Reducing joint destruction due to septic arthrosis using an adenosine2A receptor agonist.

We assessed the efficacy of a new adenosine A2A agonist ATL146e, a potent inhibitor of white blood cell chemotaxis, to reduce cartilage damage in the treatment of septic arthrosis. A live septic arthrosis model was created using Staphylococcus aureus in rabbit knees. Animals were divided into five treatment groups: (1) untreated infected control, (2) antibiotics control, and antibiotics plus ATL146e for (3) 24, (4) 48, or (5) 72 h and assessed at 1, 4, and 7 days. Knees in all ATL146e treated animals exhibited no detectable effusion, and histologic examination revealed near normal cartilage and diminished synovial inflammatory response. Synovial WBC counts decreased with the addition of ATL146e when compared to infected and antibiotic controls. Histologic grading of osteochondral specimens demonstrated improved scores for animals treated with ATL146e compared to infected (p<0.00004) and antibiotics controls (p<0.05). Analysis of glycosaminoglycan content revealed significantly decreased loss of articular cartilage following infection in the ATL146e groups when compared to infected (p<0.03) and antibiotics controls (p<0.05). Addition of an adenosine A2A agonist to antibiotic therapy decreases joint inflammation and articular cartilage destruction without compromising bacterial clearance in rabbit knees following intraarticular bacterial infection. The use of adenosine agonists selective to the A2A receptor to augment conventional treatment of joint sepsis may be chondroprotective and ultimately help prevent arthrosis.     

Adenosine A2A agonist reduces paralysis after spinal cord ischemia: correlation with A2A receptor expression on motor neurons

BACKGROUND: The adenosine A2A agonist ATL-146e ameliorates reperfusion inflammation, reducing subsequent paralysis and neuronal apoptosis after spinal cord ischemia. We hypothesized that neuroprotection with ATL-146e involves inducible neuronal adenosine A2A receptors (A2A-R) that are upregulated after ischemia. METHODS: Eighteen rabbits underwent laparotomy, and 14 sustained spinal cord ischemia from cross-clamping the infrarenal aorta for 45 minutes. One group (ischemia-reperfusion [I/R] + ATL) received ATL-146e intravenously for 3 hours during spinal cord reperfusion. A second group (I/R) received equivolume intravenous saline solution for 3 hours and served as an ischemic control, and a third group (Sham) underwent sham laparotomy. At 48 hours, all subjects were assessed for motor impairment using the Tarlov scoring system (0 to 5). Lumbar spinal cord sections were immunolabeled for A2A-R and graded in a blinded fashion using light microscopy. RESULTS: There was a significant improvement in Tarlov scores in I/R + ATL animals compared with the I/R group. Sham-operated animals demonstrated no A2A-R immunoreactivity. There was a dramatic increase in A2A-R immunoreactivity in neurons of lumbar spinal cord sections from I/R compared with I/R + ATL and sham-operated animals. CONCLUSIONS: Reduction in paralysis in animals receiving ATL-146e correlates with the new finding of A2A-R expression on lumbar spinal cord motor neurons after ischemia. Adenosine A2A agonists may exert neuroprotective effects by binding to inducible neuronal A2A-R that are upregulated during spinal cord reperfusion, and reduced in response to administration of an A2A-R-specific agonist.     

Adenosine A2A analogue reduces long-term neurologic injury after blunt spinal trauma

