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1.
Artículo en Inglés | MEDLINE | ID: mdl-39009321

RESUMEN

PURPOSE: Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. While postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. METHODS AND MATERIALS: A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. RESULTS: The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60Gy, and hyperfractionation has shown promise in reducing toxicity. CONCLUSION: These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for the clinical experts involved in the treatment of locally recurrent NPC. SUMMARY: This article provides international recommendations on postoperative management for potentially resectable locally recurrent nasopharyngeal carcinoma (NPC), with a special focus on postoperative re-irradiation (re-RT). The consensus guidelines highlight the importance of achieving clear surgical margins, suggest considering re-RT for patients with positive or close margins, recommend an optimal re-RT dose of around 60Gy, and propose the use of hyperfractionation to reduce toxicity. The aim is to improve patient outcomes in the management of resectable locally recurrent NPC.

2.
PLoS One ; 19(7): e0306857, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39037987

RESUMEN

OBJECTIVE: Using pediatric anthropomorphic phantoms (APs), we aimed to determine the scanning tube voltage/current combinations that could achieve optimal image quality and avoid excessive radiation exposure in pediatric patients. MATERIALS AND METHODS: A 64-slice scanner was used to scan a standard test phantom to determine the volume CT dose indices (CTDIvol), and three pediatric anthropomorphic phantoms (APs) with highly accurate anatomy and tissue-equivalent materials were studied. These specialized APs represented the average 1-year-old, 5-year-old, and 10-year-old children, respectively. The physical phantoms were constructed with brain tissue-equivalent materials having a density of ρ = 1.07 g/cm3, comprising 22 numbered 2.54-cm-thick sections for the 1-year-old, 26 sections for the 5-year-old, and 32 sections for the 10-year-old. They were scanned to acquire brain CT images and determine the standard deviations (SDs), effective doses (EDs), and contrast-to noise ratios (CNRs). The APs were scanned by 21 combinations of tube voltages/currents (80, 100, or 120 kVp/10, 40, 80, 120, 150, 200, or 250 mA) and rotation time/pitch settings of 1 s/0.984:1. RESULTS: The optimal tube voltage/current combinations yielding optimal image quality were 80 kVp/80 mA for the 1-year-old AP; 80 kVp/120 mA for the 5-year-old AP; and 80 kVp/150 mA for the 10-year-old AP. Because these scanning tube voltages/currents yielded SDs, respectively, of 12.81, 13.09, and 12.26 HU, along with small EDs of 0.31, 0.34, and 0.31 mSv, these parameters and the induced values were expediently defined as optimal. CONCLUSIONS: The optimal tube voltages/currents that yielded optimal brain image quality, SDs, CNRs, and EDs herein are novel and essentially important. Clinical translation of these optimal values may allow CT diagnosis with low radiation doses to children's heads.


Asunto(s)
Encéfalo , Fantasmas de Imagen , Dosis de Radiación , Tomografía Computarizada por Rayos X , Humanos , Encéfalo/diagnóstico por imagen , Niño , Preescolar , Tomografía Computarizada por Rayos X/métodos , Lactante , Masculino
4.
Nat Commun ; 14(1): 1912, 2023 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-37024479

