Adrenal Glands

肾上腺
  • 文章类型: Journal Article
    方法:这项研究的目的是研究一天中的时间对肾上腺的血清激素和基因表达的影响,研究性的影响,肥胖饮食,以及原花青素给药的时机,重点是这个腺体合成糖皮质激素。
    结果:雌性和雄性大鼠,被分配到标准食物或自助餐厅饮食组,接受每日口服剂量的葡萄籽原花青素提取物(GSPE),或车辆(当灯打开时,或当灯关闭时)。皮质酮,雌二醇,和血清睾酮水平,时钟基因和皮质酮合成途径相关基因的表达分析,被评估。血清激素水平在清道夫受体B类成员1(Scarb1)和cyp11b基因的表达中也表现出明显的时间效应。这两个基因与周期昼夜节律调节因子2(Per2)的相关性也扩展到其他时钟基因,尽管程度较小:隐色素(Cry)和核受体亚家族1组D成员1(Rev-erba)。
    结论:发现的强相关性表明,局部Per2(还有Cry和Rev-erbA)在调节皮质酮合成途径相关酶的表达中具有重要作用。肾上腺时钟基因的表达受性别和饮食的影响,但不受GSPE的影响。
    METHODS: The aim of this study is to investigate the effect of time-of-day on serum hormones and gene expression in adrenal glands, studying the impact of sex, obesogenic diet, and timing of proanthocyanidins administration, with a focus on glucocorticoids synthesis by this gland.
    RESULTS: Female and male rats, assigned to a standard chow or a cafeteria diet-fed group, receive a daily oral dose of a grape seed proanthocyanidin extract (GSPE), or a vehicle (when light is turned on, or when light is turned off). Corticosterone, estradiol, and testosterone serum levels, and the expression analysis of clock genes and genes related to corticosterone synthesis pathway, are assessed. Serum hormone levels exhibited a marked time-of-day effect also see in the expression of scavenger receptor class B member 1 (Scarb1) and cyp11b genes. The correlation between these two genes and period circadian regulator 2 (Per2) is also extended to other clock genes, although to a lesser extent: cryptochrome (Cry) and nuclear receptor subfamily 1 group D member 1 (Rev-erba).
    CONCLUSIONS: The strong correlations found suggest an important role of local Per2 (but also of Cry and Rev-erbA) in regulating the expression of the enzymes involved in the corticosterone synthesis pathway. The expression of clock genes in adrenals is influenced by sex and diet but not by GSPE.
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  • 文章类型: English Abstract
    Objective: To analyze the anatomical characteristics of the adrenal veins through adrenal venography to improve the success rate of adrenal venography (AVS). Methods: This study was a cross-sectional study. Patients who were diagnosed with primary aldosteronism and underwent AVS from January 2019 to October 2023 at the First Affiliated Hospital of Dalian Medical University were included. Adrenal vein imaging was collected from the enrolled patients. We performed statistical analysis on the adrenal vein orifice position, inflow angle, and adrenal venography morphology. The adrenal venous orifice was defined as the location where the catheter was placed at the end of the calm inhalation. Spearman correlation analysis was used to explore the relationship between the positions of bilateral adrenal vein orifices and body mass index (BMI). Results: A total of 282 patients with successful bilateral AVS and complete bilateral adrenal vein imaging were enrolled, of whom 57.1% (161/282) were male and the age was (53.3±10.7) years old. The orifice of the left adrenal vein was located between the middle segment of the 11th thoracic vertebra and the upper segment of the 2nd lumbar vertebra. The inflow angle relative to the position of the orifice was all leftward and upward. The orifice of the right adrenal vein was located between the upper segment of the 11th thoracic vertebra and the lower segment of the 1st lumbar vertebra, and 91.1% (257/282) had a rightward and downward angle of inflow relative to the position of the orifice. The position of the adrenal vein orifices on both the left (r=0.211, P<0.001) and right (r=0.196, P=0.001) showed positive correlation with BMI. The position of the right adrenal vein orifice also increased with the position of the left adrenal orifice (r=0.530, P<0.001). The most common adrenal venography morphology on the right side was triangular (36.5%, 103/282), while the most common venography morphology on the left side was glandular (66.3%, 187/282). Conclusions: The anatomical morphology of adrenal veins are diverse. Being familiar with the morphological characteristics of the adrenal vein and identifying the adrenal vein accurately during surgery has important clinical value in improving the success rate of AVS.