BACKGROUND: ATL-146e is an adenosine A(2A) agonist that has recently been demonstrated to improve neurological outcome in spinal cord injury in animals. In the current study, we extended the treatment paradigm and tested neurobehavioral functioning out to 1 week after injury to assess if early neurological improvement is sustained long term by an adenosine analogue. MATERIALS AND METHODS: New Zealand White rabbits (3.0-3.5 kg) sustained mid-thoracic blunt spinal cord injury using a weight-drop model (10 g weight dropped from 6 cm directly onto dura). Animals received either (1) 3 h iv infusion of saline carrier (Trauma, N = 21); (2) 3 h iv infusion of 0.06 microg/kg/min ATL-146e followed by intraperitoneal bolus of 10.8 microg/kg ATL-146e at 3 h postinjury (ATL, N = 14); or (3) 3 h iv infusion of 0.06 microg/kg/min ATL-146e followed by intraperitoneal bolus injection of 10.8 microg/kg ATL-146e at 3, 12, and 24 h postinjury (ATL-PLUS, N = 11). Fourteen animals underwent sham injury. Hemodynamic parameters were monitored and hind limb motor functioning was assessed by Tarlov scores (0 = paralyzed to 5 = normal hop) for 7 days after injury. RESULTS: ATL-146e significantly improved Tarlov scores of ATL-146e groups compared with saline-treated controls (P < 0.01 12, 24, 36, and 48 h). Control animals, severely neurologically impaired at 48 h (Tarlov 1.61 +/- 0.35), were euthanized early due to ethical concerns, thus not permitting later statistical comparisons. Early neurological improvements in both ATL-146e-treated groups were sustained longer term (7 day mean Tarlov, SHAM 4.9 +/- 0.30, ATL 5.0 +/- 0, ATL-PLUS 4.25 +/- 0.31). CONCLUSIONS: ATL-146e given immediately after blunt spinal cord trauma significantly improves neurological outcome, which is sustained through 7 days. Early adenosine A2A receptor agonism may be critical since additional IP administration afforded no further neurological improvement. The current data further support the potential clinical utility of adenosine A(2A) agonists in the treatment of spinal cord injury.     

Utility of Diagnostic Markers in Late Periprosthetic Joint Infection Workup for Total Knee Arthroplasty Patients Who Received Antibiotics 48 Hours Before Aspiration

BackgroundDiagnosing periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) remains challenging despite recent advancements in testing and evolving criteria over the last decade. Moreover, the effects of antibiotic use on diagnostic markers are not fully understood. Thus, this study sought to determine the influence of antibiotic use within 48 hours before knee aspiration on synovial and serum laboratory values for suspected late PJI.MethodsPatients who underwent a TKA and subsequent knee arthrocentesis for PJI workup at least 6 weeks after their index arthroplasty were reviewed across a single healthcare system from 2013 to 2020. Median synovial white blood cell (WBC) count, synovial polymorphonuclear (PMN) percentage, serum erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), and serum WBC count were compared between immediate antibiotic and nonantibiotic PJI groups. Receiver operating characteristic (ROC) curves and Youden’s index were used to determine test performance and diagnostic cutoffs for the immediate antibiotics group.ResultsThe immediate antibiotics group had significantly more culture-negative PJIs than the no antibiotics group (38.1 versus 16.2%, P = .0124). Synovial WBC count demonstrated excellent discriminatory ability for late PJI in the immediate antibiotics group (area under curve, AUC = 0.97), followed by synovial PMN percentage (AUC = 0.88), serum CRP (AUC = 0.86), and serum ESR (AUC = 0.82).ConclusionAntibiotic use immediately preceding knee aspiration should not preclude the utility of synovial and serum lab values for the diagnosis of late PJI. Instead, these markers should be considered thoroughly during infection workup considering the high rate of culture-negative PJI in these patients.Level of EvidenceLevel III, retrospective comparative study.     

Anatomy of the distal knee joint and pyarthrosis following external fixation.

OBJECTIVE: To determine the limits of the distal synovial reflection of the human knee joint. SPECIMENS: Six paired knees studied by magnetic resonance imaging (MRI), fluoroscopic arthrography, and gross dissection. The right knees of five patients with chronic idiopathic knee effusions were studied by MRI. Cadaveric knees were injected with saline prior to MRI. The joint capsules were dissected to visualize local anatomy and check for capsular tears. In each modality (MRI, fluoroscopy, and dissection), the most distal extent of knee synovial fluid was measured. RESULTS: The right versus left agreement for paired specimens was generally two to three millimeters. Some specimens showed asymmetric capsular reflection. Medial fluid was identified at distances greater than forty-nine millimeters from the subchondral bone in seven knees and less than fifteen millimeters in four knees (range 0 to 70 millimeters, mean thirty-three millimeters). Laterally, the range was ten to thirty-five millimeters (mean twenty-three millimeters). In six of the twelve cadaveric specimens, there was evidence of a communication between the knee joint and the proximal tibiofibularjoint. In the knees of volunteers, joint fluid tracked medially to a range of ten to fifty millimeters and laterally to a range of six to fifteen millimeters, with means of twenty-six and eleven millimeters, respectively. The knees of the volunteers had no evidence of tibiofibular joint communication with the knee. CONCLUSION: Insertion of external fixation pins within sixty to seventy millimeters of the proximal articular surface of the tibia is associated with a high probability of synovial penetration and possibly provides a conduit for the introduction of bacteria, which may be etiologic in iatrogenic pyarthrosis.     

