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https://www.nature.com/articles/s41413-019-0061-z
读图 相关解读为AI生成 
上图描述了耐甲氧西林金黄色葡萄球菌 (MRSA) 感染性人工全关节置换术 (TJR) 翻修手术过程中的坏死骨和生物膜污染部件清除。 a-c：单阶段翻修术的适应症 a：术前 X 光片显示感染性人工全髋关节置换术的放射学证据，包括骨膜反应和未愈合的股骨骨折（黄色箭头）。 b：开放性感染的大腿需要切除坏死软组织和白色（坏死）骨骼，以及保留邻近的红色（活）骨骼以成功挽救肢体。完全清除坏死骨骼、骨水泥和坏死组织可以为新的假体创造更健康的植入环境。 c：股骨缺损术后 X 光片，植入了模块化髋关节假体。
d-g：植入物上的细菌生物膜 d-e：股骨全膝关节置换部件表面的照片，分别在染色四氧化锇前后（d），染色后可识别骨水泥上的细菌生物膜（e）。 f：植入物扫描电镜 (SEM) 图像显示植入物表面上的生物膜细菌（黄色箭头） (x10000)。 g：植入物上附着于纤维蛋白的细菌 (x10000)。
上图详细描述了慢性骨髓炎中细菌的三种不同储存库。 1.组织切片观察到的葡萄球菌脓肿聚集体 (Staphylococcus abscess communities, SACs)（a-e）：- 图像展示了感染后 7 天 (a) 和 14 天 (c) 小鼠胫骨的组织切片染色结果，并用箭头标注了骨髓和周围软组织中的葡萄球菌脓肿聚集体 (SACs)。
- 图中框选区域 (a, c) 利用布朗-布伦染色 (Brown and Brenn stain) 进行对照切片染色 (b, d)，可以清楚地区分革兰氏阳性细菌 (深蓝色)，周围充满因 NETosis 死亡或垂死的嗜中性粒细胞 (红色细胞)，并被巨噬细胞层 (白色层) 包围。
- 通过针对精氨酸酶-1 (arginase-1) 的抗体进行免疫染色 (e)，可以看出到第 14 天时，造血性骨髓 (BM) 完全被炎性组织替代，并且脓肿聚集体周围存在 M2 巨噬细胞 (棕色细胞)，表明慢性感染已经确立。
2.扫描电镜观察到的植入物上的生物膜 (f-j)：- 生物膜的形成始于浮游细菌的附着 (f)，例如图中展示的体外实验，葡萄球菌附着于流水槽系统中培养的 不锈钢丝上 (×10000)。
- 经胫骨植入后，浮游细菌会迅速转变为生物膜 (g)，可以看到术后 14 天不锈钢针表面被均匀的糖萼层覆盖 (×200)。
- 植入物生物膜的高倍图像显示球菌附着在纤维素链上 (h, ×2 500)，以及葡萄球菌聚集形成细菌荚 (bacterial pods) (i, ×5 000)。到第 14 天，可以观察到空腔，表明细菌已经从荚中完全逸出 (j, ×30 000)。
3.透射电子显微镜观察到的皮质骨上的细菌定植 (k-m)：- 葡萄球菌通过消除骨衬细胞来暴露通向骨细胞 (osteocyte, OC) 的细管 (canaliculi) (蓝色箭头)，从而开始定植皮质骨 (k, ×6 000)。
- 随后，葡萄球菌通过骨细胞 lacuno-canalicular network (OLCN) 侵入和传播，使生物膜细菌 (*) 对骨外的活化中性粒细胞 (蓝色箭头) 无法接近 (l, ×1 800)。
- 无法抑制的细菌会使皮质骨脱矿并消耗骨骼以扩大细管，并传播到邻近的细管 (黄色箭头)，到达远处的骨细胞 (红色箭头)。
- 图 m 是对 (l) 中被葡萄球菌占据腔隙并杀死的骨细胞的高倍透射电镜图像 (×12 000)。
这段话通过组织切片、扫描电镜和透射电镜三种显微学技术，展示了慢性骨髓炎中葡萄球菌如何在骨骼及其植入物上形成藏匿处，对治疗带来挑战。Osteomyelitis is defined as inflammation of the bone often caused by bacterial infection. It is one of the oldest diseases in history and has a significant impact:
骨髓炎被定义为通常由细菌感染引起的骨炎症。它是历史上最古老的疾病之一，具有重大影响： It is the most severe and devastating risk associated with orthopedic implants, such as total hip and knee replacements.