RESUMEN

Despite the intense CD8+ T-cell infiltration in the tumor microenvironment of nasopharyngeal carcinoma, anti-PD-1 immunotherapy shows an unsatisfactory response rate in clinical trials, hindered by immunosuppressive signals. To understand how microenvironmental characteristics alter immune homeostasis and limit immunotherapy efficacy in nasopharyngeal carcinoma, here we establish a multi-center single-cell cohort based on public data, containing 357,206 cells from 50 patient samples. We reveal that nasopharyngeal carcinoma cells enhance development and suppressive activity of regulatory T cells via CD70-CD27 interaction. CD70 blocking reverts Treg-mediated suppression and thus reinvigorate CD8+ T-cell immunity. Anti-CD70+ anti-PD-1 therapy is evaluated in xenograft-derived organoids and humanized mice, exhibiting an improved tumor-killing efficacy. Mechanistically, CD70 knockout inhibits a collective lipid signaling network in CD4+ naïve and regulatory T cells involving mitochondrial integrity, cholesterol homeostasis, and fatty acid metabolism. Furthermore, ATAC-Seq delineates that CD70 is transcriptionally upregulated by NFKB2 via an Epstein-Barr virus-dependent epigenetic modification. Our findings identify CD70+ nasopharyngeal carcinoma cells as a metabolic switch that enforces the lipid-driven development, functional specialization and homeostasis of Tregs, leading to immune evasion. This study also demonstrates that CD70 blockade can act synergistically with anti-PD-1 treatment to reinvigorate T-cell immunity against nasopharyngeal carcinoma.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Animales , Ratones , Linfocitos T Reguladores , Carcinoma Nasofaríngeo/genética , Ligando CD27/genética , Ligando CD27/metabolismo , Herpesvirus Humano 4/metabolismo , Neoplasias Nasofaríngeas/genética , Lípidos , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo , Microambiente Tumoral
5.
Diagnostics (Basel) ; 13(5)2023 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-36900104

RESUMEN

Novel metrics extracted from pH-impedance monitoring can augment the diagnosis of gastroesophageal reflux disease (GERD). Artificial intelligence (AI) is being widely used to improve the diagnostic capabilities of various diseases. In this review, we update the current literature regarding applications of artificial intelligence in measuring novel pH-impedance metrics. AI demonstrates high performance in the measurement of impedance metrics, including numbers of reflux episodes and post-reflux swallow-induced peristaltic wave index and, furthermore, extracts baseline impedance from the entire pH-impedance study. AI is expected to play a reliable role in facilitating measuring novel impedance metrics in patients with GERD in the near future.

6.
Neurogastroenterol Motil ; 35(3): e14506, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36458529

RESUMEN

BACKGROUND/AIM: Reflux episodes and postreflux swallow-induced peristaltic wave (PSPW) index are useful impedance parameters that can augment the diagnosis of gastroesophageal reflux disease (GERD). However, manual analysis of pH-impedance tracings is time consuming, resulting in limited use of these novel impedance metrics. This study aims to evaluate whether a supervised learning artificial intelligence (AI) model is useful to identify reflux episodes and PSPW index. METHODS: Consecutive patients underwent 24-h impedance-pH monitoring were enrolled for analysis. Multiple AI and machine learning with a deep residual net model for image recognition were explored based on manual interpretation of reflux episodes and PSPW according to criteria from the Wingate Consensus. Intraclass correlation coefficients (ICCs) were used to measure the strength of inter-rater agreement of data between manual and AI interpretations. RESULTS: We analyzed 106 eligible patients with 7939 impedance events, of whom 38 patients with pathological acid exposure time (AET) and 68 patients with physiological AET. On the manual interpretation, patients with pathological AET had more reflux episodes and lower PSPW index than those with physiological AET. Overall accuracy of AI identification for reflux episodes and PSPW achieved 87% and 82%, respectively. Inter-rater agreements between AI and manual interpretations achieved excellent for individual numbers of reflux episodes and PSPW index (ICC = 0.965 and ICC = 0.921). CONCLUSIONS: AI has the potential to accurately and efficiently measure impedance metrics including reflux episodes and PSPW index. AI can be a reliable adjunct for measuring novel impedance metrics for GERD in the near future.


Asunto(s)
Monitorización del pH Esofágico , Reflujo Gastroesofágico , Humanos , Monitorización del pH Esofágico/métodos , Impedancia Eléctrica , Inteligencia Artificial , Reflujo Gastroesofágico/diagnóstico , Concentración de Iones de Hidrógeno
7.
8.
Front Genet ; 13: 989081, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36338975

