在面对疾病时，我们常常会思考一个问题：究竟是依靠身体自身的修复能力（自愈力），还是需要医生的专业治疗？这似乎是一个非此即彼的选择题，但事实远非如此。人体是极其精密的生物机器，天生就携带着强大的“自愈系统”，能够在没有外部干预的情况下处理许多健康问题。小到普通的感冒发烧，大到伤口愈合，都离不开这种神奇的力量。然而，现代医学的飞速发展也为我们提供了前所未有的治疗手段，帮助我们应对那些超出身体自愈能力范围的疾病，甚至在许多情况下挽救生命。
本文将深入探讨人体自愈力与医生医疗干预之间的复杂而精妙的关系。我们将看到，两者并非相互对立，而是紧密相连、协同作用的伙伴。医生的角色不仅仅是“治病”，更是通过诊断、治疗、管理，为身体的自愈创造条件、清除障碍、提供支持，从而加速康复，甚至在自愈力不足时接替其功能。通过科普的方式，本文旨在帮助读者建立对自身健康和疾病的科学认知，理解何时可以信赖身体的自愈，何时又应及时寻求医疗帮助，最终实现身体自愈与医生治疗的“1+1>2”的协同康复模式。
1. 人体自带的“修复系统”：自愈力的底层逻辑
1.1 从感冒到小伤口：日常自愈的典型场景
自愈力是人体与生俱来的核心能力，它渗透在我们日常生活的方方面面，是维持生命和健康的基础。最常见的例子莫过于普通感冒。当鼻病毒（Rhinovirus）等病原体入侵呼吸道时，我们的免疫系统会立即启动防御机制。首先，宿主细胞会识别病毒成分，如双链RNA，并通过模式识别受体（PRRs）激活，进而产生I型干扰素和其他抗病毒物质 12。这些干扰素能够抑制病毒复制，并阻止病毒向未感染细胞扩散 1。同时，免疫细胞，如T细胞和B细胞，也会被激活，产生特异性抗体来中和病毒，并清除受感染的细胞，从而在几天内帮助我们从感冒中恢复，而这整个过程往往不需要药物干预 34。
除了对抗内部入侵者，自愈力在应对外部损伤时也表现卓越。例如，当皮肤不慎被擦伤时，身体会迅速启动一系列精密的修复程序。首先是止血阶段，血液中的血小板和凝血因子迅速聚集，形成血栓堵塞伤口，防止进一步失血 5。紧接着是炎症阶段，免疫细胞被招募到伤口部位，清除细菌和坏死组织，为后续的组织再生创造清洁的环境 56。随后，在增殖阶段，皮肤细胞（如成纤维细胞和角质形成细胞）开始大量分裂和迁移，覆盖伤口表面，并生成新的胶原蛋白和其他细胞外基质成分，形成肉芽组织 57。最终，在重塑阶段，新形成的组织会逐渐成熟，恢复皮肤的结构和功能 7。整个过程虽然可能留下疤痕，但伤口大部分都能在没有外部缝合或特殊处理的情况下自行愈合 8。这些日常场景无不展现了自愈力作为人体固有防御修复能力的强大和高效。例如，有研究表明，通过特殊材料如壳聚糖制备的创可贴，能有效促进伤口愈合并具有抗菌作用，这正是辅助了身体的自然修复过程 9。
1.2 科学视角下的自愈机制
从更深层次的科学视角来看，人体的自愈并非简单的“身体自己会好”，而是一套高度复杂且精密的协调机制，涉及神经、免疫、内分泌三大系统的协同作用。
免疫系统：精准识别与清除
免疫系统是自愈力的核心防御力量，它能够识别并清除体内外的病原体、癌细胞以及受损细胞10。这个系统拥有先天性免疫和适应性免疫两大支柱。先天性免疫提供即时、非特异性的防御，而适应性免疫则能针对特定病原体产生记忆，实现更精准、更快速的二次响应11。例如，当细菌入侵时，巨噬细胞、中性粒细胞等先天免疫细胞会立即吞噬病原体；同时，T细胞和B细胞等适应性免疫细胞会启动，产生特异性抗体和细胞毒性T淋巴细胞，有效清除感染10。肠道上皮细胞不仅是物理屏障，也是免疫防御和免疫细胞与微生物群之间串扰的协调中心12。
组织再生：细胞修复与干细胞潜能
除了免疫防御，人体的自愈还体现在强大的组织再生能力上。这主要依赖于体内存在的各种干细胞，它们是身体的“备用零件库”和“维修队”。间充质干细胞（MSCs）是多能细胞，具有自我更新和分化成多种细胞类型的能力，在组织愈合和再生医学中发挥关键作用13。骨髓间充质干细胞（BMSCs）在愈合过程中，通过外周循环从骨髓动员并迁移到受损组织，其迁移受机械和化学因素的调节13。研究表明，MSCs及其分泌的细胞外囊泡（EVs）具有再生效应，可通过旁分泌功能或直接募集到受损组织来促进心脏、肝脏、肺、肾脏等器官的再生1415。此外，成人干细胞在维持组织完整性中至关重要，它们作为细胞储备，支持正常的组织更新，并在急性损伤后启动再生反应16。例如，在骨折愈合过程中，成骨细胞祖细胞（SSC）在骨折部位增殖分化，通过内软骨骨化和膜内成骨形成骨痂，最终使骨骼恢复连续性171819。
神经-免疫-内分泌的协同：身心合一的调节
人体的自愈力并非孤立运行，而是受到神经系统、内分泌系统和免疫系统之间复杂网络的调控。这三个系统通过神经肽、激素和细胞因子等信号分子相互作用，形成一个动态平衡的整体。例如，催产素分泌系统能整合神经、内分泌、代谢和免疫信息，在免疫系统的发育和功能中发挥关键作用，如促进胸腺和骨髓的发育，并抑制炎症、促进伤口愈合20。神经肽P物质（Substance P, SP）除了具有促炎作用外，与胰岛素样生长因子-1结合还能促进角膜上皮伤口愈合21。
更令人惊叹的是，心理状态对自愈力也具有显著影响。研究发现，压力会显著减缓伤口愈合，而通过运动、社会支持等干预措施减轻压力，可以预防应激引起的愈合障碍22。正念冥想（Mindfulness meditation）作为一种身心干预手段，已被证明能有效改善多种身心疾病症状，如焦虑、抑郁、慢性疼痛和失眠等2324。在肠易激综合征（IBS）患者的研究中，冥想显著提高了患者的生活质量，降低了疼痛评分，这表明心理状态的积极调节可以增强身体的自我修复能力25。这些证据共同描绘了自愈力是一个综合性的生理过程，涵盖了从微观的细胞分子层面到宏观的心理生理层面，充分体现了人体身心合一的强大自我修复潜力。
2. 医生的“助攻”时刻：何时需要医疗介入
虽然人体拥有强大的自愈能力，但并非所有疾病都能依靠自身力量痊愈。在许多情况下，疾病的严重程度、病原体的毒性、并发症的风险以及患者自身的免疫状况等因素，都可能导致自愈力“独木难支”，此时，医疗介入就显得至关重要，甚至是挽救生命的关键。医生如同身体的“助攻”，在自愈力无法有效发挥作用时，提供必要的支持和干预。
2.1 轻症与重症的分界线
区分疾病的轻重程度，是决定是否需要医疗介入的首要考量。有些疾病，如普通感冒，在大多数情况下，人体免疫系统能够有效清除病毒，症状会在一周左右自行缓解。此时，医生可能会建议多休息、多饮水，辅以对症治疗以缓解不适，但主要还是依靠身体的自愈力。然而，当病原体超出自愈能力或引发并发症时，医疗干预的必要性就凸显出来。
以肺炎为例，这是一种常见的肺部感染。轻微的病毒性肺炎可能通过自愈缓解，但由细菌引起的肺炎，特别是社区获得性肺炎（Community-acquired pneumonia, CAP），往往需要及时、适当的抗生素治疗。如果不进行医疗干预，细菌会在肺部大量繁殖，引起严重的炎症反应，导致肺功能受损，甚至可能发展为脓毒症，危及生命2627。针对社区获得性肺炎，医生会根据感染的严重程度、患者的伴随疾病和当地病原体流行情况，选择合适的经验性抗生素治疗，例如大环内酯类、氟喹诺酮类或β-内酰胺类药物26。对于重症肺炎患者，可能还需要住院治疗，甚至进入重症监护室，使用皮质类固醇等辅助疗法来降低死亡率27。例如，有研究表明，对于重症社区获得性细菌性肺炎患者，每日低于400mg氢化可的松等效剂量的低剂量皮质类固醇治疗，可以降低30天死亡率（10% vs 16%）27。而针对特殊病原体如耶氏肺孢子虫（Pneumocystis jirovecii）引起的肺炎，虽然发病率较低，但其造成的严重肺炎可能导致30%至50%的死亡率，对于免疫功能受损的患者来说，更需要积极的医疗干预，如使用复方磺胺甲噁唑（TMP-SMX）进行治疗或预防28。
再如阑尾炎，这是一种常见的急性腹部疾病。虽然近年来关于阑尾炎是否可以仅用抗生素保守治疗的讨论日益增多，但总体而言，阑尾切除术仍然是治疗急性阑尾炎的“金标准”2930。当阑尾发生炎症时，如果不及时手术切除，炎症可能进展为穿孔、腹膜炎或形成脓肿，这些并发症都可能导致严重的感染，甚至败血症，此时疾病可能进一步恶化。医生通过手术切除病变的阑尾，旨在消除感染源，从而避免并发症并促进患者康复293132。一项系统综述指出，对于未并发症的阑尾炎，抗生素治疗的再入院率更高（OR 6.10），且后期仍需手术的几率也更高（OR 20.09），尤其是在儿童患者中29。这表明，尽管抗生素可能在某些情况下作为替代方案，但手术干预对于彻底清除感染源、避免复发和并发症的发生具有不可替代的价值，是协助身体从根本上“自愈”的关键一步。
3. 1+1＞2：自愈与医疗的协同模式
自愈与医疗并非相互排斥，而是一种互补共生的关系，在许多疾病的治疗过程中，两者协同作用，能够实现“1+1>2”的康复效果。医疗的介入往往是为了创造或优化身体自愈的环境，移除自愈的障碍，或者在自愈能力不足时提供关键性的支持。
3.1 急性病中的“急救-修复”链条
在急性疾病和创伤中，医疗干预通常扮演着“急救”的角色，迅速稳定病情，阻止进一步恶化，并为身体的“修复”过程创造最佳条件。骨折是这种“急救-修复”链条的典型例子。
当人体骨骼遭受外力冲击而发生骨折时，骨骼的完整性被破坏，疼痛、肿胀和功能障碍随之而来。骨骼本身具有强大的再生能力，能够修复损伤，例如通过非编码RNA等机制调控骨骼的再生过程33。然而，如果骨折部位未能得到有效固定，骨折端会不断错位，不仅会加剧疼痛，还会干扰骨痂的形成，导致骨折不愈合或畸形愈合。此时，医生的介入就显得至关重要。
医生首先会进行复位，即将错位的骨折段恢复到正常的解剖位置。随后，通过固定（例如石膏、支具或手术植入内固定器械），将骨折部位稳定住，使其在愈合过程中保持对位良好，避免再移位34。这种医疗干预的目的并非替代身体的自愈，而是为骨骼的自然修复创造一个稳定、有利的环境。在一个稳定的环境下，骨折断端能够有效地连接起来，非编码RNA等分子在调控干细胞向成骨细胞分化，促进骨再生中发挥作用33。研究表明，手术（如锁定钢板或半关节置换）与非手术治疗（如吊带固定）在肩关节近端肱骨骨折患者一年和两年后的患者报告肩部和上肢功能方面没有临床重要差异，但手术组需要二次手术的风险更高3536。这表明，在某些骨折类型中，非手术的固定同样能有效支持自愈，而手术的主要作用在于提供更稳定的固定，避免并发症。
此外，术后护理在优化自愈过程中也扮演着关键角色。例如，负压伤口治疗（Negative Pressure Wound Therapy, NPWT）在骨折手术后的伤口管理中被广泛应用。手术切口是细菌入侵的潜在门户，感染会严重阻碍伤口愈合和骨折康复。负压伤口治疗通过在伤口表面形成负压环境，可以作为预防手术部位感染（Surgical Site Infection, SSI）的手段之一37。一项针对创伤性下肢骨折手术后深部手术部位感染的研究发现，负压伤口治疗与标准敷料相比，在降低深部感染率方面没有显著差异，但总体而言，负压伤口治疗在减少手术部位感染方面可能比传统清创和敷料更有效3839。这说明，通过减少感染风险，医疗手段能够为身体的自愈提供一个清洁、健康的环境，让免疫系统能够更专注于修复损伤，而不是对抗感染，从而使自愈过程更高效、更顺畅。
骨折后的康复训练也是协同模式的重要组成部分。虽然骨骼在愈合，但周围的肌肉、韧带和关节可能因制动而僵硬、萎缩。物理治疗师通过指导患者进行循序渐进的康复运动，帮助患者恢复关节活动度、肌肉力量和协调性，加速功能恢复。有研究指出，踝关节骨折患者在解除固定后，接受指导下的运动方案和建议与仅提供建议相比，在活动受限或生活质量方面并没有额外的益处，这提示并非所有骨折都需要密集的监督康复，但个性化的康复方案仍是自愈后期功能重建的关键40。这些康复措施同样是在“助攻”身体的自愈，让受损的肢体能够尽快恢复到最佳功能状态。
这种“急救-修复”链条清晰地展示了医疗和自愈的协同作用：医生通过专业技术稳定病情、清除障碍、提供支持，为身体的自愈创造最佳条件；而身体则在这些条件的保障下，充分发挥自身的修复潜能，完成最终的愈合和康复。
3.2 慢性病中的“动态平衡”
在慢性病的管理中，自愈力与医疗干预之间的关系更为复杂，它体现为一种长期的“动态平衡”和“双向协作”。医生并非“治愈”慢性病，而是通过精细的药物调整、生活方式指导和持续的健康教育，帮助患者维持身体的稳定状态，延缓疾病进展，最大限度地提高生活质量。在这个过程中，患者的主动参与和自身调节能力的发挥，即广义上的“自愈”，至关重要。
以高血压为例，这是一种常见的慢性病，其特点是动脉血压持续升高，若不加以控制，可能导致心脏病、中风、肾脏疾病等严重并发症 41。医生在高血压管理中的作用是多方面的。首先，他们通过药物治疗来直接降低血压，如使用利尿剂、β受体阻滞剂、ACEI抑制剂或钙通道阻滞剂等。医生会根据患者的具体情况，如年龄、合并症、血压水平以及对药物的反应，来选择和调整药物方案，旨在将血压控制在目标范围内，从而减轻血管压力，保护器官功能 41。有研究指出，例如对于高肾素/高醛固酮的肾性高血压，血管紧张素受体拮抗剂是最佳治疗选择；而对于原发性醛固酮增多症（低肾素/高醛固酮），醛固酮拮抗剂（如螺内酯）效果更好 41。这些药物的运用，正是医生在帮助患者纠正身体内部失衡，使其生理指标回归正常，从而为身体维持稳定运行提供必要的“外部支持”。
然而，仅仅依靠药物是不够的。医生还会强调生活方式干预的重要性。这包括建议患者采取低钠饮食（如地中海饮食或DASH饮食）来降低血压，并鼓励他们进行规律的体育锻炼，以改善血管弹性，增强心血管功能 4142。此外，避免过度饮酒、戒烟、控制体重等也是管理高血压的关键 41。这些生活方式的调整，本质上是在激活和强化身体自身的调节能力，使其能够更好地应对血压波动，减少对药物的依赖。患者通过积极的自我管理，如规律监测血压、遵医嘱用药、调整饮食和运动习惯，成为自身健康的“第一责任人”。这种由医生提供的专业指导与患者长期坚持的健康行为相结合，共同构成了慢性病管理中的“动态平衡”。
值得注意的是，心理状态在慢性病管理中也扮演着不可忽视的角色。情绪管理，尤其是压力和焦虑的缓解，被证明能有效增强人体的自愈能力 43。冥想，特别是正念冥想（Mindfulness-Based Stress Reduction, MBSR），通过调节神经内分泌系统，可以改善心理-神经-免疫网络的功能 434445。研究表明，冥想能够促进血清素、催产素和褪黑素的释放，这些神经递质和激素与情绪调节、压力缓解及免疫功能改善密切相关 44。例如，有研究显示，冥想可以帮助慢性病患者提高生活质量，减少身体疼痛，并提升对健康的内在控制感 46。对于伴有精神疾病的慢性病患者，自我管理干预（包括改善睡眠、饮食和锻炼）可以显著改善睡眠质量、饮食习惯和锻炼频率 47。因此，医生在慢性病管理中，除了关注生理指标，也应引导患者进行情绪管理和心理调适，这不仅能提升患者的整体幸福感，也能间接增强身体的自我修复和调节能力，从而更好地实现自愈与医疗的协同效应。
综上所述，在慢性病管理中，医生通过药物和专业指导帮助身体维持平衡，而患者则通过积极的生活方式干预和情绪管理来强化自身的调节机制。这种“双向协作”和“动态平衡”的模式，是现代慢性病管理的核心，它让自愈与医疗不再是简单的叠加，而是深度融合，共同为患者的长期健康保驾护航。
4.1 过度医疗：干扰自愈的隐形代价
在追求快速康复和彻底治疗的过程中，有时会出现“过度医疗”的现象，这不仅可能浪费医疗资源，更可能对人体自身的自愈能力造成隐形损害。过度医疗的典型表现包括抗生素的滥用、不必要的输液以及患者的自我用药误区等，这些行为都可能干扰身体的自然调节机制，削弱其固有的防御能力。
抗生素滥用与菌群失衡
抗生素无疑是现代医学的伟大发明，在治疗细菌感染方面发挥了不可替代的作用。然而，抗生素的过度使用和不当使用已成为全球性的健康挑战。当人们在非细菌感染（如病毒性感冒）时使用抗生素，或者不遵医嘱随意使用抗生素时，不仅对病毒无效，还会对人体内的微生物群，特别是肠道菌群造成严重干扰 4849。
肠道微生物群在人体健康中扮演着多重角色，包括帮助消化、合成维生素、调节免疫系统以及抵抗病原体入侵等 50。抗生素的广谱杀菌作用不分敌我，在杀灭有害菌的同时，也会大量杀灭有益菌，导致肠道菌群多样性降低和生态失衡 4851。这种失衡不仅可能引起腹泻、消化不良等短期副作用，更可能带来长期的健康风险，例如增加过敏、自身免疫性疾病的风险，甚至促进耐药菌的产生和传播 48495051。一旦体内耐药菌增多，当真正发生严重细菌感染时，常用的抗生素可能失效，使得治疗变得更加困难。因此，盲目依赖抗生素，实际上是以破坏自身菌群平衡为代价，反而削弱了身体通过免疫系统抵抗感染的自愈能力。
过度输液与身体负担
输液是临床上常用的给药途径，尤其在需要快速补充液体、电解质或药物时。然而，不必要的或过度输液也可能对身体造成负担。例如，在感冒等轻症疾病中，如果患者能够正常饮食和饮水，通常不需要通过输液来补充液体。过度输液可能导致体液容量过负荷，增加心脏和肾脏的负担，严重时甚至可能引起心力衰竭或肺水肿。
在重症监护领域，液体平衡的管理尤为关键。一项针对猪的实验研究显示，高液体平衡（约4升）的动物出现了更严重的腹水，并导致呼气末肺容积下降，这表明高液体负荷可能通过间接方式加剧肺损伤 52。虽然这项研究是针对肺损伤模型，但它从侧面提示了过度液体补充对身体内环境的潜在负面影响。对于一般患者而言，如果身体的消化吸收功能正常，口服补充液体和营养通常是更符合生理的途径。过度依赖输液，可能会抑制身体自身对水盐代谢的调节能力，从长远来看，不利于身体自愈机制的正常运作。
自我用药的风险
公众的自我用药（Self-medication）行为也日益普遍，这在一定程度上反映了人们希望主动管理自身健康的愿望。然而，不负责任的自我用药，特别是对抗生素和止痛药的滥用，隐藏着巨大的风险 535455。研究表明，自我用药的潜在风险包括：错误诊断、延误就医、出现严重不良反应、危险的药物相互作用、不正确的给药方式或剂量、错误的选择疗法，以及掩盖严重疾病的症状，甚至导致药物依赖或滥用 5355。例如，在对自我用药决定因素的系统回顾和荟萃分析中发现，男性、对医疗服务/医生不满、低龄（在高收入国家）、以及对医生/医疗机构的不信任感等因素与抗生素自我用药行为相关联 56。
这些自我用药的误区，往往源于缺乏专业的医学知识，错误地评估了疾病的严重性，或者盲目相信某种药物的“神奇”效果。例如，许多人会在没有医生指导的情况下，自行服用抗生素治疗病毒性感冒，这不仅无效，反而加速了细菌耐药性的发展 48。还有一些人长期依赖止痛药来掩盖慢性疼痛，而不是寻求根本原因的诊断和治疗，从而延误了疾病的发现和干预，使得自愈的机会丧失。老年患者由于合并症多，用药种类复杂，更容易出现药物相互作用或不良反应 57585960。这些案例都说明，盲目依赖药物或不当用药，非但不能促进自愈，反而可能对身体造成新的伤害，干扰自愈过程，甚至产生比原发疾病更严重的问题。
4.2 忽视医疗：“硬扛”的潜在风险
与过度医疗的危害相对，另一种极端情况是“忽视医疗”，即在需要专业干预时，患者选择“硬扛”或延误就医。这种行为同样可能带来严重的后果，有时甚至比不当医疗更为致命，因为错过最佳治疗窗口期，可能会让身体的自愈机制彻底失效，或导致不可逆转的损伤。在某些疾病面前，医疗介入并非替代自愈，而是启动、引导甚至挽救自愈的关键力量。
以糖尿病足为例，这是一种糖尿病常见的严重并发症，指糖尿病患者因神经病变、血管病变以及感染等因素导致的足部皮肤破损、溃疡，甚至深层组织坏死。糖尿病患者的神经病变导致足部感觉减退，即使足部出现小的损伤或溃疡，患者也常常感觉不到疼痛，容易忽视616263。血管病变则导致足部血液循环不良，使得伤口愈合能力大大降低62。如果患者对早期症状（如足部麻木、皮肤颜色改变、出现小水泡或破溃）不加以重视，不及时就医，伤口就会逐渐扩大、感染，甚至发展为骨髓炎或坏疽6163。
此时，如果患者仍旧选择“硬扛”，寄希望于身体自愈，结果往往是灾难性的。糖尿病足的溃疡由于血供不足和感染控制困难，自身愈合能力非常有限。而医生在此刻的介入，正是启动自愈、防止病情恶化的关键。医疗干预通常包括：
- 清创术：医生会彻底清除坏死组织、脓液和感染物，为伤口提供一个清洁的愈合环境。这相当于移除了自愈的最大障碍。
- 感染控制：通过细菌培养明确感染菌种，并使用敏感抗生素控制感染。如果没有抗生素的帮助，身体的免疫系统往往难以独自对抗顽固的细菌感染，特别是糖尿病患者免疫力本身就可能受损62。
- 改善血供：对于血管病变严重的患者，可能需要通过血管重建手术（如支架植入或旁路移植）来恢复足部血流，为伤口愈合提供充足的氧气和营养物质。
- 压力管理：采用特殊的减压鞋具或石膏固定，减轻足部溃疡部位的压力，避免持续摩擦和损伤，为愈合创造有利条件。
多项研究强调了糖尿病足早期诊断和治疗的重要性。例如，一项审查指出，糖尿病足的诊断和治疗往往被延迟，这增加了截肢的风险，因此需要紧急行动，如同对待急性心肌梗死和中风一样，确保患者在数小时内得到多学科团队的专业诊治64。另一项研究也提到，神经病变性关节病的诊断延迟可能导致有害后果，包括截肢61。这些都充分说明，在面对像糖尿病足这样进展迅速、后果严重的疾病时，及时寻求医疗帮助，通过专业手段“启动”身体的自愈过程，是避免悲剧发生的唯一途径。
类似的例子还包括急性脑卒中（中风）。缺血性脑卒中发病后，每延迟一分钟，都有大量的脑细胞死亡。医生在发病后的数小时内（通常是3-4.5小时内）进行静脉溶栓治疗，或在更长的时间窗内进行血管内取栓治疗，能够溶解血栓、恢复脑部血流，这在很大程度上是在与时间赛跑，为脑细胞的“自愈”（损伤的脑细胞功能恢复）创造机会6566。如果患者因忽视症状或不及时就医而错过这个“黄金时间窗”，即使存活下来，也可能留下严重的神经功能障碍，导致残疾。
此外，椎间盘突出的自愈机制虽然存在，部分患者的突出椎间盘可以自行吸收67，但如果症状严重且保守治疗无效，或出现神经功能障碍，延误手术干预可能导致神经压迫进一步加重，造成永久性损伤。研究表明，从症状出现到手术的时间延迟与术后效果不佳呈负相关68。这再次印证了在某些情况下，医疗的及时介入是对自愈力的关键“助推”，甚至能避免自愈能力的彻底丧失。
因此，“硬扛”的风险在于，它可能让身体错失最佳的干预时机，使得原本可能通过医疗介入辅助自愈的疾病，演变为无法挽回的重症，最终导致比疾病本身更糟糕的结局。
5. 科学认知下的健康观：自愈是基础，医生是助力
回顾人体面对疾病时的复杂历程，我们不难发现，身体的自愈能力与医生的专业治疗并非对立的两面，而是构成了一幅协同作战、互为补充的完整图景。自愈，作为人体在漫长进化过程中形成的核心能力，是生命得以维系和修复的基础。从骨骼的自我修复等现象，都无不彰显着身体内蕴藏的强大智慧和潜能 69。它通过精密的生物学机制，识别、清除病原体，修复受损组织，维持内环境的动态平衡。
然而, 人体的自愈力并非万能。面对超出其应对极限的病原体入侵、严重的创伤、慢性疾病的长期消耗，或是在病理机制高度复杂的情况下，自愈力可能会显得力不从心，甚至无能为力。此时，医生的角色便变得不可或缺。医生就像一位经验丰富的指挥官，通过诊断、治疗、教育等多种手段，为身体的自愈提供强有力的“助攻”：
- 消除障碍：通过手术切除感染源（如阑尾炎）、清除坏死组织（如糖尿病足），为身体的修复铺平道路。
- 提供支持：通过药物控制感染（如肺炎抗生素）、稳定生理指标（如高血压药物），为自愈争取时间和条件。
- 创造环境：通过骨折复位固定，为骨骼的正确愈合提供稳定的物理环境 6970。
- 激发与引导：通过健康教育、生活方式指导，帮助患者主动管理自身健康，激发身体的长期调节能力 7172。
- 弥补不足：在自愈能力无法完全恢复功能时，通过辅助设备、康复训练等手段，帮助患者最大化恢复功能。
因此，建立科学的健康观，意味着我们应该认识到：自愈是人体健康的基石，是身体本能的防御和修复机制；而医生则是这个机制的强力助力者，通过专业的医疗干预，放大自愈的效果，清除自愈的阻碍，并在自愈力无法触及的领域，提供决定性的挽救和支持。忽视任何一方，都可能带来风险——过度医疗可能干扰自愈的自然进程，而忽视医疗则可能错过最佳的干预时机，导致不可逆转的后果。
展望未来，医学的发展趋势将更加注重与自愈力的深度结合，而非单纯地替代它。精准医学、再生医学、免疫疗法等前沿领域，都致力于更精确地激活和调控人体的自愈潜能：
- 干细胞疗法：利用干细胞的自我更新和多向分化能力，修复或替换受损组织和器官，如在神经损伤、骨骼修复中的应用 73747576。
- 免疫调节：通过调节免疫系统的功能，使其更高效地对抗疾病，例如通过间充质干细胞（MSC）进行免疫调节，治疗自身免疫性疾病相关的肺纤维化 77。
- 基因编辑技术：修正导致疾病的基因缺陷，从根源上恢复细胞的正常功能，从而让身体具备自我纠正的能力。
- 个性化治疗：根据个体的基因组、生活方式和环境因素，制定最适合其身体自愈特点的治疗方案。
- 生物材料与组织工程：开发新型生物材料，例如可注射的具有自修复能力的凝胶，结合干细胞促进骨再生和免疫调节，为受损组织提供支架和信号，引导其更好地自我修复 78。
- 物理疗法：例如低强度激光疗法（LLLT）已被证明能促进成骨细胞分化，诱导骨折愈合，体现了通过物理手段促进自愈的潜力 79。
总之，健康的维护是一个动态平衡的过程。在这个过程中，我们既要敬畏和信任身体强大的自愈能力，也要理性地认识到现代医学的边界与力量。医生和医疗体系的价值，在于作为身体自愈的智慧盟友，在关键时刻伸出援手，帮助我们清除障碍、抵御威胁，共同维护生命的活力与健康。未来的医疗，将是医生与身体自愈力之间更加紧密、更加智能的协同合作，共同书写人类健康的新篇章。
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参考文献
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Zuqin Yang, Hannah Mitländer, Tytti Vuorinen, et al.
Front Immunol. 2021 Oct 6;12:731846. doi: 10.3389/fimmu.2021.731846. eCollection 2021.