这是与骨科植入物相关的最严重和最具破坏性的风险，如全髋关节和膝关节置换术。 While advances in prophylaxis have reduced infection rates after elective surgery, the rates cannot be reduced below 1-2%.
虽然预防措施的进步降低了择期手术后的感染率，但感染率不能降低到1- 2%以下。 Rates of recurrent or persistent infection following revision surgery for infected joint replacements can be as high as 33%.
感染关节置换翻修手术后复发或持续感染的发生率可高达33%。 Despite aggressive treatment strategies like debridement, hardware exchange, and long-term antimicrobial therapy, infections continue to recur.
尽管积极的治疗策略，如清创术，硬件交换，和长期的抗菌治疗，感染继续复发。 The projected cost for treatment of implant-associated osteomyelitis is expected to exceed $1.62 billion by 2020 in the United States.
预计到2020年，美国治疗植入物相关骨髓炎的费用将超过16.2亿美元。 Staphylococcus aureus is the most common pathogen isolated from implant-associated osteomyelitis, with over 50% of cases caused by methicillin-resistant S. aureus (MRSA) strains, which are difficult to treat.
金黄色葡萄球菌是种植体相关性骨髓炎最常见的病原体，超过50%的病例由耐甲氧西林的金黄色葡萄球菌引起。金黄色葡萄球菌（MRSA）菌株，这是很难治疗的。 The ability of S. aureus to form biofilms, develop antimicrobial resistance, and persist intracellularly contributes to the challenges in treating osteomyelitis.
S.金黄色葡萄球菌形成生物膜、产生抗微生物剂耐药性并在细胞内持续存在的能力对治疗骨髓炎提出了挑战。
In summary, osteomyelitis, particularly implant-associated osteomyelitis caused by S. aureus, is a significant clinical problem with substantial patient morbidity, mortality, and economic burden, highlighting the need for novel prevention and treatment strategies.
总之，骨髓炎，特别是S。金黄色葡萄球菌感染是一个重要的临床问题，具有相当大的患者发病率、死亡率和经济负担，突出了对新的预防和治疗策略的需要。 Introduction 介绍 Definition and impact of osteomyelitis
骨髓炎的定义和影响 Staphylococcus aureus as the primary causative pathogen
金黄色葡萄球菌为主要致病菌 Need for novel strategies to prevent and treat osteomyelitis
需要新的策略来预防和治疗骨髓炎
Three Distinct Reservoirs of Biofilm Bacteria in Chronic Osteomyelitis
慢性骨髓炎中生物膜细菌的三种不同储存库 Staphylococcal Abscess Communities (SACs)
葡萄球菌脓肿群落（SAC） Glycocalyx on Implants 植入物上的多糖包被 Colonization of Osteocyte-Lacuno Canalicular Network (OLCN)
骨细胞-陷窝小管网（OLCN）的定植
Role of Intracellular Persistence in Osteomyelitis
细胞内存留在骨髓炎中的作用 Classification of Acute and Chronic Osteomyelitis
急性和慢性骨髓炎的分类 Antibodies and S. aureus Orthopedic Infections
抗体和金葡菌感染 Novel Antibiotic Therapies
新型抗生素疗法 Antibiotic-laden bone cement spacers
含抗生素骨水泥占位器 3D-printed antibiotic-impregnated scaffolds
3D打印的浸渍有抗菌药的支架 Silver, antibiotics, antimicrobial peptides, and bacteriophages
银、抗生素、抗微生物肽和噬菌体 Implant Coatings 植入物涂层 Dead Space Management 死腔管理
Conclusion 结论 Need for further research on OLCN invasion and antibiotic efficacy
需要进一步研究OLCN侵袭和抗生素疗效 Potential for immunotherapies and diagnostics
免疫治疗和诊断的潜力 Investigation of non-FDA-approved antibiotic bone cement
非FDA批准的抗生素骨水泥的研究 Exploration of 3D-printed antibiotic-impregnated spacer technologies
3D打印浸胶垫片技术的探索
关键问题问答 可盖住右侧答案，尝试自我测试 | Question 问题 | Answer 答案 |
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What are the three distinct reservoirs of biofilm bacteria in chronic osteomyelitis?