RESUMEN

Background: Head and neck squamous cell carcinoma (HNSC) is a prevalent and heterogeneous malignancy with poor prognosis and high mortality rates. There is significant evidence of alternative splicing (AS) contributing to tumor development, suggesting its potential in predicting prognosis and therapeutic efficacy. This study aims to establish an AS-based prognostic signature in HNSC patients. Methods: The expression profiles and clinical information of 486 HNSC patients were downloaded from the TCGA database, and the AS data were downloaded from the TCGA SpliceSeq database. The survival-associated AS events were identified by conducting a Cox regression analysis and utilized to develop a prognostic signature by fitting into a LASSO-regularized Cox regression model. Survival analysis, univariate and multivariate Cox regression analysis, and receiver operating characteristic (ROC) curve analysis were performed to evaluate the signature and an independent cohort was used for validation. The immune cell function and infiltration were analyzed by CIBERSORT and the ssGSEA algorithm. Results: Univariate Cox regression analysis identified 2726 survival-associated AS events from 1714 genes. The correlation network reported DDX39B, PRPF39, and ARGLU1 as key splicing factors (SF) regulating these AS events. Eight survival-associated AS events were selected and validated by LASSO regression to develop a prognostic signature. It was confirmed that this signature could predict HNSC outcomes independent of other variables via multivariate Cox regression analysis. The risk score AUC was more than 0.75 for 3 years, highlighting the signature's prediction capability. Immune infiltration analysis reported different immune cell distributions between the two risk groups. The immune cell content was higher in the high-risk group than in the low-risk group. The correlation analysis revealed a significant correlation between risk score, immune cell subsets, and immune checkpoint expression. Conclusion: The prognostic signature developed from survival-associated AS events could predict the prognosis of HNSC patients and their clinical response to immunotherapy. However, this signature requires further research and validation in larger cohort studies.

9.
CNS Neurosci Ther ; 28(1): 92-104, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34643338

RESUMEN

AIMS: The effects of subthalamic nucleus (STN)-deep brain stimulation (DBS) on brain topological metrics, functional connectivity (FC), and white matter integrity were studied in levodopa-treated Parkinson's disease (PD) patients before and after DBS. METHODS: Clinical assessment, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) were performed pre- and post-DBS in 15 PD patients, using a within-subject design. The rs-fMRI identified brain network topological metric and FC changes using graph-theory- and seed-based methods. White matter integrity was determined by DTI and tract-based spatial statistics. RESULTS: Unified Parkinson's Disease Rating Scale III (UPDRS- III) scores were significantly improved by 35.3% (p < 0.01) after DBS in PD patients, compared with pre-DBS patients without medication. Post-DBS PD patients showed a significant decrease in the graph-theory-based degree and cost in the middle temporal gyrus and temporo-occipital part-Right. Changes in FC were seen in four brain regions, and a decrease in white matter integrity was seen in the left anterior corona radiata. The topological metrics changes were correlated with Beck Depression Inventory II (BDI-II) and the FC changes with UPDRS-III scores. CONCLUSION: STN-DBS modulated graph-theoretical metrics, FC, and white matter integrity. Brain connectivity changes observed with multi-modal imaging were also associated with postoperative clinical improvement. These findings suggest that the effects of STN-DBS are caused by brain network alterations.


Asunto(s)
Estimulación Encefálica Profunda , Enfermedad de Parkinson/terapia , Sustancia Blanca/patología , Anciano , Encéfalo/patología , Imagen de Difusión Tensora , Femenino , Humanos , Levodopa/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/cirugía , Núcleo Subtalámico/patología
10.
PLoS One ; 16(11): e0259772, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34767600

