BACKGROUND & AIMS: OBJECTIVE:To assess and compare immediate effects of chest physiotherapy with positive expiratory pressure (PEP) versus oscillating PEP on transcutaneously measured blood-gas tensions in patients with cystic fibrosis. METHODS:Fifteen patients (mean age 12.5 y, range 6.9-21.5 y) participated. The treatments were randomized and performed on 2 separate occasions, 8 weeks apart. Spirometry was conducted before and after each treatment. We transcutaneously measured oxygen tension (P(tO2). RESULTS:There were no changes in spirometry values. During PEP, different trends in blood-gas tension were seen, and there were no consistent changes. During oscillating PEP, P(tO2) increased and P(tCO2) decreased. During oscillating PEP, P(tCO2) was lower and the intra-individual change in P(tCO2) was more pronounced than during PEP. The results obtained immediately after oscillating PEP showed a higher P(tO2) and a lower P(tCO2) than with PEP. CONCLUSION:PEP and oscillating PEP can both cause transitory effects on blood gases in patients with cystic fibrosis. However, oscillating PEP alters blood-gas tensions more than does PEP, and hyperventilation during oscillating PEP may reduce treatment time.

背景与目标：

BACKGROUND & AIMS: A 53-year-old man was admitted to the hospital for management of pneumonia and a giant fluid-filled bulla. He appeared acutely ill and had persistent fever despite prolonged therapy with parenteral antibiotics and aggressive bronchial drainage. Percutaneous placement of an 8.5F catheter into the bulla enabled drainage of both fluid and air within the bulla and led to resolution of his symptoms within 24 h. This report demonstrates that drainage of giant fluid-filled bullae may lead to rapid resolution of symptoms and describes a novel management technique for this condition.

背景与目标： 一名53岁的男子因治疗肺炎和巨大的充满液体的bulla而入院。尽管长期使用肠胃外抗生素治疗和积极的支气管引流，但他似乎病情严重，并持续发热。将8.5F导管经皮放置到大疱中，可以在大疱中排出液体和空气，并在24小时内缓解症状。该报告表明，巨大的充满液体的大疱的引流可能会导致症状的快速解决，并描述了一种针对这种情况的新颖管理技术。

