perianal fistula

肛周瘘
  • 文章类型: Case Reports
    这是一个由三名患有复杂肛门直肠瘘的患者组成的病例系列。每位患者都接受了生物网修复复杂的肛门直肠瘘。我们将讨论每个案例以及我们机构对这种相对较新的技术的经验。此病例系列演示了生物网状物用于修复复杂的肛门直肠瘘的用途。讨论了三名患者,他们由两名独立的外科医生使用ACell网状物修复了肛周瘘。我们将讨论提供这种治疗的理由,以及优点和缺点。在肛周瘘中使用生物网格是一个相对较新的话题,需要进一步研究。对于患者和外科医生来说,肛周瘘可能难以管理。修复有很多选择,从简单到复杂。复杂瘘的生物网可能是一个有用的选择,以避免更复杂的修复的发病率。如襟翼。
    This is a case series of three patients who presented with complex anorectal fistulas. Each patient underwent repair of complex anorectal fistulas with biologic mesh. We will discuss each case and our institution\'s experience with this relatively new technique. This case series demonstrates the use of biologic mesh for the repair of complex anorectal fistulas. Three patients are discussed who underwent repair of perianal fistulas using ACell mesh by two separate surgeons. We will discuss the rationale for offering this treatment, as well as the advantages and disadvantages. The use of biologic mesh in perianal fistulas is a relatively new topic that needs further investigation. Perianal fistulas can be difficult to manage for both patients and surgeons. There are many options for repair, ranging from simple to complex. Biologic mesh for complex fistulas may be a useful option to avoid the morbidity of more complex repairs, such as flaps.
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  • 文章类型: Journal Article
    目的:肛周瘘是克罗恩病的一种具有挑战性的表型,对生活质量有重大影响。历史上,瘘管在解剖学上与括约肌复合体有关,管理指南已经泛化,缺乏对临床异质性的关注。最近的“TOpClass分类系统”用于肛周吻合克罗恩病(PFCD)解决了这个问题,并将患者分为确定的组,这提供了与疾病特征和患者目标相一致的瘘管管理的重点。在这篇文章中,我们讨论了TOpClass模型的临床适用性,并为其在临床实践中的使用提供了指导。
    方法:一组国际肛周临床医生参与了一项专家共识,以确定如何将TOpClass系统纳入现实生活中。这包括胃肠病学家,IBD外科医生,和专门从事PFCD的放射科医生。北美八个高容量瘘管病中心的多学科团队管理为这一过程提供了信息,欧洲,和澳大利亚。
    结果:该过程产生了职位陈述,以伴随分类系统并指导PFCD管理。陈述范围从静止的肛周疾病患者的管理到需要分流造口术和/或前切除术的严重PFCD患者。医学疗法的优化,以及手术的使用,在瘘管闭合和症状管理方面,我们对每个分类组进行了探讨.
    结论:本文概述了该系统在临床实践中的应用。它的目的是使临床医生有一个务实的和患者目标为中心的方法,以医疗和外科管理选择PFCD的个体患者。
    OBJECTIVE: Perianal fistulation is a challenging phenotype of Crohn\'s disease with significant impact on quality of life. Historically, fistulae have been classified anatomically in relation to the sphincter complex, and management guidelines have been generalised, with lack of attention to the clinical heterogenicity seen. The recent \'TOpClass classification system\' for perianal fistulising Crohn\'s disease (PFCD) addresses this issue, and classifies patients into defined groups, which provide a focus for fistula management that aligns with disease characteristics and patient goals. In this article, we discuss the clinical applicability of the TOpClass model and provide direction on its use in clinical practice.
    METHODS: An international group of perianal clinicians participated in an expert consensus to define how the TOpClass system can be incorporated into real-life practice. This included gastroenterologists, IBD surgeons, and radiologists specialised in PFCD. The process was informed by the multi-disciplinary team management of eight high-volume fistula centres in North America, Europe, and Australia.
    RESULTS: The process produced position statements to accompany the classification system and guide PFCD management. The statements range from the management of patients with quiescent perianal disease to those with severe PFCD requiring diverting-ostomy and/or proctectomy. The optimisation of medical therapies, as well as the use of surgery, in fistula closure and symptom management is explored across each classification group.