RESUMEN

Exposure to ionizing radiation can cause cancer, especially in children. In computed tomography (CT), a trade-off exists between the radiation dose and image quality. Few studies have investigated the effect of dose reduction on image quality in pediatric neck CT. We aimed to assess the effect of peak kilovoltage on the radiation dose and image quality in pediatric neck multidetector-row CT. Measurements were made using three phantoms representative of children aged 1, 5, and 10 years, with tube voltages of 80, 100, and 120 kilovoltage peak (kVp); tube current of 10, 40, 80, 120, 150, 200, and 250 mA; and exposure time = 0.5 s (pitch, 0.984:1). Radiation dose estimates were derived from the dose-length product with a 64-multidetector-row CT scanner. Images obtained from the control protocol (120 kVp) were compared with the 80- and 100-kVp protocols. The effective dose (ED) was determined for each protocol and compared with the 120-kVp protocol. Quantitative analysis entailed noise measurements by recording the standard deviation of attenuation for a circular 1-cm2 region of interest placed on homogeneous soft tissue structures in the phantom. The mean noise of the various kVp protocols was compared using the unpaired Student t-test. Reduction of ED was 37.58% and 68.58% for neck CT with 100 kVp and 80 kVp, respectively. The image noise level increased with the decrease in peak kilovoltage. Noise values were higher at 80 kVp at all neck levels, but did not increase at 100 kVp, compared to 120 kVp in the three phantoms. The measured noise difference was the greatest at 80 kVp (absolute increases<2.5 HU). The subjective image quality did not differ among the protocols. Thus, reducing voltage from 120 to 80 kVp for neck CT may achieve ED reduction of 68.58%, without compromising image quality.


Asunto(s)
Tomografía Computarizada Multidetector/métodos , Cuello/diagnóstico por imagen , Dosis de Radiación , Radiación Ionizante , Niño , Preescolar , Humanos , Lactante
11.
Front Oncol ; 11: 744889, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34568077

RESUMEN

The evolution of the tumor microenvironment (TME) is a cancer-dependent and dynamic process. The TME is often a complex ecosystem with immunosuppressive and tumor-promoting functions. Conventional chemotherapy and radiotherapy, primarily focus on inducing tumor apoptosis and hijacking tumor growth, whereas the tumor-protective microenvironment cannot be altered or destructed. Thus, tumor cells can quickly escape from extraneous attack and develop therapeutic resistance, eventually leading to treatment failure. As an Epstein Barr virus (EBV)-associated malignancy, nasopharyngeal carcinoma (NPC) is frequently infiltrated with varied stromal cells, making its microenvironment a highly heterogeneous and suppressive harbor protecting tumor cells from drug penetration, immune attack, and facilitating tumor development. In the last decade, targeted therapy and immunotherapy have emerged as promising options to treat advanced, metastatic, recurrent, and resistant NPC, but lack of understanding of the TME had hindered the therapeutic development and optimization. Single-cell sequencing of NPC-infiltrating cells has recently deciphered stromal composition and functional dynamics in the TME and non-malignant counterpart. In this review, we aim to depict the stromal landscape of NPC in detail based on recent advances, and propose various microenvironment-based approaches for precision therapy.

12.
Artículo en Chino | MEDLINE | ID: mdl-34304473

RESUMEN

Objective:To summarize and analyze the effect of extracranial/intracranial vascular bypass in the treatment of internal carotid artery burst hemorrhage after radiotherapy for nasopharyngeal carcinoma(NPC). Methods:A retrospective analysis of the data of 9 patients with nasopharyngeal carcinoma and carotid artery blowout syndrome(CBS) who underwent extracranial/intracranial vascular bypass. Collected patient demographics, treatment course and dose of radiotherapy, analyze the effect of extracranial/intracranial vascular bypass on the prognosis of patients with internal carotid artery burst hemorrhage, including perioperative stroke and death, overall survival rate, and rebleeding rate. Results:Nine patients were included in the study. The average age is 53.5 years. The pathological types were all non-keratinizing squamous cell carcinoma, undifferentiated, stage Ⅳ; 7 cases of local NPC recurrence, 2 cases of skull base osteonecrosis; all 9 cases had internal carotid artery hemorrhage, including 7 cases of petrous carotid artery and 2 cases of cervical carotid artery; 3 cases of typeⅠthreatened CBS(33.3%), 2 cases of type Ⅱ impending CBS(22.2%), and 4 cases of type Ⅲ acute CBS(44.45%). All patients underwent extracranial/intracranial vascular bypass surgery, and there were no perioperative deaths and strokes. The mean follow-up was 16.7 months. The median overall survival time of the patients was 22.1 months and the 90-day, 1-year and 2-year survival rates were 100.0%, 75.0% and 30.0%, respectively. Conclusion:Patients with internal carotid artery burst hemorrhage after radiotherapy for nasopharyngeal carcinoma can be safely treated by extracranial/intracranial vascular bypass surgery and obtain a longer survival rate.


