Neurogenic lower urinary tract dysfunction

神经源性下尿路功能障碍
  • 文章类型: Journal Article
    DNA甲基化是一种表观遗传过程,通常发生在基因启动子中,并导致基因的转录沉默。DNA甲基化是膀胱癌中常见的事件,参与肿瘤的发生和进展。膀胱癌是患有神经源性下尿路功能障碍(NTUTD)的患者的主要健康问题,尽管该病的发病机制尚不清楚。在这个人群中,膀胱癌的特点是侵袭性组织病理学,在诊断的晚期阶段,和高死亡率。为了评估NTUTD患者膀胱组织中已知与膀胱癌相关的五个基因启动子的DNA甲基化谱,我们进行了一项前瞻性研究,招募了公立教学医院神经泌尿科的NNUTD患者.在获得书面知情同意书后,对所有患者进行膀胱镜检查联合活检进行膀胱癌筛查。定量甲基化特异性PCR检测RASSF1、RARβ、DAPK,hTERT,和膀胱组织样本中的APC基因启动子。这项研究招募了24名患有混合的NULTD病因的患者,中位持续时间为10(IQR:12)年。在所有组织样品的组中的至少一个基因中检测到DNA超甲基化。RAR-β在91.7%的样本中高度甲基化,83.3%的样本中RASSF和DAPK高度甲基化,APC37.5%样品,和TERT都不在组织样本中。在45.8%的样品中,小组的三个基因被高度甲基化,在29.2%的基因中,有四个基因是高甲基化的,在16.7%和8.3%的样本中,两个和一个基因高度甲基化,分别。该组的高甲基化基因的数量与复发性UTI显着相关(p=0.0048)。在DNA超甲基化或超甲基化基因的数量与患者的临床特征之间没有发现其他显着关联。8.3%的患者组织病理学检查结果正常,而慢性炎症在83.3%的患者中发现,鳞状细胞化生在16.7%的患者中发现。在这项研究中,我们观察到在NNUTD患者中与膀胱癌相关的基因的DNA高甲基化率,提示表观遗传场效应和膀胱癌发展的可能风险。反复发生的UTI似乎与DNA超甲基化增加有关。需要进一步的研究来评估UTI复发和慢性炎症对NULTD患者DNA高甲基化和膀胱癌病因的影响。
    DNA methylation is an epigenetic process that commonly occurs in genes\' promoters and results in the transcriptional silencing of genes. DNA methylation is a frequent event in bladder cancer, participating in tumor initiation and progression. Bladder cancer is a major health issue in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD), although the pathogenetic mechanisms of the disease remain unclear. In this population, bladder cancer is characterized by aggressive histopathology, advanced stage during diagnosis, and high mortality rates. To assess the DNA methylation profiles of five genes\' promoters previously known to be associated with bladder cancer in bladder tissue of NLUTD patients, we conducted a prospective study recruiting NLUTD patients from the neuro-urology unit of a public teaching hospital. Cystoscopy combined with biopsy for bladder cancer screening was performed in all patients following written informed consent being obtained. Quantitative methylation-specific PCR was used to determine the methylation status of RASSF1, RARβ, DAPK, hTERT, and APC genes\' promoters in bladder tissue samples. Twenty-four patients suffering from mixed NLUTD etiology for a median duration of 10 (IQR: 12) years were recruited in this study. DNA hypermethylation was detected in at least one gene of the panel in all tissue samples. RAR-β was hypermethylated in 91.7% samples, RASSF and DAPK were hypermethylated in 83.3% samples, APC 37.5% samples, and TERT in none of the tissue samples. In 45.8% of the samples, three genes of the panel were hypermethylated, in 29.2% four genes were hypermethylated, and in 16.7% and in 8.3% of the samples, two and one gene were hypermethylated, respectively. The number of hypermethylated genes of the panel was significantly associated with recurrent UTIs (p = 0.0048). No other significant association was found between DNA hypermethylation or the number of hypermethylated genes and the clinical characteristics of the patients. Histopathological findings were normal in 8.3% of patients, while chronic inflammation was found in 83.3% of patients and squamous cell metaplasia in 16.7% of patients. In this study, we observed high rates of DNA hypermethylation of genes associated with bladder cancer in NLUTD patients, suggesting an epigenetic field effect and possible risk of bladder cancer development. Recurrent UTIs seem to be associated with increased DNA hypermethylation. Further research is needed to evaluate the impact of recurrent UTIs and chronic inflammation in DNA hypermethylation and bladder cancer etiopathogenesis in NLUTD patients.