    CONCLUSIONS: This article provides an overview of the system\'s use in clinical practice. It aims to enable clinicians to have a pragmatic and patient-goal centred approach to medical and surgical management options for individual patients with PFCD.
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  • 文章类型: Journal Article
    背景:艾滋病毒感染儿童的儿科医疗保健涉及处理复杂的挑战,包括严重影响其生活质量的会阴问题。我们引入术语“会阴崩解综合征”(PDS)来描述以脓肿和涉及肛门的各种瘘为特征的病症,直肠,尿道,或生殖道。关于PDS的文献有限,缺乏标准化的治疗方法和普遍接受的术语。我们对新术语的提议旨在标准化术语,并刺激有针对性的研究,以改善这一弱势群体的管理和成果。
    目的:本研究的目的是对儿科HIV患者PDS的现有文献进行综合分析,以揭示关键发现,确定知识差距,并概述临床护理和未来研究的实际意义和建议。
    方法:在儿科HIV患者中,对数据库进行了系统的搜索,这些数据库具有全面的关键词,确定了有关PDS的相关文章。
    结果:这篇综述强调了非洲国家PDS文献的重点,强调迫切需要在艾滋病毒/艾滋病负担沉重的地区进行研究和临床关注。诊断和管理PDS的挑战,其原因的不确定性,并揭示了在资源有限的环境中缺乏标准化的管理方法。
    结论:这篇综述强调了前瞻性研究的重要性,标准化方案和以患者为中心的多学科护理在儿科HIV患者PDS管理中,以改善该人群的护理和预后。
    方法:I.
    BACKGROUND: Paediatric healthcare for children with HIV involves managing complex challenges, including severe perineal issues that significantly affect their quality of life. We introduce the term \"perineal disintegration syndrome\" (PDS) to describe conditions characterised by abscesses and various fistulae involving the anus, rectum, urethra, or reproductive tracts. The literature on PDS is limited and lacks a standardised treatment approach and universally accepted terminology. Our proposal for a new term aims to standardise nomenclature and stimulate targeted research to improve management and outcomes for this vulnerable group.
    OBJECTIVE: The aim of the study was to conduct a comprehensive analysis of the existing literature on PDS in paediatric HIV patients to uncover key findings, identify knowledge gaps, and outline practical implications and recommendations for clinical care and future research.
    METHODS: A systematic search across databases with comprehensive keywords identified relevant articles on PDS in paediatric HIV patients was conducted.
    RESULTS: The review emphasises the focus of PDS literature in African nations, highlighting the urgent need for research and clinical attention in HIV/AIDS-burdened regions. Challenges in diagnosing and managing PDS, uncertainties in its causes, and the lack of standardised management approaches in resource-constrained settings were revealed.
    CONCLUSIONS: This review emphasises the importance of prospective research, standardised protocols and patient-centred multidisciplinary care in managing PDS in paediatric HIV patients to improve care and outcomes of this population.
    METHODS: I.
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  • 文章类型: Journal Article
    背景:瘘管激光闭合术(FiLaC™)在肛周造瘘性克罗恩病(pfCD)中显示出有希望的结果。然而,大多数研究在较短的随访期内评估了包含pfCD和隐腺管瘘的混合队列.本研究旨在评估FiLaC™在复杂pfCD患者中的长期治疗结果。
    方法:回顾性分析2019年1月至2020年12月在克罗恩病深度缓解期间接受FiLaC™治疗的复杂pfCD患者的数据。患者人口统计学,手术史,术前登记用药策略。随访安排在FiLaC™后1、2和3个月,此后每隔2个月。主要终点是临床愈合,而临床缓解/未愈/复发被归类为未愈。此外,记录不良事件和Wexner大便失禁评分.