The evolution of ischemic spinal cord injury in function, cytoarchitecture, and inflammation and the effects of adenosine A2A receptor activation

OBJECTIVE: Spinal cord ischemia/reperfusion injury involves multiple factors that may be modulated by adenosine A 2A receptor activation. This study defines injury progression in terms of function, cytoarchitecture, and inflammation and assesses whether adenosine A 2A receptor activation by ATL-146e limits injury progression. METHODS: Mature swine were divided into 3 groups: sham thoracotomy, IR (30 minutes of ischemia followed by reperfusion), and ATL (ischemia/reperfusion with ATL-146e administration for the first 3 hours of reperfusion). Subgroups were killed at 0, 3, 6, 12, 24, and 48 hours after reperfusion. Function was followed up with Tarlov scores. Spinal cord tissue was evaluated for neuronal viability, microtubule-associated protein-2 immunohistochemistry, and neutrophil sequestration (myeloperoxidase assay). Spinal cord tissue, cerebrospinal fluid, and serum were evaluated for tumor necrosis factor-alpha by enzyme-linked immunosorbent assay. RESULTS: Function was significantly impaired at 24, 36, and 48 hours in the IR group compared with the sham and ATL groups ( P < .05). Neuronal viability and microtubule-associated protein-2 staining were significantly preserved in the sham and ATL groups compared with the IR group at 24 and 48 hours ( P < .05). Spinal cord myeloperoxidase levels were significantly higher in the IR group than in the sham and ATL groups at 24 and 48 hours. Although negligible in serum and cerebrospinal fluid, tumor necrosis factor-alpha levels in the spinal cord peaked significantly higher in the IR group compared with the sham and ATL groups at 6 and 24 hours ( P < .05). CONCLUSIONS: Spinal cord ischemia/reperfusion induced changes in neutrophil sequestration, microtubule-associated protein-2 expression, and neuronal viability within 24 hours of reperfusion. Spinal cord tumor necrosis factor-alpha increased significantly by 6 to 12 hours after reperfusion. Adenosine A 2A receptor activation attenuates spinal cord inflammation, which may be critical for the preservation of neuronal function and cytoarchitecture after ischemia/reperfusion.     

Adenosine A2A agonist reduces paralysis after spinal cord ischemia: correlation with A2A receptor expression on motor neurons

Background. The adenosine A_2A agonist ATL-146e ameliorates reperfusion inflammation, reducing subsequent paralysis and neuronal apoptosis after spinal cord ischemia. We hypothesized that neuroprotection with ATL-146e involves inducible neuronal adenosine A_2A receptors (A_2A-R) that are upregulated after ischemia.Methods. Eighteen rabbits underwent laparotomy, and 14 sustained spinal cord ischemia from cross-clamping the infrarenal aorta for 45 minutes. One group (ischemia-reperfusion [I/R] + ATL) received ATL-146e intravenously for 3 hours during spinal cord reperfusion. A second group (I/R) received equivolume intravenous saline solution for 3 hours and served as an ischemic control, and a third group (Sham) underwent sham laparotomy. At 48 hours, all subjects were assessed for motor impairment using the Tarlov scoring system (0 to 5). Lumbar spinal cord sections were immunolabeled for A_2A-R and graded in a blinded fashion using light microscopy.Results. There was a significant improvement in Tarlov scores in I/R + ATL animals compared with the I/R group. Sham-operated animals demonstrated no A_2A-R immunoreactivity. There was a dramatic increase in A_2A-R immunoreactivity in neurons of lumbar spinal cord sections from I/R compared with I/R + ATL and sham-operated animals.Conclusions. Reduction in paralysis in animals receiving ATL-146e correlates with the new finding of A_2A-R expression on lumbar spinal cord motor neurons after ischemia. Adenosine A_2A agonists may exert neuroprotective effects by binding to inducible neuronal A_2A-R that are upregulated during spinal cord reperfusion, and reduced in response to administration of an A_2A-R-specific agonist.     