    目的: 通过肾上腺静脉造影分析肾上腺静脉的解剖形态特征,以提高肾上腺静脉取血成功率。 方法: 本研究为横断面研究。选取2019年1月至2023年10月于大连医科大学附属第一医院确诊为原发性醛固酮增多症并行肾上腺静脉取血的患者。收集入选患者的肾上腺静脉影像资料,统计分析肾上腺静脉开口位置、流入角度和肾上腺静脉形态。肾上腺静脉开口位置定义为平静吸气末导管位置。采用Spearman相关性分析探讨两侧肾上腺静脉开口位置的关系及其与体重指数的相关性。 结果: 纳入282例双侧肾上腺静脉取血成功且双侧肾上腺静脉显影完全的患者,男性占比57.1%(161/282),年龄(53.3±10.7)岁。左侧肾上腺静脉开口位于第11胸椎中段至第2腰椎上段,其相对于开口位置的流入角度均为向左向上。右侧肾上腺静脉开口位于第11胸椎上段至第1腰椎下段,91.1%(257/282)相对于开口位置的流入角度是向右向下的。左(r=0.211,P<0.001)、右(r=0.196,P=0.001)两侧肾上腺静脉开口位置均随体重指数增大而增高。右侧肾上腺静脉开口位置随左侧肾上腺开口位置增高而增高(r=0.530,P<0.001)。右侧肾上腺静脉造影形态以三角型最为常见[36.5%(103/282)],而左侧以腺体型最为常见[66.3%(187/282)]。 结论: 肾上腺静脉解剖形态多样。熟悉肾上腺静脉形态特点,术中快速准确判别肾上腺静脉对提高肾上腺静脉取血成功率有重要临床价值。.
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  • 文章类型: Journal Article
    这项研究的目的是探讨肥胖对库欣综合征患者腹腔镜肾上腺手术结果的影响。
    这项回顾性研究于2010年1月至2023年1月在Erciyes大学医学院普通外科进行。我们的分析包括库欣综合征患者,这些患者接受了经腹外侧入路的单侧腹腔镜肾上腺切除术(LA)。对所有患者进行年龄评估,性别,肿瘤直径,体重指数(BMI),美国麻醉医师协会身体状况分类,发病率,手术史,肿瘤侧,手术时间,转换为开放手术,并发症,和住院时间。
    共有90名患者(75名女性和15名男性)接受了经腹膜LA。根据BMI将患者分为2组:肥胖组(≥30kg/m2;n=53,58.8%)和非肥胖组(<30kg/m2;n=37,41.2%)。将所有患者分为3个亚组:肥胖患者组,BMI≥30-39kg/m2(n=23);病态肥胖患者组,BMI≥40kg/m2(n=14);非肥胖患者组,BMI<30kg/m2(n=53)。术中并发症无显著差异,转换为开放手术,手术时间,或两组之间的住院时间。在单变量和多变量分析中,仅转换为开放手术是术后并发症的危险因素(比值比,15.4;95%置信区间,1.277-185.599;P=0.031)。
    我们的结果表明,LA对病态肥胖的库欣综合征患者是安全有效的,允许可接受的发病率和住院时间。
    UNASSIGNED: The aim of this study is to investigate the effect of obesity on the results of laparoscopic adrenal surgery in patients with Cushing syndrome.
    UNASSIGNED: This retrospective study was performed in Department of General Surgery at Erciyes University School of Medicine between January 2010 and January 2023. Our analysis included Cushing syndrome patients who underwent unilateral laparoscopic adrenalectomy (LA) with the transabdominal lateral approach. All patients were evaluated in terms of age, sex, tumor diameter, body mass index (BMI), American Society of Anesthesiologists physical status classification, morbidities, surgery history, tumor side, operative time, conversion to open surgery, complications, and length of hospital stay.