BACKGROUND & AIMS: The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

背景与目标： 比较了慢性癌痛患者持续静脉输注 (CIVI) 吗啡与持续皮下输注 (CSCI) 吗啡的剂量，疗效和副作用。符合条件的患者被转诊到姑息治疗计划，并正在接受稳定剂量的CIVI吗啡。该设计是患者内部的单向交叉; 其中每个患者在吗啡从CIVI切换到CSCI之前和之后提供数据。“抢救” 剂量是根据需要每2小时给予的每小时剂量的50%。通过McGaw/AccuPro容积输液泵静脉内 (i.v.) 和皮下 (s.c.) 注入吗啡。获得包括副作用和疼痛评估在内的基线数据后，每天两次评估患者的毒性和镇痛效果。那些连续48小时稳定的CIVI剂量的人以与静脉 (i.v.) 阶段相同的剂量交叉到CSCI。稳定剂量定义为无剂量变化，在之前的24小时内有四个或更少的抢救剂量，并且疼痛等级为无或轻度。如果连续96个小时保持这些标准，CIVI被认为等于CSCI。进入了57名患者，其中40名可评估 (15名女性和25名男性)。中位年龄为67岁 (范围30-83岁)。所有40名参与者在整个静脉内保持稳定剂量后。阶段，越过s.C.阶段并保留在s.c.至少48小时。32名患者在整个静脉内保持稳定剂量。和南卡罗来纳州阶段。平均稳定的静脉注射。剂量 (第2天) 为5.05 mg/hr，平均稳定s.c.剂量 (第4天) 为5.7 mg/hr (P = 0.01)。第2天的平均抢救剂量为每24小时0.83次，而第4天的平均抢救剂量为每24小时0.80次 (P = 0.6)。第2天和第4天的平均分类疼痛评分为0.83，0.85 (P = 0.7)。第2天的平均视觉模拟量表 (VAS) 为22.9毫米，第4天为17.6毫米 (P = 0.1)。第2天和第4天的平均副作用发生率为1.7，2.0 (P = 0.2)。没有患者因不可接受的毒性而退出或剂量减少。有两份关于SC针插入点局部毒性 (轻度红斑) 的报告，需要改变部位。我们的40名患者均使用CIVI和CSCI吗啡进行了足够的疼痛控制。在没有保持相同i.v.的八名参与者中。和南卡罗来纳州剂量，都有足够的疼痛控制，并且在较高的s.C.上有相似的副作用。吗啡剂量。这些数据表明，静脉注射和南卡罗来纳州当作为连续输注给药时，大多数患者的途径是等镇痛。疼痛控制和副作用特征非常相似且可以接受。吗啡是静脉注射的绝佳替代品需要胃肠外吗啡治疗疼痛的住院患者和门诊患者的吗啡。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Sympathetically maintained pain could either be mediated by ephaptic interactions between sympathetic efferent and afferent nociceptive fibers or by catecholamine-induced activation of nociceptive nerve endings. We report here single fiber recordings from C nociceptors in a patient with sympathetically maintained pain, in whom sympathetic blockade had repeatedly eliminated the ongoing pain in both legs. We classified eight C-fibers as mechano-responsive and six as mechano-insensitive nociceptors according to their mechanical responsiveness and activity-dependent slowing of conduction velocity (latency increase of 0.5+/-1.1 vs. 7.1+/-2.0 ms for 20 pulses at 0.125 Hz). Two C-fibers were activated with a delay of several seconds following strong endogenous sympathetic bursts; they were also excited for about 3 min following the injection of norepinephrine (10 microl, 0.05%) into their innervation territory. In these two fibers, a prolonged activation by injection of low pH solution (phosphate buffer, pH 6.0, 10 microl) and sensitization of their heat response following prostaglandin E2 injection were recorded, evidencing their afferent nature. Moreover, their activity-dependent slowing was typical for mechano-insensitive nociceptors. We conclude that sensitized mechano-insensitive nociceptors can be activated by endogenously released catecholamines and thereby may contribute to sympathetically maintained pain. No evidence for ephaptic interaction between sympathetic efferent and nociceptive afferent fibers was found.

背景与目标： : 交感神经的维持性疼痛可以通过交感神经传出和传入伤害性纤维之间的触感相互作用来介导，也可以通过儿茶酚胺诱导的伤害性神经末梢的激活来介导。我们在此报告了一名患有交感持续疼痛的患者的C伤害感受器的单纤维记录，其中交感神经阻滞反复消除了双腿的持续疼痛。我们根据八种C纤维的机械响应性和与活动有关的传导速度减慢 (在0.125Hz下20个脉冲的0.5/-1.1与7.1/-2.0 ms的潜伏期增加)，将它们分类为机械敏感的伤害感受器。强烈的内源性交感神经爆发后，两根C纤维被激活，延迟数秒; 在将去甲肾上腺素 (10 microl，0.05%) 注射到其神经支配区域后，它们也被兴奋约3分钟。在这两种纤维中，记录了通过注射低pH溶液 (磷酸盐缓冲液，pH 6.0，10μl) 而延长的活化以及前列腺素E2注射后它们的热响应的敏化，证明了它们的传入性质。此外，对于机械不敏感的伤害感受器，它们的活性依赖性减慢是典型的。我们得出的结论是，内源性释放的儿茶酚胺可以激活敏感的机械不敏感伤害感受器，从而可能导致交感疼痛。没有发现交感传出和伤害性传入纤维之间的触觉相互作用的证据。

BACKGROUND & AIMS: AIM:To research possible associations between previous exposure to specific torture techniques and prevalent pain in the head and face, back, and feet. METHODS:221 refugees, 193 males and 28 females, previously exposed to torture in their home country, were subject to a clinical interview at a rehabilitation clinic for torture victims. The interview focused on exposure to torture and somatic symptoms prevalent at examination. RESULTS:The mean number of times imprisoned was 2.3; the mean number of months imprisoned was 19.7; the mean duration from initial imprisonment to final release was 3.7 years; and the mean duration from final release to preliminary interview was 8.4 years. The most frequent physical torture method reported was beating (92.3%) and the main mental torture method was deprivation (84.6%). Pain in the head and face was found to be strongly associated with torture against head and face (OR 3.89, 95% CI 1.49-10.20) and with the cumulative number of physical torture methods exposed to. Pain in the back was associated with sexual torture (OR 2.75, 95% CI 1.07-7.12). Besides beating of the lower extremities (OR 5.98, 95% CI 2.47-14.48), the strongest predictor for pain in the feet was general abuse of the whole body (OR 5.64, 95% CI 1.93-16.45). CONCLUSION:In spite of many factors being potentially co-responsible for prevalent pain, years after the torture took place it presents itself as strongly associated with specific loci of pain, with generalized effects, and with somatizing.