The majority of asthma exacerbations in children are caused by Rhinovirus (RV), a positive sense single stranded RNA virus of the Picornavirus family. The host has developed virus defense mechanisms that are mediated by the upregulation of interferon-activated signaling. However, the virus evades the immune system by inducing immunosuppressive cytokines and surface molecules like programmed cell death protein 1 (PD-1) and its ligand (PD-L1) on immunocompetent cells. Initially, RV infects epithelial cells, which constitute a physiologic mucosal barrier. Upon virus entrance, the host cell immediately recognizes viral components like dsRNA, ssRNA, viral glycoproteins or CpG-DNA by host pattern recognition receptors (PRRs). Activation of toll like receptors (TLR) 3, 7 and 8 within the endosome and through MDA-5 and RIG-I in the cytosol leads to the production of interferon (IFN) type I and other antiviral agents. Every cell type expresses IFNAR1/IFNAR2 receptors thus allowing a generalized antiviral activity of IFN type I resulting in the inhibition of viral replication in infected cells and preventing viral spread to non-infected cells. Among immune evasion mechanisms of the virus, there is downregulation of IFN type I and its receptor as well as induction of the immunosuppressive cytokine TGF-β. TGF-β promotes viral replication and is associated with induction of the immunosuppression signature markers LAP3, IDO and PD-L1. This article reviews the recent advances on the regulation of interferon type I expression in association with RV infection in asthmatics and the immunosuppression induced by the virus.
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Michael Carty, Coralie Guy, Andrew G Bowie
Biochem Pharmacol. 2021 Jan;183:114316. doi: 10.1016/j.bcp.2020.114316. Epub 2020 Nov 3.
Pattern recognition receptors (PRRs) and inflammasomes are a key part of the anti-viral innate immune system as they detect conserved viral pathogen-associated molecular patterns (PAMPs). A successful host response to viral infections critically depend on the initial activation of PRRs by viruses, mainly by viral DNA and RNA. The signalling pathways activated by PRRs leads to the expression of pro-inflammatory cytokines, to recruit immune cells, and type I and type III interferons which leads to the induction of interferon stimulated genes (ISG), powerful virus restriction factors that establish the "antiviral state". Inflammasomes contribute to anti-viral responses through the maturation of interleukin (IL)-1 and IL-18 and through triggering pyroptotic cell death. The activity of the innate immune system along with the adaptive immune response normally leads to successful virus elimination, although disproportionate innate responses contribute to viral pathology. In this review we will discuss recent insights into the influence of PRR activation and inflammasomes on viral infections and what this means for the mammalian host. We will also comment on how specific PRRs and inflammasomes may be relevant to how SARS-CoV-2, the virus responsible for the current COVID-19 pandemic, interacts with host innate immunity.
3Adaptive immunity.PubMed
Francisco A Bonilla, Hans C Oettgen
J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S33-40. doi: 10.1016/j.jaci.2009.09.017. Epub 2010 Jan 12.
The innate immune system provides critical mechanisms for the rapid sensing and elimination of pathogens. Adaptive immunity has evolved to provide a broader and more finely tuned repertoire of recognition for both self- and nonself-antigens. Adaptive immunity involves a tightly regulated interplay between antigen-presenting cells and T and B lymphocytes, which facilitate pathogen-specific immunologic effector pathways, generation of immunologic memory, and regulation of host immune homeostasis. Lymphocytes develop and are activated within a series of lymphoid organs comprising the lymphatic system. During development, sets of gene segments are rearranged and assembled to create genes encoding the specific antigen receptors of T and B lymphocytes. The rearrangement mechanism generates a tremendously diverse repertoire of receptor specificities capable of recognizing components of all potential pathogens. In addition to specificity, another principal feature of adaptive immunity is the generation of immunologic memory. During the first encounter with an antigen (pathogen), sets of long-lived memory T and B cells are established. In subsequent encounters with the same pathogen, the memory cells are quickly activated to yield a more rapid and robust protective response.
4Viral and bacterial infections in the development and progression of asthma.PubMed
J E Gern
J Allergy Clin Immunol. 2000 Feb;105(2 Pt 2):S497-502. doi: 10.1016/s0091-6749(00)90050-2.
Viral respiratory infections produce wheezing illnesses in patients of all ages. In infancy, infections with respiratory syncytial virus and parainfluenza virus are the major cause of bronchiolitis and croup, whereas infections with common cold viruses such as rhinoviruses are the principal triggers for wheezing in older children and adults with asthma. In addition to causing increased wheezing in asthma, there is mounting evidence that infections early in childhood can affect the development of the immune system and thereby modify the risk for the subsequent development of allergies and asthma. Both of these effects appear to be mediated by virus-induced immune responses. Early during the course of viral infection, resident cells in the airway are activated in an antigen-independent fashion, triggering antiviral responses but also activating and recruiting cells to the airway that could contribute to airway obstruction and respiratory symptoms. Virus-specific T- and B-cell responses may also have dual effects in the presence of preexisting airway inflammation. Finally, there is evidence of synergistic interactions between allergen- and virus-induced airway inflammation. It is likely that greater definition of mechanisms of virus-induced inflammation will provide therapeutic targets for the treatment and possibly the prevention of allergies and asthma.
5Physiology of wound healing.PubMed
T K Hunt, H Hopf, Z Hussain
Adv Skin Wound Care. 2000 May-Jun;13(2 Suppl):6-11.
Wound healing is a complicated process that recruits at least 4 distinct cell types. Though the process is continuous, it is commonly referred to as occurring in "phases." The main phases of wound healing include coagulation, which begins immediately after injury; inflammation, which initiates shortly thereafter; a migratory and proliferative process, which begins within days and includes the major processes of healing; and a remodeling process, which may last for up to a year and is responsible for scar tissue formation and development of new skin. Wound healing is affected by several factors. These include local factors (growth factors, edema and ischemia, low oxygen tension, and infection), regional factors (arterial insufficiency, venous insufficiency, and neuropathy), systemic factors (inadequate perfusion and metabolic disease), and other miscellaneous factors, such as nutritional state, preexisting illnesses, exposure to radiation therapy, and smoking. In general, chronic wounds may be managed by preventing or medically treating infections through debridement and occlusive dressings. For wounds that are unresponsive to such interventions, the use of skin replacements is becoming a viable option. In this regard, a product such as Graftskin (APLIGRAF, Organogenesis Inc, Canton, MA, and Novartis Pharmaceuticals Corporation, East Hanover, NJ), a bilayered living skin construct with allogeneic dermis and epidermis, is a positive development.
6Osteoimmunology of Fracture Healing.PubMed
Kristin Happ Molitoris, Mingjian Huang, Gurpreet Singh Baht
Curr Osteoporos Rep. 2024 Jun;22(3):330-339. doi: 10.1007/s11914-024-00869-z. Epub 2024 Apr 15.
PURPOSE OF REVIEW: The purpose of this review is to summarize what is known in the literature about the role inflammation plays during bone fracture healing. Bone fracture healing progresses through four distinct yet overlapping phases: formation of the hematoma, development of the cartilaginous callus, development of the bony callus, and finally remodeling of the fracture callus. Throughout this process, inflammation plays a critical role in robust bone fracture healing. RECENT FINDINGS: At the onset of injury, vessel and matrix disruption lead to the generation of an inflammatory response: inflammatory cells are recruited to the injury site where they differentiate, activate, and/or polarize to secrete cytokines for the purposes of cell signaling and cell recruitment. This process is altered by age and by sex. Bone fracture healing is heavily influenced by the presence of inflammatory cells and cytokines within the healing tissue.
7Healing Mechanisms in Cutaneous Wounds: Tipping the Balance.PubMed
Adam J Singer
Tissue Eng Part B Rev. 2022 Oct;28(5):1151-1167. doi: 10.1089/ten.TEB.2021.0114. Epub 2022 Mar 11.
Acute and chronic cutaneous wounds pose a significant health and economic burden. Cutaneous wound healing is a complex process that occurs in four distinct, yet overlapping, highly coordinated stages: hemostasis, inflammation, proliferation, and remodeling. Postnatal wound healing is reparative, which can lead to the formation of scar tissue. Regenerative wound healing occurs during fetal development and in restricted postnatal tissues. This process can restore the wound to an uninjured state by producing new skin cells from stem cell reservoirs, resulting in healing with minimal or no scarring. Focusing on the pathophysiology of acute burn wounds, this review highlights reparative and regenerative healing mechanisms (including the role of cells, signaling molecules, and the extracellular matrix) and discusses how components of regenerative healing are being used to drive the development of novel approaches and therapeutics aimed at improving clinical outcomes. Important components of regenerative healing, such as stem cells, growth factors, and decellularized dermal matrices, are all being evaluated to recapitulate more closely the natural regenerative healing process. Impact Statement Acute wounds from thermal injury are common; they exert substantial physical and psychological effects on a patient and result in significant morbidity and mortality. This review provides a detailed overview of the mechanisms of reparative and regenerative wound healing; discusses the key cell types, signaling molecules, and molecular targets that influence these important biological pathways; and highlights current therapeutic approaches aimed at promoting regenerative wound healing. An increased understanding of the underlying mechanisms of reparative and regenerative healing will contribute to the development of innovative strategies for the clinical treatment of patients with severe burns.
8Laceration Repair: A Practical Approach.PubMed
Randall T Forsch, Sahoko H Little, Christa Williams
Am Fam Physician. 2017 May 15;95(10):628-636.