    UNASSIGNED: A total of 90 patients (75 females and 15 males) underwent a transperitoneal LA. Patients were divided into 2 groups according to their BMI: obese group (≥30 kg/m2; n = 53, 58.8%) and nonobese group (<30 kg/m2; n = 37, 41.2%). All patients were classified into 3 subgroups: obese patient group, BMI ≥30-39 kg/m2 (n = 23); morbidly obese patient group, BMI ≥40 kg/m2 (n = 14); and nonobese patient group, BMI <30 kg/m2 (n = 53). There was no significant difference in intraoperative complications, conversion to open surgery, operative time, or length of hospital stay between the groups. Only conversion to open surgery was a risk factor for postoperative complications in univariate and multivariate analyses (odds ratio, 15.4; 95% confidence interval, 1.277-185.599; P = 0.031).
    UNASSIGNED: Our results showed that LA is safe and effective in patients with Cushing syndrome with morbid obesity, allowing acceptable morbidity and length of hospital stay.
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  • 文章类型: Case Reports
    UNASSIGNED: Adrenal gland cysts are a rare entity, with a reported incidence in post-mortem series of 0.06-0.18%. However, the incidence seems to be increasing in recent years. The presentation of adrenal gland cysts is usually asymptomatic, but those cases in which symptoms are present are usually non-specific, which makes adrenal cysts generally recognized as incidentalomas. The finding is mainly made by computed tomography. The main objective of this article was to describe the clinical course of a patient with an adrenal gland pseudocyst, which is accompanied by symptoms of compression and persistent pain of long evolution in the left flank.
    UNASSIGNED: A 65-year-old female patient attended the emergency room of a second-level hospital due to an increase in volume of the abdominal region with a sensation of fullness, heartburn, vomiting and pain. Computed tomography was performed, which reported a cystic mass and, later, exploratory laparotomy plus adrenalectomy were carried out. The pathology analysis reported a diagnosis of a 10 x 15 x 14 cm solid, cystic, and adherent tumor, coinciding with a pseudocyst of the adrenal gland.
    UNASSIGNED: Adrenal gland cysts are rare. Computed tomography is recommended for its diagnosis and the standard of treatment is surgical intervention in the presence of symptoms.
    UNASSIGNED: los quistes de glándula suprarrenal son una entidad rara, con un reporte en la incidencia de series post mortem de 0.06-0.18%. Sin embargo, la incidencia parece ir en aumento en los últimos años. La presentación de los quistes de glándula suprarrenal es habitualmente asintomática, pero en aquellos casos en que se presentan síntomas, estos suelen ser inespecíficos, lo cual hace que los quistes suprarrenales generalmente sean reconocidos como incidentalomas. El hallazgo se hace principalmente mediante tomografía computarizada. El objetivo principal de este artículo fue describir el curso clínico de una paciente con un pseudoquiste de glándula suprarrenal, que se acompaña de síntomas de compresión y dolor persistente de larga evolución en el flanco izquierdo.
    UNASSIGNED: mujer de 65 años que acudió a urgencias de un hospital de segundo nivel por aumento de volumen de región abdominal con sensación de plenitud, pirosis, vómito y dolor. Se realizó tomografía computarizada que reportó masa quística; posteriormente se realizó laparotomía exploradora y adrenalectomía. El análisis de patología reportó diagnóstico de tumor de 10 x 15 x 14 cm, sólido, quístico y adherido, coincidente con pseudoquiste de glándula suprarrenal.
    UNASSIGNED: los quistes de glándula suprarrenal son raros. Para su diagnóstico se recomienda realizar tomografía computarizada y el estándar de tratamiento es la intervención quirúrgica ante la presencia de sintomatología.