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  • 文章类型: Journal Article
    确定中国社区居住脊髓损伤患者神经源性下尿路功能障碍的不同管理模式,并探讨潜在分类的相关因素。这是一项在中国大陆社区进行的横断面研究。参与者是通过中国身体残疾人协会招募的,总共2582名参与者被纳入分析。数据是通过由社会人口因素组成的问卷收集的,疾病相关因素,并列出了8种膀胱管理方法。潜在类别分析用于确定神经源性下尿路功能障碍管理的不同潜在类别。然后应用多项logistic回归分析神经源性下尿路功能障碍管理模式与社会人口统计学和疾病相关因素之间的关系。社区脊髓损伤患者的神经源性下尿路功能障碍管理模式分为四个潜在类别:“小便器为主模式”(40.3%),“膀胱压缩主导模式”(30.7%),“间歇性导尿为主模式”(19.3%)和“尿道留置导尿为主模式”(9.6%)。多项logistic回归分析发现,就业状况,住宅区,护理需要,导管插入产品的付款方式,手功能,脊髓损伤后的时间,尿失禁和对排尿问题影响的社交互动的担忧与潜在类别显着相关。只有19.3%的人将间歇性导尿作为其主要的神经源性下尿路功能障碍管理方法。需要更加重视社区居住脊髓损伤患者间歇性导尿标准化进程的推广。四类的相关因素可用于定制和有针对性的干预措施,以增加间歇性导管插入术的使用。
    To identify different patterns of neurogenic lower urinary tract dysfunction management among Chinese community-dwelling individuals with spinal cord injury and explore the factors associated with latent classes. This was a cross-sectional study conducted in communities throughout China Mainland. Participants were recruited through the China Association of Persons with Physical Disability and a total of 2582 participants was included in the analysis. The data were collected by a questionnaire consisting of socio-demographic factors, disease-related factors, and a list of 8 bladder management methods. Latent class analysis was used to identify different latent classes of neurogenic lower urinary tract dysfunction management. Then the multinomial logistic regression was applied to analyze the relationship between neurogenic lower urinary tract dysfunction management patterns and socio-demographic and disease-related factors. Neurogenic lower urinary tract dysfunction management pattern among community-dwelling individuals with spinal cord injury was divided into four latent classes: \"urinal collecting apparatus dominated pattern\" (40.3%), \"bladder compression dominated pattern\" (30.7%), \"intermittent catheterization dominated pattern\" (19.3%) and \"urethral indwelling catheterization dominated pattern\" (9.6%). Multinomial logistic regression analysis found that the employment status, residential region, nursing need, payment method for catheterization products, hand function, time since spinal cord injury, urinary incontinence and concerns about social interaction affected by urination problems were significantly associated with latent classes. Only 19.3% of people used the intermittent catheterization as their main neurogenic lower urinary tract dysfunction management method. More attention needs to be paid to the promotion of the standardization process of intermittent catheterization in community-dwelling individuals with spinal cord injury. The associated factors of the four classes can be used for tailored and targeted interventions to increase the use of intermittent catheterization.