慢性骨髓炎中生物膜细菌的三个不同储库是什么？ | 1. Staphylococcal Abscess Communities (SACs)<br>2. Glycocalyx on Implants<br>3. Colonization of Osteocyte-Lacuno Canalicular Network (OLCN)
1.葡萄球菌脓肿社区（SAC）2.植入物 3.上的糖衣包被。骨细胞-陷窝小管网络（OLCN）的定植 | What is the role of intracellular persistence in osteomyelitis?
骨髓炎中细胞内持久性的作用是什么？ | Limited evidence of intracellular persistence in bone cells. 'Trojan Horse' leukocytes facilitate bacterial dissemination.
骨细胞内持久性的证据有限。“特洛伊木马”白细胞促进细菌传播。 | What is the issue with the classification of acute and chronic osteomyelitis?
急性和慢性骨髓炎的分类有什么问题？ | Lack of consensus on definitions. Need for new definitions incorporating biofilm biology.
对定义缺乏共识。需要纳入生物膜生物学的新定义。 | How can antibodies be useful in S. aureus orthopedic infections?
抗体如何在S.金黄色骨科感染？ | Diagnostic and prognostic utility of antibodies. Antibody-based biologics for treatment.
抗体的诊断和预后效用。用于治疗的基于抗体的生物制剂。 | What are the novel antibiotic therapies discussed for osteomyelitis?
骨髓炎的新抗生素疗法有哪些？ | 1. Implant Coatings: Silver, antibiotics, antimicrobial peptides, and bacteriophages.<br>2. Dead Space Management: Antibiotic-laden bone cement spacers and 3D-printed antibiotic-impregnated scaffolds.
1.植入物涂层：银、抗生素、抗菌肽和噬菌体。2.死腔管理：含抗生素的骨水泥垫片和3D打印的骨水泥浸渍支架。 |
This article highlights several significant points that are relevant for clinicians in preventing and treating postoperative osteomyelitis infections:
本文强调了临床医生在预防和治疗术后骨髓炎感染方面的几个要点： Understanding the distinct bacterial reservoirs:
了解不同的细菌储库： Clinicians need to be aware of the three distinct reservoirs of biofilm bacteria (SACs, implant glycocalyx, and OLCN colonization) that can perpetuate chronic osteomyelitis.
临床医生需要了解三种不同的生物膜细菌储库（SAC、植入物糖萼和OLCN定植），它们可能使慢性骨髓炎永久化。 Recognizing these reservoirs is crucial for complete debridement and eradication of bacteria during revision surgeries.
在翻修手术中，识别这些储库对于完全清创和根除细菌至关重要。
Rethinking acute vs. chronic classification:
重新思考急性与慢性分类： The traditional classification of 'acute' and 'chronic' osteomyelitis based on time is oversimplified and lacks consensus.
传统的“急性”和“慢性”骨髓炎的分类是基于时间过于简化，缺乏共识。 New definitions that incorporate biofilm biology and bacterial invasion of the OLCN are needed to guide appropriate treatment protocols.
需要结合生物膜生物学和OLCN细菌入侵的新定义来指导适当的治疗方案。
Potential for antibody-based diagnostics and therapeutics:
基于抗体的诊断和治疗的潜力： Monitoring antibody levels (serum and MENSA) can aid in diagnosing ongoing infections, assessing treatment response, and identifying recurrence.