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  • 文章类型: Case Reports
    背景:肾上腺梗塞(AI)是一种罕见的肾上腺损害,这在系统性红斑狼疮中相对常见,抗磷脂抗体综合征(APS)和妊娠。AI的诊断主要通过计算机断层扫描(CT)和磁共振成像,但很容易与其他肾上腺疾病混淆。因此,这份报告详细介绍了系统性红斑狼疮的AI状况,APS并从影像学上做出了鉴别诊断。
    方法:我们报告了一例55岁的女性,她的窝腋窝和腹股沟区疼痛。然后CT扫描显示双侧肾上腺疾病,病人被诊断为系统性红斑狼疮,附加自身免疫检查后的APS和AI。
    方法:患者诊断为系统性红斑狼疮合并狼疮性肾炎,血液学损伤和门脑炎,APS,AI和继发性凝血障碍。
    方法:患者接受甲基强的松龙治疗,羟氯喹和低分子肝素。
    结果:患者在治疗1年后病情缓解并保持健康。
    AI可以分为出血性和非出血性,以双侧病变多见。在我们的案例中,人工智能是双边的,部分受累且非出血性,“截止符号”最早是在CT中提出的,这可能有助于诊断。
    BACKGROUND: Adrenal infarction (AI) is a rare type of adrenal damage, which is relatively common in systemic lupus erythematosus, antiphospholipid antibody syndrome (APS) and pregnancy. The diagnosis of AI is mainly by computed tomography (CT) and magnetic resonance imaging, but is easily confused with other adrenal disease. Hence, this report details a condition of AI with systemic lupus erythematosus, APS and made a differential diagnosis from imaging.
    METHODS: We report a case of a 55-year-old woman with pain in her fossa axillaries and inguinal regions. Then CT scan disclosed bilateral adrenal diseases, and the patient was diagnosed with systemic lupus erythematosus, APS and AI after additional autoimmune examinations.
    METHODS: The patient was diagnosed as systemic lupus erythematosus with lupus nephritis, hematological damage and oromeningitis, APS, AI and secondary blood coagulation disorders.
    METHODS: The patient was treated with methylprednisolone, hydroxychloroquine and low molecular heparin.
    RESULTS: The patient relieves and remains well 1 year after treatment.
    UNASSIGNED: AI can be divided hemorrhagic and non-hemorrhagic, with bilateral lesions more common. In our case, the AI was bilateral, partially involved and non-hemorrhagic, and the \"cutoff sign\" was first put forward in CT, which might assist the diagnosis.
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  • 文章类型: Journal Article
    背景:与创伤相关的肾上腺损伤(AGI)是一种罕见且经常被忽视的疾病。本研究旨在评估严重创伤患者的AGI频率,并调查AGI患者的预后。
    方法:回顾性分析2012年1月至2023年1月根据创伤方案入住三级创伤转诊中心并进行计算机断层扫描(CT)扫描的所有患者。在抵达时死亡的患者和数据不完整的患者被排除在外。他们分为两大类,成人和儿童,并根据是否存在放射学上明显的AGI进一步分类。人口统计数据,损伤机制,损伤严重程度评分(ISS),同时存在腹部损伤,比较了30天死亡率。对影响死亡率的因素进行了单独分析。
    结果:共纳入1,253名患者:950名成人和303名儿科患者。在成人组中,在45例(4.7%)患者中检测到AGI,并且更常见于以下伤害机制:机动车事故(26.7%vs.14.3%)和行人事故(37.8%与15.5%)。右侧受伤更为常见(55.6%)。AGI患者并发肝脏的发生率较高(17.8%vs.3.9%),脾脏(11.1%vs.3.6%),和肾损伤(15.6%vs.1.3%)。在儿科人群中,在30例患者中检测到AGI(14.8%),与成年组相比,比率明显更高。类似于成人团体,AGI通常与并发腹部损伤相关,并且具有右侧优势(60%),但小儿组并发腹部损伤的发生率更高(80%vs.46%)。与无AGI的患者相比,成人和儿童AGI组的30天死亡率均显着较高(成人:15.6%vs.2.9%,儿科:10%vs.1.8%)。在AGI患者中,主要的头颈部损伤和胸部损伤与死亡率相关.
    结论:外伤引起的肾上腺损伤并不少见。它们通常与钝性创伤和其他并发的腹部器官损伤有关。AGI患者死亡的主要原因是严重的头颈部损伤和胸部损伤。
    BACKGROUND: Adrenal gland injury (AGI) associated with trauma is an uncommon and often overlooked condition. This study aimed to evaluate the frequency of AGI in individuals with severe trauma injuries and investigate the outcomes of patients with AGI.