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  • 文章类型: Journal Article
    骶神经调节(SNM)为患有特发性膀胱过度活动症(OAB)综合征的泌尿外科患者提供了一种治疗方法,有或没有尿失禁和非阻塞性尿潴留(NOR),对保守或医学疗法没有反应或不服从的人。SNM的确切作用机制尚未完全了解,但周围传入对脊髓反射和脑网络的调节被认为是主要途径。多年来,手术技术改进,导致现代两阶段植入技术的发展。四极导线在透视引导下经皮定位,沿着S3的轨迹穿过第三骶骨孔。该过程可以在患者处于俯卧位的情况下在局部或全身麻醉下进行。由于设备的最新改进,使其不仅在膀胱过度活动症和非阻塞性尿潴留等情况下,而且在神经源性下尿路功能障碍中,都是一种有价值的选择,因此当前在泌尿科中的应用正在增加。
    Sacral neuromodulation (SNM) offers a therapeutic approach to urological patients suffering from idiopathic overactive bladder (OAB) syndrome, with or without incontinence and non-obstructive urinary retention (NOR), who are not responding to or are not compliant with conservative or medical therapies. The exact mechanism of action of SNM is not fully understood but modulation of the spinal cord reflexes and brain networks by peripheral afferents is regarded as the main pathway. Over the years, surgical techniques improved, leading to the development of the modern two-stage implantation technique. The quadripolar lead is positioned percutaneously under fluoroscopy guidance through the third sacral foramen following the trajectory of S3. The procedure can be performed under local or general anesthesia with the patient in prone position. Current applications of sacral neuromodulation in urology are increasing thanks to the recent improvements of the devices that make this a valuable option not only in conditions such as overactive bladder and non-obstructing urinary retention but also neurogenic lower urinary tract dysfunction.
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  • 文章类型: Journal Article
    背景:简短形式Qualiveen(SF-Qualiveen)问卷评估了膀胱和泌尿症状对神经系统疾病引起的泌尿系统损害患者生活质量(QoL)的影响。没有经过验证的阿拉伯语SF-Qualiveen问卷,因此,这项研究旨在为讲阿拉伯语的多发性硬化症(MS)患者提供SF-Qualiveen问卷的翻译和验证版本。
    方法:使用语言和文化适应算法将SF-Qualiveen的英文版翻译成阿拉伯语。MS患者完成了SF-Qualiveen,和神经源性膀胱症状评分(NBSS)问卷。心理测量特征,如内容和结构有效性,测试-重测可靠性,并对内部一致性进行了分析。通过将SF-Qualiveen与BSS问卷进行对比来评估结构效度。内部一致性是用克朗巴赫的阿尔法测量的,而采用组内相关系数(ICC)评估重测信度.
    结果:本研究纳入了一百零二名MS患者。总SF-Qualiveen的内部一致性,和域\"有限制的烦恼,\"\"恐惧,\"\"感觉,“”和“限制频率”显示出良好的内部一致性(Cronbach的alpha>0.7)。ICC为0.91,总分为0.85,有限制的另一个,0.81的恐惧,0.86的感觉,限制频率为0.81。相关分析显示,BSS的总分与SF-Qualiveen的领域之间呈正相关。包括受到限制的打扰(r=0.473,p=0.027),恐惧(r=0.611,p=0.031),感觉(r=0.572,p=0.04),和限制频率(r=0.514,p=0.013)。
    结论:这项验证研究的结果表明,SF-Qualiveen在研究和临床实践中都是适用于讲阿拉伯语的MS患者的可靠且有效的仪器。
    BACKGROUND: The Short Form Qualiveen (SF-Qualiveen) questionnaire assesses the effect of bladder and urinary symptoms on patients\' quality of life (QoL) with urological impairment caused by neurological diseases. There is no validated SF-Qualiveen questionnaire in Arabic, so this study aims to provide a translated and validated version of the SF-Qualiveen questionnaire among Arabic-speaking patients with multiple sclerosis (MS).
    METHODS: The English version of the SF-Qualiveen was translated into Arabic using an algorithm for linguistic and cultural adaptation. MS patients completed the SF-Qualiveen, and the Neurogenic Bladder Symptom Score(NBSS) questionnaire. Psychometric features such as content and construct validity, test-retest reliability, and internal consistency were analyzed. Construct validity was evaluated by contrasting the SF-Qualiveen with the NBSS questionnaire. Internal consistency was measured using Cronbach\'s alpha, whereas the intraclass correlation coefficient (ICC) was employed to assess the test-retest reliability.
