 100% and 97% (p = 0.005), sensitivity of 100% and 98% (p = 0.016), and specificity of 100% (p = 0.929), respectively. In the test dataset, the accuracy was 97% and 96% (p = 0.25), sensitivity was 97% and 92% (p = 0.109), and specificity was 100% (p = 0.123), respectively. For patients with cerebellar subungual herniation less than 5 mm, three out of the 10 CVI-based retrained models reached 100% sensitivity. CONCLUSIONS: Our results revealed that the CNN models demonstrated excellent diagnostic performance for CMI. The models had higher sensitivity than the application of cerebellar tonsillar herniation alone and could identify features in the posterior cranial fossa and craniocervical junction area of patients. Our preliminary experiments provided a feasible method for the diagnosis and study of CMI using CNN models. However, further studies are needed to identify the morphologic characteristics of patients with different clinical outcomes, as well as patients who may benefit from surgery.
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Malformação de Arnold-Chiari , Adulto , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/patologia , Fossa Craniana Posterior/patologia , Encefalocele/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Redes Neurais de ComputaçãoRESUMO
PURPOSE: The safety of an MRI simulation-guided boost after short-course preoperative radiotherapy (SCPRT) for unresectable rectal cancer is assessed with a planned interim analysis. METHODS AND MATERIALS: Patients diagnosed with clinical stage T3-4 or regional lymph node-positive disease with positive mesorectal fascia or T4b disease evaluated by pelvic MRI were randomly assigned to the SCPRT-boost group (25 Gy in 5 fractions plus 4 Gy delivered to the gross tumor volume, followed by four cycles of chemotherapy) or preoperative chemoradiotherapy group (50 Gy in 25 fractions with concurrent chemotherapy). Then, patients received total mesorectal excision surgery after preoperative treatment. The primary endpoint was the R0 resection rate. The interim analysis was performed when 42 patients completed their assigned treatments. RESULTS: From October 2018 to November 2019, a total of 43 patients were enrolled, and 42 patients were included in the interim analysis. During preoperative therapy, grade 3 or above toxicities were observed in 10/21 (47.6%) patients in the experimental group, and 4/21 (19.0%) patients in the control group. A total of 17 (81.0%) and 13 (61.9%) patients in the experimental group and control group underwent surgery, respectively. Overall, 65.1% of the patients achieved R0 resection in the intention-to-treat analysis. Surgery-related adverse complications were observed in 2 patients (11.8%) in the experimental group and 1 patient (7.7%) in the control group. CONCLUSION: Our results show that the toxicity of an MRI simulation-guided boost after SCPRT for unresectable rectal cancer is acceptable. Thus, this clinical trial will be continued as planned.
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Imageamento por Ressonância Magnética , Neoplasias Retais , Humanos , Quimiorradioterapia , Imageamento por Ressonância Magnética/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgiaRESUMO
Microglia are the resident immune cells in the central nervous system (CNS). After traumatic spinal cord injury (SCI), microglia undergo activation, proliferation, and changes in gene and protein expression and morphology, with detrimental and beneficial effects. Activated microglia cause secondary neuronal injury via the production of proinflammatory cytokines, reactive oxygen species, and proteases. However, activated microglia also promote neuronal repair through the secretion of anti-inflammatory growth factors and cytokines. Proinflammatory cytokines increase endothelial permeability, promote A1 astrocyte activation and axonal demyelination, and reduce neural stem/progenitor cells (NSPCs), leading to the exacerbation of neuronal injury. In contrast, anti-inflammatory factors facilitate angiogenesis, reduce reactive astrocytes, and promote axonal remyelination and the propagation of NSPCs, contributing to tissue repair and locomotor recovery. Due to its limited regenerative capacity, the CNS requires beneficial microglia for continuous protection against injury. Understanding and regulating microglial activation status are beneficial to reducing detrimental effects and promoting repair behaviors and to obtain more information on efficient therapies for traumatic SCI. This review discusses microglial activation and the differences between microglia and similar immune cells, microglial interactions with other cells in the spinal cord, and the progress in the development of therapies targeting microglia in SCI.
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Tumor recurrence is a common clinical dilemma in diffuse gliomas. We aimed to identify a recurrence-related signature to predict the prognosis for glioma patients. In the public Chinese Glioma Genome Atlas dataset, we enrolled multi-omics data including genome, epigenome and transcriptome across primary and recurrent gliomas. We included RNA sequencing data from the batch 1 patients (325 patients) as the training set, while RNA sequencing data from the batch 2 patients (693 patients) were selected as the validation set. The R language was used for subsequent analysis. Compared with primary gliomas, more somatic mutations and copy number alterations were revealed in recurrent gliomas. In recurrent gliomas, we identified 113 genes whose methylation levels were significantly different from those of the primary glioma. Through differential expression analysis between primary and recurrent gliomas, we screened 121 recurrence-related genes. Based on these 121 gene expression profiles, consensus clustering of 325 patients yielded two robust groups with different molecular and prognostic features. We developed a recurrence-related risk signature with the lasso regression algorithm. High-risk group had shorter survival and earlier tumor recurrence than the low-risk group. Compared with traditional indicators, the signature showed better prognostic value. In addition, we constructed a nomogram model to predict glioma survival. Functional characteristics analysis found that the signature was associated with cell division and cell cycle. Immune analysis suggested that immunosuppressive status and macrophages might promote glioma recurrence. We demonstrated a novel 18-gene signature that could effectively predict recurrence and prognosis for glioma patients.