What is the Role of Serological Testing Between Stages of Two-stage Reconstruction of the Infected Prosthetic Knee?

Background  

Two-stage exchange arthroplasty is the gold standard for treatment of infected TKA. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and synovial fluid white blood cell (WBC) count with differential are often used to determine treatment response; however, it is unclear whether these tests can answer the critical question of whether joint sepsis has been controlled between stages and if reimplantation is indicated.     

关节镜下清创及灌洗引流治疗急性化脓性膝关节炎

目的探讨关节镜下清创、持续闭式灌洗引流治疗急性化脓性膝关节炎的临床效果,研究其相关指标,提高急性化脓性膝关节炎的诊治水平。 方法2006年10月至2016年10月,盐城市第一人民医院骨科共对43例(43膝)急性化脓性膝关节炎患者进行了关节镜下清创、持续闭式灌洗引流治疗。纳入标准为关节疼痛、积液、体温高于38℃;排除标准为关节液白细胞少于<11×10⁸个/L。男性,22例;女性,21例。年龄14～71岁,平均(43±12)岁。研究其术前及术后的相关指标,包括：体温、膝关节疼痛、活动度、C反应蛋白(CRP)、血沉(ESR)、降钙素原(PCT),关节液镜检,关节液一般细菌培养＋药敏试验,组织培养。末次随访采用美国膝关节协会评分(KSS)进行功能评分。 结果术后随访平均(22±10)个月,末次随访时KSS功能评分平均(85±11)分,治疗总有效率为95.3%。术后患者体温在术后3～5 d均恢复正常,膝关节疼痛明显减轻,活动度明显改善,CRP、ESR、PCT明显下降。术后第3、5、7天关节液细菌培养共3次,均为无菌生长。 结论关节镜下清创、持续闭式灌洗引流治疗膝关节腔感染,病原菌消失快,感染控制可靠,抗生素使用时间短,疗效满意。     

Adenosine A2A receptor activation reduces inflammation and preserves pulmonary function in an in vivo model of lung transplantation

BACKGROUND: Reperfusion injury continues to significantly affect patients undergoing lung transplantation. Isolated lung models have demonstrated that adenosine A 2A receptor activation preserves function while decreasing inflammation. We hypothesized that adenosine A 2A receptor activation by ATL-146e during the initial reperfusion period preserves pulmonary function and attenuates inflammation in a porcine model of lung transplantation. METHODS: Mature pig lungs preserved with Viaspan (Barr Laboratories, Pomona, NY) underwent 6 hours of cold ischemia before transplantation and 4 hours of reperfusion. Animals were treated with (ATL group, n = 7) and without (IR group, n = 7) ATL-146e (0.05 microg kg -1 . min -1 ATL-146e administered intravenously for 3 hours). With occlusion of the opposite pulmonary artery, the animal was maintained for the final 30 minutes on the allograft alone. Recipient lung physiology was monitored before tissue evaluation of pulmonary edema (wet-to-dry weight ratio), myeloperoxidase assay, and tissue tumor necrosis factor alpha by means of enzyme-linked immunosorbent assay. RESULTS: When the ATL group was compared with the IR group, the ATL group had better partial pressure of carbon dioxide (43.8 +/- 4.1 vs 68.9 +/- 6.3 mm Hg, P < .01) and partial pressure of oxygen (272.3 +/- 132.7 vs 100.1 +/- 21.4 mm Hg, P < .01). ATL-146e-treated animals exhibited lower pulmonary artery pressures (33.6 +/- 2.1 vs 47.9 +/- 3.5 mm Hg, P < .01) and mean airway pressures (16.25 +/- 0.08 vs 16.64 +/- 0.15 mm Hg, P = .04). ATL-146e-treated lungs had lower wet-to-dry ratios (5.9 +/- 0.39 vs 7.3 +/- 0.38, P < .02), lower myeloperoxidase levels (2.9 x 10 -5 +/- 1.2 x 10 -5 vs 1.3 x 10 -4 +/- 4.0 x 10 -5 DeltaOD mg -1 . min -1 , P = .03), and a trend toward decreased lung tumor necrosis factor alpha levels (57 +/- 12 vs 96 +/- 15 pg/mL, P = .06). The ATL group demonstrated significantly less inflammation on histology. CONCLUSION: Adenosine A 2A activation during early reperfusion attenuated lung inflammation and preserved pulmonary function in this model of lung transplantation. ATL-146e and similar compounds could play a significant role in improving outcomes of pulmonary transplantation.     