监测抗体水平（血清和MENSA）可以帮助诊断正在进行的感染，评估治疗反应，并确定复发。 Antibody-based biologics targeting S. aureus virulence factors and immunoevasion mechanisms may serve as adjunctive therapies to antibiotics.
针对S.金黄色葡萄球菌毒力因子和免疫逃避机制可能作为抗生素的免疫治疗。
Exploring novel antibiotic delivery strategies:
探索新型抗生素递送策略： Implant coatings with antimicrobials (silver, antibiotics, AMPs, phages) can prevent bacterial adhesion and biofilm formation.
抗菌剂（银、抗生素、AMP、抗菌素）的植入物涂层可防止细菌粘附和生物膜形成。 3D-printed antibiotic-impregnated scaffolds offer improved dead space management and sustained local antibiotic delivery compared to traditional antibiotic-laden bone cement.
与传统的骨水泥相比，3D打印的骨水泥浸渍支架提供了更好的死腔管理和持续的局部抗生素输送。
Addressing intracellular persistence:
解决细胞内持久性：
By understanding these advances in the pathogenesis, diagnosis, and treatment of osteomyelitis, clinicians can potentially improve prevention strategies, treatment outcomes, and patient care in cases of postoperative infections.
通过了解骨髓炎的发病机制、诊断和治疗方面的进展，临床医生可以潜在地改善预防策略、治疗结果和术后感染病例的患者护理。 The review article discusses three distinct reservoirs of biofilm bacteria found in chronic osteomyelitis:
综述文章讨论了慢性骨髓炎中发现的三种不同的生物膜细菌储库： Staphylococcal Abscess Communities (SACs):
葡萄球菌脓肿群落（SAC）：
SACs are collections of bacteria surrounded by immune cells like neutrophils and macrophages.
SAC是由免疫细胞（如中性粒细胞和巨噬细胞）包围的细菌集合。 They typically form in soft tissues and bone marrow adjacent to the infected site.
它们通常在感染部位附近的软组织和骨髓中形成。 The bacteria at the core of the SAC are protected from immune cells by a fibrin margin.
位于SAC核心的细菌通过纤维蛋白边缘免受免疫细胞的侵害。 As SACs mature over weeks, immune cells are restricted to the periphery, allowing bacterial persistence at the center.
随着SAC在数周内成熟，免疫细胞被限制在外围，使细菌在中心持续存在。 SACs serve as a reservoir of bacteria and can rupture, leading to further bacterial dissemination if not surgically debrided.
SAC作为细菌的储存库，如果不进行手术清创，可能破裂，导致进一步的细菌传播。
Glycocalyx formation on implant hardware:
植入物硬件上的糖萼形成：
Bacteria adhere to the implant surface via microbial surface components recognizing adhesive matrix molecules (MSCRAMMs).
细菌通过识别粘附基质分子的微生物表面成分（MSCRAbind）粘附到植入物表面。 The adhered bacteria proliferate and form a biofilm by producing an extracellular polymeric substance (EPS) matrix called glycocalyx.
粘附的细菌增殖并通过产生称为糖萼的细胞外聚合物（EPS）基质形成生物膜。 The glycocalyx encases the bacteria, protecting them from immune cells and antibiotics.
糖萼包裹着细菌，保护它们免受免疫细胞和抗生素的侵害。 The mature biofilm has a complex structure with bacterial pods, void spaces, and nutrient channels.
成熟的生物膜具有复杂的结构，包括细菌荚、空隙空间和营养通道。 Bacteria can disperse from the biofilm and spread to new sites, making complete removal of infected implants crucial.
细菌可以从生物膜中扩散并扩散到新的部位，这使得完全清除受感染的植入物至关重要。
Colonization of the osteocyte-lacuno canalicular network (OLCN) of cortical bone:
皮质骨细胞-骨陷窝小管网络（OLCN）的定植：
S. aureus can invade and colonize the submicron canaliculi and lacunar spaces within cortical bone that normally house osteocytes.