背景与目标：

BACKGROUND & AIMS: :Chronic pain may result from hyperexcitability following activation of spinal NMDA receptors. A naturally-derived mammalian peptide, histogranin, may possess NMDA antagonist activity. This study explored the possibility that stable analog [Ser1]Histogranin (SHG) could reduce chronic pain. Neuropathic pain was induced using the chronic constriction injury model (CCI). Intrathecal injection of SHG markedly attenuated the hyperalgesia and allodynia resulting from CCI, nearly normalizing responses. These results suggest that the natural peptide histogranin may be a novel adjunct in neuropathic pain management.

背景与目标： : 脊髓NMDA受体激活后过度兴奋可能导致慢性疼痛。天然衍生的哺乳动物肽组织蛋白可能具有NMDA拮抗剂活性。这项研究探讨了稳定的类似物 [Ser1] 组织蛋白 (SHG) 可以减轻慢性疼痛的可能性。使用慢性收缩损伤模型 (CCI) 诱发神经病理性疼痛。鞘内注射SHG可显着减轻由CCI引起的痛觉过敏和异常性疼痛，几乎使反应正常化。这些结果表明，天然肽组织粒蛋白可能是神经性疼痛管理的新型辅助手段。

BACKGROUND & AIMS: :Peripheral neuropathic pain is a unique form of chronic pain that afflicts up to 50% of persons with AIDS. The purpose of this pilot study was to examine the effects of ice massage to reduce neuropathic pain and improve sleep quality and to determine the feasibility of a larger study. A repeated measures design was used. The three treatments consisted of ice massage, dry-towel massage, and presence. Consecutive sampling was used to select 33 persons with AIDS who had neuropathic pain. Although the results of the study were negative, there was a decrease in pain intensity over time with both the ice massage and towel massage, suggesting that the intervention has some clinical benefit.

背景与目标： : 周围神经性疼痛是一种独特的慢性疼痛形式，困扰多达50% 的艾滋病患者。这项初步研究的目的是检查冰按摩减轻神经性疼痛和改善睡眠质量的效果，并确定进行更大规模研究的可行性。使用了重复测量设计。这三种治疗方法包括冰按摩，干毛巾按摩和在场。连续抽样选择33例患有神经性疼痛的艾滋病患者。尽管研究结果为阴性，但随着时间的推移，冰按摩和毛巾按摩的疼痛强度有所降低，这表明该干预措施具有一定的临床益处。

BACKGROUND & AIMS: CONTEXT:Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. OBJECTIVES:This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. METHODS:In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. RESULTS:The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. CONCLUSION:This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.

背景与目标：

BACKGROUND & AIMS: :The perception of visceral pain is a complex process involving the spinal cord and higher order brain structures. Increasing evidence implicates the gut microbiota as a key regulator of brain and behavior, yet it remains to be determined if gut bacteria play a role in visceral sensitivity. We used germ-free mice (GF) to assess visceral sensitivity, spinal cord gene expression and pain-related brain structures. GF mice displayed visceral hypersensitivity accompanied by increases in Toll-like receptor and cytokine gene expression in the spinal cord, which were normalized by postnatal colonization with microbiota from conventionally colonized (CC). In GF mice, the volumes of the anterior cingulate cortex (ACC) and periaqueductal grey, areas involved in pain processing, were decreased and enlarged, respectively, and dendritic changes in the ACC were evident. These findings indicate that the gut microbiota is required for the normal visceral pain sensation.