The goals of laceration repair are to achieve hemostasis and optimal cosmetic results without increasing the risk of infection. Many aspects of laceration repair have not changed over the years, but there is evidence to support some updates to standard management. Studies have been unable to define a "golden period" for which a wound can safely be repaired without increasing risk of infection. Depending on the type of wound, it may be reasonable to close even 18 or more hours after injury. The use of nonsterile gloves during laceration repair does not increase the risk of wound infection compared with sterile gloves. Irrigation with potable tap water rather than sterile saline also does not increase the risk of wound infection. Good evidence suggests that local anesthetic with epinephrine in a concentration of up to 1:100,000 is safe for use on digits. Local anesthetic with epinephrine in a concentration of 1:200,000 is safe for use on the nose and ears. Tissue adhesives and wound adhesive strips can be used effectively in low-tension skin areas. Wounds heal faster in a moist environment and therefore occlusive and semiocclusive dressings should be considered when available. Tetanus prophylaxis should be provided if indicated. Timing of suture removal depends on location and is based on expert opinion and experience.
9Shape memory and antibacterial chitosan-based cryogel with hemostasis and skin wound repair.PubMed
Shujun Cao, Zhanjian Bi, Qiujing Li, et al.
Carbohydr Polym. 2023 Apr 1;305:120545. doi: 10.1016/j.carbpol.2023.120545. Epub 2023 Jan 7.
Massive damage to the skin can lead to heavy bleeding and potential wound infection. Therefore, the preparation of low-cost wound dressings that meet these requirements by simple methods has a good application prospect. In the study, a shape memory cryogel prepared at low temperatures by mixing chitosan (CS) and citric acid (CA). Silver nanoparticles (Ag NPs) introduced into the cryogel through the reduction of Ag with tannic acid (TA) as a reducing agent. The CS/CA/Ag cryogel has good mechanical properties and interconnected macroporous structures. The results of hemostasis tests show that CS/CA/Ag cryogel can absorb a large amount of blood and promote blood cell adhesion compared with commercial gelatin sponges and gauze. Meanwhile, CS/CA/Ag cryogel has a good antibacterial ability against S. aureus and E. coli. Furthermore, CS/CA/Ag cryogel significantly promotes wound healing in the full-thickness wound model infected with S. aureus. In conclusion, the cryogel prepared by the simple method has great advantages in rapid hemostasis and promoting wound healing.
10Overview of the immune response.PubMed
David D Chaplin
J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S3-23. doi: 10.1016/j.jaci.2009.12.980.
The immune system has evolved to protect the host from a universe of pathogenic microbes that are themselves constantly evolving. The immune system also helps the host eliminate toxic or allergenic substances that enter through mucosal surfaces. Central to the immune system's ability to mobilize a response to an invading pathogen, toxin, or allergen is its ability to distinguish self from nonself. The host uses both innate and adaptive mechanisms to detect and eliminate pathogenic microbes, and both of these mechanisms include self-nonself discrimination. This overview identifies key mechanisms used by the immune system to respond to invading microbes and other exogenous threats and identifies settings in which disturbed immune function exacerbates tissue injury.
11Innate Immune Memory and the Host Response to Infection.PubMed
Edward R Sherwood, Katherine R Burelbach, Margaret A McBride, et al.
J Immunol. 2022 Feb 15;208(4):785-792. doi: 10.4049/jimmunol.2101058.
Unlike the adaptive immune system, the innate immune system has classically been characterized as being devoid of memory functions. However, recent research shows that innate myeloid and lymphoid cells have the ability to retain memory of prior pathogen exposure and become primed to elicit a robust, broad-spectrum response to subsequent infection. This phenomenon has been termed innate immune memory or trained immunity. Innate immune memory is induced via activation of pattern recognition receptors and the actions of cytokines on hematopoietic progenitors and stem cells in bone marrow and innate leukocytes in the periphery. The trained phenotype is induced and sustained via epigenetic modifications that reprogram transcriptional patterns and metabolism. These modifications augment antimicrobial functions, such as leukocyte expansion, chemotaxis, phagocytosis, and microbial killing, to facilitate an augmented host response to infection. Alternatively, innate immune memory may contribute to the pathogenesis of chronic diseases, such as atherosclerosis and Alzheimer's disease.
12The Intestinal Epithelium: Central Coordinator of Mucosal Immunity.PubMed
Joannie M Allaire, Shauna M Crowley, Hong T Law, et al.
Trends Immunol. 2018 Sep;39(9):677-696. doi: 10.1016/j.it.2018.04.002. Epub 2018 Apr 30.
The gastrointestinal (GI) tract represents a unique challenge to the mammalian immune system. It must tolerate the presence of the luminal microbiota and thus not respond to their products, but still protect the intestinal mucosa from potentially harmful dietary antigens and invading pathogens. The intestinal epithelium, composed of a single layer of cells, is crucial for preserving gut homeostasis and acts both as a physical barrier and as a coordinating hub for immune defense and crosstalk between bacteria and immune cells. We highlight here recent findings regarding communication between microbes and intestinal epithelial cells (IECs), as well as the immune mechanisms employed by distinct IEC subsets to promote homeostasis, emphasizing the central and active role that these cells play in host enteric defense.
13Mesenchymal Stem Cell Migration and Tissue Repair.PubMed
Xiaorong Fu, Ge Liu, Alexander Halim, et al.
Cells. 2019 Jul 28;8(8):784. doi: 10.3390/cells8080784.
Mesenchymal stem cells (MSCs) are multilineage cells with the ability to self-renew and differentiate into a variety of cell types, which play key roles in tissue healing and regenerative medicine. Bone marrow-derived mesenchymal stem cells (BMSCs) are the most frequently used stem cells in cell therapy and tissue engineering. However, it is prerequisite for BMSCs to mobilize from bone marrow and migrate into injured tissues during the healing process, through peripheral circulation. The migration of BMSCs is regulated by mechanical and chemical factors in this trafficking process. In this paper, we review the effects of several main regulatory factors on BMSC migration and its underlying mechanism; discuss two critical roles of BMSCs-namely, directed differentiation and the paracrine function-in tissue repair; and provide insight into the relationship between BMSC migration and tissue repair, which may provide a better guide for clinical applications in tissue repair through the efficient regulation of BMSC migration.
14Therapeutic Strategy of Mesenchymal-Stem-Cell-Derived Extracellular Vesicles as Regenerative Medicine.PubMed
Yasunari Matsuzaka, Ryu Yashiro
Int J Mol Sci. 2022 Jun 9;23(12):6480. doi: 10.3390/ijms23126480.
Extracellular vesicles (EVs) are lipid bilayer membrane particles that play critical roles in intracellular communication through EV-encapsulated informative content, including proteins, lipids, and nucleic acids. Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewal ability derived from bone marrow, fat, umbilical cord, menstruation blood, pulp, etc., which they use to induce tissue regeneration by their direct recruitment into injured tissues, including the heart, liver, lung, kidney, etc., or secreting factors, such as or insulin-like growth factor. Recently, MSC-derived EVs have been shown to have regenerative effects against various diseases, partially due to the post-transcriptional regulation of target genes by miRNAs. Furthermore, EVs have garnered attention as novel drug delivery systems, because they can specially encapsulate various target molecules. In this review, we summarize the regenerative effects and molecular mechanisms of MSC-derived EVs.
15Immunomodulatory properties of mesenchymal stem cells/dental stem cells and their therapeutic applications.PubMed
Peishan Li, Qianmin Ou, Songtao Shi, et al.
Cell Mol Immunol. 2023 Jun;20(6):558-569. doi: 10.1038/s41423-023-00998-y. Epub 2023 Mar 27.
Mesenchymal stem/stromal cells (MSCs) are widely distributed in the body and play essential roles in tissue regeneration and homeostasis. MSCs can be isolated from discarded tissues, expanded in vitro and used as therapeutics for autoimmune diseases and other chronic disorders. MSCs promote tissue regeneration and homeostasis by primarily acting on immune cells. At least six different types of MSCs have been isolated from postnatal dental tissues and have remarkable immunomodulatory properties. Dental stem cells (DSCs) have been demonstrated to have therapeutic effects on several systemic inflammatory diseases. Conversely, MSCs derived from nondental tissues such as the umbilical cord exhibit great benefits in the management of periodontitis in preclinical studies. Here, we discuss the main therapeutic uses of MSCs/DSCs, their mechanisms, extrinsic inflammatory cues and the intrinsic metabolic circuitries that govern the immunomodulatory functions of MSCs/DSCs. Increased understanding of the mechanisms underpinning the immunomodulatory functions of MSCs/DSCs is expected to aid in the development of more potent and precise MSC/DSC-based therapeutics.
16Regulation of adult stem cell quiescence and its functions in the maintenance of tissue integrity.PubMed
Antoine de Morree, Thomas A Rando
Nat Rev Mol Cell Biol. 2023 May;24(5):334-354. doi: 10.1038/s41580-022-00568-6. Epub 2023 Mar 15.
Adult stem cells are important for mammalian tissues, where they act as a cell reserve that supports normal tissue turnover and can mount a regenerative response following acute injuries. Quiescent stem cells are well established in certain tissues, such as skeletal muscle, brain, and bone marrow. The quiescent state is actively controlled and is essential for long-term maintenance of stem cell pools. In this Review, we discuss the importance of maintaining a functional pool of quiescent adult stem cells, including haematopoietic stem cells, skeletal muscle stem cells, neural stem cells, hair follicle stem cells, and mesenchymal stem cells such as fibro-adipogenic progenitors, to ensure tissue maintenance and repair. We discuss the molecular mechanisms that regulate the entry into, maintenance of, and exit from the quiescent state in mice. Recent studies revealed that quiescent stem cells have a discordance between RNA and protein levels, indicating the importance of post-transcriptional mechanisms, such as alternative polyadenylation, alternative splicing, and translation repression, in the control of stem cell quiescence. Understanding how these mechanisms guide stem cell function during homeostasis and regeneration has important implications for regenerative medicine.
17Impact of osteoporosis and osteoporosis medications on fracture healing: a narrative review.PubMed
M Chandran, K E Akesson, M K Javaid, et al.
Osteoporos Int. 2024 Aug;35(8):1337-1358. doi: 10.1007/s00198-024-07059-8. Epub 2024 Apr 8.
UNLABELLED: Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. BACKGROUND: Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. METHODS: Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). RESULTS: Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. CONCLUSION: Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved.
18Clinical Assessments of Fracture Healing and Basic Science Correlates: Is There Room for Convergence?PubMed
Luke A Lopas, Huaishuang Shen, Ning Zhang, et al.
Curr Osteoporos Rep. 2023 Apr;21(2):216-227. doi: 10.1007/s11914-022-00770-7. Epub 2022 Dec 19.
PURPOSE OF REVIEW: The purpose of this review is to summarize the clinical and basic science methods used to assess fracture healing and propose a framework to improve the translational possibilities. RECENT FINDINGS: Mainstays of fracture healing assessment include clinical examination, various imaging modalities, and assessment of function. Pre-clinical studies have yielded insight into biomechanical progression as well as the genetic, molecular, and cellular processes of fracture healing. Efforts are emerging to identify early markers to predict impaired healing and possibly early intervention to alter these processes. Despite of the differences in clinical and preclinical research, opportunities exist to unify and improve the translational efforts between these arenas to develop and optimize our ability to assess and predict fracture healing, thereby improving the clinical care of these patients.
19Site-Specific Fracture Healing: Comparison between Diaphysis and Metaphysis in the Mouse Long Bone.PubMed
Satoshi Inoue, Jiro Takito, Masanori Nakamura
Int J Mol Sci. 2021 Aug 27;22(17):9299. doi: 10.3390/ijms22179299.
The process of fracture healing varies depending upon internal and external factors, such as the fracture site, mode of injury, and mechanical environment. This review focuses on site-specific fracture healing, particularly diaphyseal and metaphyseal healing in mouse long bones. Diaphyseal fractures heal by forming the periosteal and medullary callus, whereas metaphyseal fractures heal by forming the medullary callus. Bone healing in ovariectomized mice is accompanied by a decrease in the medullary callus formation both in the diaphysis and metaphysis. Administration of estrogen after fracture significantly recovers the decrease in diaphyseal healing but fails to recover the metaphyseal healing. Thus, the two bones show different osteogenic potentials after fracture in ovariectomized mice. This difference may be attributed to the heterogeneity of the skeletal stem cells (SSCs)/osteoblast progenitors of the two bones. The genes that specify the patterning of the mammalian skeleton during embryogenesis are upregulated during the diaphyseal healing. genes positively regulate the differentiation of osteoblasts from SSCs in vitro. During bone grafting, the SSCs in the donor's bone express with adaptability in the heterologous bone. These novel functions of the genes are discussed herein with reference to the site-specificity of fracture healing.
20Approaches Mediating Oxytocin Regulation of the Immune System.PubMed
Tong Li, Ping Wang, Stephani C Wang, et al.
Front Immunol. 2017 Jan 10;7:693. doi: 10.3389/fimmu.2016.00693. eCollection 2016.
The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo-neurohypophysial system (HNS) emerged as an important component of neuroendocrine-immune network, wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus, their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic, and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic-pituitary-immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly its relationship with other hypothalamic-pituitary-immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of the immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine-immune network.
21Role of Substance P Neuropeptide in Inflammation, Wound Healing, and Tissue Homeostasis.PubMed
Susmit Suvas
J Immunol. 2017 Sep 1;199(5):1543-1552. doi: 10.4049/jimmunol.1601751.
Substance P (SP) is an undecapeptide present in the CNS and the peripheral nervous system. SP released from the peripheral nerves exerts its biological and immunological activity via high-affinity neurokinin 1 receptor (NK1R). SP is also produced by immune cells and acts as an autocrine or paracrine fashion to regulate the function of immune cells. In addition to its proinflammatory role, SP and its metabolites in combination with insulin-like growth factor-1 are shown to promote the corneal epithelial wound healing. Recently, we showed an altered ocular surface homeostasis in unmanipulated NK1R mice, suggesting the role of SP-NK1R signaling in ocular surface homeostasis under steady-state. This review summarizes the immunobiology of SP and its effect on immune cells and immunity to microbial infection. In addition, the effect of SP in inflammation, wound healing, and corneal epithelial homeostasis in the eye is discussed.
22Stress and wound healing.PubMed
Lisa M Christian, Jennifer E Graham, David A Padgett, et al.
Neuroimmunomodulation. 2006;13(5-6):337-46. doi: 10.1159/000104862. Epub 2007 Aug 6.
Over the past decade it has become clear that stress can significantly slow wound healing: stressors ranging in magnitude and duration impair healing in humans and animals. For example, in humans, the chronic stress of caregiving as well as the relatively brief stress of academic examinations impedes healing. Similarly, restraint stress slows healing in mice. The interactive effects of glucocorticoids (e.g. cortisol and corticosterone) and proinflammatory cytokines [e.g. interleukin-1beta (IL-1beta), IL-1alpha, IL-6, IL-8, and tumor necrosis factor-alpha] are primary physiological mechanisms underlying the stress and healing connection. The effects of stress on healing have important implications in the context of surgery and naturally occurring wounds, particularly among at-risk and chronically ill populations. In research with clinical populations, greater attention to measurement of health behaviors is needed to better separate behavioral versus direct physiological effects of stress on healing. Recent evidence suggests that interventions designed to reduce stress and its concomitants (e.g., exercise, social support) can prevent stress-induced impairments in healing. Moreover, specific physiological mechanisms are associated with certain types of interventions. In future research, an increased focus on mechanisms will help to more clearly elucidate pathways linking stress and healing processes.
23Demystifying mindfulness.PubMed
Karen Lawson
Minn Med. 2011 Jan;94(1):37-9.
Mindfulness-based stress reduction (MBSR) is an approach to health and wellness that an increasing number of health care providers are practicing and recommending to their patients. This article describes MBSR, its use in health care, and its benefits for patients with conditions such as anxiety, depression, chronic pain syndromes, and insomnia. It also offers advice about how physicians can incorporate elements of MBSR into their daily practices in order to reduce stress in their lives and prevent burnout.
24Mindfulness meditation: a path of transformation & healing.PubMed
Mary Jane Ott
J Psychosoc Nurs Ment Health Serv. 2004 Jul;42(7):22-9. doi: 10.3928/02793695-20040701-04.
As nurses, we have the unique privilege of witnessing and nurturing the healing process of the whole person--mind, body, and spirit. Teaching mindfulness meditation is a nursing intervention that can foster healing. The consistent practice of mindfulness meditation has been shown to decrease the subjective experience of pain and stress in a variety of research settings. Formal and informal daily practice fosters development of a profound inner calmness and nonreactivity of the mind, allowing individuals to face, and even embrace, all aspects of daily life, regardless of circumstances. By emphasizing being, not doing, mindfulness meditation provides a way through suffering for patients, families, and staff. This practice allows individuals to become compassionate witnesses to their own experiences, to avoid making premature decisions, and to be open to new possibilities, transformation, and healing.
25Meditation and Irritable Bowel Syndrome, a Systematic Review and Meta-Analysis.PubMed
Cristian-Ioan Baboș, Daniel-Corneliu Leucuța, Dan Lucian Dumitrașcu
J Clin Med. 2022 Nov 2;11(21):6516. doi: 10.3390/jcm11216516.
Mind-body interventions have shown efficacy in many conditions that have psychosomatic mechanisms, as well as for other pathologies. The aim of this study was to assess the effectiveness of meditation/mindfulness at improving the symptoms severity, quality of life and other associated mood and mental conditions, measured in patients with irritable bowel syndrome (IBS). A systematic review of randomized controlled trials in adult participants with IBS was conducted. Eight databases were searched for articles. We performed a meta-analysis evaluating the effects of meditation-based therapy on symptomatology, quality of life, anxiety and depression. Out of 604 articles screened, six were selected for quantitative review. The standardized mean difference (SMD) of the mindfulness group and the control group was of -36.95 (95% CI -74.61-0.7), = 0.054 regarding the IBS symptom score; of 12.58 (95% CI 4.42-20.74), = 0.003 regarding the IBS quality of life; SMD = 2.8 (95% CI 1.01-4.6), = 0.002 for spiritual scale; and of 15.49 (95% CI -28.43--2.55), = 0.019 regarding the pain score in IBS. Our study found that the quality of life and the spiritual scale scores (i.e., mindful awareness) were statistically significantly higher in the mindfulness group, while the pain score was statistically significantly lower in the mindfulness group.
26Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America.PubMed
Joshua P Metlay, Grant W Waterer, Ann C Long, et al.
Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67. doi: 10.1164/rccm.201908-1581ST.
This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia. A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations. The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions. The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.
27Low-Dose Corticosteroids for Critically Ill Adults With Severe Pulmonary Infections: A Review.PubMed
Romain Pirracchio, Balasubramanian Venkatesh, Matthieu Legrand
JAMA. 2024 Jul 23;332(4):318-328. doi: 10.1001/jama.2024.6096.