Periprosthetic joint infection diagnosis: a complete understanding of white blood cell count and differential

Recent research has raised doubts regarding the utility of serum white blood cell count (WBC) for diagnosis of periprosthetic joint infection (PJI). As synovial WBC and neutrophil (PMN) percentage have been adopted as accurate markers of PJI, this study investigated the correlation of WBC in serum versus joint fluid and diagnostic value of all WBC levels for failed arthroplasty patients. 153 patients (73 PJI) undergoing revision knee arthroplasty were identified. Weak correlations between joint fluid and serum for WBC (R = 0.19), PMN count (R = 0.31), and lymphocyte count (R = -0.22) were observed. Diagnostic accuracy of PMN (93%) and WBC (93%) synovial count relative to serum was similar to synovial WBC (93%) and PMN% (95%) alone. Serum WBC analysis does little to improve the accurate diagnosis of PJI.     

Assessment of the efficacy of joint lavage in rabbits with osteoarthritis of the Knee

We investigated the efficacy of joint lavage to alter the progression of the disease process in a rabbit model of knee OA in varying stages of the disease. Thirty‐three white rabbits were operated to induce OA, and then the rabbits were divided into three groups (10 in each) randomly. In group 1, on week 1 after the operation, joint lavage was performed on both knees in five rabbits as treatment group, and the other five rabbits were used as control group received no intervention. By the end of week 2 after operation, the rabbits were sacrificed. In group 2, five received joint lavage on week 2, and all were sacrificed on week 3. In group3, five received joint lavage on week 3, and all were sacrificed on week 4. In each group, histological evaluation showed that both the breakdown of articular cartilage and the inflammation of synovium were less in the knees treated with joint lavage than that in the control knees. The enzyme‐linked immunosorbent assay revealed that the expression of IL‐1β and TNF‐α in synovial fluid decreased significantly in the treatment group. Our findings suggested that joint lavage was beneficial for OA at different phases of OA in rabbit models. Joint lavage may be a beneficial method for the treatment of OA clinically. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:91–96, 2009     

Functional and cytoarchitectural spinal cord protection by ATL-146e after ischemia/reperfusion is mediated by adenosine receptor agonism

BACKGROUND: ATL-146e protects the spinal cord from ischemia/reperfusion injury, presumably via adenosine A(2A) receptor activation, but this relationship remains unproven. We hypothesized that spinal cord functional and cytoarchitectural preservation from ATL-146e would be lost with simultaneous administration of the specific adenosine A(2A) antagonist ZM241385 (ZM), thus proving that adenosine A(2A) receptor activation is responsible for the protective effects of this compound. METHODS: New Zealand White rabbits underwent 45 minutes of infrarenal aortic cross-clamping. Groups (n = 10) included sham, ischemia, ischemia plus ATL-146e (ATL-146E), ischemia plus ZM, or ischemia with both compounds (agonist-antagonist). Tarlov scores were recorded every 12 hours. After 48 hours, the spinal cord was fixed for histology and microtubule-associated protein 2 immunohistochemistry. RESULTS: Tarlov scores at 48 hours were significantly better in the sham and ATL-146E groups (5.0 and 3.9, respectively) compared with the other three groups (all < or =1.3; P < .001). On hematoxylin and eosin, neuronal viability was higher in the sham, ATL-146E, and agonist-antagonist groups compared with the control and ZM groups (P < .05). Microtubule-associated protein 2 expression was preserved in the sham and ATL-146E groups but was lost in the ATL + ZM, ZM241385, and control groups. CONCLUSIONS: ATL-146e preserves the spinal cord in terms of both cytoarchitecture and function after reperfusion of the ischemic spinal cord, but this preservation is not completely blocked by competitive adenosine A(2A) receptor antagonism. Although ATL-146e does seem to partially function through activation of the adenosine A(2A) receptor, the neuroprotective mechanism may not be limited to this particular receptor.     