    结果:纳入49名患者(40名男性和9名女性),中位年龄为26.0(19.0-35.5)岁,中位随访时间为50.0(39.5-54.0)个月。其中,31例(63.3%)患者实现瘘管愈合,3(6.1%)经历了改善,3(6.1%)仍未愈合,12例(24.5%)复发。治疗组的蒙特利尔A组较低(P<0.001)。无重大并发症,如出血或大便或尿失禁,被观察到,疼痛是短暂的。在最后一次可用的随访中,Wexner失禁评分显着下降,表明术后失禁功能完整(P=0.014)。未愈合组PCDAI评分明显高于未愈合组(P=0.041)。
    结论:FiLaC™对于复杂pfCD患者是一种有效且安全的保括约肌手术。
    BACKGROUND: Fistula-tract laser closure (FiLaC™) has shown promising outcomes in perianal fistulizing Crohn\'s disease (pfCD). However, most studies assessed a mixed cohort encompassing pfCD and cryptoglandular fistulas during a short follow-up period. This study aimed to evaluate the long-term treatment outcomes of FiLaC™ in patients with complex pfCD.
    METHODS: Data from patients with complex pfCD who underwent FiLaC™ during deep remission of Crohn\'s disease between January 2019 and December 2020 were retrospectively analyzed. Patient demographics, surgery history, and medication strategy were registered before surgery. Follow-ups were scheduled at 1, 2, and 3 months after FiLaC™, and at 2-month intervals thereafter. The primary endpoint was clinic healing, while clinic remission/unhealed/recurrence were classified as unhealed. Additionally, adverse events and Wexner fecal incontinence score were documented.
    RESULTS: Forty-nine patients (40 men and 9 women) with a median age of 26.0 (19.0-35.5) years were included with a median follow-up of 50.0 (39.5-54.0) months. Of these, 31 (63.3%) patients achieved fistula healing, 3 (6.1%) experienced improvement, 3 (6.1%) remained unhealed, and 12 (24.5%) experienced recurrence. Montreal A category was lower in the healed group (P < 0.001). No major complications, such as bleeding or fecal or urinary incontinence, were observed, and pain was transient. The Wexner incontinence score decreased significantly at the last available follow-up, indicating an intact postoperative continence function (P = 0.014). PCDAI scores were significantly higher in the unhealed group (P = 0.041).
    CONCLUSIONS: FiLaC™ is an efficient and safe sphincter-saving procedure for patients with complex pfCD.
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  • 文章类型: Journal Article
    背景和目的:肛周克罗恩(CD)瘘患者通常需要重复手术,没有一种已建立的技术被证明是优越或优选的。此外,瘘管Seton引流的长期结局没有得到很好的描述.这项研究的目的是分析大型患者队列中CD肛周瘘的长期愈合和复发率。材料和方法:瑞士IBD(炎症性肠病)队列研究的数据库分析。结果:对365例肛瘘患者进行了576例手术干预,中位随访时间为7.5年(0-12.6)。39.7%的患者需要一个以上的手术。首次手术干预是瘘管切除术±粘膜滑动皮瓣(59.2%),西顿排水(29.6%),瘘管塞或纤维蛋白胶安装(2.5%)和联合手术(8.8%)。69%的患者不需要更多的手术,25%的额外手术和6%的额外手术,随访7.5年的闭合率为77.1%,74.1%和66.7%,分别。在使用Seton引流作为索引手术的患者中,52%的人不需要手术,超过75%的人在10年后实现了瘘管闭合。结论:一线瘘管切除术,在可行的情况下,达到了最高的治愈率,但是三分之一的患者需要额外的手术,四分之一的患者将在10年后保持瘘管。最初的Seton引流和同时的药物治疗可以实现75%的瘘管闭合。然而,在50%的患者中,需要更多的手术,只有三分之二的患者实现了瘘管闭合。
    Background and Objectives: Patients with perianal Crohn\'s (CD) fistula often need repetitive surgeries and none of the established techniques was shown to be superior or preferable. Furthermore, the long-term outcome of fistula Seton drainage is not well described. The aims of this study were to analyze the long-term healing and recurrence rate of CD perianal fistulas in a large patient cohort. Materials and Methods: Database analysis of the Swiss IBD (Inflammatory Bowel Disease) cohort study. Results: 365 perianal fistula patients with 576 surgical interventions and a median follow-up of 7.5 years (0-12.6) were analyzed. 39.7% of patients required more than one procedure. The first surgical interventions were fistulectomies ± mucosal sliding flap (59.2%), Seton drainage (29.6%), fistula plugs or fibrin glue installations (2.5%) and combined procedures (8.8%). Fistulectomy patients required no more surgery in 69%, one additional surgery in 25% and more than one additional surgery in 6%, with closure rates at 7.5 years follow-up of 77.1%, 74.1% and 66.7%, respectively. In patients with Seton drainage as index surgery, 52% required no more surgery, and over 75% achieved fistula closure after 10 years. Conclusions: First-line fistulectomies, when feasible, achieved the highest healing rates, but one-third of patients required additional surgeries, and one-fourth of patients will remain with a fistula at 10 years. Initial Seton drainage and concurrent medical therapy can achieve fistula closure in 75%. However, in 50% of patients, more surgeries are needed, and fistula closure is achieved in only two-thirds of patients.