Asunto(s)
Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Arteria Carótida Interna , Humanos , Persona de Mediana Edad , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Estudios Retrospectivos
13.
Radiat Prot Dosimetry ; 194(1): 36-41, 2021 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-33969422

RESUMEN

This study aimed to establish the diagnostic reference levels (DRLs) for coronary computed tomography angiography (CCTA) and coronary arterial calcium score (CACS) owing to a large variability in patient radiation dose and the lack of dose recommendations in Taiwan. Volume computed tomography dose index (CTDIvol) and dose-length product (DLP) were obtained using CCTAs and the CACS of 445 patients over a 3-y period in a single medical center in Taiwan. CCTAs were performed using routine protocols and 256-detector CT scanners. Electrocardiogram gating was retrospective. The obtained data were analyzed using Prism 6 to determine the 25th, 50th (median) and 75th DRL percentiles for CTDIvol and DLP. These DRL results were compared with existing DRLs from seven countries. The DRLs for CCTA determined from this survey were similar to the existing data from other countries. Such DRLs could provide a useful tool for the optimization of radiation dose for CCTA in Taiwan.


Asunto(s)
Angiografía por Tomografía Computarizada , Niveles de Referencia para Diagnóstico , Humanos , Dosis de Radiación , Valores de Referencia , Estudios Retrospectivos , Taiwán , Tomografía Computarizada por Rayos X
14.
Nat Commun ; 12(1): 1540, 2021 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-33750785

RESUMEN

The tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME.


Asunto(s)
Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Microambiente Tumoral/fisiología , Linfocitos B , Fibroblastos , Regulación Neoplásica de la Expresión Génica , Humanos , Células Mieloides , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/inmunología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/inmunología , Fenotipo , Pronóstico , Supervivencia sin Progresión , Análisis de Secuencia de ARN , Células del Estroma , Linfocitos T , Microambiente Tumoral/inmunología
15.
Laryngoscope ; 131(7): 1548-1556, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33571390

RESUMEN

OBJECTIVE/HYPOTHESIS: To investigate the endovascular intervention or extracranial/intracranial (EC/IC) vascular bypass in the management of patients with head and neck cancer-related carotid blowout syndrome (CBS). STUDY DESIGN: Retrospective case series. METHODS: Retrospective analysis of clinical data of patients with head and neck cancer-related CBS treated by endovascular intervention and/or EC/IC vascular bypass, analysis of its bleeding control, neurological complications, and survival results. RESULTS: Thrity-seven patients were included. Twenty-five were associated with external carotid artery (ECA); twelve were associated with internal or common carotid artery (ICA/CCA). All patients with ECA hemorrhage were treated with endovascular embolization. Of the 12 patients with ICA/CCA hemorrhage, 9 underwent EC/IC bypass, 1 underwent endovascular embolization, and 3 underwent endovascular stenting. For patients with ECA-related CBS, the median survival was 6 months, and the 90-day, 1-year, and 2-year survival rates were 67.1%, 44.7%, and 33.6%, respectively; the estimated rebleeding risk at 1-month, 6-month, and 2-year was 7.1%, 20.0%, and 31.6%, respectively. For patients with ICA/CCA-related CBS, the median survival was 22.5 months, and the 90-day, 1-year, and 2-year survival rates were 92.3%, 71.8%, and 41.0%, respectively; the estimated rebleeding risk at 1 month, 6 months, and 2 years is 7.7%,15.4%, and 15.4%, respectively. ICA/CCA-related CBS patients have significantly longer survival time and lower risk of rebleeding, which may be related to the more use of EC/IC vascular bypass as a definite treatment. CONCLUSIONS: For patients with ICA/CCA-related CBS, if there is more stable hemodynamics, longer expected survival, EC/IC vascular bypass is preferred. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1548-1556, 2021.