IMPORTANCE: Severe pulmonary infections, including COVID-19, community-acquired pneumonia, influenza, and Pneumocystis pneumonia, are a leading cause of death among adults worldwide. Pulmonary infections in critically ill patients may cause septic shock, acute respiratory distress syndrome, or both, which are associated with mortality rates ranging between 30% and 50%. OBSERVATIONS: Corticosteroids mitigate the immune response to infection and improve outcomes for patients with several types of severe pulmonary infections. Low-dose corticosteroids, defined as less than or equal to 400 mg hydrocortisone equivalent daily, can reduce mortality of patients with severe COVID-19, community-acquired pneumonia, and Pneumocystis pneumonia. A randomized clinical trial of 6425 patients hospitalized with COVID-19 who required supplemental oxygen or noninvasive or invasive mechanical ventilation reported that dexamethasone 6 mg daily for 10 days decreased 28-day mortality (23% vs 26%). A meta-analysis that included 7 randomized clinical trials of 1689 patients treated in the intensive care unit for severe bacterial community-acquired pneumonia reported that hydrocortisone equivalent less than or equal to 400 mg daily for 8 days or fewer was associated with lower 30-day mortality compared with placebo (10% vs 16%). In a meta-analysis of 6 randomized clinical trials, low-dose corticosteroids were associated with lower mortality rates compared with placebo for patients with HIV and moderate to severe Pneumocystis pneumonia (13% vs 25%). In a predefined subgroup analysis of a trial of low-dose steroid treatment for septic shock, patients with community-acquired pneumonia randomized to 7 days of intravenous hydrocortisone 50 mg every 6 hours and fludrocortisone 50 μg daily had decreased mortality compared with the placebo group (39% vs 51%). For patients with acute respiratory distress syndrome caused by various conditions, low-dose corticosteroids were associated with decreased in-hospital mortality (34% vs 45%) according to a meta-analysis of 8 studies that included 1091 patients. Adverse effects of low-dose corticosteroids may include hyperglycemia, gastrointestinal bleeding, neuropsychiatric disorders, muscle weakness, hypernatremia, and secondary infections. CONCLUSIONS AND RELEVANCE: Treatment with low-dose corticosteroids is associated with decreased mortality for patients with severe COVID-19 infection, severe community-acquired bacterial pneumonia, and moderate to severe Pneumocystis pneumonia (for patients with HIV). Low-dose corticosteroids may also benefit critically ill patients with respiratory infections who have septic shock, acute respiratory distress syndrome, or both.
28Pneumocystis jirovecii: a review with a focus on prevention and treatment.PubMed
R Benson Weyant, Dima Kabbani, Karen Doucette, et al.
Expert Opin Pharmacother. 2021 Aug;22(12):1579-1592. doi: 10.1080/14656566.2021.1915989. Epub 2021 Apr 19.
: (PJ) is an opportunistic fungal pathogen that can cause severe pneumonia in immunocompromised hosts. Risk factors for pneumonia (PJP) include HIV, organ transplant, malignancy, certain inflammatory or rheumatologic conditions, and associated therapies and conditions that result in cell-mediated immune deficiency. Clinical signs of PJP are nonspecific and definitive diagnosis requires direct detection of the organism in lower respiratory secretions or tissue. First-line therapy for prophylaxis and treatment remains trimethoprim-sulfamethoxazole (TMP-SMX), though intolerance or allergy, and rarely treatment failure, may necessitate alternate therapeutics, such as dapsone, pentamidine, atovaquone, clindamycin, primaquine and most recently, echinocandins as adjunctive therapy. In people living with HIV (PLWH), adjunctive corticosteroid use in treatment has shown a mortality benefit.: This review article covers the epidemiology, pathophysiology, diagnosis, microbiology, prophylaxis indications, prophylactic therapies, and treatments.: TMP-SMX has been first-line therapy for treating and preventing pneumocystis for decades. However, its adverse effects are not uncommon, particularly during treatment. Second-line therapies may be better tolerated, but often sacrifice efficacy. Echinocandins show some promise for new combination therapies; however, further studies are needed to define optimal antimicrobial therapy for PJP as well as the role of corticosteroids in those without HIV.
29Diagnosis and treatment of appendicitis: systematic review and meta-analysis.PubMed
Ryan Lamm, Sunjay S Kumar, Amelia T Collings, et al.
Surg Endosc. 2023 Dec;37(12):8933-8990. doi: 10.1007/s00464-023-10456-5. Epub 2023 Nov 1.
BACKGROUND: The optimal diagnosis and treatment of appendicitis remains controversial. This systematic review details the evidence and current best practices for the evaluation and management of uncomplicated and complicated appendicitis in adults and children. METHODS: Eight questions regarding the diagnosis and management of appendicitis were formulated. PubMed, Embase, CINAHL, Cochrane and clinicaltrials.gov/NLM were queried for articles published from 2010 to 2022 with key words related to at least one question. Randomized and non-randomized studies were included. Two reviewers screened each publication for eligibility and then extracted data from eligible studies. Random effects meta-analyses were performed on all quantitative data. The quality of randomized and non-randomized studies was assessed using the Cochrane Risk of Bias 2.0 or Newcastle Ottawa Scale, respectively. RESULTS: 2792 studies were screened and 261 were included. Most had a high risk of bias. Computerized tomography scan yielded the highest sensitivity (> 80%) and specificity (> 93%) in the adult population, although high variability existed. In adults with uncomplicated appendicitis, non-operative management resulted in higher odds of readmission (OR 6.10) and need for operation (OR 20.09), but less time to return to work/school (SMD - 1.78). In pediatric patients with uncomplicated appendicitis, non-operative management also resulted in higher odds of need for operation (OR 38.31). In adult patients with complicated appendicitis, there were higher odds of need for operation following antibiotic treatment only (OR 29.00), while pediatric patients had higher odds of abscess formation (OR 2.23). In pediatric patients undergoing appendectomy for complicated appendicitis, higher risk of reoperation at any time point was observed in patients who had drains placed at the time of operation (RR 2.04). CONCLUSIONS: This review demonstrates the diagnosis and treatment of appendicitis remains nuanced. A personalized approach and appropriate patient selection remain key to treatment success. Further research on controversies in treatment would be useful for optimal management.
30Appendectomy versus antibiotic treatment for acute appendicitis.PubMed
Brett Doleman, Siv Fonnes, Jon N Lund, et al.
Cochrane Database Syst Rev. 2024 Apr 29;4(4):CD015038. doi: 10.1002/14651858.CD015038.pub2.
BACKGROUND: Acute appendicitis is one of the most common emergency general surgical conditions worldwide. Uncomplicated/simple appendicitis can be treated with appendectomy or antibiotics. Some studies have suggested possible benefits with antibiotics with reduced complications, length of hospital stay, and the number of days off work. However, surgery may improve success of treatment as antibiotic treatment is associated with recurrence and future need for surgery. OBJECTIVES: To assess the effects of antibiotic treatment for uncomplicated/simple acute appendicitis compared with appendectomy for resolution of symptoms and complications. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registers (World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov) on 19 July 2022. We also searched for unpublished studies in conference proceedings together with reference checking and citation search. There were no restrictions on date, publication status, or language of publication. SELECTION CRITERIA: We included parallel-group randomised controlled trials (RCTs) only. We included studies where most participants were adults with uncomplicated/simple appendicitis. Interventions included antibiotics (by any route) compared with appendectomy (open or laparoscopic). DATA COLLECTION AND ANALYSIS: We used standard methodology expected by Cochrane. We used GRADE to assess the certainty of evidence for each outcome. Primary outcomes included mortality and success of treatment, and secondary outcomes included number of participants requiring appendectomy in the antibiotic group, complications, pain, length of hospital stay, sick leave, malignancy in the antibiotic group, negative appendectomy rate, and quality of life. Success of treatment definitions were heterogeneous although mainly based on resolution of symptoms rather than incorporation of long-term recurrence or need for surgery in the antibiotic group. MAIN RESULTS: We included 13 studies in the review covering 1675 participants randomised to antibiotics and 1683 participants randomised to appendectomy. One study was unpublished. All were conducted in secondary care and two studies received pharmaceutical funding. All studies used broad-spectrum antibiotic regimens expected to cover gastrointestinal bacteria. Most studies used predominantly laparoscopic surgery, but some included mainly open procedures. Six studies included adults and children. Almost all studies aimed to exclude participants with complicated appendicitis prior to randomisation, although one study included 12% with perforation. The diagnostic technique was clinical assessment and imaging in most studies. Only one study limited inclusion by sex (male only). Follow-up ranged from hospital admission only to seven years. Certainty of evidence was mainly affected by risk of bias (due to lack of blinding and loss to follow-up) and imprecision. Primary outcomes It is uncertain whether there was any difference in mortality due to the very low-certainty evidence (Peto odds ratio (OR) 0.51, 95% confidence interval (CI) 0.05 to 4.95; 1 study, 492 participants). There may be 76 more people per 1000 having unsuccessful treatment in the antibiotic group compared with surgery, which did not reach our predefined level for clinical significance (risk ratio (RR) 0.91, 95% CI 0.87 to 0.96; I = 69%; 7 studies, 2471 participants; low-certainty evidence). Secondary outcomes At one year, 30.7% (95% CI 24.0 to 37.8; I = 80%; 9 studies, 1396 participants) of participants in the antibiotic group required appendectomy or, alternatively, more than two-thirds of antibiotic-treated participants avoided surgery in the first year, but the evidence is very uncertain. Regarding complications, it is uncertain whether there is any difference in episodes of Clostridium difficile diarrhoea due to very low-certainty evidence (Peto OR 0.97, 95% CI 0.24 to 3.89; 1 study, 1332 participants). There may be a clinically significant reduction in wound infections with antibiotics (RR 0.25, 95% CI 0.09 to 0.68; I = 16%; 9 studies, 2606 participants; low-certainty evidence). It is uncertain whether antibiotics affect the incidence of intra-abdominal abscess or collection (RR 1.58, 95% CI 0.61 to 4.07; I = 19%; 6 studies, 1831 participants), or reoperation (Peto OR 0.13, 95% CI 0.01 to 2.16; 1 study, 492 participants) due to very low-certainty evidence, mainly due to rare events causing imprecision and risk of bias. It is uncertain if antibiotics prolonged length of hospital stay by half a day due to the very low-certainty evidence (MD 0.54, 95% CI 0.06 to 1.01; I = 97%; 11 studies, 3192 participants). The incidence of malignancy was 0.3% (95% CI 0 to 1.5; 5 studies, 403 participants) in the antibiotic group although follow-up was variable. Antibiotics probably increased the number of negative appendectomies at surgery (RR 3.16, 95% CI 1.54 to 6.49; I = 17%; 5 studies, 707 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Antibiotics may be associated with higher rates of unsuccessful treatment for 76 per 1000 people, although differences may not be clinically significant. It is uncertain if antibiotics increase length of hospital stay by half a day. Antibiotics may reduce wound infections. A third of the participants initially treated with antibiotics required subsequent appendectomy or two-thirds avoided surgery within one year, but the evidence is very uncertain. There were too few data from the included studies to comment on major complications.
31Laparoscopic appendectomy versus antibiotic treatment for acute appendicitis-a systematic review.PubMed
Franziska Köhler, Anne Hendricks, Carolin Kastner, et al.
Int J Colorectal Dis. 2021 Oct;36(10):2283-2286. doi: 10.1007/s00384-021-03927-5. Epub 2021 Apr 14.
BACKGROUND: Over the last years, laparoscopic appendectomy has progressively replaced open appendectomy and become the current gold standard treatment for suspected, uncomplicated appendicitis. At the same time, though, it is an ongoing discussion that antibiotic therapy can be an equivalent treatment for patients with uncomplicated appendicitis. The aim of this systematic review was to determine the safety and efficacy of antibiotic therapy and compare it to the laparoscopic appendectomy for acute, uncomplicated appendicitis. METHODS: The PubMed database, Embase database, and Cochrane library were scanned for studies comparing laparoscopic appendectomy with antibiotic treatment. Two independent reviewers performed the study selection and data extraction. The primary endpoint was defined as successful treatment of appendicitis. Secondary endpoints were pain intensity, duration of hospitalization, absence from work, and incidence of complications. RESULTS: No studies were found that exclusively compared laparoscopic appendectomy with antibiotic treatment for acute, uncomplicated appendicitis. CONCLUSIONS: To date, there are no studies comparing antibiotic treatment to laparoscopic appendectomy for patients with acute uncomplicated appendicitis, thus emphasizing the lack of evidence and need for further investigation.
32Early versus delayed appendicectomy for appendiceal phlegmon or abscess.PubMed
Shiyi Zhou, Yao Cheng, Nansheng Cheng, et al.
Cochrane Database Syst Rev. 2024 May 2;5(5):CD011670. doi: 10.1002/14651858.CD011670.pub3.
BACKGROUND: This is an update of a Cochrane review first published in 2017. Acute appendicitis (inflammation of the appendix) can be simple or complicated. Appendiceal phlegmon and appendiceal abscess are examples of complicated appendicitis. Appendiceal phlegmon is a diffuse inflammation in the bottom right of the appendix, while appendiceal abscess is a discrete inflamed mass in the abdomen that contains pus. Appendiceal phlegmon and abscess account for 2% to 10% of acute appendicitis. People with appendiceal phlegmon or abscess usually need an appendicectomy to relieve their symptoms (e.g. abdominal pain, loss of appetite, nausea, and vomiting) and avoid complications (e.g. peritonitis (infection of abdominal lining)). Surgery for people with appendiceal phlegmon or abscess may be early (immediately after hospital admission or within a few days of admission), or delayed (several weeks later in a subsequent hospital admission). The optimal timing of appendicectomy for appendiceal phlegmon or abscess is debated. OBJECTIVES: To assess the effects of early appendicectomy compared to delayed appendicectomy on overall morbidity and mortality in people with appendiceal phlegmon or abscess. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and five trials registers on 11 June 2023, together with reference checking to identify additional studies. SELECTION CRITERIA: We included all individual and cluster-randomised controlled trials (RCTs), irrespective of language, publication status, or age of participants, comparing early versus delayed appendicectomy in people with appendiceal phlegmon or abscess. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included eight RCTs that randomised 828 participants to early or delayed appendicectomy for appendiceal phlegmon (7 trials) or appendiceal abscess (1 trial). The studies were conducted in the USA, India, Nepal, and Pakistan. All RCTs were at high risk of bias because of lack of blinding and lack of published protocols. They were also unclear about methods of randomisation and length of follow-up. 1. Early versus delayed open or laparoscopic appendicectomy for appendiceal phlegmon We included seven trials involving 788 paediatric and adult participants with appendiceal phlegmon: 394 of the participants were randomised to the early appendicectomy group (open or laparoscopic appendicectomy as soon as the appendiceal mass resolved within the same admission), and 394 were randomised to the delayed appendicectomy group (initial conservative treatment followed by delayed open or laparoscopic appendicectomy several weeks later). There was no mortality in either group. The evidence is very uncertain about the effect of early appendicectomy on overall morbidity (risk ratio (RR) 0.74, 95% confidence interval (CI) 0.19 to 2.86; 3 trials, 146 participants; very low-certainty evidence), the proportion of participants who developed wound infections (RR 0.99, 95% CI 0.48 to 2.02; 7 trials, 788 participants), and the proportion of participants who developed faecal fistulas (RR 1.75, 95% CI 0.36 to 8.49; 5 trials, 388 participants). Early appendicectomy may reduce the abdominal abscess rate (RR 0.26, 95% CI 0.08 to 0.80; 4 trials, 626 participants; very low-certainty evidence), reduce the total length of hospital stay by about two days (mean difference (MD) -2.02 days, 95% CI -3.13 to -0.91; 5 trials, 680 participants), and increase the time away from normal activities by about five days (MD 5.00 days; 95% CI 1.52 to 8.48; 1 trial, 40 participants), but the evidence is very uncertain. 2. Early versus delayed laparoscopic appendicectomy for appendiceal abscess We included one trial involving 40 paediatric participants with appendiceal abscess: 20 were randomised to the early appendicectomy group (emergent laparoscopic appendicectomy), and 20 were randomised to the delayed appendicectomy group (initial conservative treatment followed by delayed laparoscopic appendicectomy 10 weeks later). There was no mortality in either group. The trial did not report on overall morbidity, various complications, or time away from normal activities. The evidence is very uncertain about the effect of early appendicectomy on the total length of hospital stay (MD -0.20 days, 95% CI -3.54 to 3.14; very low-certainty evidence). AUTHORS' CONCLUSIONS: For the comparison of early versus delayed open or laparoscopic appendicectomy for paediatric and adult participants with appendiceal phlegmon, very low-certainty evidence suggests that early appendicectomy may reduce the abdominal abscess rate. The evidence is very uncertain whether early appendicectomy prevents overall morbidity or other complications. Early appendicectomy may reduce the total length of hospital stay and increase the time away from normal activities, but the evidence is very uncertain. For the comparison of early versus delayed laparoscopic appendicectomy for paediatric participants with appendiceal abscess, data are sparse, and we cannot rule out significant benefits or harms of early versus delayed appendicectomy. Further trials on this topic are urgently needed and should specify a set of criteria for use of antibiotics, percutaneous drainage of the appendiceal abscess prior to surgery, and resolution of the appendiceal phlegmon or abscess. Future trials should include outcomes such as time away from normal activities and length of hospital stay.
33The role of long non-coding RNAs and circular RNAs in bone regeneration: Modulating miRNAs function.PubMed
Jianfeng Ping, Laifeng Li, Yongqiang Dong, et al.
J Tissue Eng Regen Med. 2022 Mar;16(3):227-243. doi: 10.1002/term.3277. Epub 2022 Jan 11.
Although bone is a self-healing organ and is able to repair and restore most fractures, large bone fractures, about 10%, are not repairable. Bone grafting, as a gold standard, and bone tissue engineering using biomaterials, growth factors, and stem cells have been developed to restore large bone defects. Since bone regeneration is a complex and multiple-step process and the majority of the human genome, about 98%, is composed of the non-protein-coding regions, non-coding RNAs (ncRNAs) play essential roles in bone regeneration. Recent studies demonstrated that long ncRNAs (lncRNAs) and circular RNAs (circRNAs), as members of ncRNAs, are widely involved in bone regeneration by interaction with microRNAs (miRNAs) and constructing a lncRNA or circRNA/miRNA/mRNA regulatory network. The constructed network regulates the differentiation of stem cells into osteoblasts and their commitment to osteogenesis. This review will present the structure and biogenesis of lncRNAs and circRNAs, the mechanism of bone repair, and the bone tissue engineering in bone defects. Finally, we will discuss the role of lncRNAs and circRNAs in osteogenesis and bone fracture healing through constructing various lncRNA or circRNA/miRNA/mRNA networks and the involved pathways.
34Postoperative Immobilization of Scaphoid Fractures: A Comprehensive Review of the Literature.PubMed
Michael Simon, Pasquale Gencarelli, Jason Yang, et al.
Hand (N Y). 2023 Sep;18(6):905-911. doi: 10.1177/15589447221093675. Epub 2022 May 16.
The optimal protocol for postoperative immobilization following operative treatment of scaphoid fractures remains controversial. Reports of successful management with brief postoperative immobilization suggest that earlier restoration of function may be achieved by limiting the duration of immobilization. However, the risk of nonunion and its associated complications suggest that a more conservative approach with extended immobilization could optimize fracture healing. This paper presents a thorough review of the relevant literature and summarizes the myriad postoperative immobilization protocols and their reported outcomes. Postoperative immobilization protocols and reported outcomes for displaced, comminuted, and proximal pole fractures are discussed separately. The literature is reviewed following different operative techniques, including open reduction internal fixation and percutaneous screw fixation. Vigilant postoperative care of scaphoid fractures managed surgically is warranted to monitor for signs of nonunion while attempting to regain motion and strength to the injured wrist.
35Interventions for treating proximal humeral fractures in adults.PubMed
Helen H G Handoll, Stig Brorson
Cochrane Database Syst Rev. 2015 Nov 11(11):CD000434. doi: 10.1002/14651858.CD000434.pub4.