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  • 文章类型: Case Reports
    肛周瘘的存在构成克罗恩病(CD)的更严重表型,通常需要强化药物治疗。伤口护理,和手术干预。尽管炎症性肠病的治疗进展,肛周瘘的治疗仍然具有挑战性.高压氧疗法(HBOT)已被提议作为诱导瘘管愈合的辅助治疗方式。我们说明了一例HBOT在患有严重难治性肛周克罗恩病(pCD)的年轻患者中实现瘘管愈合的情况。我们还回顾了当前的文献,并讨论了HBOT在pCD治疗中的作用。
    The presence of perianal fistulae constitutes a more severe phenotype of Crohn\'s disease (CD) that often requires intensive medical therapy, wound care, and surgical intervention. Despite therapeutic advances in inflammatory bowel disease, the treatment of perianal fistulae remains challenging. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment modality for induction of fistula healing. We illustrate a case in which HBOT achieved fistula healing in a young patient with severe refractory perianal Crohn\'s disease (pCD). We also review the current literature and discuss the role of HBOT in the treatment armamentarium of pCD.
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  • 文章类型: Journal Article
    痔疮影响全球75%的人。外科痔疮切除术仍然是严重病例的决定性干预措施。术后伤口护理至关重要,和替代疗法,像没药一样,由于其潜在的伤口愈合特性,人们越来越感兴趣。本研究旨在比较安全性,功效,以及采用标准临床护理的没药坐浴促进痔切除术后伤口愈合的治疗结果。
    使用Abha私立医院的病历进行了2022年1月至12月的回顾性队列研究。收集接受痔疮切除术的患者的数据,并根据术后伤口护理分为两组:A组,基于没药的伤口护理作为自我药物治疗,B组,用于标准伤口护理。
    该研究包括67例接受痔疮切除术的患者。在这些病人中,52人接受了标准的伤口护理,而15则在没有医疗建议的情况下使用基于没药的伤口护理作为自我治疗。没药组患者明显年龄较大,合并症较多。与标准护理组2/52(3.8%)相比,Myrrh组具有显著的III级伤口愈合结果9/15(60%)(p<0.001)。然而,尽管治疗效果更好,Myrrh组的并发症发生率7/15(46.7%)显著高于标准治疗组1/52(1.9%)(p<0.001).这些结果表明,尽管没药有很好的愈合能力,必须谨慎使用。
    没药坐浴在促进痔疮切除术后愈合方面比标准伤口护理更有效。然而,并发症的增加表明有必要对其安全性进行综合评估和研究。这些发现可以指导与术后伤口护理相关的未来研究和临床实践。
    UNASSIGNED: Hemorrhoids affect 75% of people worldwide. surgical hemorrhoidectomy remains the definitive intervention for severe cases. Postoperative wound care is critical, and alternative treatments, like Myrrh, are of growing interest due to their potential wound-healing properties. This study aimed to compare the safety, efficacy, and treatment outcomes of Myrrh sitz baths with standard clinical care in promoting wound healing after hemorrhoidectomy.
    UNASSIGNED: A retrospective cohort study was carried out using medical records from Abha Private Hospital for the period of January-December 2022. The data of patients who underwent hemorrhoidectomy were collected and categorized based on postoperative wound care into two groups: Group A for Myrrh-based wound care as a self-medication and Group B for standard wound care.