背景与目标： 内脏疼痛的感知是一个复杂的过程，涉及脊髓和高阶脑结构。越来越多的证据表明肠道菌群是大脑和行为的关键调节剂，但肠道细菌是否在内脏敏感性中起作用尚待确定。我们使用无菌小鼠 (GF) 评估内脏敏感性，脊髓基因表达和与疼痛相关的大脑结构。GF小鼠表现出内脏超敏反应，并伴有脊髓中Toll样受体和细胞因子基因表达的增加，这通过出生后用常规定植 (CC) 的微生物群定植而标准化。在GF小鼠中，前扣带回皮层 (ACC) 和导水管周围灰色 (涉及疼痛处理的区域) 的体积分别减少和扩大，并且ACC的树突状变化明显。这些发现表明，正常的内脏疼痛感需要肠道菌群。

BACKGROUND & AIMS: :The feasibility of using a subcutaneously implanted portal system attached to a conventional 16-gauge epidural catheter has been evaluated in 50 patients with sever pain associated with cancer. This technique allowed for the percutaneous epidural administration of morphine at 8-12-hourly intervals for pain control. The mean duration of implantation was 12 weeks and the longest period a portal remained in situ was 36 weeks. Five portals had to be removed for various reasons. The injection system has blocked on eight occasions due to catheter blockage (six times) and portal blockage (two occasions). These patients have continued to obtain excellent analgesia when either catheter or portal were replaced. In a cadaver, 300 injections were simulated using either 22-gauge Huber point needles or disposable needles (25 gauge) and the injectate examined by both light and scanning electron microscopy. Both needle types resulted in particulate contamination which was greater with the recommended Huber point needles.

背景与目标： : 已在50例与癌症相关的严重疼痛患者中评估了使用固定在常规16号硬膜外导管上的皮下植入门静脉系统的可行性。该技术允许以8-12小时的间隔经皮硬膜外施用吗啡以控制疼痛。植入的平均持续时间为12周，而原位保留的最长时间为36周。由于各种原因，必须删除五个门户。由于导管阻塞 (六次) 和门静脉阻塞 (两次)，注射系统有八次阻塞。当更换导管或门静脉时，这些患者继续获得出色的镇痛效果。在尸体中，使用22号Huber点针或一次性针 (25号) 模拟300注射，并通过光学和扫描电子显微镜检查注射物。两种类型的针头都会导致颗粒污染，推荐的Huber点针头会更大。

BACKGROUND & AIMS: :Neuropathic pain is a result of complex interactions between peripheral and central mechanisms with multiple potential therapeutic targets. However, the complexity of these mechanisms and relative youth of translational pain research, which is in its infancy, have prevented translation of successful basic bench research to human therapy. Most of the clinically available neuropathic pain treatments are borrowed from other therapeutic areas, such as antidepressants and antiepileptics, or involve application of older therapy, such as opioids. Exceptions are ziconotide, tapentadol, and the high-concentration capsaicin patch. Similar to all other analgesic agents, these provide only partial pain relief in subsets of patients. The standard of care for patients with chronic neuropathic pain is multimodal and multidisciplinary. For most patients to achieve and maintain satisfactory pain relief a combination of therapeutic agents is necessary, providing the empiric basis for rational polypharmacy, which has become a standard approach as well.

背景与目标： 神经性疼痛是周围和中枢机制与多个潜在治疗靶点之间复杂相互作用的结果。然而，这些机制的复杂性以及尚处于起步阶段的转化疼痛研究的相对年轻，阻碍了成功的基础研究转化为人类治疗。大多数临床上可用的神经性疼痛治疗方法都是从其他治疗领域借来的，例如抗抑郁药和抗癫痫药，或者涉及应用较旧的治疗方法，例如阿片类药物。齐康宁、他喷他多和高浓度辣椒素贴剂是例外。与所有其他镇痛剂相似，这些镇痛剂仅可部分缓解患者的疼痛。慢性神经性疼痛患者的护理标准是多模式和多学科。为了使大多数患者达到并保持令人满意的疼痛缓解，必须结合治疗剂，为合理的多药治疗提供经验基础，这也已成为一种标准方法。