    RESULTS: One hundred and two patients with MS were included in this study. The internal consistency of the total SF-Qualiveen, and the domains \"Bother with limitations,\" \"Fear,\" \"Feeling,\" and \"Frequency of limitations\" showed good internal consistency (Cronbach\'s alpha of > 0.7). ICC was 0.91 for the total score 0.85 for the Bother with limitations, 0.81 for Fears, 0.86 for Feeling, and 0.81 for Frequency of limitations. The correlation analysis revealed a positive association between the total scores on the NBSS and the domains of the SF-Qualiveen, comprising bother with limitations (r = 0.473, p = 0.027), fears (r = 0.611, p = 0.031), feelings (r = 0.572, p = 0.04), and frequency of limitations (r = 0.514, p = 0.013).
    CONCLUSIONS: The findings of this validation study revealed that the SF-Qualiveen is a reliable and valid instrument appropriate for Arabic-speaking patients with MS in both research and clinical practice.
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  • 文章类型: Review
    目的:神经源性压力性尿失禁(N-SUI)是一种严重影响生活质量的疾病。人工尿道括约肌(AUS)在几种治疗方式中脱颖而出,是解决括约肌功能不全的最合适技术。在这篇文章中,目的是描述实际考虑,结果,以及男性和女性神经括约肌缺乏症中人工尿道括约肌的并发症。
    方法:对现有文献进行叙述性回顾。
    结果:NUTD患者的AUS结果相当好,讨论了这种复杂和异质患者群体的手术技术以及局限性和特殊考虑因素。
    结论:现有证据表明,与没有神经功能缺损的患者相比,神经源性下尿路功能障碍(NTUTD)患者的疗效和功能耐久性可能较低。然而,研究表明,AUS仍然可以在男性和女性患者中提供有效和安全的尿失禁结果,设备的长期生存率从几年到十多年不等。
    OBJECTIVE: Neurogenic stress urinary incontinence (N-SUI) is a condition with serious impact on the quality of life. There are several treatment modalities of which the artificial urinary sphincter (AUS) stands out as the most suitable technique for addressing sphincter insufficiency. In this article, the purpose is to describe practical considerations, outcomes, and complications of the artificial urinary sphincter in neurological sphincter deficiency in both males and females.
    METHODS: A narrative review of the current literature.
    RESULTS: The outcomes of AUS are reasonably good in patients with NLUTD, the surgical technique is discussed as well as the limitations and special considerations in this complex and heterogeneous patient population.
    CONCLUSIONS: The available evidence suggests that its efficacy and functional durability may be lower in patients with neurogenic lower urinary tract dysfunction (NLUTD) compared to those without neurological deficits. However, studies have shown that AUS can still provide effective and safe continence outcomes in both male and female patients, with long-term device survival rates ranging from several years to over a decade.
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  • 文章类型: Journal Article
    背景:简短形式的Qualiveen(SF-Qualiveen)问卷评估了膀胱和泌尿症状对神经系统疾病引起的泌尿系统损害患者生活质量(QoL)的影响。没有经过验证的阿拉伯语SF-Qualiveen问卷,因此,这项研究旨在为经历脊髓损伤(SCI)的阿拉伯患者提供SF-Qualiveen问卷的翻译和验证版本。
    方法:心理测量特征,如内容和结构效度,测试-重测可靠性,并对内部一致性进行了分析。通过比较SF-Qualiveen与神经源性膀胱症状评分简表(NBSS-SF)问卷来评估结构效度。内部一致性是用克朗巴赫的阿尔法测量的,而采用组内相关系数(ICC)评估重测信度.通过主成分分析(PCA)建立因子效度。
    结果:总SF-Qualiveen和有限制的域的内部一致性,\"\"恐惧,\"\"感觉,“”和“限制频率”显示出良好的内部一致性(Cronbach的alpha>0.7)。ICC总分为0.90,0.83的烦恼与限制,0.80的恐惧,0.84的感觉,限制频率为0.81。相关分析显示,NBSS-SF的总分与SF-Qualiveen的领域之间呈正相关。包括受到限制的打扰(r=0.53,p=0.02),恐惧(r=0.44,p=0.03),感觉(r=0.49,p=0.04),和限制频率(r=0.46,p=0.02)。确认整体项目社区的最佳拟合四因素模型范围为0.552至0.814,这表明中等到高社区,并使用PCA确认SF-Qualiveen的同质性。
    结论:这项验证研究的结果表明,SF-Qualiveen在研究和临床实践中都是适用于讲阿拉伯语的SCI患者的可靠有效工具。
    BACKGROUND: The Short-Form Qualiveen (SF-Qualiveen) questionnaire assesses the effect of bladder and urinary symptoms on patients\' quality of life (QoL) with urological impairment caused by neurological diseases. There is no validated SF-Qualiveen questionnaire in Arabic, so this study aims to provide a translated and validated version of the SF-Qualiveen questionnaire among Arabic patients experiencing spinal cord injury (SCI).