Asunto(s)
Enfermedades de las Arterias Carótidas/cirugía , Revascularización Cerebral/métodos , Procedimientos Endovasculares/métodos , Neoplasias de Cabeza y Cuello/complicaciones , Hemorragia/cirugía , Adulto , Anciano , Enfermedades de las Arterias Carótidas/etiología , Enfermedades de las Arterias Carótidas/mortalidad , Arteria Carótida Externa/cirugía , Arteria Carótida Interna/cirugía , Revascularización Cerebral/instrumentación , Revascularización Cerebral/estadística & datos numéricos , Embolización Terapéutica/estadística & datos numéricos , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/mortalidad , Hemorragia/etiología , Hemorragia/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Medición de Riesgo/estadística & datos numéricos , Rotura Espontánea/etiología , Rotura Espontánea/mortalidad , Rotura Espontánea/cirugía , Prevención Secundaria/instrumentación , Prevención Secundaria/métodos , Prevención Secundaria/estadística & datos numéricos , Stents , Tasa de Supervivencia , Resultado del Tratamiento
16.
Sci Rep ; 10(1): 12501, 2020 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-32719414

RESUMEN

Cephalic arch stenosis (CAS) is a common cause of AV dialysis access failure and is notoriously difficult to treat with conventional venoplasty. Although stent graft (SG) placement has improved patency rate, they are prone to stent failure caused by edge stenosis. We investigate the effect of SG diameter relative to cephalic vein on patency rate among hemodialysis patients with dysfunctional arteriovenous access caused by CAS. We identified 22 patients with recalcitrant cephalic arch stenosis or post-venoplasty vessel rupture and received SG placement. Patients were divided into two groups based on the stent-to-vessel diameter (S/V) ratio: undersized group, < 1; and apposed group, 1-1.2. Outcomes were assessed through follow-up angiography. S/V ratio was significant smaller in the undersized patient group (p < 0.001). Placement of undersized SG demonstrated higher primary stent (p = 0.001) and access patency rates (p = 0.021) and a reduced number of post-treatment reinterventions per access year (p = 0.021). A decreased number of lateral edge stenosis was noted in undersized SG (p = 0.005). Increased S/V ratio was significantly associated with lateral edge stenosis (OR = 5.19; p = 0.027). Undersized SG is associated with higher primary stent and access patency rate, and decreased number of post-SG interventions, and are suggested in the treatment of cephalic arch stenosis.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Diálisis Renal , Stents , Venas/patología , Adulto , Anciano , Constricción Patológica , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Flebografía , Factores de Riesgo , Resultado del Tratamiento , Grado de Desobstrucción Vascular , Venas/diagnóstico por imagen , Venas/fisiopatología
17.
Amino Acids ; 52(1): 87-102, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31875259

RESUMEN

Type 2 Diabetes causes learning and memory deficits that might be mediated by hippocampus neuron apoptosis. Studies found that taurine might improve cognitive deficits under diabetic condition because of its ability to prevent hippocampus neuron apoptosis. However, the effect and mechanism is not clear. In this study, we explore the effect and mechanism of taurine on inhibiting hippocampus neuron apoptosis. Sixty male Sprague-Dawley rats were randomly divided into control, T2D, taurine treatment (giving 0.5%, 1%, and 2% taurine in drinking water) groups. Streptozotocin was used to establish the diabetes model. HT-22 cell (hippocampus neurons line) was used for in vitro experiments. Morris Water Maze test was used to check the learning and memory ability, TUNEL assay was used to measure apoptosis and nerve growth factor (NGF); Akt/Bad pathway relevant protein was detected by western blot. Taurine improved learning and memory ability and significantly decreased apoptosis of the hippocampus neurons in T2D rats. Moreover, taurine supplement also inhibited high glucose-induced apoptosis in HT-22 cell in vitro. Mechanistically, taurine increased the expression of NGF, phosphorylation of Trka, Akt, and Bad, as well as reduced cytochrome c release from mitochondria to cytosol. However, beneficial effects of taurine were blocked in the presence of anti-NGF antibody or Akt inhibitor. Taurine could inhibit hippocampus neuron apoptosis via NGF-Akt/Bad pathway. These results provide some clues that taurine might be efficient and feasible candidate for improvement of learning and memory ability in T2D rats.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Factor de Crecimiento Nervioso/genética , Receptor trkA/genética , Taurina/farmacología , Animales , Apoptosis/efectos de los fármacos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Glucosa/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/patología , Humanos , Aprendizaje por Laberinto , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Ratas , Transducción de Señal , Proteína Letal Asociada a bcl/genética
18.
Adv Exp Med Biol ; 1155: C1, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31605371