    UNASSIGNED: The study included 67 patients who underwent hemorrhoidectomy. Out of these patients, 52 had standard wound care, while 15 used Myrrh-based wound care as self-treatment without medical advice. The Myrrh group patients were significantly older with more comorbidities. The Myrrh group had significant Grade III wound healing outcomes 9/15 (60%) compared to the standard care group 2/52 (3.8%) (p < 0.001). However, despite the better healing outcomes, the Myrrh group had a significantly higher complication rate 7/15(46.7%) than the standard care group 1/52 (1.9%) (p < 0.001). These results indicate that despite the good healing capacity of Myrrh, cautious usage must be considered.
    UNASSIGNED: Myrrh sitz baths appear more effective than standard wound care in enhancing healing after hemorrhoidectomy. However, increased complications suggest the necessity for comprehensive evaluation and research on its safety profile. These findings can guide future research and clinical practices related to postoperative wound care.
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  • 文章类型: Journal Article
    背景:在影像学上观察复杂的肛周瘘的过程可能很困难。据推测,肛周瘘的三维(3D)模型可以提高对肛周病理学的理解,有助于手术决策,甚至可能改善手术治疗的未来结局。当前研究的目的是研究3D打印肛周瘘模型与磁共振成像(MRI)相比的准确性。
    方法:选择15例经括约肌和括约肌间瘘患者的MRI扫描,然后由经验丰富的腹部和结直肠放射科医师进行评估。技术医学物理学家和外科医生在对3D打印特别感兴趣的培训中开发了一种创建隐腺性肛瘘的3D打印解剖模型的标准化方法。由训练有素的技术医学物理学家对瘘管和外括约肌进行手动分割。解剖模型以1:1的比例进行3D打印,并由两名结直肠外科医生进行评估。然后用3D扫描仪扫描3D打印的模型。将3D打印模型的体积与手动分割进行比较。计算了评估者间的可靠性统计数据,以确保评估MRI扫描的放射科医生与评估3D打印模型的外科医生之间的一致性。MRI的评估被认为是“黄金标准”。还确定了评估3D打印模型的两名外科医生之间的协议。
    结果:放射科医生和外科医生之间的一致性在分类方面几乎是完美的(κ=0.87,κ=0.87),复杂性(κ=0.73,κ=0.74)和内孔位置(κ=0.73,κ=0.73),经括约肌瘘中肛门外括约肌的百分比适中(ICC0.63,ICC0.52)。两位外科医生之间的协议是实质性的分类(κ=0.73),复杂度(κ=0.74),内孔的位置(κ=0.75)和经括约肌瘘中涉及肛门外括约肌的百分比(ICC0.77)。
    结论:我们的肛周瘘的3D打印解剖模型是MRI的准确反映。需要进一步的研究来确定3D打印解剖模型在术前计划和教育中的附加价值。
    BACKGROUND: Visualising the course of a complex perianal fistula on imaging can be difficult. It has been postulated that three-dimensional (3D) models of perianal fistulas improve understanding of the perianal pathology, contribute to surgical decision-making and might even improve future outcomes of surgical treatment. The aim of the current study is to investigate the accuracy of 3D-printed models of perianal fistulas compared with magnetic resonance imaging (MRI).
    METHODS: MRI scans of 15 patients with transsphincteric and intersphincteric fistulas were selected and then assessed by an experienced abdominal and colorectal radiologist. A standardised method of creating a 3D-printed anatomical model of cryptoglandular perianal fistula was developed by a technical medical physicist and a surgeon in training with special interest in 3D printing. Manual segmentation of the fistula and external sphincter was performed by a trained technical medical physicist. The anatomical models were 3D printed in a 1:1 ratio and assessed by two colorectal surgeons. The 3D-printed models were then scanned with a 3D scanner. Volume of the 3D-printed model was compared with manual segmentation. Inter-rater reliability statistics were calculated for consistency between the radiologist who assessed the MRI scans and the surgeons who assessed the 3D-printed models. The assessment of the MRI was considered the \'gold standard\'. Agreement between the two surgeons who assessed the 3D printed models was also determined.