    METHODS: Psychometric features such as content and construct validity, test-retest reliability, and internal consistency were analyzed. Construct validity was evaluated by contrasting the SF-Qualiveen with the Neurogenic Bladder Symptom Score Short-Form (NBSS-SF) questionnaire. Internal consistency was measured using Cronbach\'s alpha, whereas the intraclass correlation coefficient (ICC) was employed to assess the test-retest reliability. Factorial validity was established by principal component analysis (PCA).
    RESULTS: The internal consistency of the total SF-Qualiveen and the domains \"Bother with limitations,\" \"Fear,\" \"Feeling,\" and \"Frequency of limitations\" showed good internal consistency (Cronbach\'s alpha of > 0.7). ICC was 0.90 for the total score, 0.83 for the bother with limitations, 0.80 for fears, 0.84 for feeling, and 0.81 for frequency of limitations. The correlation analysis revealed a positive association between the total scores on the NBSS-SF and the domains of the SF-Qualiveen, comprising bother with limitations (r = 0.53, p = 0.02), fears (r = 0.44, p = 0.03), feelings (r = 0.49, p = 0.04), and frequency of limitations (r = 0.46, p = 0.02). The best-fit four-factor model for confirming overall item communalities ranged from 0.552 to 0.814, which indicates moderate to high communalities, and confirms the homogeneity of the SF-Qualiveen using PCA.
    CONCLUSIONS: The findings of this validation study revealed that the SF-Qualiveen is a reliable and valid instrument appropriate for Arabic-speaking patients with SCI in both research and clinical practices.
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  • 文章类型: Journal Article
    了解神经泌尿系统疾病的分子机制对于发展有针对性的治疗干预措施至关重要。通过建立综合性生物银行,研究人员可以收集和储存各种生物标本,包括尿液,血,组织,和DNA样本,研究这些机制。在神经泌尿学方面,生物带有利于遗传变异的识别,表观遗传修饰,和与神经源性下尿路功能障碍相关的基因表达模式。这些情况通常表现为神经疾病的症状,如阿尔茨海默病,多发性硬化症,帕金森病,脊髓损伤,和许多其他人。对这些患者的组织样本进行生物分析对于理解为什么这些疾病会导致各自的症状以及可以采取什么措施来缓解这些症状至关重要。利用高通量技术,如下一代测序和基因表达谱分析,使研究人员能够以前所未有的方式探索这些条件的分子景观。这些努力导致的特定和可靠的生物标志物的开发可能有助于早期检测,准确诊断,以及对神经泌尿系统状况的有效监测,改善患者护理和管理。此外,这些生物标志物可能有助于监测神经泌尿学临床试验中目前正在研究的新疗法.这篇全面的综述探讨了神经泌尿学和生物样本的协同整合,特别强调神经泌尿学分子研究中生物库方法的翻译。我们讨论了神经泌尿学研究中生物库的优势,采集的标本类型及其在转化研究中的应用。此外,我们强调了在收集样品时标准化和质量保证的重要性,并讨论了可能损害样品质量并限制其后续使用的挑战。最后,我们为多中心研究中的抽样提供建议,检查与生物作业相关的可持续性问题,并为这个动态领域提供未来的方向。
    Understanding the molecular mechanisms underlying neuro-urological disorders is crucial for the development of targeted therapeutic interventions. Through the establishment of comprehensive biobanks, researchers can collect and store various biological specimens, including urine, blood, tissue, and DNA samples, to study these mechanisms. In the context of neuro-urology, biobanking facilitates the identification of genetic variations, epigenetic modifications, and gene expression patterns associated with neurogenic lower urinary tract dysfunction. These conditions often present as symptoms of neurological diseases such as Alzheimer\'s disease, multiple sclerosis, Parkinson\'s disease, spinal cord injury, and many others. Biobanking of tissue specimens from such patients is essential to understand why these diseases cause the respective symptoms and what can be done to alleviate them. The utilization of high-throughput technologies, such as next-generation sequencing and gene expression profiling, enables researchers to explore the molecular landscape of these conditions in an unprecedented