Synovial Cell Count Before Reimplantation Can Predict the Outcome of Patients with Periprosthetic Knee Infections Undergoing Two-stage Exchange

BackgroundAlthough synovial fluid can be used to diagnose periprosthetic joint infections (PJI) effectively, only the cutoff values adopted at the time of PJI diagnosis have been standardized, and few data are currently available about effectiveness of synovial fluid examination before definitive reimplantation.Questions/purposesWe asked: (1) What are the most appropriate thresholds for synovial fluid leukocyte counts (WBC) and neutrophil percentage (PMN percentage) in a patient group undergoing definitive reimplantation after an uninterrupted course of antibiotic therapy for chronic PJI? (2) What is the predictive value of our synovial WBC and PMN percentage threshold compared with previously proposed thresholds?MethodsIn all, 101 patients with PJI were evaluated for inclusion from January 2016 to December 2018. Nineteen percent (19 of 101) of patients were excluded because of the presence of a chronic inflammatory disease, acute/late hematogenous infection, low amount of synovial fluid for laboratory investigations or infection persistence after spacer placement, and adequate antibiotic therapy. Finally, 81% (82 of 101) of patients with a median (range) age of 74 years (48 to 92) undergoing two-stage revision for chronic TKA infection, who were followed up at our institution for a period 96 weeks or more, were included in this study. The patients did not discontinue antibiotic treatment before reimplantation and were treated for 15 days after reimplantation if intraoperative cultures were negative. No patient remained on suppressive treatment after reimplantation. Synovial fluid was aspirated aseptically with a knee spacer in place to evaluate the cell counts before reimplantation. Thirteen percent (11 of 82) of patients had persistent or recurrent infection, defined as continually elevated erythrocyte sedimentation rate or C-reactive protein levels coupled with local signs and symptoms or positive cultures. The synovial fluid WBC counts and PMN percentage from the 11 patients with persistent or recurrent PJI were compared with the 71 patients who were believed to be free of PJI. Receiver operating characteristic (ROC) curve analyses assessed the predictive value of the parameters, and the areas under the curves (AUCs) were evaluated. The sensitivities, specificities, and positive and negative predictive values were determined for the WBC count and PMN percentage. Patients with persistent or recurrent infection had higher median WBC counts (471 cells/µL versus 1344 cells/µL; p < 0.001) and PMN percentage (36% versus 61%; p < 0.001) than did patients believed to be free of PJI.ResultsROC curve analysis identified the best threshold values to be a WBC count of 934 cells/µL or more (sensitivity 0.82 [95% CI 0.71 to 0.89], specificity 0.82 [95% CI 0.71 to 0.89]) as well as a PMN percentage of at least 52% (sensitivity 0.82 [95% CI 0.71 to 0.89] and specificity 0.78 [95% CI 0.67 to 0.86]. We found no difference between the AUCs for the WBC count and the PMN percentage (0.87 [95% CI 0.79 to 0.96] versus 0.84 [95% CI 0.73 to 0.95]. Comparing the sensitivities and specificities of the synovial fluid WBC count and PMN percentage proposed by other authors, we find that a PMN percentage more than 52% showed better predictive value than previously reported.ConclusionBased on our findings, we believe that patients with WBC counts of at least 934 and PMN percentage of 52% or more should not undergo reimplantation but rather a repeat debridement, as their risk of persistent or recurrent PJI appears prohibitively high. The accuracy of the proposed cutoffs is better than previously reported.Level of EvidenceLevel III, diagnostic study.     