BACKGROUND: Fracture of the proximal humerus, often termed shoulder fracture, is a common injury in older people. The management of these fractures varies widely. This is an update of a Cochrane Review first published in 2001 and last updated in 2012. OBJECTIVES: To assess the effects (benefits and harms) of treatment and rehabilitation interventions for proximal humeral fractures in adults. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and other databases, conference proceedings and bibliographies of trial reports. The full search ended in November 2014. SELECTION CRITERIA: We considered all randomised controlled trials (RCTs) and quasi-randomised controlled trials pertinent to the management of proximal humeral fractures in adults. DATA COLLECTION AND ANALYSIS: Both review authors performed independent study selection, risk of bias assessment and data extraction. Only limited meta-analysis was performed. MAIN RESULTS: We included 31 heterogeneous RCTs (1941 participants). Most of the 18 separate treatment comparisons were tested by small single-centre trials. The main exception was the surgical versus non-surgical treatment comparison tested by eight trials. Except for a large multicentre trial, bias in these trials could not be ruled out. The quality of the evidence was either low or very low for all comparisons except the largest comparison.Nine trials evaluated non-surgical treatment in mainly minimally displaced fractures. Four trials compared early (usually one week) versus delayed (three or four weeks) mobilisation after fracture but only limited pooling was possible and most of the data were from one trial (86 participants). This found some evidence that early mobilisation resulted in better recovery and less pain in people with mainly minimally displaced fractures. There was evidence of little difference between the two groups in shoulder complications (2/127 early mobilisation versus 3/132 delayed mobilisation; 4 trials) and fracture displacement and non-union (2/52 versus 1/54; 2 trials).One quasi-randomised trial (28 participants) found the Gilchrist-type sling was generally more comfortable than the Desault-type sling (body bandage). One trial (48 participants) testing pulsed electromagnetic high-frequency energy provided no evidence. Two trials (62 participants) provided evidence indicating little difference in outcome between instruction for home exercises versus supervised physiotherapy. One trial (48 participants) reported, without presentable data, that home exercise alone gave better early and comparable long-term results than supervised exercise in a swimming pool plus home exercise.Eight trials, involving 567 older participants, evaluated surgical intervention for displaced fractures. There was high quality evidence of no clinically important difference in patient-reported shoulder and upper-limb function at one- or two-year follow-up between surgical (primarily locking plate fixation or hemiarthroplasty) and non-surgical treatment (sling immobilisation) for the majority of displaced proximal humeral fractures; and moderate quality evidence of no clinically important difference between the two groups in quality of life at two years (and at interim follow-ups at six and 12 months). There was moderate quality evidence of little difference between groups in mortality in the surgery group (17/248 versus 12/248; risk ratio (RR) 1.40 favouring non-surgical treatment, 95% confidence interval (CI) 0.69 to 2.83; P = 0.35; 6 trials); only one death was explicitly linked with the treatment. There was moderate quality evidence of a higher risk of additional surgery in the surgery group (34/262 versus 16/261; RR 2.06, 95% CI 1.18 to 3.60; P = 0.01; 7 trials). Although there was moderate evidence of a higher risk of adverse events after surgery, the 95% confidence intervals for adverse events also included the potential for a greater risk of adverse events after non-surgical treatment.Different methods of surgical management were tested in 12 trials. One trial (57 participants) comparing two types of locking plate versus a locking nail for treating two-part surgical neck fractures found some evidence of slightly better function after plate fixation but also of a higher rate of surgically-related complications. One trial (61 participants) comparing a locking plate versus minimally invasive fixation with distally inserted intramedullary K-wires found little difference between the two implants at two years. Compared with hemiarthroplasty, one trial (32 participants) found similar results with locking plate fixation in function and re-operation rates, whereas another trial (30 participants) reported all five re-operations occurred in the tension-band fixation group. One trial (62 participants) found better patient-rated (Quick DASH) and composite shoulder function scores at a minimum of two years follow-up and a lower incidence of re-operation and complications after reverse shoulder arthroplasty (RSA) compared with hemiarthroplasty.No important between-group differences were found in one trial (120 participants) comparing the deltoid-split approach versus deltopectoral approach for non-contact bridging plate fixation, and two trials (180 participants) comparing 'polyaxial' and 'monaxial' screws in locking plate fixation. One trial (68 participants) produced some preliminary evidence that tended to support the use of medial support locking screws in locking plate fixation. One trial (54 participants) found fewer adverse events, including re-operations, for the newer of two types of intramedullary nail. One trial (35 participants) found better functional results for one of two types of hemiarthroplasty. One trial (45 participants) found no important effects of tenodesis of the long head of the biceps for people undergoing hemiarthroplasty.Very limited evidence suggested similar outcomes from early versus later mobilisation after either surgical fixation (one trial: 64 participants) or hemiarthroplasty (one trial: 49 participants). AUTHORS' CONCLUSIONS: There is high or moderate quality evidence that, compared with non-surgical treatment, surgery does not result in a better outcome at one and two years after injury for people with displaced proximal humeral fractures involving the humeral neck and is likely to result in a greater need for subsequent surgery. The evidence does not cover the treatment of two-part tuberosity fractures, fractures in young people, high energy trauma, nor the less common fractures such as fracture dislocations and head splitting fractures.There is insufficient evidence from RCTs to inform the choices between different non-surgical, surgical, or rehabilitation interventions for these fractures.
36The ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation) trial - a pragmatic multicentre randomised controlled trial evaluating the clinical effectiveness and cost-effectiveness of surgical compared with non-surgical treatment for proximal fracture of the humerus in adults.PubMed
Helen Handoll, Stephen Brealey, Amar Rangan, et al.
Health Technol Assess. 2015 Mar;19(24):1-280. doi: 10.3310/hta19240.
BACKGROUND: Proximal humeral fractures account for 5-6% of all fractures in adults. There is considerable variation in whether or not surgery is used in the management of displaced fractures involving the surgical neck. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of surgical compared with non-surgical treatment of the majority of displaced fractures of the proximal humerus involving the surgical neck in adults. DESIGN: A pragmatic parallel-group multicentre randomised controlled trial with an economic evaluation. Follow-up was for 2 years. SETTING: Recruitment was undertaken in the orthopaedic departments of 33 acute NHS hospitals in the UK. Patient care pathways included outpatient and community-based rehabilitation. PARTICIPANTS: Adults (aged ≥ 16 years) presenting within 3 weeks of their injury with a displaced fracture of the proximal humerus involving the surgical neck. INTERVENTIONS: The choice of surgical intervention was left to the treating surgeons, who used techniques with which they were experienced. Non-surgical treatment was initial sling immobilisation followed by active rehabilitation. Provision of rehabilitation was comparable in both groups. MAIN OUTCOME MEASURES: The primary outcome was the Oxford Shoulder Score (OSS) assessed at 6, 12 and 24 months. Secondary outcomes were the 12-item Short Form health survey, surgical and other shoulder fracture-related complications, secondary surgery to the shoulder or increased/new shoulder-related therapy, medical complications during inpatient stay and mortality. European Quality of Life-5 Dimensions data and treatment costs were also collected. RESULTS: The mean age of the 250 trial participants was 66 years and 192 (77%) were female. Independent assessment using the Neer classification identified 18 one-part fractures, 128 two-part fractures and 104 three- or four-part fractures. OSS data were available for 215 participants at 2 years. We found no statistically or clinically significant differences in OSS scores between the two treatment groups (scale 0-48, with a higher score indicating a better outcome) over the 2-year period [difference of 0.75 points in favour of the surgery group, 95% confidence interval (CI) -1.33 to 2.84; p = 0.479; data from 114 surgery and 117 non-surgery participants] or at individual time points. We found no statistically significant differences between surgical and non-surgical group participants in SF-12 physical or mental component summary scores; surgical or shoulder fracture-related complications (30 vs. 23 respectively); those undergoing further shoulder-related therapy, either surgery (11 vs. 11 respectively) or other therapy (seven vs. four respectively); or mortality (nine vs. five respectively). The base-case economic analysis showed that, at 2 years, the cost of surgical intervention was, on average, £1780.73 more per patient (95% CI £1152.71 to £2408.75) than the cost of non-surgical intervention. It was also slightly less beneficial in terms of utilities, although this difference was not statistically significant. The net monetary benefit associated with surgery is negative. There was only a 5% probability of surgery achieving the criterion of costing < £20,000 to gain a quality-adjusted life-year, which was confirmed by extensive sensitivity analyses. CONCLUSIONS: Current surgical practice does not result in a better outcome for most patients with displaced fractures of the proximal humerus involving the surgical neck and is not cost-effective in the UK setting. Two areas for future work are the setting up of a national database of these fractures, including the collection of patient-reported outcomes, and research on the best ways of informing patients with these and other upper limb fractures about initial self-care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN50850043. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 24. See the NIHR Journals Library website for further project information.
37Negative pressure wound therapy for surgical wounds healing by primary closure.PubMed
Joan Webster, Zhenmi Liu, Gill Norman, et al.
Cochrane Database Syst Rev. 2019 Mar 26;3(3):CD009261. doi: 10.1002/14651858.CD009261.pub4.
BACKGROUND: Indications for the use of negative pressure wound therapy (NPWT) are broad and include prophylaxis for surgical site infections (SSIs). While existing evidence for the effectiveness of NPWT remains uncertain, new trials necessitated an updated review of the evidence for the effects of NPWT on postoperative wounds healing by primary closure. OBJECTIVES: To assess the effects of negative pressure wound therapy for preventing surgical site infection in wounds healing through primary closure. SEARCH METHODS: We searched the Cochrane Wounds Specialised Register, CENTRAL, Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus in February 2018. We also searched clinical trials registries for ongoing and unpublished studies, and checked reference lists of relevant included studies as well as reviews, meta-analyses, and health technology reports to identify additional studies. There were no restrictions on language, publication date, or setting. SELECTION CRITERIA: We included trials if they allocated participants to treatment randomly and compared NPWT with any other type of wound dressing, or compared one type of NPWT with another type of NPWT. DATA COLLECTION AND ANALYSIS: Four review authors independently assessed trials using predetermined inclusion criteria. We carried out data extraction, 'Risk of bias' assessment using the Cochrane 'Risk of bias' tool, and quality assessment according to GRADE methodology. MAIN RESULTS: In this second update we added 25 intervention trials, resulting in a total of 30 intervention trials (2957 participants), and two economic studies nested in trials. Surgeries included abdominal and colorectal (n = 5); caesarean section (n = 5); knee or hip arthroplasties (n = 5); groin surgery (n = 5); fractures (n = 5); laparotomy (n = 1); vascular surgery (n = 1); sternotomy (n = 1); breast reduction mammoplasty (n = 1); and mixed (n = 1). In three key domains four studies were at low risk of bias; six studies were at high risk of bias; and 20 studies were at unclear risk of bias. We judged the evidence to be of low or very low certainty for all outcomes, downgrading the level of the evidence on the basis of risk of bias and imprecision.Primary outcomesThree studies reported mortality (416 participants; follow-up 30 to 90 days or unspecified). It is uncertain whether NPWT has an impact on risk of death compared with standard dressings (risk ratio (RR) 0.63, 95% confidence interval (CI) 0.25 to 1.56; very low-certainty evidence, downgraded once for serious risk of bias and twice for very serious imprecision).Twenty-five studies reported on SSI. The evidence from 23 studies (2533 participants; 2547 wounds; follow-up 30 days to 12 months or unspecified) showed that NPWT may reduce the rate of SSIs (RR 0.67, 95% CI 0.53 to 0.85; low-certainty evidence, downgraded twice for very serious risk of bias).Fourteen studies reported dehiscence. We combined results from 12 studies (1507 wounds; 1475 participants; follow-up 30 days to an average of 113 days or unspecified) that compared NPWT with standard dressings. It is uncertain whether NPWT reduces the risk of wound dehiscence compared with standard dressings (RR 0.80, 95% CI 0.55 to 1.18; very low-certainty evidence, downgraded twice for very serious risk of bias and once for serious imprecision).Secondary outcomesWe are uncertain whether NPWT increases or decreases reoperation rates when compared with a standard dressing (RR 1.09, 95% CI 0.73 to 1.63; 6 trials; 1021 participants; very low-certainty evidence, downgraded for very serious risk of bias and serious imprecision) or if there is any clinical benefit associated with NPWT for reducing wound-related readmission to hospital within 30 days (RR 0.86, 95% CI 0.47 to 1.57; 7 studies; 1271 participants; very low-certainty evidence, downgraded for very serious risk of bias and serious imprecision). It is also uncertain whether NPWT reduces incidence of seroma compared with standard dressings (RR 0.67, 95% CI 0.45 to 1.00; 6 studies; 568 participants; very low-certainty evidence, downgraded twice for very serious risk of bias and once for serious imprecision). It is uncertain if NPWT reduces or increases the risk of haematoma when compared with a standard dressing (RR 1.05, 95% CI 0.32 to 3.42; 6 trials; 831 participants; very low-certainty evidence, downgraded twice for very serious risk of bias and twice for very serious imprecision. It is uncertain if there is a higher risk of developing blisters when NPWT is compared with a standard dressing (RR 6.64, 95% CI 3.16 to 13.95; 6 studies; 597 participants; very low-certainty evidence, downgraded twice for very serious risk of bias and twice for very serious imprecision).Quality of life was not reported separately by group but was used in two economic evaluations to calculate quality-adjusted life years (QALYs). There was no clear difference in incremental QALYs for NPWT relative to standard dressing when results from the two trials were combined (mean difference 0.00, 95% CI -0.00 to 0.00; moderate-certainty evidence).One trial concluded that NPWT may be more cost-effective than standard care, estimating an incremental cost-effectiveness ratio (ICER) value of GBP 20.65 per QALY gained. A second cost-effectiveness study estimated that when compared with standard dressings NPWT was cost saving and improved QALYs. We rated the overall quality of the reports as very good; we did not grade the evidence beyond this as it was based on modelling assumptions. AUTHORS' CONCLUSIONS: Despite the addition of 25 trials, results are consistent with our earlier review, with the evidence judged to be of low or very low certainty for all outcomes. Consequently, uncertainty remains about whether NPWT compared with a standard dressing reduces or increases the incidence of important outcomes such as mortality, dehiscence, seroma, or if it increases costs. Given the cost and widespread use of NPWT for SSI prophylaxis, there is an urgent need for larger, well-designed and well-conducted trials to evaluate the effects of newer NPWT products designed for use on clean, closed surgical incisions. Such trials should initially focus on wounds that may be difficult to heal, such as sternal wounds or incisions on obese patients.
38Negative pressure wound therapy for surgical site infections: A systematic review and meta-analysis.PubMed
Junru Gao, Yunyun Wang, Jingyu Song, et al.
J Adv Nurs. 2021 Oct;77(10):3980-3990. doi: 10.1111/jan.14876. Epub 2021 Apr 27.
OBJECTIVE: Negative pressure wound therapy is one of the most common treatments for infected wounds. The aim of this meta-analysis was to compare the efficacy of negative pressure wound therapy with conventional treatment methods in the treatment of surgical site infection. DESIGN: This study is registered with International Prospective Register of Systematic Reviews. DATA SOURCES: The Pubmed, Embase and the Cochrane Central Register of Controlled Trials databases were searched. METHODS: The systematic review was searched by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method. All trials reporting the use of negative pressure wound therapy for surgical site infection treatment were included regardless of surgery type. The primary outcome measure was wound healing. Secondary outcomes were length of hospital stay, medical costs, adverse events, and reoperation rates. Results are presented with 95% confidence intervals and report estimates as odds ratios. Heterogeneity was determined through the I test, with I > 50% indicating substantial heterogeneity and p < .10 significance. The search was performed on 10 March 2020. RESULTS: We identified 13 eligible trial comparisons, of which 2 were randomized controlled trials and 11 cohort study. Negative pressure wound therapy in surgical site infection (SSI) patients significantly increased wound healing rate, accelerated wound healing time, increased daily wound healing area, reduced hospital stay, and reduced adverse events. However, negative pressure wound therapy was associated with increased medical costs. CONCLUSION: Negative pressure wound therapy may be more effective for the treatment of surgical site infection relative to conventional debridement, dressings and other treatments. However, further high-quality randomized controlled trials are needed to determine the most optimal application of negative pressure wound therapy. IMPACT: Negative pressure wound therapy is the best treatment strategy for surgical site infection. This study can improve medical practitioners' awareness of negative pressure wound therapy for surgical site infection, promoting the development of relevant randomized controlled trials.
39Effect of Incisional Negative Pressure Wound Therapy vs Standard Wound Dressing on Deep Surgical Site Infection After Surgery for Lower Limb Fractures Associated With Major Trauma: The WHIST Randomized Clinical Trial.PubMed
Matthew L Costa, Juul Achten, Ruth Knight, et al.
JAMA. 2020 Feb 11;323(6):519-526. doi: 10.1001/jama.2020.0059.
IMPORTANCE: Following surgery to treat major trauma-related fractures, deep wound infection rates are high. It is not known if negative pressure wound therapy can reduce infection rates in this setting. OBJECTIVE: To assess outcomes in patients who have incisions resulting from surgery for lower limb fractures related to major trauma and were treated with either incisional negative pressure wound therapy or standard wound dressing. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial conducted at 24 trauma hospitals representing the UK Major Trauma Network that included 1548 patients aged 16 years or older who underwent surgery for a lower limb fracture caused by major trauma from July 7, 2016, through April 17, 2018, with follow-up to December 11, 2018. INTERVENTIONS: Incisional negative pressure wound therapy (n = 785), which involved a specialized dressing used to create negative pressure over the wound, vs standard wound dressing not involving negative pressure (n = 763). MAIN OUTCOMES AND MEASURES: The primary outcome measure was deep surgical site infection at 30 days diagnosed according to the criteria from the US Centers for Disease Control and Prevention. A preplanned secondary analysis of the primary outcome was performed at 90 days. The secondary outcomes were patient-reported disability (Disability Rating Index), health-related quality of life (EuroQol 5-level EQ-5D), surgical scar assessment (Patient and Observer Scar Assessment Scale), and chronic pain (Douleur Neuropathique Questionnaire) at 3 and 6 months, as well as other local wound healing complications at 30 days. RESULTS: Among 1548 participants who were randomized (mean [SD] age, 49.8 [20.3] years; 561 [36%] were aged ≤40 years; 583 [38%] women; and 881 [57%] had multiple injuries), 1519 (98%) had data available for the primary outcome. At 30 days, deep surgical site infection occurred in 5.84% (45 of 770 patients) of the incisional negative pressure wound therapy group and in 6.68% (50 of 749 patients) of the standard wound dressing group (odds ratio, 0.87 [95% CI, 0.57 to 1.33]; absolute risk difference, -0.77% [95% CI, -3.19% to 1.66%]; P = .52). There was no significant difference in the deep surgical site infection rate at 90 days (11.4% [72 of 629 patients] in the incisional negative pressure wound therapy group vs 13.2% [78 of 590 patients] in the standard wound dressing group; odds ratio, 0.84 [95% CI, 0.59 to 1.19]; absolute risk difference, -1.76% [95% CI, -5.41% to 1.90%]; P = .32). For the 5 prespecified secondary outcomes reported, there were no significant differences at any time point. CONCLUSIONS AND RELEVANCE: Among patients who underwent surgery for major trauma-related lower limb fractures, use of incisional negative pressure wound therapy, compared with standard wound dressing, resulted in no significant difference in the rate of deep surgical site infection. The findings do not support the use of incisional negative pressure wound therapy in this setting, although the event rate at 30 days was lower than expected. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN12702354.