manner. The development of specific and reliable biomarkers resulting from these efforts may help in early detection, accurate diagnosis, and effective monitoring of neuro-urological conditions, leading to improved patient care and management. Furthermore, these biomarkers could potentially facilitate the monitoring of novel therapies currently under investigation in neuro-urological clinical trials. This comprehensive review explores the synergistic integration of neuro-urology and biobanking, with particular emphasis on the translation of biobanking approaches in molecular research in neuro-urology. We discuss the advantages of biobanking in neuro-urological studies, the types of specimens collected and their applications in translational research. Furthermore, we highlight the importance of standardization and quality assurance when collecting samples and discuss challenges that may compromise sample quality and impose limitations on their subsequent utilization. Finally, we give recommendations for sampling in multicenter studies, examine sustainability issues associated with biobanking, and provide future directions for this dynamic field.
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  • 文章类型: Journal Article
    这项回顾性探索性研究的目的是调查最低意识状态(MCS)/反应迟钝的觉醒综合征(UWS)患者在视频尿动力学研究(VUDS)中不利发现的发生率,以及下尿路(LUT)的管理是否相应调整。在2011年至2020年期间,我们在我们的康复中心进行了回顾性图表审查,以筛选诊断为MCS/UWS的患者。包括18岁或以上的患者,并在诊断为MCS/UWS后接受基线VUDS。我们分析了该队列中的尿动力学参数和随后的LUT管理变化。总的来说,32名患者(7名女性,25名男性,中位年龄37岁)的MCS/UWS纳入分析。而至少有一个不利的VUDS发现(即,神经性逼尿肌过度活跃[NDO],逼尿肌括约肌协同失调{DSD,储存阶段最大逼尿肌压力高[>40cmH2O],低顺应性膀胱[<20mL/cmH2O],并且在每位患者中发现了膀胱输尿管肾反流[VUR]),NDO(78.1%,25/32)和DSD(68.8%,22/32)是两个最常见的不利VUDS发现。在基线VUDS之后,56.3%(18/32)的患者建立了新的LUT治疗方案.此外,46.9%(15/32)的患者改变了膀胱排空方法,导致更少的患者依赖留置导管。我们的回顾性探索性研究揭示了NDO和DSD在MCS/UWS患者中的高患病率。说明了VUDS在此队列中相应调整LUT管理的重要性。
    The aim of this retrospective exploratory study was to investigate the prevalence of unfavorable findings during video-urodynamic studies (VUDS) in patients with minimally conscious state (MCS)/unresponsive wakefulness syndrome (UWS) and whether management of the lower urinary tract (LUT) was adjusted accordingly. A retrospective chart review was conducted to screen for patients diagnosed with MCS/UWS at our rehabilitation center between 2011 and 2020. Patients 18 years or older were included and underwent baseline VUDS after being diagnosed with MCS/UWS. We analyzed urodynamic parameters and subsequent changes in LUT management in this cohort. In total, 32 patients (7 females, 25 males, median age 37 years) with MCS/UWS were included for analysis. While at least one unfavorable VUDS finding (i.e., neurogenic detrusor overactivity [NDO], detrusor sphincter dyssynergia {DSD, high maximum detrusor pressure during storage phase [>40 cmH2O], low-compliance bladder [<20 mL/cmH2O], and vesico-uretero-renal reflux [VUR]) was found in each patient, NDO (78.1%, 25/32) and DSD (68.8%, 22/32) were the two most frequent unfavorable VUDS findings. Following baseline VUDS, new LUT treatment options were established in 56.3% (18/32) of all patients. In addition, bladder-emptying methods were changed in 46.9% (15/32) of all patients, resulting in fewer patients relying on indwelling catheters. Our retrospective exploratory study revealed a high prevalence of NDO and DSD in patients with MCS/UWS, illustrating the importance of VUDS to adapt LUT management in this cohort accordingly.