    METHODS: All patients admitted to a tertiary trauma referral center under the trauma protocol who had a computed tomography (CT) scan between January 2012 and January 2023 were analyzed retrospectively. Patients who were dead on arrival and patients with incomplete data were excluded. They were classified into two main groups, adult and pediatric, and further subcategorized by the presence or absence of radiologically evident AGI. Demographic data, mechanism of injury, injury severity scores (ISS), presence of concurrent abdominal injury, and 30-day mortality rates were compared. A separate analysis was performed for factors affecting mortality rates.
    RESULTS: A total of 1,253 patients were included: 950 adults and 303 pediatric patients. In the adult group, AGI was detected in 45 (4.7%) patients and was more commonly associated with the following mechanisms of injury: motor vehicle accidents (26.7% vs. 14.3%) and pedestrian accidents (37.8% vs. 15.5%). Injury to the right side was more common (55.6%). Patients with AGI had higher rates of concurrent liver (17.8% vs. 3.9%), spleen (11.1% vs. 3.6%), and kidney injuries (15.6% vs. 1.3%). In the pediatric population, AGI was detected in 30 patients (14.8%), a significantly higher rate compared to the adult group. Similar to the adult group, AGI was more commonly associated with concurrent abdominal injuries and had a right-sided dominance (60%), but the rate of concurrent abdominal injuries was higher in the pediatric group (80% vs. 46%). The 30-day mortality was significantly higher in both adult and pediatric AGI groups compared to patients without AGI (adult: 15.6% vs. 2.9%, pediatric: 10% vs. 1.8%). In patients with AGI, major head and neck injuries and chest injuries were associated with mortality.
    CONCLUSIONS: Adrenal gland injuries due to trauma are not uncommon. They are usually associated with blunt trauma and other concurrent abdominal organ injuries. The major contributors to mortality in patients with AGI were major head and neck injuries and chest injuries.
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  • 文章类型: Journal Article
    卡比咪唑对不同的身体器官有缺点,尤其是甲状腺,很少,肾上腺.大多数研究没有提出任何解决方案或药物来改善药物对腺体的有害作用。我们的研究集中在低聚木糖(XOS)的生产上,which,当与卡比马唑共同给药时,减轻药物对肾上腺的毒性作用。除了加速肾上腺细胞的再生,XOS显著降低肥胖引起的氧化应激。这种由曲霉木聚糖酶产生的XOS使用微生物硬葡聚糖凝胶珠共价固定,提高了固定化产量,效率,和操作稳定性。在宽pH范围(6-7.5)内,与游离形式相比,木聚糖酶在硬葡聚糖上的共价固定增加了木聚糖酶的活性。此外,反应温度升至65℃。然而,固定化酶表现出优异的热稳定性,在60°C下保持其原始活性的80.22%120分钟。此外,连续12个循环后,固定化酶的全部活性得以维持,18个周期后活性达到78.33%。在4°C下储存41天后,固定化酶仍有约98%的活性。固定化酶具有产生低聚木糖(XOS)的能力。随后,这些XOS可以与卡比马唑共同给药,以减轻药物对肾上腺的不良反应.除了加速肾上腺细胞的再生,XOS显著降低肥胖引起的氧化应激。
    Carbimazole has disadvantages on different body organs, especially the thyroid gland and, rarely, the adrenal glands. Most studies have not suggested any solution or medication for ameliorating the noxious effects of drugs on the glands. Our study focused on the production of xylooligosaccharide (XOS), which, when coadministered with carbimazole, relieves the toxic effects of the drug on the adrenal glands. In addition to accelerating the regeneration of adrenal gland cells, XOS significantly decreases the oxidative stress caused by obesity. This XOS produced by Aspergillus terreus xylanase was covalently immobilized using microbial Scleroglucan gel beads, which improved the immobilization yield, efficiency, and operational stability. Over a wide pH range (6-7.5), the covalent immobilization of xylanase on scleroglucan increased xylanase activity compared to that of its free form. Additionally, the reaction temperature was increased to 65 °C. However, the immobilized enzyme demonstrated superior thermal stability, sustaining 80.22% of its original activity at 60 °C for 120 min. Additionally, the full activity of the immobilized enzyme was sustained after 12 consecutive cycles, and the activity reached 78.33% after 18 cycles. After 41 days of storage at 4 °C, the immobilized enzyme was still active at approximately 98%. The immobilized enzyme has the capability to produce xylo-oligosaccharides (XOSs). Subsequently, these XOSs can be coadministered alongside carbimazole to mitigate the adverse effects of the drug on the adrenal glands. In addition to accelerating the regeneration of adrenal gland cells, XOS significantly decreases the oxidative stress caused by obesity.