40Rehabilitation After Immobilization for Ankle Fracture: The EXACT Randomized Clinical Trial.PubMed
Anne M Moseley, Paula R Beckenkamp, Marion Haas, et al.
JAMA. 2015 Oct 6;314(13):1376-85. doi: 10.1001/jama.2015.12180.
IMPORTANCE: The benefits of rehabilitation after immobilization for ankle fracture are unclear. OBJECTIVES: To determine the effectiveness of a supervised exercise program and advice (rehabilitation) compared with advice alone and to determine if effects are moderated by fracture severity or age and sex. DESIGN, SETTING, AND PARTICIPANTS: The EXACT trial was a pragmatic, randomized clinical trial conducted from December 2010 to June 2014. Patients with isolated ankle fracture presenting to fracture clinics in 7 Australian hospitals were randomized on the day of removal of immobilization. Of 571 eligible patients, 357 chose not to participate and 214 were allocated to rehabilitation (n = 106) or advice alone (n = 108), with 194 (91%) followed up at 1 month, 173 (81%) at 3 months, and 170 (79%) at 6 months. There were no withdrawals attributed to adverse effects. Recruitment terminated early on December 31, 2013 (planned enrollment, 342; actual, 214), because funding was exhausted. INTERVENTIONS: Supervised exercise program and advice about self-management (rehabilitation) (individually tailored, prescribed, monitored, and progressed) or advice alone, both delivered by a physical therapist. MAIN OUTCOMES AND MEASURES: Primary outcomes were activity limitation assessed using the Lower Extremity Functional Scale (score range, 0-80; higher scores indicate better activity), and quality of life assessed using the Assessment of Quality of Life (score range, 0-1; higher scores indicate better quality of life), measured at baseline and at 1, 3 (primary time point), and 6 months. RESULTS: Mean activity limitation and quality of life at baseline were 30.1 (SD, 12.5) and 0.51 (SD, 0.24), respectively, for advice and 30.2 (SD, 13.2) and 0.54 (SD, 0.24) for rehabilitation, increasing to 64.3 (SD, 13.5) and 0.85 (SD, 0.17) for advice vs 64.3 (SD, 15.1) and 0.85 (SD, 0.20) for rehabilitation at 3 months. Rehabilitation was not more effective than advice for activity limitation (mean effect at 3 months, 0.4 [95% CI, -3.3 to 4.1]) or quality of life (-0.01 [95% CI, -0.06 to 0.04]). Treatment effects were not moderated by fracture severity or age and sex. CONCLUSIONS AND RELEVANCE: A supervised exercise program and advice did not confer additional benefits in activity limitation or quality of life compared with advice alone for patients with isolated and uncomplicated ankle fracture. These findings do not support the routine use of supervised exercise programs after removal of immobilization for patients with isolated and uncomplicated ankle fracture. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12610000979055.
41Controlling resistant hypertension.PubMed
J David Spence
Stroke Vasc Neurol. 2018 Feb 24;3(2):69-75. doi: 10.1136/svn-2017-000138. eCollection 2018 Jun.
Resistant hypertension (failure to achieve target blood pressures with three or more antihypertensive drugs including a diuretic) is an important and preventable cause of stroke. Hypertension is highly prevalent in China (>60% of persons above age 65), and only ~6% of hypertensives in China are controlled to target levels. Most strokes occur among persons with resistant hypertension; approximately half of strokes could be prevented by blood pressure control. Reasons for uncontrolled hypertension include (1) non-compliance; (2) consumption of substances that aggravated hypertension, such as excess salt, alcohol, licorice, decongestants and oral contraceptives; (3) therapeutic inertia (failure to intensify therapy when target blood pressures are not achieved); and (4) diagnostic inertia (failure to investigate the cause of resistant hypertension). In China, an additional factor is lack of availability of appropriate antihypertensive therapy in many healthcare settings. Sodium restriction in combination with a diet similar to the Cretan Mediterranean or the DASH (Dietary Approaches to Stop Hypertension) diet can lower blood pressure in proportion to the severity of hypertension. Physiologically individualised therapy for hypertension based on phenotyping by plasma renin activity and aldosterone can markedly improve blood pressure control. Renal hypertension (high renin/high aldosterone) is best treated with angiotensin receptor antagonists; primary aldosteronism (low renin/high aldosterone) is best treated with aldosterone antagonists (spironolactone or eplerenone); and hypertension due to overactivity of the renal epithelial sodium channel (low renin/low aldosterone; Liddle phenotype) is best treated with amiloride. The latter is far more common than most physicians suppose.
42Nutrition, physical activity, and quality of life in older adults: summary.PubMed
A Drewnowski, W J Evans
J Gerontol A Biol Sci Med Sci. 2001 Oct;56 Spec No 2:89-94. doi: 10.1093/gerona/56.suppl_2.89.
If health-related quality of life--and not longevity--is the key goal for health promotion, then it is captured only partly by the existing mortality and morbidity indexes. Researchers now urge that government agencies and health care providers begin collecting quality-of-life data on the populations they serve. Adding life to years, not years to life, is the current agenda for productive and successful aging. Policies and programs on aging are increasingly focused on identifying ways to improve quality of life and health status rather than just extending life span. In the Healthy People 2000 report, the chief goal of health promotion was to increase the span of healthy life. The focus was on mortality and morbidity data and symptom checklists as the principal measures of ill health. In contrast, the new emphasis in the Healthy People 2010 report is on quality of life and overall well-being. Helping people to increase life expectancy and improve their quality of life is the primary goal of the Healthy People 2010 report. The authors of this special issue of the Journals of Gerontology: Biological Sciences and Medical Sciences are united in the belief that optimal nutrition and physical activity make a significant contribution to the overall quality of life at any age and especially for older adults. The key research challenge lies in deciding which aspects of improved fitness, nutrition, and diet contribute the most to quality-of-life measures. We have attempted to provide a comprehensive review of research on exercise, nutrition, diet, and health in elderly adults. Past studies on diet, nutrition, and fitness have largely addressed biomedical outcomes, pointing to substantial benefits in physical functioning, remission of disease symptoms, and improved health. This special issue goes a step further in assessing the effect of improved nutrition and physical activity on the global quality of life and its four principal domains. Although links between diet and exercise and chronic disease risks have been well documented, more needs to be known about motivations for behavioral change and perceived benefits as assessed using quality-of-life measures. No single segment of our society can benefit more from regularly performed exercise and improved diet than elderly adults. These important articles provide a link between diet and exercise and quality-of-life issues, as outlined in the Healthy People 2010 report.
43Chronic physical illness: a psychophysiological approach for chronic physical illness.PubMed
Jana Purdy
Yale J Biol Med. 2013 Mar;86(1):15-28. Epub 2013 Mar 12.
Growing evidence demonstrates that psychological risk variables can contribute to physical disease. In an effort to thoroughly investigate potential etiological origins and optimal interventions, this broad review is divided into five sections: the stress response, chronic diseases, mind-body theoretical models, psychophysiological interventions, and integrated health care solutions. The stress response and its correlation to chronic disorders such as cardiovascular, gastrointestinal, autoimmune, metabolic syndrome, and chronic pain are comprehensively explored. Current mind-body theoretical models, including peripheral nerve pathway, neurophysiological, and integrative theories, are reviewed to elucidate the biological mechanisms behind psychophysiological interventions. Specific interventions included are psychotherapy, mindfulness meditation, yoga, and psychopharmacology. Finally, the author advocates for an integrated care approach as a means by which to blur the sharp distinction between physical and psychological health. Integrated care approaches can utilize psychiatric nurse practitioners for behavioral assessment, intervention, research, advocacy, consultation, and education to optimize health outcomes.
44Yoga for Preventive Health: A Holistic Approach.PubMed
Shobhit Madan, Jasraj Sembhi, Navpreet Khurana, et al.
Am J Lifestyle Med. 2022 Jan 4;17(3):418-423. doi: 10.1177/15598276211059758. eCollection 2023 May-Jun.
Yoga has been prevalent for over 5000 years; it originated in India and has become an essential lifestyle ingredient for achieving optimal health. The goal of this article in lifestyle modification is to increase awareness about the benefits of yoga and how its practice can reduce the overall risk of chronic diseases. Yoga has been proven to be therapeutic for enhancing immunity and support management of chronic diseases such as cardiovascular, respiratory, endocrine disorders, obesity, cancer, and metabolic syndrome. Yoga techniques called asanas, such as pranayama for breathing regulation and dhyana for meditation, boost innate immune response, interrupt inflammation, and thereby prevent the manifestation of chronic diseases. Yoga also provides symptomatic relief for chronic arthritis by increasing joint flexibility and microcirculation. Yoga and meditation regulate neurotransmitters, neuropeptides, hormones, and cytokines that mediate interactions between the central nervous system and the immune system. These techniques reduce the psychological and physiological effects of chronic stress. Serotonin, oxytocin, and melatonin released directly due to practicing yoga have been shown to better manage anxiety and fear, especially during the pandemic. We believe the current trends of chronic disease management will become more effective with the implementation of lifestyle changes using yoga.
45Mindfulness-Based Stress Reduction in Advanced Nursing Practice: A Nonpharmacologic Approach to Health Promotion, Chronic Disease Management, and Symptom Control.PubMed
Hants Williams, Leigh Ann Simmons, Paula Tanabe
J Holist Nurs. 2015 Sep;33(3):247-59. doi: 10.1177/0898010115569349. Epub 2015 Feb 11.
The aim of this article is to discuss how advanced practice nurses (APNs) can incorporate mindfulness-based stress reduction (MBSR) as a nonpharmacologic clinical tool in their practice. Over the last 30 years, patients and providers have increasingly used complementary and holistic therapies for the nonpharmacologic management of acute and chronic diseases. Mindfulness-based interventions, specifically MBSR, have been tested and applied within a variety of patient populations. There is strong evidence to support that the use of MBSR can improve a range of biological and psychological outcomes in a variety of medical illnesses, including acute and chronic pain, hypertension, and disease prevention. This article will review the many ways APNs can incorporate MBSR approaches for health promotion and disease/symptom management into their practice. We conclude with a discussion of how nurses can obtain training and certification in MBSR. Given the significant and growing literature supporting the use of MBSR in the prevention and treatment of chronic disease, increased attention on how APNs can incorporate MBSR into clinical practice is necessary.
46Self-reported health and satisfaction of patients with chronic diseases who meditate: a case-control study.PubMed
Romy Lauche, Jost Langhorst, Anna Paul, et al.
Qual Life Res. 2014 Nov;23(9):2639-44. doi: 10.1007/s11136-014-0714-8. Epub 2014 May 16.
PURPOSE: While many clinical trials suggest that meditation is effective in reducing disease-related symptoms and increasing quality of life in diseased samples, subjective health benefits associated with the use of meditation under naturalistic conditions have not yet been investigated. The aim of this study was to investigate the differences in quality of life, mental health, and satisfaction in patients with chronic diseases who regularly use meditation versus those who do not. METHODS: The study applied a case-control design. Patients with chronic diseases who regularly used meditation were selected from a larger observational trial and compared to matched control patients who did not meditate regularly. They were compared in terms of their reported quality of life (SF-36 questionnaire), mental health (Hospital Anxiety and Depression Scale), life and health satisfaction (Questionnaire for Life Satisfaction), and medication usage as well as health locus of control (German version of the Multidimensional Health Locus of Control Scale). RESULTS: A total of 115 meditators and 115 controls were compared. Cases showed higher quality of life on the bodily pain subscale, higher internal and less external health locus of control, and higher life satisfaction than controls. No group differences were found for general health perception, most other aspects of quality of life, anxiety, depression, and medication use and health satisfaction. CONCLUSIONS: Regular practice of meditation was not clearly associated with better health perception in chronically diseased patients. However, those who regularly used meditation reported better pain-related quality of life and are more satisfied with their life.
47Improved Sleep, Diet, and Exercise in Adults with Serious Mental Illness: Results from a Pilot Self-Management Intervention.PubMed
Timothy Schmutte, Larry Davidson, Maria O'Connell
Psychiatr Q. 2018 Mar;89(1):61-71. doi: 10.1007/s11126-017-9516-9.
Compared to the general population, adults with serious mental illnesses have elevated rates of medical morbidity resulting in a reduced life expectancy of approximately 15 years. Chronic disease self-management programs for adults with serious mental and chronic medical illnesses show some promise in improving physical health-related outcomes, yet none of them address sleep quality. Poor sleep affects a majority of adults with serious mental illness and is robust risk factor for physical morbidity and premature mortality. This pilot project examined the impact of a 14-week educational and support group that included sleep quality as a cornerstone in promoting wellness and self-management in 78 adults with serious mental illness and poor health. Results provide preliminary data that the self-management program was associated with significant improvements in self-reported sleep quality at post-intervention. At 3-month follow-up, participants reported additional increases in sleep quality as well as in healthy diet and exercise frequency. Addressing sleep quality as part of self-management and wellness programs may be a viable approach to assist adults with chronic mental and physical illnesses to adopt health-promoting changes.
48Antibiotic Resistance and Microbiota Response.PubMed
Luigi Santacroce, Marina Di Domenico, Monica Montagnani, et al.
Curr Pharm Des. 2023;29(5):356-364. doi: 10.2174/1381612829666221219093450.
Use of antibiotics has dramatically eradicated bacterial infections in humans and animals. However, antibiotic overdose and abuse are responsible for the emergence of so-called multi-drug resistant bacteria. Gut microbiota deserves many functions in the host, and among them, integrity of epithelial barrier and enhancement of protective immune responses are included. There is evidence that antibiotic treatment decreases the diversity of gut microbiota species, also provoking metabolic changes, increased susceptibility to colonization and decrease of antimicrobial peptide secretion, leading to antibiotic resistance. In this review, the major mechanisms involved in antibiotic resistance will be illustrated. However, novel findings on the potential use of alternative treatments to overcome antibiotic resistance will be elucidated. In this regard, special emphasis will be placed on microcins, prebiotics, probiotics and postbiotics, as well as phage therapy and fecal microbial transplantation.
49Antibiotic-Induced Changes in the Intestinal Microbiota and Disease.PubMed
Simone Becattini, Ying Taur, Eric G Pamer
Trends Mol Med. 2016 Jun;22(6):458-478. doi: 10.1016/j.molmed.2016.04.003. Epub 2016 May 10.
The gut microbiota is a key player in many physiological and pathological processes occurring in humans. Recent investigations suggest that the efficacy of some clinical approaches depends on the action of commensal bacteria. Antibiotics are invaluable weapons to fight infectious diseases. However, by altering the composition and functions of the microbiota, they can also produce long-lasting deleterious effects for the host. The emergence of multidrug-resistant pathogens raises concerns about the common, and at times inappropriate, use of antimicrobial agents. Here we review the most recently discovered connections between host pathophysiology, microbiota, and antibiotics highlighting technological platforms, mechanistic insights, and clinical strategies to enhance resistance to diseases by preserving the beneficial functions of the microbiota.
50The Gut Microbiome as a Reservoir for Antimicrobial Resistance.PubMed
Winston E Anthony, Carey-Ann D Burnham, Gautam Dantas, et al.
J Infect Dis. 2021 Jun 16;223(12 Suppl 2):S209-S213. doi: 10.1093/infdis/jiaa497.
This review will consider the gut as a reservoir for antimicrobial resistance, colonization resistance, and how disruption of the microbiome can lead to colonization by pathogenic organisms. There is a focus on the gut as a reservoir for β-lactam and plasmid-mediated quinolone resistance. Finally, the role of functional metagenomics and long-read sequencing technologies to detect and understand antimicrobial resistance genes within the gut microbiome is discussed, along with the potential for future microbiome-directed methods to detect and prevent infection.
51Understanding the impact of antibiotic perturbation on the human microbiome.PubMed
Drew J Schwartz, Amy E Langdon, Gautam Dantas
Genome Med. 2020 Sep 28;12(1):82. doi: 10.1186/s13073-020-00782-x.
The human gut microbiome is a dynamic collection of bacteria, archaea, fungi, and viruses that performs essential functions for immune development, pathogen colonization resistance, and food metabolism. Perturbation of the gut microbiome's ecological balance, commonly by antibiotics, can cause and exacerbate diseases. To predict and successfully rescue such perturbations, first, we must understand the underlying taxonomic and functional dynamics of the microbiome as it changes throughout infancy, childhood, and adulthood. We offer an overview of the healthy gut bacterial architecture over these life stages and comment on vulnerability to short and long courses of antibiotics. Second, the resilience of the microbiome after antibiotic perturbation depends on key characteristics, such as the nature, timing, duration, and spectrum of a course of antibiotics, as well as microbiome modulatory factors such as age, travel, underlying illness, antibiotic resistance pattern, and diet. In this review, we discuss acute and chronic antibiotic perturbations to the microbiome and resistome in the context of microbiome stability and dynamics. We specifically discuss key taxonomic and resistance gene changes that accompany antibiotic treatment of neonates, children, and adults. Restoration of a healthy gut microbial ecosystem after routine antibiotics will require rationally managed exposure to specific antibiotics and microbes. To that end, we review the use of fecal microbiota transplantation and probiotics to direct recolonization of the gut ecosystem. We conclude with our perspectives on how best to assess, predict, and aid recovery of the microbiome after antibiotic perturbation.
52Impact of Fluid Balance on the Development of Lung Injury.PubMed
Simone Gattarello, Tommaso Pozzi, Mauro Galizia, et al.
Am J Respir Crit Care Med. 2025 Mar;211(3):331-338. doi: 10.1164/rccm.202406-1240OC.
The pathophysiological relationship among fluid administration, fluid balance, and mechanical ventilation in the development of lung injury is unclear. To quantify the relative contributions of mechanical power and fluid balance in the development of lung injury. Thirty-nine healthy female pigs, divided into four groups, were ventilated for 48 hours with high (∼18 J/min) or low (∼6 J/min) mechanical power and high (∼4 L) or low (∼1 L) targeted fluid balance. We measured physiological variables (e.g., end-expiratory lung gas volume, respiratory system mechanics, gas exchange, hemodynamics) and pathological variables (i.e., lung weight, wet-to-dry ratio, and histology score of lung injury). End-expiratory lung gas volume, respiratory system elastance, strain, and oxygenation significantly worsened in the two groups assigned to receive high fluid balance, irrespective of the mechanical power received. All four groups had similar lung weights (i.e., lung edema), lung wet-to-dry ratios, and pathological variables. Animals with higher fluid balance developed more ascites, which was associated with a decrease in end-expiratory lung gas volume. Our study did not detect a significant difference in lung injury between high and low mechanical power. Some damage is directly attributable to mechanical power, while additional injury appears to result indirectly from high fluid balance, which reduces end-expiratory lung gas volume, with ascites playing an important role in this process.
53Risks of self-medication practices.PubMed
Maria Esperanza Ruiz
Curr Drug Saf. 2010 Oct;5(4):315-23. doi: 10.2174/157488610792245966.