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  • 文章类型: Journal Article
    背景:患有神经源性下尿路功能障碍(NTUTD)的膀胱癌(BCa)由于其诊断的晚期和高死亡率而受到关注。目前,在这些患者中缺乏BCa筛查的具体指南.BCa尿液生物标志物的开发似乎是该患者人群中筛查或风险分层的有吸引力的非侵入性方法。DNA甲基化是一种表观遗传修饰,导致肿瘤抑制基因的转录沉默,经常在BCa患者的尿液中检测到。目的:我们旨在研究5个基因启动子的DNA甲基化,以前与BCa有关,在NUUTD患者的尿液中,与健康对照相比。设计,背景和参与者:这是一项前瞻性病例对照研究,该研究从一家公立教学医院招募了患有NNUTD至少5年的神经内科门诊患者.在书面知情同意后,他们都接受了膀胱镜检查结合活检进行BCa筛查。提取DNA并评估RASSF1,RARβ,DAPK,TERT和APC基因启动子通过定量甲基化特异性PCR在来自患者和对照的尿液样本中。结果:纳入41例NTUTD病因混合的患者和35例对照。在36例患者的尿液标本和22例对照中检测到DNA。在尿液样本中,在17/36例患者和3/22例对照中,5个基因启动子中的至少一个中DNA被高度甲基化(47.22%vs.13.64%,分别,p=0.009)。10/17(58.82%)标本中RASSF1高甲基化,检测到甲基化,APC在7/17(41.18%),DAPK在4/17(23.53%),RAR-β2在3/17(17.56%),TERT在无。根据多元逻辑回归分析,NNUTD和男性与甲基化显著相关(OR=7.43,p=0.007和OR=4.21;p=0.04)。在组织标本中,组织学检查显示,两名患者为TaLGBCa,五名患者为尿路上皮鳞状化生。慢性膀胱炎症存在于35/41膀胱活检中。结论:NULTD患者尿液中五个BCa相关基因的DNA甲基化明显高于对照组。我们的结果值得在纵向研究中进一步评估,评估DNA超甲基化之间的临床意义和可能的关联,NTUTD人群中的慢性炎症和BCa。
    Background: Bladder cancer (BCa) in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD) is a significant concern due to its advanced stage at diagnosis and high mortality rate. Currently, there is a scarcity of specific guidelines for BCa screening in these patients. The development of urine biomarkers for BCa seems to be an attractive non-invasive method of screening or risk stratification in this patient population. DNA methylation is an epigenetic modification, resulting in the transcriptional silencing of tumor suppression genes, that is frequently detected in the urine of BCa patients. Objectives: We aimed to investigate DNA hypermethylation in five gene promoters, previously associated with BCa, in the urine of NLUTD patients, and in comparison with healthy controls. Design, setting and participants: This was a prospective case-control study that recruited neurourology outpatients from a public teaching hospital who had suffered from NLUTD for at least 5 years. They all underwent cystoscopy combined with biopsy for BCa screening following written informed consent. DNA was extracted and DNA methylation was assessed for the RASSF1, RARβ, DAPK, TERT and APC gene promoters via quantitative methylation-specific PCR in urine specimens from the patients and controls. Results: Forty-one patients of mixed NLUTD etiology and 35 controls were enrolled. DNA was detected in 36 patients\' urine specimens and in those of 22 controls. In the urine specimens, DNA was hypermethylated in at least one of five gene promoters in 17/36 patients and in 3/22 controls (47.22% vs. 13.64%, respectively, p = 0.009). RASSF1 was hypermethylated in 10/17 (58.82%) specimens with detected methylation, APC in 7/17 (41.18%), DAPK in 4/17 (23.53%), RAR-β2 in 3/17 (17.56%) and TERT in none. According to a multivariate logistic regression analysis, NLUTD and male gender were significantly associated with hypermethylation (OR = 7.43, p = 0.007 and OR = 4.21; p = 0.04, respectively). In the tissue specimens, histology revealed TaLG BCa in two patients and urothelial squamous metaplasia in five patients. Chronic bladder inflammation was present in 35/41 bladder biopsies. Conclusions: DNA hypermethylation in a panel of five BCa-associated genes in the urine was significantly more frequent in NLUTD patients than in the controls. Our results warrant further evaluation in longitudinal studies assessing the clinical implications and possible associations between DNA hypermethylation, chronic inflammation and BCa in the NLUTD population.