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  • 文章类型: Journal Article
    肾上腺是常见的转移部位之一,区分转移性疾病与肾上腺原发性肿瘤对于患者的准确临床管理至关重要。我们的研究旨在阐明在学术机构的肾上腺转移性实体瘤的频谱和临床病理特征,特殊重点患者表现为孤立性肾上腺肿块,而先前没有已知的恶性肿瘤。我们的部门数据库(2013-2022)进行了回顾性搜索,并确定了129例涉及肾上腺的转移性实体瘤患者。初次诊断转移性疾病的中位年龄为64岁(范围,54-70岁)。大多数疾病表现为单侧(n=118)或单灶性(n=119)。大多数患者已知先前或同时患有恶性肿瘤(n=125),而肾上腺受累是4例患者的最初临床表现。最常见的原发癌包括肾细胞癌(n=84),肺腺癌(n=21),尿路上皮癌(n=3)和肝细胞癌(n=3)。在104例(80%)患者中,可获得随访(中位数为39个月,范围0-81个月),43例患者死于疾病。当临床上已知恶性原发性时,通常在鉴别诊断中使用转移性疾病。在没有临床已知恶性肿瘤的患者中,密切的临床和放射学相关性以及彻底的相关临床工作至关重要,因为临床隐匿性恶性肿瘤可能在最初表现时作为孤立性肿块转移到肾上腺,虽然它是罕见的。
    The adrenal gland is one of the common sites of metastasis and distinguishing metastatic diseases from adrenal primary neoplasms is essential for accurate clinical management of patients. Our study aimed to elucidate the spectrum and clinicopathologic features of metastatic solid tumors to the adrenal gland at an academic institution, with special focus patients presented with solitary adrenal masses without previously known malignancies. Our departmental database (2013-2022) was retrospectively searched and 129 patients with metastatic solid tumors involving the adrenal gland were identified. The median age at the initial diagnosis of metastatic diseases was 64 years old (range, 54-70 years). The majority of the diseases were presented as unilateral (n=118) or unifocal (n=119) involvement. Most patients had known prior or concurrent malignancies (n=125), whereas adrenal gland involvement was the initial clinical presentation in 4 patients. The most common primary carcinomas included renal cell carcinoma (n=84), lung adenocarcinoma (n=21), urothelial carcinoma (n=3) and hepatocellular carcinoma (n=3). In 104 (80 %) patients with available follow up (median of 39 months, ranging 0-81 months), 43 patients died of disease. Metastatic diseases are usually exercised in the differential diagnosis when there is clinically known malignant primary. In patients without clinical known malignancies, close clinical and radiologic correlation and thorough relevant clinical work up are critical, because clinical occult malignancy may metastasize to the adrenal gland as a solitary mass at the initial presentation, although it is rare.
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  • 文章类型: English Abstract
    Laparoscopic adrenalectomy is worldwide currently considered the gold standard technique for patients suffering from benign lesions. There has been an increasing number of robotic-assisted adrenalectomies in the last decade due to the systematic further development of minimally invasive surgery resulting in the implementation of robot-assisted surgery. Interestingly, the available studies show some perioperative advantages for robotic surgery but overall the current evidence is weak and there are economic aspects that are not negligible. Therefore, further high-quality studies about robotic-assisted adrenalectomy are mandatory to strengthen the current evidence.