RESUMEN

Affiliations of authors Muhammad Shahbaz and Shahid Alam were incorrect in the published book. This has now been corrected as below.

19.
Adv Exp Med Biol ; 1155: 787-799, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31468448

RESUMEN

It was reported that apoptosis of Schwann cells could increase in the diabetic rats. The studies showed that taurine inhibited apoptosis in a variety of cells. However, there were few reports on studying the protection of taurine against apoptosis of Schwann cells induced by high glucose (HG) and the underlying mechanism. In our study, the cells were divided into five groups: Control: the normal medium; HG group: 50 mM high glucose; T1: 50 mM high glucose+Taurine (10 mM) group; T2: 50 mM high glucose+Taurine (20 mM) group; T3: 50 mM high glucose+Taurine (40 mM) group. We used MTT and Tunel assays to measure the cell viability and apoptosis, respectively. Then, we also used western blotting to detect the protein levels of apoptosis-related protein. The results demonstrate that taurine promoted cell viability and decreased apoptosis in RSC96 cells exposed to HG. Furthermore, taurine markedly improved imbalance of Bax and Bcl-2, inhibited the translocation of Cytochrome C (Cyt C) from mitochondria to cytosol and reduced caspase-3 activity in HG-induced RSC96 cells. Our results indicate that taurine protect against apoptosis of Schwann cells induced by HG via inhibiting mitochondria-dependent caspase-3 pathway.


Asunto(s)
Apoptosis , Células de Schwann/efectos de los fármacos , Taurina/farmacología , Animales , Células Cultivadas , Diabetes Mellitus Experimental , Glucosa/efectos adversos , Ratas , Células de Schwann/citología
20.
Adv Exp Med Biol ; 1155: 875-887, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31468454

RESUMEN

Diabetes mellitus (DM) is a condition characterized by chronic hyperglycemia, which leads to diabetic neuropathy and apoptosis in the spinal cord. Taurine has been found to ameliorate the diabetic neuropathy and control apoptosis in various tissues. However, there are few reports that discuss the direct relationship between spinal cord and anti-apoptotic effect of taurine. In this study, DM was induced in male SD rats with STZ @ 25 mg/Kg of body weight in combination with high fat diet. After 2 weeks, they were divided into four groups as DM: diabetic rats, T1 (0.5%), T2 (1%) and T3 (2%) taurine solution, while control group was non-diabetic rats (no treatment). The results showed that DM increased apoptosis, decreased phosphorylated Akt and Bad. DM decreased expression of Bcl-2 and increased the Bax. Moreover, the release of cytochrome c into cytosol was increased in DM and activation of caspase-3 was also increased. However, taurine reversed all these abnormal changes in a dose dependent manner. Our results suggested the involvement of Akt/Bad signaling pathway and mitochondrial apoptosis pathway in protective effect of taurine against apoptosis in the spinal cord of diabetic rats. Therefore, taurine may be a potential medicine against diabetic neuropathy by controlling apoptosis.


Asunto(s)
Apoptosis , Neuropatías Diabéticas , Médula Espinal/efectos de los fármacos , Taurina/farmacología , Animales , Diabetes Mellitus Experimental , Masculino , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Médula Espinal/citología
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