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BACKGROUND: The critical role of vascular health on brain function has received much attention in recent years. At the single-cell level, studies on the developmental processes of cerebral vascular growth are still relatively few. Techniques for constructing gene regulatory networks (GRNs) based on single-cell transcriptome expression data have made significant progress in recent years. Herein, we constructed a single-cell transcriptional regulatory network of mouse cerebrovascular cells. METHODS: The single-cell RNA-seq dataset of mouse brain vessels was downloaded from GEO (GSE98816). This cell clustering was annotated separately using singleR and CellMarker. We then used a modified version of the SCENIC method to construct GRNs. Next, we used a mouse version of SEEK to assess whether genes in the regulon were coexpressed. Finally, regulatory module analysis was performed to complete the cell type relationship quantification. RESULTS: Single-cell RNA-seq data were used to analyze the heterogeneity of mouse cerebrovascular cells, whereby four cell types including endothelial cells, fibroblasts, microglia, and oligodendrocytes were defined. These subpopulations of cells and marker genes together characterize the molecular profile of mouse cerebrovascular cells. Through these signatures, key transcriptional regulators that maintain cell identity were identified. Our findings identified genes like Lmo2, which play an important role in endothelial cells. The same cell type, for instance, fibroblasts, was found to have different regulatory networks, which may influence the functional characteristics of local tissues. CONCLUSIONS: In this study, a transcriptional regulatory network based on single-cell analysis was constructed. Additionally, the study identified and profiled mouse cerebrovascular cells using single-cell transcriptome data as well as defined TFs that affect the regulatory network of the mouse brain vasculature.
Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Regulação da Expressão Gênica , Análise de Célula Única , Transcriptoma/genética , Animais , Biomarcadores/metabolismo , Encéfalo/citologia , Células Endoteliais/metabolismo , Fibroblastos/metabolismo , Redes Reguladoras de Genes , Camundongos , Análise de Sequência de RNARESUMO
Background: The association between anticoagulation outcomes and prior history of venous thromboembolism (VTE) in chronic thromboembolic pulmonary hypertension (CTEPH) has not been established. This study aimed to compare the efficacy and safety of anticoagulation treatment in CTEPH patients with and without prior history of VTE. Methods: A total of 333 CTEPH patients prescribed anticoagulants were retrospectively included from May 2013 to April 2019. The clinical characteristics were collected at their first admission. Incidental recurrent VTE and clinically relevant bleeding were recorded during follow-up. The Cox proportional regression models were used to identify potential factors associated with recurrent VTE and clinically relevant bleeding. Results: Seventy patients (21%) without a prior history of VTE did not experience recurrent VTE during anticoagulation. Compared to CTEPH patients without a prior history of VTE, those with a prior history of VTE had an increased risk of recurrent VTE [2.27/100 person-year vs. 0/100 person-year; hazard ratio (HR), 8.92; 95% confidence interval (CI), 1.18-1142.00; P = 0.029] but a similar risk of clinically relevant bleeding (3.90/100 person-year vs. 4.59/100 person-year; HR, 0.83; 95% CI, 0.38-1.78; P = 0.623). Multivariate Cox analyses suggested that a prior history of VTE and interruption of anticoagulation treatments were significantly associated with an increased risk of recurrent VTE, while anemia and glucocorticoid use were significantly associated with a higher risk of clinically relevant bleeding. Conclusions: This study is the first to reveal that a prior history of VTE significantly increases the risk of recurrent VTE in CTEPH patients during anticoagulation treatment. This finding should be further evaluated in prospective studies.
RESUMO
BACKGROUND: Supraventricular tachycardia (SVT) occurs commonly and is strongly correlated with clinical deterioration in patients with pulmonary hypertension (PH). This study aimed to investigate the feasibility and long-term outcome of radiofrequency catheter ablation (RFCA) in PH patients with SVT. MATERIALS AND METHODS: Consecutive PH patients with SVT who were scheduled to undergo electrophysiological study and RFCA between September 2010 and July 2019 were included. The acute results and long-term success of RFCA were assessed after the procedure. RESULTS: In total, 71 PH patients with 76 episodes of SVT were analyzed. Cavotricuspid isthmus-dependent atrial flutter (n = 33, 43.5%) was the most common SVT type, followed by atrioventricular nodal reentrant tachycardia (n = 16, 21.1%). Of the 71 patients, 60 (84.5%) underwent successful electrophysiological study and were subsequently treated by RFCA. Among them, acute sinus rhythm was restored in 54 (90.0%) patients, and procedure-related complications were observed in 4 (6.7%) patients. Univariate logistic regression analysis showed that cavotricuspid isthmus-independent atrial flutter [odds ratio (OR) 25.00, 95% confidence interval (CI) 3.45-180.98, p = 0.001] and wider pulmonary artery diameter (OR 1.19, 95% CI 1.03-1.38; p = 0.016) were associated with RFCA failure. During a median follow-up of 36 (range, 3-108) months, 7 patients with atrial flutter experienced recurrence, yielding a 78.3% 3-year success rate for RFCA treatment. CONCLUSION: The findings suggest that RFCA of SVT in PH patients is feasible and has a good long-term success rate. Cavotricuspid isthmus-independent atrial flutter and a wider PAD could increase the risk for ablation failure.