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  • 文章类型: Journal Article
    背景:患有神经源性下尿路功能障碍(NLUTD)的患者通常依靠某种类型的导尿来进行膀胱排空。间歇性导管插入术(IC)被认为是金标准,优于连续导管插入术。因为它被认为比留置导尿引起的尿路感染(UTI)更少。我们研究的主要目的是描述使用留置导管的患者与进行IC的患者之间的UTI患病率(就诊时)和发生率(过去12个月内)以及尿培养特征。
    方法:在这项横断面研究中,我们对2020年2月至2021年1月因预防性原因或UTI症状而接受尿液培养的NUUTD患者进行了前瞻性评估.参观时,所有患者均接受了关于当前UTI症状以及过去一年内UTI病史和抗生素使用情况的标准化访谈.使用留置导管(n=206)或IC(n=299)的患者被纳入分析。主要结果是关于UTI特征的组间差异。
    结果:使用留置导管的患者年龄较大(留置导管vsIC:中位年龄66(Q1-Q3:55-77)vs55(42-67)),并且表现出更高的Charlson合并症指数(留置导管vsIC:中位年龄4(Q1-Q3:2-6)vs2(1-4)(均p<0·001)。两组共有40名患者在就诊时被诊断为UTI(留置导管vsIC:8%(16/206)vs8%(24/299);p=0·782),过去12个月的UTI数量在组间无显著差异.总的来说,大肠杆菌(21%),粪肠球菌(17%),和克雷伯菌属。(12%)是最经常检出的细菌。
    结论:在这个NUTD患者队列中,我们没有发现两组之间UTI频率的相关差异.这些结果表明,在为患者提供导管相关的膀胱排空方法咨询时,不应过分强调与UTI相关的问题。
    BACKGROUND: Patients with neurogenic lower urinary tract dysfunction (NLUTD) often rely on some type of catheterization for bladder emptying. Intermittent catheterization (IC) is considered the gold standard and is preferred over continuous catheterization, since it is considered to cause fewer urinary tract infections (UTIs) than indwelling catheterization. The main objective of our study was to describe UTI prevalence (at visit) and incidence (within the last 12 months) and urine culture characteristics between patients using an indwelling catheter versus (vs) those performing IC.
    METHODS: In this cross-sectional study, we prospectively evaluated from 02/2020 to 01/2021 patients with NLUTD undergoing urine cultures for prophylactic reasons or due to UTI symptoms. At visit, all patients underwent a standardized interview on current UTI symptoms as well as UTI history and antibiotic consumption within the past year. Patients using an indwelling catheter (n = 206) or IC (n = 299) were included in the analysis. The main outcome was between-group differences regarding UTI characteristics.
    RESULTS: Patients using an indwelling catheter were older (indwelling catheter vs IC: median 66 (Q1-Q3: 55-77) vs 55 (42-67) years of age) and showed a higher Charlson comorbidity index (indwelling catheter vs IC: median 4 (Q1-Q3: 2-6) vs 2 (1-4) (both p < 0·001). A total of 40 patients from both groups were diagnosed with a UTI at visit (indwelling catheters vs IC: 8% (16/206) vs 8% (24/299); p = 0·782), and the number of UTIs within the past 12 months was not significantly different between groups. Overall, Escherichia coli (21%), Enterococcus faecalis (17%), and Klebsiella spp. (12%) were the most frequently detected bacteria.
    CONCLUSIONS: In this cohort of patients with NLUTD, we did not find relevant differences in UTI frequency between groups. These results suggest that UTI-related concerns should not be given undue emphasis when counseling patients for catheter-related bladder emptying methods.
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