    RESULTS: Consistency between the radiologist and the surgeons was almost perfect for classification (κ = 0.87, κ = 0.87), substantial for complexity (κ = 0.73, κ = 0.74) and location of the internal orifice (κ = 0.73, κ = 0.73) and moderate for the percentage of involved external anal sphincter in transsphincteric fistulas (ICC 0.63, ICC 0.52). Agreement between the two surgeons was substantial for classification (κ = 0.73), complexity (κ = 0.74), location of the internal orifice (κ = 0.75) and percentage of involved external anal sphincter in transsphincteric fistulas (ICC 0.77).
    CONCLUSIONS: Our 3D-printed anatomical models of perianal fistulas are an accurate reflection of the MRI. Further research is needed to determine the added value of 3D-printed anatomical models in preoperative planning and education.
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  • 文章类型: Journal Article
    背景:肛周脓肿是肛周区域的临床感染性和/或炎性集合,一大组肛门和肛周疾病的一个实体。根据圣詹姆斯大学医院分类,肛周脓肿通常被视为2级和4级肛周瘘的并发症。过去已经尝试了几种成像方式,以通过对比增强磁共振成像(CE-MRI)提供最准确的结果来充分评估肛周脓肿。弥散加权成像(DWI)是一种新兴的序列,可以在诊断和表征肛周脓肿方面提供与CE-MRI相当的结果。这项研究的主要目的是评估DWI在充分识别和评估肛周脓肿中的作用,并将最终结果与对比增强图像进行比较。
    方法:对20例临床怀疑肛周脓肿的复杂性肛瘘患者进行DWI和CE-MRI评估。这项研究是在放射诊断和成像部门进行的比较横断面研究,全印度医学科学研究所,博帕尔,印度。进行卡方检验以找到分类变量之间的关联。使用Kappa检验来发现两个不同测试之间的一致性。进行受试者工作特征(ROC)分析以估计预测结果的曲线下面积。灵敏度,特异性,正预测值,阴性预测值和准确性用于衡量测试的有效性.
    结果:DWI是一种非常敏感的MRI序列,相当于CE-MRI,可以检测复杂性肛瘘病例中脓肿的位置并分析其局部范围。DWI在区分肛周脓肿与无脓肿的肛周炎症方面也非常敏感,优于T2短tau倒置恢复(STIR)。
    结论:DWI可作为对比后脂肪抑制MRI的替代方法,用于精确确定复杂性瘘管病例中肛门和肛周脓肿的位置和范围以及疾病活动。
    BACKGROUND: Perianal abscess is a clinical infective and/or inflammatory collection in the perianal region, one entity of a large group of anal and perianal disorders. Perianal abscesses are often seen as a complication of grade 2 and grade 4 perianal fistulas from St. James\'s University Hospital classification. Several imaging modalities have been tried in the past for adequate assessment of perianal abscess with contrast-enhanced magnetic resonance imaging (CE-MRI) providing the most accurate results. Diffusion-weighted imaging (DWI) is an emerging sequence that can provide comparable results to CE-MRI in diagnosing and characterizing perianal abscess. The main objective of this study is to assess the role of DWI in adequate identification and assessment of perianal abscess and compare the final results with contrast-enhanced images.
    METHODS: Twenty patients with complicated perianal fistula with clinically suspected perianal abscess were evaluated with DWI and CE-MRI. This study was a comparative cross-sectional study conducted in the Department of Radiodiagnosis and Imaging, All India Institute of Medical Sciences, Bhopal, India. Chi-square test was done to find the association between categorical variables. Kappa test was used to find the agreement between two different tests. Receiver operating characteristics (ROC) analysis was done to estimate the area under the curve in predicting the outcome. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were used to measure the validity of the tests.
    RESULTS: DWI is a very sensitive MRI sequence and is equivalent to CE-MRI to detect the location and analyzing the loco-regional extent of abscess in complicated perianal fistula cases. DWI is also very sensitive and superior to T2 short tau inversion recovery (STIR) in differentiating perianal abscess from perianal inflammation without abscess.
    CONCLUSIONS: DWI can be used as an alternative to post-contrast fat-suppressed MRI in precisely defining the location and extent of anal and perianal abscesses and disease activity in complicated fistula cases.