S.金黄色葡萄球菌可以侵入并定殖通常容纳骨细胞的皮质骨内的亚微米小管和腔隙空间。 The bacteria demineralize and consume the bone matrix as they spread through the OLCN.
当细菌通过OLCN传播时，它们会去矿化并消耗骨基质。 Once inside the OLCN, the bacteria are inaccessible to immune cells outside the bone.
一旦进入OLCN，细菌就无法接近骨外的免疫细胞。 This privileged niche may allow bacterial persistence for decades, explaining recurrence of osteomyelitis after long periods of quiescence.
这种特殊的生态位可能允许细菌持续存在数十年，解释了长期静止后骨髓炎的复发。
The review highlights that eradicating all three of these distinct biofilm reservoirs is essential for curing chronic osteomyelitis, as any remaining bacteria can lead to re-infection and treatment failure.
该综述强调，根除所有这三种不同的生物膜储库对于治疗慢性骨髓炎至关重要，因为任何剩余的细菌都可能导致再次感染和治疗失败。 Based on the information provided in the review, here is a table summarizing the diagnosis and potential treatment approaches for the three distinct reservoirs of biofilm bacteria in chronic osteomyelitis:
根据综述中提供的信息，以下表格总结了慢性骨髓炎中三种不同生物膜细菌储库的诊断和潜在治疗方法： | Biofilm Reservoir 生物膜水库 | Diagnosis 诊断 | Potential Treatments 潜在的治疗方法 |
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Staphylococcal Abscess Communities (SACs)
葡萄球菌脓肿群落（SAC） | - Clinical signs of infection- Imaging (radiographs, MRI, etc.) to detect soft tissue/bone lesions- Histological examination of biopsied tissue to identify abscesses
- 感染的临床体征-成像（X线片、MRI等）检测软组织/骨病变-活检组织的组织学检查，以识别病变 | - Surgical debridement of soft tissue and bone marrow to remove abscesses- Local antibiotic therapy (e.g. antibiotic-loaded cement spacers)
- 软组织和骨髓的外科清创术，以清除脓肿-局部抗生素治疗（例如，骨水泥填充器） | Glycocalyx formation on implant hardware
植入物硬件上的糖萼形成 | - Clinical signs of infection- Imaging to detect implant loosening/osteolysis- Intraoperative visualization of biofilm on explanted hardware
- 感染的临床体征-成像以检测植入物松动/骨质溶解-术中可视化植入硬件上的生物膜 | - Complete removal of infected implant hardware- Antibiotic-coated implants to prevent new biofilm formation- Local antibiotic therapy
- 完全清除感染的植入物硬件-抗生素涂层植入物以防止新生物膜形成-局部抗生素治疗 | Colonization of Osteocyte Lacuno-Canalicular Network (OLCN)
骨细胞腔隙-小管网络（OLCN）的定植 | - No specific diagnostic method mentioned<br>- Potentially detectable by advanced imaging techniques or bone biopsy with electron microscopy
- 未提及特异性诊断方法-通过先进的成像技术或电子显微镜骨活检可能检测到 | - Unclear if standard antibiotic therapy is effective- Extensive surgical debridement of infected bone may be required- Novel therapies targeting OLCN invasion need to be developed
- 尚不清楚标准抗生素治疗是否有效-可能需要对感染骨进行广泛的手术清创-需要开发针对OLCN侵袭的新疗法 |
The review emphasizes the lack of diagnostic methods to specifically detect OLCN colonization and the need for novel therapies targeting this privileged niche of bacteria within cortical bone. Complete surgical removal of all three reservoirs combined with local and systemic antibiotic therapy is currently the recommended approach to treat chronic osteomyelitis involving these distinct biofilm populations.
该综述强调缺乏特异性检测OLCN定植的诊断方法，以及需要针对皮质骨内细菌的特殊小生境的新疗法。目前推荐的治疗慢性骨髓炎的方法是通过手术完全清除所有三个储库，并结合局部和全身抗生素治疗，以治疗这些不同的生物膜群体。 对于AO Surgery Reference的使用，如果用电脑、用app都比较麻烦。
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