兔膝关节置换假体感染模型的建立

目的 制作兔膝关节置换假体感染模型,为人工关节假体感染研究提供依据.方法 成年新西兰大白兔32只,雌雄不限,体重2.5～3.5 k,平均3.0 kg.将采用超高分子量聚乙烯(UHMWPE)制成的兔膝关节且垒骨假体植入兔膝关节.32只动物随机分为四组,关节置换术后1周分别向膝关节内注入无菌生理盐水、1×10~4 CFU、1×10~6 CFU和1×10~8 CFU的ATCC35984葡萄球菌菌液,模拟膝关节置换假体感染.1 周后取材,进行感染率和炎症程度评定、影像学和病理学检查、细菌学评定.结果 接种1×10~6 CFU的细菌足以致所有动物关节感染,超过此剂量则会引起败血症,细菌接种量在0～1×10~8 CFU时感染率和接种细菌量呈正相关(R~2=0.9939).大体观察感染膝关节充满脓液,关节滑膜红肿.激光共聚焦显微镜观察:假体表面黏附大量细菌,并有片状胞外黏质物.病理学检查为急性炎症反应.细菌定量分析发现关节液内细菌量明显高于假体表面和组织内细菌量.结论 制作的兔膝关节置换假体感染模型较好地模拟了临床膝关节感染情况,是一种较为成功的膝关节置换假体感染模型,可用于人工关节假体感染预防、诊断和治疗的研究.     

关节液分析对诊断假体周围感染价值的探讨

背景:假体周围感染(PJI)是人工关节置换术后最为严重的并发症之一.诊断PJI的各项实验室检查都存在一定的优劣性.目的:探讨血清C反应蛋白(CRP)、红细胞沉降率(ESR)、关节液白细胞计数及白细胞分类对PJI的诊断效力.方法:回顾性分析2017年1月至2019年12月接受人工髋、膝关节翻修术230例患者的临床资料,包...     

Increased Synovial Inflammatory Markers in Aseptic Total Hip Arthroplasty Dislocation

BackgroundIn cases of total hip arthroplasty (THA) dislocation, a synovial fluid aspiration is often performed to evaluate for periprosthetic joint infection (PJI). It is currently unclear how aseptic dislocation of a THA influences synovial fluid white blood cell (WBC) count and polymorphonuclear percentage (PMN%). The primary aim of this study is to investigate the influence of THA dislocation on synovial WBC count and PMN%.MethodsTwenty-eight patients who underwent a synovial aspiration of a THA between 2014 and 2019 were identified and enrolled in our case-control study. Patients with an aseptic THA dislocation and synovial hip aspiration were matched against patients without dislocation, patients undergoing hip aspiration before aseptic THA revision surgery, and patients undergoing hip aspiration before septic THA revision surgery.ResultsSynovial WBC count was significantly increased in the dislocation vs aseptic THA revision group (P = .015), as well as between the septic revision group vs dislocation and aseptic THA revision group (both P < .001). The PMN% did not differ significantly between the dislocation and aseptic revision groups (P = .294). Mean C-reactive protein values were 12.4 ± 14.9 mg/dL in THA dislocation, 24.1 ± 37.7 mg/dL in THA without infection compared to 85.7 ± 84.9 mg/dL in THA infection group (P < .001).ConclusionThis study shows that THA dislocation has a significant impact on synovial WBC count in joint aspiration. Our data suggest that in the setting of THA dislocation, synovial WBC and PMN% may not be the best method to evaluate for PJI. Further research should be performed to establish new thresholds for these synovial inflammatory markers in the setting of THA dislocation and PJI.Level of evidenceLevel III; retrospective trial.     

Synovial fluid leukocyte cell count before versus after administration of antibiotics in patients with septic arthritis of a native joint