    UNASSIGNED: Die laparoskopische Adrenalektomie ist bei benignen Raumforderungen der Nebenniere der therapeutische Goldstandard. Durch die stetige Weiterentwicklung der minimal-invasiven Chirurgie mit Einführung der roboterassistierten Chirurgie ist es in den letzten Jahren zu einem stetigen Anstieg robotisch assistierter Adrenalektomien gekommen. Die aktuelle Evidenzlage verspricht gewisse perioperative Vorteile für die Robotik, bei jedoch insgesamt als noch schwach zu wertender Evidenzlage und nicht zu ignorierenden ökonomischen Belastungen. Weitere qualitativ hochwertige Studien zur robotischen Adrenalektomie sind daher dringend notwendig.
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  • 文章类型: Journal Article
    背景:哮喘通常采用吸入性皮质类固醇(ICS)治疗。服用ICS的哮喘患者肾上腺抑制的风险增加,长期糖皮质激素暴露的潜在严重影响;然而,人们对这种关系知之甚少。因此,本研究旨在确定与服用ICS的哮喘患者肾上腺抑制相关的代谢物生物标志物.
    方法:分析了200名哮喘患儿的571种尿液代谢物,这些代谢物在吸入类固醇的肾上腺抑制药物遗传学(PASS)队列中接受ICS治疗。通过峰值血浆皮质醇测量将样品分组为肾上腺足够(>350nmol/L)或不足(≤350nmol/L)(结果)。利用回归和基于判别的统计模型结合网络分析来评估代谢物与结果之间的关系。最后,使用与PASS特征相似的儿童哮喘管理(CAMP)队列辅助研究的数据验证了优先代谢物。
    结果:90种代谢物与肾上腺抑制显著相关,其中57也可以区分肾上腺状态。虽然26代谢物(主要是类固醇)在肾上腺功能不全患者中存在较低水平,该组中14个显著升高;顶级代谢物,甘露醇/山梨醇,以前与哮喘恶化有关。网络分析确定了与类固醇相关的独特代谢物簇,脂肪酸氧化,和核苷代谢,分别。四种代谢物,包括尿封酸,乙酰肉碱,尿嘧啶,和山梨糖醇在CAMP队列中对肾上腺抑制进行了验证.
    结论:服用ICS的哮喘患者的尿代谢产物不同,肾上腺状态。虽然肾上腺功能差的患者的类固醇代谢物减少,我们的发现还暗示了以前未报道的涉及氨基酸的代谢物,脂质,和核苷代谢。
    BACKGROUND: Asthma is routinely treated with inhaled corticosteroids (ICS). Asthma patients on ICS are at increased risk of adrenal suppression, a potentially serious effect of long-term glucocorticoid exposure; however, this relationship is poorly understood. Therefore, this study aims to identify metabolite biomarkers related to adrenal suppression in asthma patients taking ICS.
    METHODS: A total of 571 urine metabolites from 200 children with asthma on ICS in the Pharmacogenetics of Adrenal Suppression with Inhaled Steroids (PASS) cohort were profiled. Samples were grouped by peak plasma cortisol measurement as adrenal sufficient (>350 nmol/L) or insufficient (≤350 nmol/L) (outcome). Regression and discriminant-based statistical models combined with network analyses were utilized to assess relationships between metabolites and the outcome. Finally, prioritized metabolites were validated using data from an ancillary study of the Childhood Asthma Management (CAMP) cohort with similar characteristics to PASS.
    RESULTS: Ninety metabolites were significantly associated with adrenal suppression, of which 57 also could discriminate adrenal status. While 26 metabolites (primarily steroids) were present at lower levels in the adrenal insufficient patients, 14 were significantly elevated in this group; the top metabolite, mannitol/sorbitol, was previously associated with asthma exacerbations. Network analyses identified unique clusters of metabolites related to steroids, fatty acid oxidation, and nucleoside metabolism, respectively. Four metabolites including urocanic acid, acetylcarnitine, uracil, and sorbitol were validated in CAMP cohort for adrenal suppression.
    CONCLUSIONS: Urinary metabolites differ among asthma patients on ICS, by adrenal status. While steroid metabolites were reduced in patients with poor adrenal function, our findings also implicate previously unreported metabolites involved in amino acid, lipid, and nucleoside metabolism.
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