Self-medication is defined as the selection and use of medicines by individuals (or a member of the individuals' family) to treat self-recognized or self-diagnosed conditions or symptoms. Several benefits have been linked to appropriate self-medication, among them: increased access to medication and relief for the patient, the active role of the patient in his or her own health care, better use of physicians and pharmacists skills and reduced (or at least optimized) burden of governments due to health expenditure linked to the treatment of minor health conditions However, self-medication is far from being a completely safe practice, in particular in the case of non-responsible self-medication. Potential risks of self-medication practices include: incorrect self-diagnosis, delays in seeking medical advice when needed, infrequent but severe adverse reactions, dangerous drug interactions, incorrect manner of administration, incorrect dosage, incorrect choice of therapy, masking of a severe disease and risk of dependence and abuse. In this short review the author analyzes recent literature on some of the most important dangers related to self-medication practices, particularly: polypharmacy and drug interactions, medications abuse or dependence, misdiagnosis and incorrect choice of treatment. The author also proposes measures that could be adopted in order to solve or improve these issues.
54Benefits and risks of self medication.PubMed
C M Hughes, J C McElnay, G F Fleming
Drug Saf. 2001;24(14):1027-37. doi: 10.2165/00002018-200124140-00002.
Self medication is becoming an increasingly important area within healthcare. It moves patients towards greater independence in making decisions about management of minor illnesses, thereby promoting empowerment. Self medication also has advantages for healthcare systems as it facilitates better use of clinical skills, increases access to medication and may contribute to reducing prescribed drug costs associated with publicly funded health programmes. However, self medication is associated with risks such as misdiagnosis, use of excessive drug dosage, prolonged duration of use, drug interactions and polypharmacy. The latter may be particularly problematic in the elderly. Monitoring systems, a partnership between patients, physicians and pharmacists and the provision of education and information to all concerned on safe self medication, are proposed strategies for maximising benefit and minimising risk.
55Pharmacovigilance, risks and adverse effects of self-medication.PubMed
Jean-Louis Montastruc, Emmanuelle Bondon-Guitton, Delphine Abadie, et al.
Therapie. 2016 Apr;71(2):257-62. doi: 10.1016/j.therap.2016.02.012. Epub 2016 Feb 6.
Self-medication means resorting to one or more drugs in order to treat oneself without the help of a doctor. This phenomenon is developing fast. In this review, we will discuss the main definitions of self-medication; we will then present a few important characteristics of this therapeutic practice: prevalence, reasons, populations involved and drugs used. Whilst the theoretical risks of self-medication have been abundantly discussed in the literature (adverse effects, interactions, product, dosage or treatment duration errors, difficulty in self-diagnosis, risk of addiction or abuse…), there is in fact very little detailed pharmacovigilance data concerning the characteristics and the consequences of this usage in real life. This study therefore describes the all too rare data that is available: patients, clinical characteristics, "seriousness" and drugs involved in the adverse effects of self-medication. It also discusses leads to be followed in order to minimize medication risks, which are obviously not well known and clearly not sufficiently notified.
56Determinants of antibiotic self-medication: A systematic review and meta-analysis.PubMed
Iftekhar Ahmed, Rebecca King, Sharmin Akter, et al.
Res Social Adm Pharm. 2023 Jul;19(7):1007-1017. doi: 10.1016/j.sapharm.2023.03.009. Epub 2023 Mar 21.
BACKGROUND: Decreasing the prevalence of antibiotic self-medication among the public requires proper understanding of the risk factors involved. However, the determinants of antibiotic self-medication are not well defined. OBJECTIVES: To identify patient and health system-related determinants of antibiotic self-medication among the public. METHODS: A systematic review of quantitative observational studies and qualitative studies was undertaken. PubMed, Embase, and Web of Science were searched to identify studies on determinants of antibiotic self-medication. The data were analyzed using meta-analysis, descriptive analysis, and thematic analysis. RESULTS: Sixty-eight studies were included in the review. From meta-analyses, male sex (pooled odds ratio [POR]: 1.52, 95% confidence interval [CI]: 1.19-1.75), lack of satisfaction with healthcare services/physicians (POR: 3.53, 95% CI: 2.26-4.75) were associated with antibiotic self-medication. In subgroup analysis, lower age was directly associated with self-medication in high-income countries (POR: 1.61, 95% CI: 1.10-2.36). In low- and middle-income countries, people with greater knowledge of antibiotics were less likely to self-medicate (POR: 0.2, 95% CI: 0.08-0.47). Patient-related determinants identified from descriptive and qualitative studies included previous experience with antibiotics and similar symptoms, perceived low severity of disease, intention to save time and get better quickly, cultural beliefs about curative power of antibiotics, advice from family/friends, and having home stock of antibiotics. Health system-related determinants included high cost of consulting physicians and low cost of self-medication, lack of access to physician/medical care, lack of trust/confidence in physicians, greater trust in pharmacists, long distance of physicians/healthcare facilities, long waiting time at healthcare facilities, easy access to antibiotics from pharmacies, and convenience associated with self-medication. CONCLUSIONS: Patient and health system-related determinants are associated with antibiotic self-medication. Interventions to decrease antibiotic self-medication should incorporate community programs along with appropriate policies and healthcare reforms targeting these determinants with specific attention to population at high risk of self-medication.
57Management of hypoglycemia in older adults with type 2 diabetes.PubMed
Jeffrey Freeman
Postgrad Med. 2019 May;131(4):241-250. doi: 10.1080/00325481.2019.1578590. Epub 2019 Feb 26.
Treatment of older adults with type 2 diabetes (T2D) is complex because they represent a heterogeneous group with a broad range of comorbidities, functional abilities, socioeconomic status, and life expectancy. Older adults with T2D are at high risk of recurring hypoglycemia, a condition associated with marked morbidity and mortality, because their counter-regulatory mechanism to hypoglycemia is attenuated, and recurring hypoglycemic episodes can lead to hypoglycemia unawareness. In addition, polypharmacy, a result of multiple chronic comorbidities (including heart disease, stroke, and chronic kidney disease), can increase the risk of severe hypoglycemia, especially when patients are taking sulfonylureas or insulin. Often the signs of hypoglycemia are nonspecific (sweating, dizziness, confusion, visual disturbances) and are mistaken for neurological symptoms or dementia. Consequences of hypoglycemia include acute and long-term cognitive changes, cardiac arrhythmia and myocardial infarction, serious falls, frailty, and death, often resulting in hospitalization, which come at a high economic cost. The American Diabetes Association has recently added three new recommendations regarding hypoglycemia in the elderly, highlighting individualized pharmacotherapy with glucose-lowering agents with a low risk of hypoglycemia and proven cardiovascular safety, avoidance of overtreatment, and simplifying treatment regimens while maintaining HbA1c targets. Thus, glycemic goals can be relaxed in the older population as part of individualized care, and physicians must make treatment decisions that best serve their patients' circumstances. This article highlights the issues faced by older people with T2D, the risk factors for hypoglycemia in this population, and the challenges faced by health care providers regarding glycemic management in this patient group.
58Pharmacological treatment of diabetes in older people.PubMed
W M Valencia, H Florez
Diabetes Obes Metab. 2014 Dec;16(12):1192-203. doi: 10.1111/dom.12362. Epub 2014 Sep 11.
The pharmacological management of diabetes in older people is complex and challenging. It requires a comprehensive understanding of the individual beyond the diabetes itself. Through the ageing years, the older individual presents with diabetes-related and non-related comorbidities and complications, develops functional limitations and psychological issues, and may lack social support and access to care. A disturbance in these categories, known as the four geriatric domains, will negatively affect diabetes self-management and self-efficacy, leading to poor outcomes and complications. Furthermore, older people with diabetes may be more interested in the management of other chronic conditions such as pain or impaired mobility, and diabetes may be lower in their list of priorities. Proper education must be provided to the older individual and caregivers, with continuous monitoring and counselling, especially when pharmacological interventions offer risks of side effects, adverse reactions and interactions with other medications. Informed shared medical decisions will help to improve adherence to the regimen; however, such discussions ought to be based on the best evidence available, which is unfortunately limited in this age group. We performed a review focused on pharmacological agents and summarize current evidence on their use for the treatment of diabetes in older people. We encourage clinicians to investigate and incorporate the four geriatrics domains in the selection and monitoring of these agents.
59Prescription drug misuse/abuse in the elderly.PubMed
John W Culberson, Martin Ziska
Geriatrics. 2008 Sep 1;63(9):22-31.
One quarter of the prescription drugs sold in the United States are used by the elderly, often for problems such as chronic pain, insomnia, and anxiety. The prevalence of abuse may be as high as 11 percent with female gender, social isolation, depression, and history of substance abuse increasing risk. Screening instruments for prescription drug abuse have not been validated in the geriatric population. Benzodiazepines, opiate analgesics, and some skeletal muscle relaxants may result in physical dependence; however, tolerance, withdrawal syndrome, and dose escalation may be less common in the older patient. Lower doses may decrease the risk of abuse and dependence; however, fear of abuse often results in a failure to adequately treat symptoms such as anxiety, pain, and insomnia.
60Geropharmacology: a primer for advanced practice acute care and critical care nurses, part I.PubMed
Catherine G Ferrario
AACN Adv Crit Care. 2008 Jan-Mar;19(1):23-35; quiz 36-7. doi: 10.1097/01.AACN.0000310748.00911.93.
Advanced practice nurses' challenge in managing older adults' medication regimens from an evidence base is difficult because older adults are vulnerable to medication errors and adverse drug reactions related to a number of factors. Predicting patients' responses to drugs is compounded during critical illness, adding to the heterogeneity and unpredictability of drug effects that are prevalent premorbidly. In the first part of this 2-part continuing education series, sources of medication errors and older adults' vulnerability are discussed, including normal changes of aging affecting pharmacokinetics and pharmacodynamics, polypharmacy, self-medicating, patient-family noncompliance, and inappropriately prescribed medications. In the second part, drug classes and drugs posing particular problems for older adults and cautions for acute care and critical care nurses who manage the medications of older adults are highlighted.
61The Charcot foot: pathophysiology, diagnosis and classification.PubMed
K Trieb
Bone Joint J. 2016 Sep;98-B(9):1155-9. doi: 10.1302/0301-620X.98B9.37038.
Neuropathic changes in the foot are common with a prevalence of approximately 1%. The diagnosis of neuropathic arthropathy is often delayed in diabetic patients with harmful consequences including amputation. The appropriate diagnosis and treatment can avoid an extensive programme of treatment with significant morbidity for the patient, high costs and delayed surgery. The pathogenesis of a Charcot foot involves repetitive micro-trauma in a foot with impaired sensation and neurovascular changes caused by pathological innervation of the blood vessels. In most cases, changes are due to a combination of both pathophysiological factors. The Charcot foot is triggered by a combination of mechanical, vascular and biological factors which can lead to late diagnosis and incorrect treatment and eventually to destruction of the foot. This review aims to raise awareness of the diagnosis of the Charcot foot (diabetic neuropathic osteoarthropathy and the differential diagnosis, erysipelas, peripheral arterial occlusive disease) and describe the ways in which the diagnosis may be made. The clinical diagnostic pathways based on different classifications are presented. Cite this article: Bone Joint J 2016;98-B:1155-9.
62Cutaneous Manifestations of Diabetes Mellitus: A Review.PubMed
Ana Luiza Lima, Tanja Illing, Sibylle Schliemann, et al.
Am J Clin Dermatol. 2017 Aug;18(4):541-553. doi: 10.1007/s40257-017-0275-z.
Diabetes mellitus is a widespread endocrine disease with severe impact on health systems worldwide. Increased serum glucose causes damage to a wide range of cell types, including endothelial cells, neurons, and renal cells, but also keratinocytes and fibroblasts. Skin disorders can be found in about one third of all people with diabetes and frequently occur before the diagnosis, thus playing an important role in the initial recognition of underlying disease. Noninfectious as well as infectious diseases have been described as dermatologic manifestations of diabetes mellitus. Moreover, diabetic neuropathy and angiopathy may also affect the skin. Pruritus, necrobiosis lipoidica, scleredema adultorum of Buschke, and granuloma annulare are examples of frequent noninfectious skin diseases. Bacterial and fungal skin infections are more frequent in people with diabetes. Diabetic neuropathy and angiopathy are responsible for diabetic foot syndrome and diabetic dermopathy. Furthermore, antidiabetic therapies may provoke dermatologic adverse events. Treatment with insulin may evoke local reactions like lipohypertrophy, lipoatrophy and both instant and delayed type allergy. Erythema multiforme, leukocytoclastic vasculitis, drug eruptions, and photosensitivity have been described as adverse reactions to oral antidiabetics. The identification of lesions may be crucial for the first diagnosis and for proper therapy of diabetes.
63Charcot foot syndrome.PubMed
W J Jeffcoate
Diabet Med. 2015 Jun;32(6):760-70. doi: 10.1111/dme.12754. Epub 2015 Apr 15.
Charcot foot syndrome is an uncommon complication of diabetes but is potentially devastating in its consequences. Outcome is made worse by widespread professional ignorance leading to delayed diagnosis, but it is also hampered by lack of understanding of its causes and lack of treatments with proven effectiveness, other than offloading. There remains a desperate need for studies into its causes as well as comparative audit and trials designed to determine the best treatment for this difficult condition. Such work can probably only be effectively carried out through the establishment of multicentre networks. Nevertheless, improved understanding in recent years of the likely role of inflammatory pathways has raised awareness of the multiple ways in which the effects of neuropathy may be manifest in the development of the Charcot foot. This awareness is also leading to the realization that similar processes may conceivably contribute to the refractoriness of other foot diseases in diabetes, including both chronic unhealing ulcers and osteomyelitis.
64[Not Available].PubMed
Ole Lander Svendsen, Klaus Kirketerp-Møller, Johnny Baumann Olsen, et al.
Ugeskr Laeger. 2024 Apr 29;186(18). doi: 10.61409/V09230598.
This review summarises the present knowledge of acute foot attacks in patients with diabetes. Diagnosis and treatment of acute foot attacks in patients with diabetes are often delayed, which increases the risk of amputations. To prevent this, urgent action is necessary, as it is for acute myocardial infarction and stroke, to ensure that patients are seen by competent specialists in a multidisciplinary team within hours. By following evidence-based guidelines, such as the National Treatment Guideline for diabetic foot disease from the Danish Endocrine Society, and seeking immediate medical attention, the risk of amputation and complications can be significantly reduced.
65Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials.PubMed
Jonathan Emberson, Kennedy R Lees, Patrick Lyden, et al.
Lancet. 2014 Nov 29;384(9958):1929-35. doi: 10.1016/S0140-6736(14)60584-5. Epub 2014 Aug 5.
BACKGROUND: Alteplase is effective for treatment of acute ischaemic stroke but debate continues about its use after longer times since stroke onset, in older patients, and among patients who have had the least or most severe strokes. We assessed the role of these factors in affecting good stroke outcome in patients given alteplase. METHODS: We did a pre-specified meta-analysis of individual patient data from 6756 patients in nine randomised trials comparing alteplase with placebo or open control. We included all completed randomised phase 3 trials of intravenous alteplase for treatment of acute ischaemic stroke for which data were available. Retrospective checks confirmed that no eligible trials had been omitted. We defined a good stroke outcome as no significant disability at 3-6 months, defined by a modified Rankin Score of 0 or 1. Additional outcomes included symptomatic intracranial haemorrhage (defined by type 2 parenchymal haemorrhage within 7 days and, separately, by the SITS-MOST definition of parenchymal type 2 haemorrhage within 36 h), fatal intracranial haemorrhage within 7 days, and 90-day mortality. FINDINGS: Alteplase increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit. Treatment within 3·0 h resulted in a good outcome for 259 (32·9%) of 787 patients who received alteplase versus 176 (23·1%) of 762 who received control (OR 1·75, 95% CI 1·35-2·27); delay of greater than 3·0 h, up to 4·5 h, resulted in good outcome for 485 (35·3%) of 1375 versus 432 (30·1%) of 1437 (OR 1·26, 95% CI 1·05-1·51); and delay of more than 4·5 h resulted in good outcome for 401 (32·6%) of 1229 versus 357 (30·6%) of 1166 (OR 1·15, 95% CI 0·95-1·40). Proportional treatment benefits were similar irrespective of age or stroke severity. Alteplase significantly increased the odds of symptomatic intracranial haemorrhage (type 2 parenchymal haemorrhage definition 231 [6·8%] of 3391 vs 44 [1·3%] of 3365, OR 5·55, 95% CI 4·01-7·70, p<0·0001; SITS-MOST definition 124 [3·7%] vs 19 [0·6%], OR 6·67, 95% CI 4·11-10·84, p<0·0001) and of fatal intracranial haemorrhage within 7 days (91 [2·7%] vs 13 [0·4%]; OR 7·14, 95% CI 3·98-12·79, p<0·0001). The relative increase in fatal intracranial haemorrhage from alteplase was similar irrespective of treatment delay, age, or stroke severity, but the absolute excess risk attributable to alteplase was bigger among patients who had more severe strokes. There was no excess in other early causes of death and no significant effect on later causes of death. Consequently, mortality at 90 days was 608 (17·9%) in the alteplase group versus 556 (16·5%) in the control group (hazard ratio 1·11, 95% CI 0·99-1·25, p=0·07). Taken together, therefore, despite an average absolute increased risk of early death from intracranial haemorrhage of about 2%, by 3-6 months this risk was offset by an average absolute increase in disability-free survival of about 10% for patients treated within 3·0 h and about 5% for patients treated after 3·0 h, up to 4·5 h. INTERPRETATION: Irrespective of age or stroke severity, and despite an increased risk of fatal intracranial haemorrhage during the first few days after treatment, alteplase significantly improves the overall odds of a good stroke outcome when delivered within 4·5 h of stroke onset, with earlier treatment associated with bigger proportional benefits. FUNDING: UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.
66Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis.PubMed
Jeffrey L Saver, Mayank Goyal, Aad van der Lugt, et al.
JAMA. 2016 Sep 27;316(12):1279-88. doi: 10.1001/jama.2016.13647.
IMPORTANCE: Endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic stroke due to intracranial large-vessel occlusions. Delineation of the association of treatment time with outcomes would help to guide implementation. OBJECTIVE: To characterize the period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage. DESIGN, SETTING, AND PATIENTS: Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled from randomized phase 3 trials involving stent retrievers or other second-generation devices in a peer-reviewed publication (by July 1, 2016). The identified 5 trials enrolled patients at 89 international sites. EXPOSURES: Endovascular thrombectomy plus medical therapy vs medical therapy alone; time to treatment. MAIN OUTCOMES AND MEASURES: The primary outcome was degree of disability (mRS range, 0-6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation. RESULTS: Among all 1287 patients (endovascular thrombectomy + medical therapy [n = 634]; medical therapy alone [n = 653]) enrolled in the 5 trials (mean age, 66.5 years [SD, 13.1]; women, 47.0%), time from symptom onset to randomization was 196 minutes (IQR, 142 to 267). Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180 to 302) and symptom onset to reperfusion was 286 minutes (IQR, 215 to 363). At 90 days, the mean mRS score was 2.9 (95% CI, 2.7 to 3.1) in the endovascular group and 3.6 (95% CI, 3.5 to 3.8) in the medical therapy group. The odds of better disability outcomes at 90 days (mRS scale distribution) with the endovascular group declined with longer time from symptom onset to arterial puncture: cOR at 3 hours, 2.79 (95% CI, 1.96 to 3.98), absolute risk difference (ARD) for lower disability scores, 39.2%; cOR at 6 hours, 1.98 (95% CI, 1.30 to 3.00), ARD, 30.2%; cOR at 8 hours,1.57 (95% CI, 0.86 to 2.88), ARD, 15.7%; retaining statistical significance through 7 hours and 18 minutes. Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability (cOR, 0.84 [95% CI, 0.76 to 0.93]; ARD, -6.7%) and less functional independence (OR, 0.81 [95% CI, 0.71 to 0.92], ARD, -5.2% [95% CI, -8.3% to -2.1%]), but no change in mortality (OR, 1.12 [95% CI, 0.93 to 1.34]; ARD, 1.5% [95% CI, -0.9% to 4.2%]). CONCLUSIONS AND RELEVANCE: In this individual patient data meta-analysis of patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy + medical therapy compared with medical therapy alone was associated with lower degrees of disability at 3 months. Benefit became nonsignificant after 7.3 hours.