BackgroundAntibiotics have been shown to affect the accuracy of cultures; so antibiotics are held prior to obtaining cultures intra-operatively. No study has evaluated the effects of antibiotics on synovial fluid leukocyte cell count. The purpose of the current study is to compare the leukocyte cell count of native joints with septic arthritis when antibiotics have been given before aspiration and when no antibiotics have been given prior to aspiration.MethodsThis study was performed at a community hospital and a level 1 urban trauma hospital after IRB approval from both institutions from July 2007 to July 2017. Inclusion criteria comprised of a diagnosis of septic arthritis with positive cultures and a recorded arthrocentesis with cell count performed. Patients with septic arthritis were identified using ICD-9 codes 711.00–711.99 and ICD-10 codes M00 – M02. A retrospective chart review was performed and data was collected. Patients were placed into one of two groups. Group 1 received no antibiotics for two weeks prior to arthrocentesis, group 2 received antibiotics within 24 h prior to arthrocentesis. Demographic information, cell count number and differential, and blood lab values were collected. Timing data was also collected on timing of admission, antibiotics, joint irrigation, and discharge from the inpatient setting.ResultsThere were 81 patients meeting final inclusion criteria. The average cell count for the group which received antibiotics (n = 30) was 40,408 ± 29,433 while the average cell count for the group receiving no antibiotics (n = 51) was 93,824 ± 73,875 (p < .0001). The average length of stay was not significantly different between the antibiotic group versus no antibiotic group (14.0 days vs 12.1 days p = .4). The time from admission to arthrocentesis and admission to washout was longer for the antibiotic group versus no antibiotic group (p = .004 and p = .002, respectively).ConclusionWhen antibiotics are given prior to arthrocentesis of a septic joint, there is an associated lower synovial fluid leukocyte count compared to when no antibiotics are given prior.Level of evidenceLevel III.     

Adenosine A2A analogue ATL-146e reduces systemic tumor necrosing factor-alpha and spinal cord capillary platelet-endothelial cell adhesion molecule-1 expression after spinal cord ischemia

OBJECTIVE: Inflammation is likely a major contributor to spinal cord reperfusion injury after aortic reconstruction. Systemic 4-(3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl)-cyclohexanecarboxylic acid methyl ester (ATL-146e), a selective adenosine A(2A) agonist, has been shown to reduce paralysis after spinal cord ischemia. We hypothesized that ATL-146e reduces cytokine production during spinal cord reperfusion, curtailing inflammation and decreasing spinal cord capillary platelet-endothelial cell adhesion molecule-1 (PECAM-1) expression. Study design: New Zealand White rabbits sustained spinal cord ischemia with 45-minute cross-clamping of the infrarenal aorta. One group of animals received intravenous ATL-146e at 0.06 microg/kg/min for 3 hours during reperfusion, beginning after 30 minutes of ischemia. A second group received saline solution vehicle alone for 3 hours, serving as an ischemic control. A third group served as sham-operated animals, undergoing laparotomy with anesthesia. Serum was assayed with enzyme-linked immunosorbent assay for tumor necrosing factor-alpha (TNF-alpha). Animals were allowed to recover for 48 hours and were evaluated for hind-limb motor function with the Tarlov (0 to 5) scoring system. At necropsy, animals from each group yielded spinal cords for immunohistochemical staining for PECAM-1. Data are expressed as mean +/- standard error of the mean, with statistical analysis with Student t test and Kruskal-Wallis nonparametric test. RESULTS: Markedly improved Tarlov scores were seen in rabbits with ATL-146e (P <.001) during spinal cord reperfusion as compared with ischemic control animals. A significant reduction was found in TNF-alpha in the sera of rabbits with ATL-146e infusion (P <.01) as compared with ischemic control animals. Significantly reduced endothelial PECAM-1 staining intensity (P <.05) was seen in microscopic spinal cord sections from rabbits with ATL-146e. CONCLUSION: ATL-146e, an adenosine A(2A) agonist, reduces spinal cord reperfusion injury. The mechanism of the protection may involve a reduction in circulating TNF-alpha during a critical 3-hour reperfusion interval and reduction in spinal cord endothelial PECAM-1 upregulation.     

Resorption of intraarticular diffusible and microcolloid tracers. Rabbit studies of normal and synovitic knees

The resorption of two radiotracers (99mtechnetium-labeled microcolloid particles to study lymphatic transport and 51 chromium-EDTA to study diffusion) from the knee joint and the subcutaneous tissue of rabbits was investigated simultaneously. In 12 rabbits, synovitis was induced in the right knee 6 weeks or 3 months before the investigation; 6 rabbits served as controls. The final number of Tc-particles in the normal knees and in the subcutaneous tissue in the three groups did not differ; but removal from the synovitic knees was increased. The final number of Cr-EDTA particles did not differ within or between groups. The initial decrease was highest in the knees with acute synovitis (P less than 0.05). The results indicate (1) that in synovial tissue lymphatic transport is of little importance, (2) that leakage through the synovial membrane increases in synovitis, and (3) that a subcutaneous depot can be used as a reference instead of injections into a normal knee.