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  • 文章类型: Journal Article
    背景:克罗恩病并发肛周瘘在非洲血统的患者中更为普遍和严重。
    方法:我们从结肠直肠粘膜和瘘道分析了克罗恩病合并肛周瘘的不同患者的单细胞。进行免疫荧光以验证预测的细胞-细胞相互作用。将未刺激的单核细胞在不同的队列中慢性培养。通过单核RNA+ATAC测序分析子集。
    结果:与成对的直肠组织相比,来自完整的直肠切除术的尿道细胞显示出骨髓细胞的富集。配体受体分析突出了骨髓基质串扰和细胞衰老,通过免疫荧光验证细胞共定位。几丁质酶-3样蛋白-1(CHI3L1)是表达破坏性和纤维化基因特征的瘘基质细胞中的最高上调基因。与欧洲血统的个体相比,来自非洲血统和对照组患者的单核细胞培养物显示出分化后CHI3L1和制瘤素M(OSM)表达的差异。激活蛋白-1足迹存在于应激反应基因的ATAC-seq峰中,包括CHI3L1和OSM;观察到包括JUN足迹在内的全基因组染色质可及性,与报道的炎症记忆机制一致。调节子分析证实了已知的细胞特异性转录因子调节,并在成纤维细胞亚群中暗示了新的转录因子。所有假性聚集簇都显示出遗传基因座的富集,建立多细胞贡献。在最重要的非裔美国人克罗恩的基因位点,在前列腺素E受体4的上游,观察到以淋巴为主的ATAC-seq峰,预测的RORC足迹。
    结论:骨髓基质串扰的群体差异涉及纤维化和破坏性成纤维细胞,衰老,表观遗传记忆,和细胞特异性增强剂在肛瘘发病机制中的作用。本文提供的转录组和表观遗传学数据可以指导有前途的间充质干细胞治疗肛瘘的优化。
    背景:这项工作得到了授权U01DK062422,U24DK062429和R01DK123758的支持。
    BACKGROUND: Crohn\'s disease complicated by perianal fistulae is more prevalent and severe in patients of African ancestry.
    METHODS: We profiled single cells from diverse patients with Crohn\'s disease with perianal fistula from colorectal mucosa and fistulous tracts. Immunofluorescence was performed to validate predicted cell-cell interactions. Unstimulated monocytes were chronically cultured in diverse cohorts. A subset was analyzed by single-nucleus RNA + ATAC sequencing.
    RESULTS: Fistulous tract cells from complete proctectomies demonstrated enrichment of myeloid cells compared to paired rectal tissues. Ligand-receptor analysis highlights myeloid-stromal cross-talk and cellular senescence, with cellular co-localization validated by immunofluorescence. Chitinase-3 like-protein-1 (CHI3L1) is a top upregulated gene in stromal cells from fistulae expressing both destructive and fibrotic gene signatures. Monocyte cultures from patients of African ancestry and controls demonstrated differences in CHI3L1 and oncostatin M (OSM) expression upon differentiation compared to individuals of European ancestry. Activating protein-1 footprints are present in ATAC-seq peaks in stress response genes, including CHI3L1 and OSM; genome-wide chromatin accessibility including JUN footprints was observed, consistent with reported mechanisms of inflammatory memory. Regulon analyses confirm known cell-specific transcription factor regulation and implicate novel ones in fibroblast subsets. All pseudo-bulked clusters demonstrate enrichment of genetic loci, establishing multicellular contributions. In the most significant African American Crohn\'s genetic locus, upstream of prostaglandin E receptor 4, lymphoid-predominant ATAC-seq peaks were observed, with predicted RORC footprints.
    CONCLUSIONS: Population differences in myeloid-stromal cross-talk implicate fibrotic and destructive fibroblasts, senescence, epigenetic memory, and cell-specific enhancers in perianal fistula pathogenesis. The transcriptomic and epigenetic data provided here may guide optimization of promising mesenchymal stem cell therapies for perianal fistula.
    BACKGROUND: This work was supported by grants U01DK062422, U24DK062429, and R01DK123758.
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