67Prediction of lumbar disc herniation resorption in symptomatic patients: a prospective, multi-imaging and clinical phenotype study.PubMed
Alexander L Hornung, J Nicolas Barajas, Samuel S Rudisill, et al.
Spine J. 2023 Feb;23(2):247-260. doi: 10.1016/j.spinee.2022.10.003. Epub 2022 Oct 13.
BACKGROUND CONTEXT: Symptomatic lumbar disc herniations (LDH) are very common. LDH resorption may occur by a "self-healing" process, however this phenomenon remains poorly understood. By most guidelines, if LDH remains symptomatic after 3 months and conservative management fails, surgical intervention may be an option. PURPOSE: The following prospective study aimed to identify determinants that may predict early versus late LDH resorption. STUDY DESIGN/SETTING: Prospective study with patients recruited at a single center. PATIENT SAMPLE: Ninety-three consecutive patients diagnosed with acute symptomatic LDH were included in this study (n=23 early resorption and n=67 late resorption groups) with a mean age of 48.7±11.9 years. OUTCOMES MEASURE: Baseline assessment of patient demographics (eg, smoking status, height, weight, etc.), herniation characteristics (eg, the initial level of herniation, the direction of herniation, prevalence of multiple herniations, etc.) and MRI phenotypes (eg, Modic changes, end plate abnormalities, disc degeneration, vertebral body dimensions, etc.) were collected for further analysis. Lumbar MRIs were performed approximately every 3 months for 1 year from time of enrollment to assess disc integrity. METHODS: All patients were managed similarly. LDH resorption was classified as early (<3 months) or late (>3 months). A prediction model of pretreatment factors was constructed. RESULTS: No significant differences were noted between groups at any time-point (p>.05). Patients in the early resorption group experienced greater percent reduction of disc herniation between MRI-0-MRI-1 (p=.043), reduction of herniation size for total study duration (p=.007), and percent resorption per day compared to the late resorption group (p<.001). Based on multivariate modeling, greater L4 posterior vertebral height (coeff:14.58), greater sacral slope (coeff:0.12), and greater herniated volume (coeff:0.013) at baseline were found to be most predictive of early resorption (p<.05). CONCLUSIONS: This is the first comprehensive imaging and clinical phenotypic prospective study, to our knowledge, that has identified distinct determinants for early LDH resorption. Early resorption can occur in 24.7% of LDH patients. We developed a prediction model for early resorption which demonstrated great overall performance according to pretreatment measures of herniation size, L4 posterior body height, and sacral slope. A risk profile is proposed which may aid clinical decision-making and managing patient expectations.
68Surgical treatment delay in patients with headache disorders and neuralgia correlates with poor postoperative outcome.PubMed
Merel H J Hazewinkel, Katya Remy, Leonard Knoedler, et al.
J Plast Reconstr Aesthet Surg. 2024 Dec;99:154-159. doi: 10.1016/j.bjps.2024.09.058. Epub 2024 Sep 19.
INTRODUCTION: Although nerve decompression surgery has proven to be effective in reducing symptoms in patients with head and neck neuralgia and headache disorders, it is currently not part of the treatment algorithms for headache disorders. Therefore, patients wait an average of 20 years from the onset of symptoms to surgery, resulting in high conservative treatment costs ($989,275.65 per patient) and patient morbidity. This study evaluated the clinical impact of treatment delays on surgical outcomes. METHODS: Overall, 282 patients who underwent nerve decompression surgery at Weill Cornell Medicine and Massachusetts General Hospital between September 2012 and January 2024 were enrolled. Information regarding demographics, onset of symptoms, and headache characteristics was collected using patient surveys. The treatment outcome was evaluated by the percentage of symptom reduction in terms of frequency, duration, and pain intensity. An area under the receiver operating characteristic analysis was performed to determine the optimal timepoint to undergo surgery. RESULTS: Postoperative symptom reduction and time between the onset of symptoms and surgery were negatively correlated (r = -0.22; p < 0.001). The most significant difference in outcome was found at 2.9 years from symptom onset; patients who underwent surgery before this timepoint reported an average improvement of 79 ± 23% versus 67 ± 35% in those who were treated after the timepoint (p = 0.021). CONCLUSION: Our results indicate that delays in undergoing nerve decompression surgery beyond 2.9 years from symptom onset leads to less favorable postoperative outcomes, underscoring the need for timely referral to peripheral nerve surgeons when conservative management fails. Nonetheless, even with delays in surgical intervention, patients continued to experience significant symptom reduction.
69Fracture healing: mechanisms and interventions.PubMed
Thomas A Einhorn, Louis C Gerstenfeld
Nat Rev Rheumatol. 2015 Jan;11(1):45-54. doi: 10.1038/nrrheum.2014.164. Epub 2014 Sep 30.
Fractures are the most common large-organ, traumatic injuries to humans. The repair of bone fractures is a postnatal regenerative process that recapitulates many of the ontological events of embryonic skeletal development. Although fracture repair usually restores the damaged skeletal organ to its pre-injury cellular composition, structure and biomechanical function, about 10% of fractures will not heal normally. This article reviews the developmental progression of fracture healing at the tissue, cellular and molecular levels. Innate and adaptive immune processes are discussed as a component of the injury response, as are environmental factors, such as the extent of injury to the bone and surrounding tissue, fixation and the contribution of vascular tissues. We also present strategies for fracture treatment that have been tested in animal models and in clinical trials or case series. The biophysical and biological basis of the molecular actions of various therapeutic approaches, including recombinant human bone morphogenetic proteins and parathyroid hormone therapy, are also discussed.
70Bone regeneration: current concepts and future directions.PubMed
Rozalia Dimitriou, Elena Jones, Dennis McGonagle, et al.
BMC Med. 2011 May 31;9:66. doi: 10.1186/1741-7015-9-66.
Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis.
71Self-management education: history, definition, outcomes, and mechanisms.PubMed
Kate R Lorig, Halsted Holman
Ann Behav Med. 2003 Aug;26(1):1-7. doi: 10.1207/S15324796ABM2601_01.
Self-management has become a popular term for behavioral interventions as well as for healthful behaviors. This is especially true for the management of chronic conditions. This article offers a short history of self-management. It presents three self-management tasks--medical management, role management, and emotional management--and six self-management skills--problem solving, decision making, resource utilization, the formation of a patient-provider partnership, action planning, and self-tailoring. In addition, the article presents evidence of the effectiveness of self-management interventions and posits a possible mechanism, self-efficacy, through which these interventions work. In conclusion the article discusses problems and solutions for integrating self-management education into the mainstream health care systems.
72Self-management of hypertension using technology enabled interventions in primary care settings.PubMed
Aastha Chandak, Ashish Joshi
Technol Health Care. 2015;23(2):119-28. doi: 10.3233/THC-140886.
BACKGROUND: Self-management of hypertension by controlling Blood Pressure (BP) through technology-based interventions can effectively reduce the burden of high BP, which affects one out of every three adults in the United States. OBJECTIVE: The primary aim of this study is to explore the role of technology enabled interventions to improve or enhance self-management among individuals with hypertension. METHODS: We conducted a systematic review of the literature published between July 2008 and June 2013 on the MEDLINE database (via PubMed interface) during July 2013. The search words were "hypertension" and "primary care" in combination with each of the terms of "technology", "internet", "computer" and "cell phone". Our inclusion criteria consisted of: (a) Randomized Controlled Trials (RCTs) (b) conducted on human subjects; (c) technology-based interventions (d) to improve self-management (e) of hypertension and if the (f) final results of the study were published in the study. Our exclusion criteria included (a) management of other conditions and (b) literature reviews. RESULTS: The initial search resulted in 108 results. After applying the inclusion and exclusion criteria, a total of 12 studies were analyzed. Various technologies implemented in the studies included internet-based telemonitoring and education, telephone-based telemonitoring and education, internet-based education, telemedicine via videoconferencing, telehealth kiosks and automated modem device. Some studies also involved a physician intervention, in addition to patient intervention. The outcomes of proportion of subjects with BP control and change in mean SBP and DBP were better for the group of subjects who received combined physician and patient interventions. CONCLUSION: Interventions to improve BP control for self-management of hypertension should be aimed at both physicians as well as the patients. More interventions should utilize the JNC-7 guidelines and cost-effectiveness of the intervention should also be assessed.
73Immunomodulatory and Anti-inflammatory effect of Neural Stem/Progenitor Cells in the Central Nervous System.PubMed
Wei Ni, Murugan Ramalingam, Yumeng Li, et al.
Stem Cell Rev Rep. 2023 May;19(4):866-885. doi: 10.1007/s12015-022-10501-1. Epub 2023 Jan 17.
Neuroinflammation is a critical event that responds to disturbed homeostasis and governs various neurological diseases in the central nervous system (CNS). The excessive inflammatory microenvironment in the CNS can adversely affect endogenous neural stem cells, thereby impeding neural self-repair. Therapies with neural stem/progenitor cells (NSPCs) have shown significant inhibitory effects on inflammation, which is mainly achieved through intercellular contact and paracrine signalings. The intercellular contact between NSPCs and immune cells, the activated CNS- resident microglia, and astrocyte plays a critical role in the therapeutic NSPCs homing and immunomodulatory effects. Moreover, the paracrine effect mainly regulates infiltrating innate and adaptive immune cells, activated microglia, and astrocyte through the secretion of bioactive molecules and extracellular vesicles. However, the molecular mechanism involved in the immunomodulatory effect of NSPCs is not well discussed. This article provides a systematic analysis of the immunomodulatory mechanism of NSPCs, discusses efficient ways to enhance its immunomodulatory ability, and gives suggestions on clinical therapy.
74Elucidating the Pivotal Neuroimmunomodulation of Stem Cells in Spinal Cord Injury Repair.PubMed
Seidu A Richard, Marian Sackey
Stem Cells Int. 2021 Jul 23;2021:9230866. doi: 10.1155/2021/9230866. eCollection 2021.
Spinal cord injury (SCI) is a distressing incident with abrupt onset of the motor as well as sensory dysfunction, and most often, the injury occurs as result of high-energy or velocity accidents as well as contact sports and falls in the elderly. The key challenges associated with nerve repair are the lack of self-repair as well as neurotrophic factors and primary and secondary neuronal apoptosis, as well as factors that prevent the regeneration of axons locally. Neurons that survive the initial traumatic damage may be lost due to pathogenic activities like neuroinflammation and apoptosis. Implanted stem cells are capable of differentiating into neural cells that replace injured cells as well as offer local neurotrophic factors that aid neuroprotection, immunomodulation, axonal sprouting, axonal regeneration, and remyelination. At the microenvironment of SCI, stem cells are capable of producing growth factors like brain-derived neurotrophic factor and nerve growth factor which triggers neuronal survival as well as axonal regrowth. Although stem cells have proven to be of therapeutic value in SCI, the major disadvantage of some of the cell types is the risk for tumorigenicity due to the contamination of undifferentiated cells prior to transplantation. Local administration of stem cells via either direct cellular injection into the spinal cord parenchyma or intrathecal administration into the subarachnoid space is currently the best transplantation modality for stem cells during SCI.
75The roles of signaling pathways in bone repair and regeneration.PubMed
Maryam Majidinia, Alireza Sadeghpour, Bahman Yousefi
J Cell Physiol. 2018 Apr;233(4):2937-2948. doi: 10.1002/jcp.26042. Epub 2017 Aug 3.
Regenerative medicine has sparked interest in potential strategies for bone repair. Bone defects are widespread and could be caused by trauma, congenital malformations, infections, and surgery. Although bone has a large self-healing capacity, some defects or fractures are too big to regenerate. To regenerate bone structures which can be used for treatment of patients, bone growth must be induced by a number of bioactive implantable materials, cell types and intracellular, and extracellular molecular signaling pathways. Since mesenchymal stem cells (MSCs) and their differentiation during remodeling processes have important roles in bone regeneration, it is believed that understanding molecular signaling pathways involved is crucial to the development of bone implants, bone substitute materials, and cell-based scaffolds for bone regeneration. In this review, we briefly introduce concepts in fracture repair and regeneration following bone injuries, and then discuss the current clinical methods in bone regeneration. In the next section, we review the involvement of the various key signaling pathways in bone regeneration.
76Activation of Functional Somatic Stem Cells Promotes Endogenous Tissue Regeneration.PubMed
W Li, X Huang, W Yu, et al.
J Dent Res. 2022 Jul;101(7):802-811. doi: 10.1177/00220345211070222. Epub 2022 Feb 3.
Periodontal ligament derived stem cells (PDLSCs) are capable of differentiating into multiple cell types and inducing a promising immunomodulation for tissue regeneration and disease treatment. However, it is still challenging to develop a practical approach to activate endogenous stem cells for tissue self-healing and regeneration. In this study, transcriptome analysis reveals that resveratrol promotes PDLSC stemness through activation of stem cell, osteoprogenitor, and chondroprogenitor markers. Self-renewal and multipotent differentiation abilities are also improved in resveratrol-treated PDLSCs. In addition, immunomodulation of PDLSCs is dramatically increased after resveratrol treatment. Mechanistically, we show that resveratrol activates ERK/WNT crosstalk through elevation of olfactory and growth factor signaling pathways to upregulate the expression levels of RUNX2 and FASL for osteogenesis and immunomodulation, respectively. By using a periodontitis animal model, administration of resveratrol partially rescues bone loss through activation of endogenous somatic stem cells and inhibition of inflammatory T-cell infiltration. Taken together, our findings identify a novel pharmacological approach to achieve autotherapies for endogenous tissue regeneration.
77Immunomodulation by mesenchymal stem cells in treating human autoimmune disease-associated lung fibrosis.PubMed
Ming Liu, Xiansheng Zeng, Junli Wang, et al.
Stem Cell Res Ther. 2016 Apr 23;7(1):63. doi: 10.1186/s13287-016-0319-y.
BACKGROUND: Interstitial pneumonia in connective tissue diseases (CTD-IP) featuring inflammation and fibrosis is a leading cause of death in CTD-IP patients. The related autoimmune lung injury and disturbed self-healing process make conventional anti-inflammatory drugs ineffective. Equipped with unique immunoregulatory and regenerative properties, mesenchymal stem cells (MSCs) may represent a promising therapeutic agent in CTD-IP. In this study, we aim to define the immunopathology involved in pulmonary exacerbation during autoimmunity and to determine the potential of MSCs in correcting these disorders. METHODS: Lung and blood specimens, bronchoalveolar lavage fluid cells collected from CTD-IP patients, and human primary lung fibroblasts (HLFs) from patients pathologically diagnosed with usual interstitial pneumonia (UIP) and healthy controls were analyzed by histology, flow cytometry and molecular biology. T cell subsets involved in the process of CTD-IP were defined, while the regulatory functions of MSCs isolated from the bone marrow of normal individuals (HBMSCs) on cytotoxic T cells and CTD-UIP HLFs were investigated in vitro. RESULTS: Higher frequencies of cytotoxic T cells were observed in the lung and peripheral blood of CTD-IP patients, accompanied with a reduced regulatory T cell (Treg) level. CTD-UIP HLFs secreted proinflammatory cytokines in combination with upregulation of α-smooth muscle actin (α-SMA). The addition of HBMSCs in vitro increased Tregs concomitant with reduced cytotoxic T cells in an experimental cell model with dominant cytotoxic T cells, and promoted Tregs expansion in T cell subsets from patients with idiopathic pulmonary fibrosis (IPF). HBMSCs also significantly decreased proinflammatory chemokine/cytokine expression, and blocked α-SMA activation in CTD-UIP HLFs through a TGF-β1-mediated mechanism, which modulates excessive IL-6/STAT3 signaling leading to IP-10 expression. MSCs secreting a higher level of TGF-β1 appear to have an optimal anti-fibrotic efficacy in BLM-induced pulmonary fibrosis in mice. CONCLUSIONS: Impairment of TGF-β signal transduction relevant to a persistent IL-6/STAT3 transcriptional activation contributes to reduction of Treg differentiation in CTD-IP and to myofibroblast differentiation in CTD-UIP HLFs. HBMSCs can sensitize TGF-β1 downstream signal transduction that regulates IL-6/STAT3 activation, thereby stimulating Treg expansion and facilitating anti-fibrotic IP-10 production. This may in turn block progression of lung fibrosis in autoimmunity.
78Injectable hyaluronate-based hydrogel with a dynamic/covalent dual-crosslinked architecture for bone tissue engineering: Enhancing osteogenesis and immune regulation.PubMed
Kunyao Guo, Guanrong Li, Qianyao Yu, et al.
Int J Biol Macromol. 2024 Dec;282(Pt 5):137249. doi: 10.1016/j.ijbiomac.2024.137249. Epub 2024 Nov 4.
In orthopedic practice, accommodating irregular defects caused by trauma or surgery with traditional preformed bone graft substitutes is often challenging. As a result, injectable hydrogels with seed cells have garnered significant interest in bone repair due to their adaptability and minimally invasive properties. However, they cannot simultaneously achieve injectability and mechanical properties, providing a biophysical and biochemical environment for cell support. In this study, a novel injectable hydrogel system (OA hydrogel) loaded with aspirin and bone mesenchymal stem cells (BMSCs) was developed to enhance osteogenesis and immune regulation in small irregular bone defects. OA hydrogels possessed self-healing and shear-thinning properties due to dynamic/covalent hydrazone bonds between aldehyde-modified hyaluronic acid methacrylate (ADH-HAMA) and oxidized hyaluronic acid (OHA). By photopolymerization of the enclosed HAMA, the OA hydrogel was further reinforced, making it more suitable for cell proliferation. In vitro, composite hydrogels improved the osteogenic differentiation of BMSCs. Additionally, it promoted the M2 polarization of human monocytic leukemia (THP-1) cells. In vivo, the synergistic effect of acetylsalicylic acid (ASA) and BMSCs encapsulated within the OA hydrogel promoted new bone formation in rat calvaria through increased recruitment and polarization of M2 macrophages. These findings underscore the significant promise of hydrogels for bone tissue engineering applications.
79The Role of Low-Level Laser Therapy in Bone Healing: Systematic Review.PubMed
Micaela Berni, Alice Maria Brancato, Camilla Torriani, et al.
Int J Mol Sci. 2023 Apr 12;24(8):7094. doi: 10.3390/ijms24087094.
Low-level laser therapy (LLLT) is a treatment that is increasingly used in orthopedics practices. In vivo and in vitro studies have shown that low-level laser therapy (LLLT) promotes angiogenesis, fracture healing and osteogenic differentiation of stem cells. However, the underlying mechanisms during bone formation remain largely unknown. Factors such as wavelength, energy density, irradiation and frequency of LLLT can influence the cellular mechanisms. Moreover, the effects of LLLT are different according to cell types treated. This review aims to summarize the current knowledge of the molecular pathways activated by LLLT and its effects on the bone healing process. A better understanding of the cellular mechanisms activated by LLLT can improve its clinical application.