BACKGROUND & AIMS: OBJECTIVE:Anticipated pain with intrauterine device (IUD) insertion may be a barrier to widespread use. Our objective was to evaluate the efficacy of intracervical 2% lidocaine gel for pain relief with IUD insertion. STUDY DESIGN:We performed a double-blind, randomized controlled trial of women undergoing IUD insertion. Participants were randomly assigned to 2% lidocaine or placebo gel. Study gel (3 mL) was placed 3 minutes prior to IUD insertion. Pain scores were measured at various time points using a 10-point visual analog scale. RESULTS:Of the 200 participants randomized, 199 completed the study. Pain scores among lidocaine and placebo arms were similar at tenaculum placement (lidocaine and placebo: median, 4; range, 0-10; P = .15) and with insertion (lidocaine: median, 5; range, 1-10; placebo: median, 6; range, 0-10; P = .16). These results did not differ by parity. CONCLUSION:Topical or intracervical 2% lidocaine gel prior to IUD insertion does not decrease pain scores.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Many brain areas participate to supraspinal control of nociception. In these regions, few studies have investigated the role of glial cells in supraspinal plasticity and the effect of 7-day intrathecal nerve growth factor-like (BB14®, Blueprint Biotech, Milano, Italy) treatment. METHODS:In male Sprague-Dawley rats, we evaluated by immunohistochemistry the morphological and molecular rearrangement of neuroglial network occurring in several supraspinal brain regions involved in pain processing following spared nerve injury (SNI) of the sciatic nerve. In particular, the medial prefrontal cortex, the amygdala (Amy), the nucleus accumbens (Acb), the thalamus and the periaqueductal gray were analysed. RESULTS:Despite the modifications occurring in the dorsal horn of spinal cord following SNI, no significant changes in the Iba1 and glial fibrillary acidic protein (GFAP) expression were detected in all the analysed supraspinal regions, except for the Amy, showing a remarkable GFAP increase. Interestingly, neuropathic rats also displayed a significant increase of glial transporters (GTs) in all the supraspinal regions. Finally, the analysis of vesicular glutamate transporter 1 (vGLUT1) and vesicular gamma-aminobutyric acid (GABA) transporter (vGAT) expression revealed a significant enhancement of glutamatergic/GABAergic ratio in all selected brain regions of SNI animals, except for Acb. Both glial activation in the Amy and alteration of GTs and vGLUT/vGAT levels observed in neuropathic animals were largely reversed by BB14® treatment. CONCLUSIONS:All together, these data strengthen the role of supraspinal neuroglial network plasticity in the establishment of neuropathic pain syndrome. The hallmark is represented by the divergence between glial reaction confined to Amy and the widespread changes in the GT distribution and glutamate/GABA ratio detected in the other supraspinal region.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:Although there is evidence for a beneficial effect of increased quadriceps strength on knee symptoms, the effect on knee structure is unclear. We undertook this study to examine the relationship between change in vastus medialis cross-sectional area (CSA) and knee pain, tibial cartilage volume, and risk of knee replacement in subjects with symptomatic knee osteoarthritis (OA). METHODS:One hundred seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of the knee at baseline and at 2 and 4.5 years. Vastus medialis CSA was measured at baseline and at 2 years. Tibial cartilage volume was measured at baseline and at 2 and 4.5 years. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index at baseline and at 2 years. The frequency of knee joint replacement over 4 years was determined. Regression coefficients (B) and odds ratios were determined along with 95% confidence intervals (95% CIs). RESULTS:After adjusting for confounders, baseline vastus medialis CSA was inversely associated with current knee pain (r = -0.16, P = 0.04) and with medial tibial cartilage volume loss from baseline to 2 years (B coefficient -10.9 [95% CI -19.5, -2.3]), but not with baseline tibial cartilage volume. In addition, an increase in vastus medialis CSA from baseline to 2 years was associated with reduced knee pain over the same time period (r = 0.24, P = 0.007), reduced medial tibial cartilage loss from 2 to 4.5 years (B coefficient -16.8 [95% CI -28.9, -4.6]), and reduced risk of knee replacement over 4 years (odds ratio 0.61 [95% CI 0.40, 0.94]). CONCLUSION:In a population of patients with symptomatic knee OA, increased vastus medialis size was associated with reduced knee pain and beneficial structural changes at the knee, suggesting that management of knee pain and optimizing vastus medialis size are important in reducing OA progression and subsequent knee replacement.

背景与目标：